Lifestyle medicine [Third edition.] 9781138708846, 1138708844

Table of contents :
Cover......Page 1
Half Title......Page 2
Title Page......Page 4
Copyright Page......Page 5
Dedication......Page 6
Contents......Page 8
Preface......Page 14
Acknowledgments......Page 18
About the Editor......Page 20
Contributors......Page 22
James M. Rippe, MD......Page 38
1.1 Introduction......Page 40
1.1.1 The Pathophysiology of Atherosclerosis......Page 41
1.3 Primordial Prevention and “Ideal” Cardiovascular Health......Page 42
1.7.1 Tobacco Use......Page 43
1.7.3 Hypertension......Page 44
1.7.4 Diabetes and Glucose Intolerance......Page 45
1.7.6 Inactive Lifestyle......Page 46
1.7.7 Poor Nutritional Habits......Page 47
1.9 The Metabolic Syndrome and the Concept of Multiple
Risk Factors......Page 48
1.11 Other Risk Factors......Page 49
1.12.2 Genomic Approaches......Page 50
References......Page 51
Key Points......Page 56
2.4.1 Lifestyle Approach to Cigarette Smoking Cessation......Page 58
2.4.2 Lifestyle Approach to Management of Dyslipidemias......Page 61
2.4.3 Lifestyle Management of Hypertension......Page 63
2.5.1 Obesity Prevention and Management......Page 65
2.5.2 Diabetes/Glucose Intolerance......Page 66
2.5.3 Physical Inactivity......Page 67
2.7 Post Menopausal Estrogen Therapy......Page 68
Clinical Applications......Page 69
References......Page 70
Robert F. Zoeller Jr., PhD......Page 74
3.2 General Recommendations for Physical Activity......Page 75
3.3 Women and CHD......Page 76
3.5 Hypertension......Page 77
3.7.1 The Metabolic Syndrome, CVD, and T2DM......Page 78
3.8 Obesity......Page 79
3.9.3 Physical Activity and Sustained Weight Loss......Page 80
3.10 Lipids......Page 81
3.11.3 Physical Activity and Prevalence of the
Metabolic Syndrome......Page 82
References......Page 84
4.2 Elevated Total and LDL Cholesterol......Page 90
4.4 Triglycerides......Page 91
4.6 Lipid Classification and Treatment Targets......Page 92
4.7.1 Impact of Diet (see also chapter on Nutrition and
Cardiovascular Disease......Page 94
4.8 Weight Management......Page 96
4.9 Conclusions and Recommendations......Page 97
References......Page 98
5.1 Background......Page 102
5.3 Etiology of Hypertension and Relationship to
Cardiovascular Disease......Page 103
5.4 Physical Activity, Exercise, and Hypertension......Page 104
5.5 Dietary Modifications in the Prevention and
Management of Hypertension......Page 105
5.6 Weight Management......Page 106
5.6.1 Complementary Therapies......Page 107
References......Page 108
James M. Rippe, MD......Page 112
6.1 Introduction......Page 114
6.2.3 Bioactive Food Components......Page 115
6.3.1 Overview......Page 116
6.3.3 Evaluating the Diet......Page 117
6.3.5 Usual Diets and Total Intakes......Page 118
6.3.9 Measurement Error in Dietary Assessment......Page 119
6.3.11 Biomarkers of Nutritional Status......Page 120
6.4.1 The Dietary Reference Intakes (DRI......Page 122
6.4.2 Criteria for Setting Dietary Reference Intake
Recommendations......Page 123
6.4.3 The DRI Framework for Chronic Disease Risk......Page 124
6.4.6 The Challenges of Updating the DRI......Page 125
6.5.2 Dietary Patterns......Page 126
6.6 Other Terms Used in Describing Diets and Foods......Page 127
6.6.2 Determining Nutrient Quality of Foods and Diets......Page 128
6.7 Nutrient Information on Food Labels......Page 129
6.7.1 The Nutrition Facts Label......Page 130
6.7.6 Voluntary and Front of Package Labeling......Page 131
6.7.10 Supermarket Scoring Systems and Icons......Page 132
6.8.3 What Is Available Today......Page 133
References......Page 134
Elizabeth B. Rahavi, RDN, Jean M. Altman, MS, and Eve E. Stoody, PhD......Page 138
7.2 Background......Page 139
7.3.2 Key Recommendations......Page 140
7.3.4 Estimated Calorie Needs per Day......Page 141
7.3.5 Shifts Needed to Align with Healthy Eating Patterns......Page 142
7.4 Implementation by Health Professionals......Page 143
7.4.1.1 MyPlate Consumer Messages......Page 145
7.6 Looking Ahead to 2020—Expanding Guidance......Page 146
References......Page 147
8.1 Introduction......Page 148
8.3 Dietary Patterns......Page 149
8.4 Individual Food Items......Page 151
8.4.6 Dairy Products......Page 153
8.4.13 Garlic......Page 154
8.6.2 Aim for a Healthy Body Weight......Page 155
8.7 Specific AHA Nutrition and Lifestyle Recommendations......Page 156
References......Page 157
9.2 Current Recommendations......Page 162
9.3.5 Sodium......Page 164
9.4.1 Organ Systems......Page 165
9.4.4 Social Factors......Page 166
9.5.7 Cancer......Page 167
References......Page 168
10.2 Water Balance......Page 172
10.3 Sweating, Water Balance and Water Turnover......Page 173
10.4 Hydration Status and Performance......Page 174
10.5 Hydration for Recreational Activity (RPE, Energy Balance......Page 175
10.7 Hydration as Part of a Healthy Lifestyle......Page 176
References......Page 178
Edward M. Phillips, MD......Page 182
11.1 Introduction......Page 184
11.1.1.2 Exercise Physiologist......Page 185
11.1.1.4 Health Coach......Page 186
11.1.2.4 Park Rx and OutdoorsRx for Families......Page 187
Clinical Applications......Page 188
References......Page 189
12.1.1 Emergence of the Chronic Disease Pandemic......Page 190
12.1.4 Professional Organizations Set Expectations......Page 191
12.2.1 Seek Out Continuing Education to Fill
Knowledge Gaps......Page 193
12.2.4 Provide a Prescription......Page 194
12.2.6 Refer to Experts......Page 195
12.4 Conclusion......Page 196
References......Page 197
13.2 Aerobic and Anaerobic Fitness......Page 200
13.4 Determining Aerobic Fitness by Standardized Tests
using Indirect Methods......Page 201
13.5 Protocols......Page 203
13.7 Ramp Testing......Page 205
13.9 Walk Tests for Cardiorespiratory Fitness Assessment......Page 206
13.12 Muscular Strength......Page 207
13.15.2 Hydrodensiometry or Underwater Weighing......Page 208
13.16 Waist Circumference......Page 210
References......Page 211
Key Take-Home Points......Page 214
14.1 Physical Activity Recommendations......Page 215
14.2.2.2 Specificity......Page 216
14.2.2.6 Intensity of Exercise......Page 217
14.2.2.8 Frequency of Exercise......Page 218
14.3.1 Type of Resistance......Page 219
14.4 Flexibility Training......Page 220
14.7 Children and Adolescents......Page 221
14.9 Pregnancy and Postpartum......Page 222
14.10 Diabetes Mellitus......Page 223
14.11 Cancer......Page 224
Clinical Applications......Page 225
References......Page 226
Elizabeth Pegg Frates, MD......Page 228
Take Home Points......Page 230
References......Page 233
Key Points......Page 234
16.1.2 Theory of Reasoned Action, Theory of Planned
Behavior, Integrated Behavior Model......Page 235
16.3.1 Social Cognitive Theory......Page 237
16.4.1 Socioecological Model......Page 238
16.5 Theory-Based Healthy Lifestyle Intervention in
Research and Practice......Page 239
16.6 Summary......Page 240
References......Page 241
17.1 Introduction......Page 244
17.2 What is Motivational Interviewing......Page 245
17.2.1 Research and Evidence......Page 246
17.3.2 Engaging......Page 247
17.3.4 Evoking......Page 250
17.3.5 Planning......Page 252
References......Page 253
18.2 Stages of Change......Page 256
18.3.6 Principle 6......Page 258
18.3.7 Principle 7......Page 260
18.5 Increasing Impacts with Multiple Behavior Change
Programs......Page 261
18.7 Multiple Domains of Well-Being: From Suffering or
Struggling to Thriving......Page 262
18.8 Conclusions......Page 263
References......Page 264
Key Points......Page 266
19.1.1 The PERMA Model......Page 267
19.2.1 Positive Psychology Factors and
Cardiovascular Disease......Page 268
19.2.3 Positive Psychology Factors and Mortality......Page 269
19.3 Positive Psychology Interventions......Page 270
19.3.2 Positive Psychology Technological Devices......Page 271
19.4.2 Having Positive Health Conversations with
Patients......Page 272
19.4.4 Incorporating a Health Coach Trained in Positive
Psychology Principles into Your Practice......Page 273
References......Page 274
20.1 Introduction......Page 278
20.1.1 What Is the Intention–Behavior Gap......Page 279
20.2.4 When to Intend......Page 280
20.3.1.2 Review......Page 281
20.3.2.2 Review......Page 282
20.3.3.2 Review......Page 283
20.3.3.3 Practical Application......Page 284
20.3.4.2 Review......Page 285
20.4 Summary......Page 286
References......Page 287
21.1 Introduction......Page 290
21.1.1 Overview of Current Physical Activity Guidelines......Page 292
21.2 Emerging Technologies for Physical Activity Monitoring
and Interventions......Page 293
21.2.2 Computer and Web-Based Interventions......Page 294
21.2.3 Mobile Phones and Devices......Page 295
21.3 Expanding the Targets of Activity Promotion: Assessing
and Targeting SB......Page 296
21.4 Physical Activity Interventions in Racial /Ethnic
Underserved Samples......Page 298
21.6 Environmental Factors in PA......Page 299
21.7 Maximizing Real-World Translation—Effective PA
Intervention Dissemination......Page 300
21.7.1 Dissemination of Effective Physical Activity
Interventions through Counseling for Preventive Care
in Clinical Settings......Page 301
Clinical Applications......Page 302
References......Page 303
Key Points......Page 306
22.1.1 Nutrition, a Snapshot......Page 307
22.1.3 Portion Control......Page 308
22.2 Cultural Sensitivity and Nutrition......Page 309
22.3 Effective Counseling Techniques for the Nutritional
Prescription......Page 310
22.4 Nutrition Counseling and Education in the Group
Medical Visit Model......Page 311
22.5 Practical Culinary Skills to Ease Behavioral Change......Page 313
References......Page 316
23.1.1 Physiological Response......Page 318
23.2 Building Resilience......Page 319
23.3 Mind-Body Therapies......Page 321
23.3.1.2 Body Scan......Page 323
23.3.1.3 Guided Imagery......Page 325
23.3.2.2 Tai Chi......Page 326
23.3.3 Gratitude......Page 327
23.3.5.1 Teaching Patients to Change their Mind......Page 328
23.3.6.1 Nutrition and Stress......Page 329
23.4 The Role of Technology in Stress Management......Page 330
References......Page 331
24.1 Introduction......Page 336
24.2.1 Theoretical Platform and Historical Underpinnings......Page 337
24.2.2 Coaching versus Therapy......Page 338
24.2.4 Standardizing the Field of Health and Wellness
Coaching (HWC......Page 339
24.2.5 Health and Wellness Coach Training and
Education......Page 340
24.3.1 Client and Patient Populations and Care Settings......Page 341
24.3.3 Health and Wellness Coaching Payment Models......Page 342
24.4.1 Current Evidence Base......Page 343
24.5.3 Hiring Health and Wellness Coaches......Page 344
Clinical Applications......Page 345
References......Page 346
25.1 Introduction......Page 348
25.2 Section 1: Text Messaging......Page 350
25.2.2 Considerations for Implementation......Page 351
25.3.1 Outcomes......Page 352
25.4 Section 3: Wearables, Sensors, and Devices......Page 353
25.4.2 Considerations for Implementation......Page 354
25.5.2 Considerations for Implementation......Page 355
25.6.1 Outcomes......Page 356
25.7.2 Virtual and Augmented Reality......Page 357
25.8 Conclusion......Page 358
References......Page 359
Paulette Chandler, MD, MPH......Page 366
26.2 Epidemiology......Page 368
26.5 Epigenetics......Page 369
26.7 Screening......Page 370
26.10 Obesity......Page 371
26.10.2 Sleep......Page 372
26.10.6 Stress Reduction......Page 373
26.10.12 Vitamin E and Vitamin C......Page 374
References......Page 375
27.1 Introduction......Page 378
27.2.3 School-Based Physical Activity and Young Girls......Page 379
27.3.4 ACL Injuries in Female Athletes......Page 380
27.4.1 The Female Athlete Triad......Page 381
27.4.2 Contraceptive Use in Active and Athletic Females......Page 383
27.4.3 Exercise During Pregnancy and the Post-Partum......Page 384
27.5.5 The Role of Regular Physical Activity in Breast
Cancer Prevention and Management......Page 385
References......Page 386
Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU......Page 390
28.1 Introduction......Page 392
28.2.1 Carbohydrate Metabolism......Page 393
28.2.3 Fructose......Page 394
28.2.6 Antioxidants......Page 395
28.2.7 Plant Polyphenols......Page 396
28.2.9 Systemic Inflammation......Page 397
28.3.1 Mediterranean Diets......Page 398
28.4 Physical Activity......Page 399
References......Page 400
Karla I. Galaviz, PhD, MSc, Lisa Staimez, PhD, MPH, Lawrence S. Phillips, MD, and Mary Beth Weber, PhD, MPH......Page 404
29.2 The Role of Lifestyle Factors in the Development of
Prediabetes......Page 406
29.3 Lifestyle Interventions for Prediabetes Prevention and
Treatment......Page 408
29.4.2 Weight Loss......Page 410
29.4.4 Physical Activity and Diet Behavior Change......Page 411
29.5 Preventing and Managing Prediabetes in the Real World......Page 413
References......Page 414
30.1 Introduction......Page 420
30.3 Type 1 Diabetes......Page 421
30.3.2.2 Physical Activity/Exercise......Page 422
30.4.1.1 Medical Nutrition Therapy......Page 424
30.4.1.2 Physical Activity......Page 425
30.5 Gestational Diabetes......Page 426
30.5.1.1 Medical Nutrition Therapy......Page 427
Clinical Applications......Page 428
References......Page 429
31.1 Introduction and Context......Page 430
31.2 Primary Prevention......Page 431
31.3 Secondary and Tertiary Prevention: Can Pathology be
Reversed......Page 432
31.4.2 100% Plant-Based Eating Patterns......Page 433
31.4.5 Grain Intake......Page 436
31.4.7 Low Protein Diet......Page 437
31.4.9 Meal Timing and Intermittent Fasting......Page 438
Clinical Applications......Page 440
References......Page 441
Cindy D. Davis, PhD and Sharon Ross, PhD, MPH......Page 444
32.2 Total Fruits and Vegetables......Page 446
32.3.1 Garlic and Allium Vegetables......Page 447
32.3.2 Folate......Page 448
32.4 Dietary Fiber......Page 449
32.5 Meat Intake......Page 450
32.6 Alcohol......Page 451
References......Page 452
33.1 Introduction......Page 456
33.2 Mechanisms of Obesity Impact on Cancer......Page 457
33.3 Strategies to Disrupt the Obesity–Cancer Linkage......Page 459
33.4.1.3 Prioritize Healthy Eating Patterns—Rich
in Whole Foods, Plant-based Elements......Page 460
33.4.1.6 Lose Weight If You Are Overweight
or Obese......Page 461
33.4.2.5 Make Dietary Changes to Achieve
Weight Loss......Page 462
33.4.3 Type 2 Diabetes Mellitus and Cancer Risk......Page 463
References......Page 464
34.2.1 Overview......Page 468
34.2.2 The Role of Physical Activity in Primary Cancer
Prevention......Page 469
34.3 Defining “ Health-Enhancing” Physical Activity......Page 470
34.3.2 Physical Activity Guidelines for Cancer
Populations......Page 471
34.4.1 Barriers to Physical Activity for Healthy
Populations......Page 472
34.5 Strategies for Physical Activity Interventions......Page 473
References......Page 474
35.2 Malnutrition and Cancer Cachexia......Page 478
35.3.2 Altered Fat Metabolism......Page 479
35.4 Nutrition Screening......Page 480
35.5.2 Lifestyle Strategies When Eating During Treatment......Page 481
35.6 Complementary and Restorative Therapeutic
Treatment of Cancer......Page 483
35.6.1 Special and Alternative Diets—Metabolic
Therapy vs. Dietary Approaches......Page 484
35.6.3 Fasting Diet......Page 485
Acknowledgments......Page 486
References......Page 487
John P. Foreyt, PhD......Page 490
36.1 Obesity and Adiposity......Page 492
36.2.3.1 Body Mass index (BMI......Page 493
36.2.3.4 Waist-to-Height Ratio (WHtR) or
Waist-Stature Ratio (WSR......Page 494
36.3 Prevalence of Obesity......Page 495
36.3.1 U.S. Obesity Trends......Page 496
36.3.2 Global Obesity Trends......Page 497
36.4.1 Energy Imbalance......Page 498
36.4.3 Infections......Page 499
36.6 Economic Costs of Obesity in the U.S......Page 500
36.6.2.1 Presenteeism and Absenteeism......Page 501
36.6.2.2 Disability and Premature Mortality......Page 502
References......Page 503
37.2 Effect of Physical Activity on Prevention of Weight Gain......Page 510
37.3.3 Yoga......Page 511
37.3.6 Duration of Physical Activity Bouts......Page 512
37.3.8 The Role of Physical Activity in Surgically
Induced Weight Loss......Page 513
37.4.4 Factors Influencing Adherence to Physical Activity......Page 514
37.5.2.1 Blood Pressure......Page 515
37.6 Summary and Clinical Applications......Page 516
References......Page 517
38.2 Medical Assessment......Page 520
38.4.1 Determining Energy Expenditure......Page 521
38.5 Determining Eating Environment and Readiness For
Intervention......Page 522
38.6 Dietary Intervention......Page 523
38.7 Intensity of Intervention......Page 524
References......Page 525
39.1 Obesity: A Serious Condition......Page 528
39.3.1.1 Phentermine (Adipex, Ionamin, Lomaira......Page 529
39.3.1.4 Phendimetrazine (Bontril, Prelu-2......Page 530
39.3.2.2 Lorcaserin (Belviq TM, Belviq XR TM......Page 531
39.3.2.3 Phentermine-Topiramate ER (Qsymia......Page 532
39.3.2.4 Naltrexone ER-Bupropion SR (Contrave......Page 533
39.3.2.5 Liraglutide (Saxenda......Page 534
39.4.2 Who Should Receive Pharmacotherapy for
Obesity......Page 535
39.4.3 Special Consideration for FDA Indications and
the State Law......Page 536
39.4.5 Optimizing Weight Management During Longterm
Continuity of Care......Page 537
References......Page 538
40.1 Introduction......Page 542
40.2 Bariatric Surgical Procedures......Page 543
40.5 Weight Loss Outcomes and Improvement in Obesity-
Related Medical Conditions......Page 544
40.7.3 Prevention of Micronutrient Deficiencies after
Bariatric Surgery......Page 545
40.7.8 Recommendations for Physical Activity after
Bariatric Surgery......Page 547
40.7.12 Alcohol Misuse......Page 548
40.7.14 Comprehensive Lifestyle Interventions after
Bariatric Surgery......Page 549
References......Page 550
41.1 Introduction......Page 554
41.3 Intensive Lifestyle Intervention......Page 555
41.4 Sleep Hygiene......Page 557
41.5 Stress Reduction......Page 558
41.6.3 Endocrine Disruptors......Page 559
41.9 Community Engagement......Page 560
References......Page 561
42.1 Introduction......Page 566
42.2.3 Payment Systems that Favor Treating Obesity
Complications......Page 567
42.3.2 Accounting for Complex Systems Driving Obesity......Page 568
42.4.2 Precision Medicine......Page 569
References......Page 570
Gregory A. Hand, PhD, MPH, FACSM, FESPM......Page 574
43.2 Chronic Anti-Inflammatory Influence of Exercise Training......Page 576
43.4 Potential Mechanisms......Page 577
43.6 Moderate Physical Activity and URTI Risk......Page 578
References......Page 580
44.2.1 Monocytes and Tissue Macrophages......Page 584
44.2.3 Neutrophils......Page 585
44.4.1 Th1/Th2 Balance......Page 586
44.4.3 Excessive Training: URS or URTI......Page 587
44.5.2 Wound Healing......Page 588
Acknowledgments......Page 589
References......Page 590
45.1 Introduction......Page 592
45.4.1 Psychological Consequences......Page 593
45.4.4 Toxic Side Effects......Page 594
45.5.2 Exercise as Medicine for Managing Art Toxicities......Page 595
45.5.6 Immune System......Page 596
45.6 Conclusion......Page 597
References......Page 598
46.2 Exercise and “Inflammaging......Page 600
46.3.2 Cholinergic Anti-inflammatory Pathway......Page 601
46.5 Effect of Exercise on T-cell Mediated Immunity in
the Aged......Page 602
46.6.1 Cross-Sectional Studies......Page 603
Clinical Applications......Page 604
References......Page 605
Nicholas A. Smyrnios, MD, FACP, FCCP......Page 608
47.1 Introduction......Page 610
47.2.2.1 Spirometry......Page 611
47.2.2.4 Pulse Oximetry......Page 612
47.3.2 Physiology of Dyspnea......Page 613
47.3.3 Qualities of Dyspnea......Page 614
47.3.4.1 Timing: Acute vs. Chronic Dyspnea......Page 615
47.3.4.3 Position......Page 616
47.4.1 Definition and Physiology......Page 617
47.4.4 Subacute and Chronic Cough with Clear
Chest X-Ray......Page 618
47.4.5 Chronic Cough with an Abnormal Chest X-Ray......Page 619
47.5.2 Etiology......Page 620
47.6.2 Etiology......Page 621
47.7.2 Etiology......Page 622
47.7.3 Essentials of the History......Page 623
References......Page 624
48.1 Introduction......Page 626
48.3.2 Airway Inflammation......Page 627
48.3.4 Management......Page 628
48.3.5 Monitoring Disease Activity......Page 629
48.4.1 Environmental Control......Page 630
48.4.3 Outdoor Allergens......Page 631
48.5.1 Chronic Controllers......Page 632
48.5.5 Omalizumab......Page 633
48.5.9 Bronchial Thermoplasty......Page 634
48.6 Management of Asthma according to Severity and
Control Classification......Page 635
48.6.2 Asthma Complications......Page 637
48.6.3 Allergy Testing and Immunotherapy......Page 638
48.6.4 Exercise and Asthma......Page 639
48.6.5 Occupational Asthma......Page 640
48.6.9 Medication-Induced Asthma......Page 641
48.6.11 Pregnancy and Asthma......Page 642
References......Page 643
49.1.1 Epidemiology......Page 648
49.1.6 Clinical Presentation and Diagnosis......Page 649
49.1.10 Asbestos-Related Lung Disease......Page 650
49.1.14 Clinical Presentation and Diagnosis......Page 651
49.2 Clinical Presentation and Diagnosis......Page 652
49.5.1 High-Altitude Illnesses......Page 653
49.5.4.2 Acetazolamide......Page 654
References......Page 655
50.2 Epidemiology......Page 658
50.4 Embolization to the Pulmonary Vasculature......Page 659
50.5.2 Obesity......Page 660
50.5.3 Smoking......Page 661
50.5.4 Diagnosis......Page 662
50.5.6 Massive PE......Page 663
References......Page 664
51.3 Virology of Influenza Virus......Page 668
51.5 Epidemiology of Influenza......Page 669
51.8.1 Seasonal Influenza......Page 670
51.9 Laboratory Diagnosis of Influenza......Page 671
51.10.2 Chemoprophylaxis......Page 672
51.11 Antiviral Therapy......Page 673
References......Page 674
52.2 Secondhand Smoke......Page 676
52.5 Carbon Monoxide......Page 678
52.6 Indoor Mold......Page 679
52.8 Dust Mites......Page 680
52.11 Water Pipe Smoking (also known as Hookah......Page 681
52.13 Contamination of Home Showerheads, Dishwashers,
and CPAP Devices......Page 682
References......Page 683
Amanda McKinney, MD, FACLM, FACOG, CPE......Page 688
53.2 Ovulatory Infertility......Page 690
53.3 Pregnancy Outcomes......Page 691
53.5 Preeclampsia......Page 692
53.6 Fetal Impacts of Maternal Lifestyle......Page 693
53.7 Autism......Page 694
References......Page 695
54.1.1 Weight Management......Page 700
54.2 Glycemic Control......Page 701
54.4 Psychological Benefits......Page 702
54.9 Spontaneous Abortion......Page 703
54.11 Low Birth Weight......Page 704
54.14 Contraindications to Exercise in Pregnancy......Page 705
54.17 Duration/Frequency......Page 706
Clinical Applications......Page 707
References......Page 708
Julia Head, MD, Stephanie-Marie L. Jones, MD, Marcie K. Richardson, MD, and Angela Grone, MD, FACOG......Page 710
55.2.2 Hormonal Influences......Page 711
55.3.1 Maternal Benefits......Page 712
55.3.2.1 Gastrointestinal Effects......Page 713
55.3.2.5 Neurodevelopment......Page 714
55.4 Practical Management of Breast-Feeding......Page 715
55.4.1 Assessment of Intake Adequacy......Page 716
55.5.3 Prior Breast Surgery......Page 717
55.6.1 Pumping Breast Milk (Working and Nursing......Page 718
References......Page 719
Books for Patients......Page 722
56.1 Introduction......Page 724
56.2.1 Mechanism of Action of COCs......Page 725
56.3.1 Mechanism of Action and Clinical
Considerations with Patches......Page 726
56.4.2.1 Mechanism of Action of DMPA......Page 727
56.4.2.7 DMPA Effect on Future Fertility......Page 728
56.5.2.1 IUD Options and Mechanisms of Action......Page 729
56.6.2 Efficacy of EC......Page 730
56.7.3 Sterilization......Page 731
References......Page 732
57.1.2 Education about STIs......Page 734
57.1.5 Male Circumcision and STIs......Page 735
57.2.3.3 Lesbians, Gay, Bisexual, and
Transgender (LGBT......Page 736
57.3.3 Chlamydia......Page 737
57.3.5 Syphilis......Page 738
57.3.8 Hepatitis C Virus......Page 739
57.3.10 Herpes Simplex Virus......Page 740
57.3.13 Molluscum Contagiosum......Page 741
References......Page 742
58.1 Lifestyle-Related Menstrual Disorders......Page 744
58.3 Menopause Background......Page 745
58.4 Menopause Management......Page 746
References......Page 749
59.2.1 Epidemiology/Risk Factors......Page 752
59.2.2 Screening......Page 753
59.2.3 Lifestyle......Page 754
59.3.1 Epidemiology/Risk Factors......Page 756
59.3.2 Screening......Page 757
59.3.3 Lifestyle......Page 759
59.4.1 Epidemiology/Risk Factors......Page 760
59.4.2 Screening......Page 761
59.4.3 Lifestyle......Page 762
59.5.1 Epidemiology/Risk Factors......Page 763
59.5.3 Lifestyle......Page 764
References......Page 765
Kathy Berra, MSN, NP-BC, FAANP, FPCNA, FAHA, FAAN and Barry A. Franklin, PhD......Page 770
60.1 Optimal Medical Management in Secondary Prevention......Page 772
60.3 Medication Nonadherence: Scope of the Problem......Page 773
60.4 Factors Contributing to Medication Nonadherence......Page 774
References......Page 775
61.1 Introduction......Page 778
61.2 Effectiveness and Role of Home-based Alternative
Cardiac Rehabilitation and Secondary Prevention
Delivery Models......Page 780
61.3 Effectiveness of Digital Health Technologies for
Lifestyle Intervention and CVD Secondary Prevention......Page 781
61.5 Case Study of an Evidence-based, Digital Health
Technology-enabled, CVD Risk Reduction Program......Page 783
References......Page 786
62.1 Meet Secondary Prevention Patient Patricia......Page 788
62.3 Psychosocial Factors in Heart Disease......Page 789
62.5.1 Screening for Depression......Page 790
62.5.4 Psychotherapy......Page 791
62.5.6 Depression in Heart Failure......Page 792
62.6.2 Easier Treatments for Psychosocial Factors......Page 793
References......Page 794
63.1 A Teachable Moment......Page 798
63.4 Exercise Regularly......Page 800
63.6 Manage Stress......Page 801
Clinical Applications......Page 802
64.3 Dietary Therapy......Page 804
64.5 Managing Statin-associated Muscle Complaints......Page 805
64.6 PCSK9 Inhibitors......Page 806
References......Page 807
65.1 Introduction......Page 808
65.2 Nutrition......Page 809
65.3 Physical Activity......Page 810
65.5 Psychosocial Health......Page 812
References......Page 814
66.2.1 Social Learning Theory......Page 818
66.3.2 Efficacy of Motivational Interviewing based on
the Science......Page 819
66.5 Elements of Health Behavior Change......Page 820
References......Page 822
67.1 Introduction: Background and Rationale......Page 824
67.3 Exercise-Related Cardiovascular Events......Page 826
67.4 Prophylactic Strategies to Reduce the Risk of Activity......Page 827
67.5 Exercise Dosage and Survival: A Reverse J-Shaped
Association......Page 828
67.7 Extreme Exercise and Immunity to Heart Disease......Page 829
67.7.3 Cardiovascular Risk of Marathon Running
and Triathlon Participation......Page 830
67.9 Exercise and Atrial Fibrillation......Page 831
Clinical Implications......Page 833
References......Page 834
68.1 Introduction......Page 838
68.4 Does MHO Exist......Page 839
68.5 The Obesity Paradox......Page 840
68.7 Modifying Lifestyle......Page 842
References......Page 844
69.2 Multivitamins......Page 848
69.3.2 Niacin......Page 849
69.3.4 Vitamin D......Page 850
69.4.1 Coenzyme Q10......Page 851
69.4.2 Fish Oil......Page 852
69.4.6 Selenium......Page 853
69.5 Over-the-Counter (OTC) Dietary Supplement Selection......Page 854
Clinical Applications......Page 856
References......Page 857
70.1 Introduction: Intensive Cardiac Rehabilitation......Page 862
70.2 Evolution of Traditional and Intensive Cardiac
Rehabilitation......Page 863
70.3.2 Blood Lipid Profile......Page 864
70.3.5 Psychosocial Function and Quality of Life......Page 865
70.4 Intensive Cardiac Rehabilitation: Considerations and
Future Directions......Page 866
70.5 Conclusion......Page 867
References......Page 868
71.2 Background......Page 870
71.3 Current Models of CR......Page 871
71.6 Novel Models to Improve Delivery of CR......Page 872
71.7 Areas for Future Work......Page 873
References......Page 874
72.1 Rationale for a Life Course Approach to CVD Prevention......Page 878
72.2.2 Shared Family Environment......Page 879
72.3 Family-Focused Primordial and Primary Preventive
Interventions......Page 880
72.4 Lessons Learned and Future Directions......Page 882
References......Page 883
Stephen R. Daniels, MD, PhD......Page 886
Key Points......Page 888
73.2.1 Social-Ecological Model......Page 889
73.3 Principles of Behavior......Page 890
73.5 Family-Based Behavioral Treatment......Page 892
73.7 Skill vs. Motivation Deficits......Page 893
73.9 Behavioral Economics......Page 894
References......Page 895
74.1 Introduction......Page 898
74.2.1 Undernutrition......Page 899
74.2.2 Overnutrition......Page 900
74.2.5 Endocrine Disrupting Chemicals (EDCs......Page 901
74.3.2 Shared Environment......Page 902
74.4.2 Pregnancy......Page 903
References......Page 904
75.1 Introduction......Page 910
75.2 Habitual Physical Activity Versus Systematic Training......Page 911
75.3 Sedentary Behaviors and CMRF......Page 912
75.4 Physical Fitness and Health......Page 913
75.5.1 Anthropometry......Page 916
75.5.3 Cardiorespiratory Fitness......Page 917
75.6 Key Mechanisms Linking Physical Activity to the
Clustering of CVD Risk Factors......Page 918
References......Page 919
76.1 Introduction......Page 924
76.2.2 Diet and Lifestyle Approaches to Management......Page 925
76.2.3 Clinical Applications......Page 926
76.3.1 Definitions and Targets for Lifestyle Therapy......Page 927
76.3.2 Dietary and Other Lifestyle Approaches to
Management of Dyslipidemia......Page 928
76.3.3 Strategies to Improve Compliance to a
CHILD-2 Diet......Page 930
76.4.2.1 Weight Management......Page 931
76.4.2.3 Sodium......Page 932
References......Page 933
77.2 Poor Sleep Health in Children and Adolescents......Page 938
77.3.2 Sleep and Diet......Page 939
77.5.1 Assessment of Sleep Behaviors and Symptoms......Page 940
77.5.2 Treatment of Sleep Disorders......Page 941
Clinical Applications......Page 942
References......Page 943
78.1 Introduction......Page 946
78.4 Etiologies......Page 947
78.7.2 Clinical Weight Loss Goals......Page 948
Mind, Exercise, Nutrition…Do It! (MEND......Page 950
Meal Replacement Products......Page 951
78.7.10 Anti-Obesity Medications......Page 952
Clinical Applications......Page 953
References......Page 954
79.1 Background......Page 958
79.3.2 When Should I Screen and What Laboratory
Studies Should I Obtain......Page 959
79.3.3 Evaluation for Secondary Causes of Dyslipidemia......Page 960
79.5.1 Heterozygous Familial Hypercholesterolemia......Page 961
79.5.2 Familial Combined Hyperlipidemia......Page 962
79.6.6 How to Initiate, Titrate, and Monitor
Children on Statin Medication......Page 963
79.6.7 Therapy Goals......Page 965
79.6.8 Hydroxy-3-Methylglutaryl-CoenzymeA
Reductase Inhibitors (Statins......Page 966
79.6.10 Cholesterol Absorption Inhibitors......Page 967
79.8 Familial Hypertriglyceridemia......Page 968
79.9.2 Pharmacologic Therapy......Page 969
Clinical Applications......Page 970
References......Page 971
80.1 Introduction......Page 974
80.4 Diagnosis......Page 975
80.7 White Coat Hypertension (WCH......Page 977
80.13 Sleep Disordered Breathing (SDB) and Obstructive
Sleep Apnea (OSA......Page 978
80.16.1 Left Ventricular Hypertrophy (LVH......Page 979
80.17.3 Summary of the 2017 Clinical Practice
Guidelines Key Action Statements......Page 980
80.17.5.2 Labs......Page 981
80.17.5.3 Repeat Visit Four Weeks Later......Page 983
References......Page 985
81.2 Bone Accrual during Growth and Maturation......Page 988
81.4.1 Physical Activity......Page 989
81.4.2 Nutrition......Page 990
81.4.3 Tobacco Use......Page 991
Physical Activity......Page 992
References......Page 993
George Guthrie, MD, MPH, CDE, CNS, FAAFP, FACLM......Page 996
82.1 Defining Lifestyle Medicine......Page 998
82.2 Dimensions of the Definition......Page 999
82.3 Definition Constructs......Page 1001
82.4 Categories of Medicine......Page 1002
82.6 Unique Role of Lifestyle Medicine within
Allopathic Medicine......Page 1003
References......Page 1004
83.1 Introduction: Background and Driving Forces for Core
Competencies......Page 1006
83.4 Lifestyle Medicine Core Competencies Training......Page 1007
83.5 Competencies for Lifestyle Medicine Certification......Page 1008
83.6 The Ongoing Evolution of Lifestyle Medicine
Competencies......Page 1011
Books......Page 1012
References......Page 1013
Key Points......Page 1014
84.2.2 Physical Activity Assessment......Page 1015
84.2.3 Nutrition Assessment......Page 1018
84.2.4.3 Mental and Emotional Wellbeing......Page 1020
84.2.7 Diabetes Risk Assessment......Page 1021
84.3.3.2 Cardiorespiratory Fitness Testing......Page 1022
84.3.3.7 Muscular Fitness Testing......Page 1023
84.6 Chronic Care Model......Page 1024
84.6.1 Components of the Chronic Care Model......Page 1025
84.6.2 Sample Effective Programs......Page 1026
84.8.1 Process Mapping......Page 1027
84.8.2 Plan–Do–Study–Act......Page 1028
References......Page 1029
85.2.1 Excessive BMI and Metabolic Disorders......Page 1032
85.3 Circadian Biology in Relation to Sleep......Page 1033
85.4 Sleep Assessment......Page 1034
85.5.2 Dietary Habits for Sleep Enhancement......Page 1036
Clinical Applications......Page 1037
References......Page 1038
86.1 Introduction......Page 1040
86.3 Factors Affecting Emotional Well-Being and Mental
Health......Page 1041
86.4.5 Learn How to Deal with Anger......Page 1042
86.7 Stress Response......Page 1043
86.8 Stress Management......Page 1044
86.8.1.1 Calming the Mind and Body......Page 1045
86.8.1.5 Bright Light to Improve Mood......Page 1046
86.8.1.9 Caffeine......Page 1047
86.8.1.12 Spirituality Aids Stress Management......Page 1048
86.10 Management......Page 1049
References......Page 1050
87.1 Definition of ITLC: Contrast and Comparison with TLC
(Non-intensive Therapeutic Lifestyle Change......Page 1056
87.2 Conclusions......Page 1068
References......Page 1069
88.2.1 Summary of Male Physicians’ Health in the
United States......Page 1070
88.3 Physicians’ Personal Habits and Patient Health......Page 1071
88.5 Which Determinants Matter Most When It Comes to
Physicians Counseling Patients......Page 1072
88.5.2 Individual Case Study #2: Exercise Vanquishes
Stress......Page 1073
88.7 Healthier Physician Habits: Patients Respond......Page 1075
88.9 The Healthy Doctor = Healthy Patient Project......Page 1076
88.9.1 More on Medical Students and Personal–
Clinical Relationships......Page 1077
88.9.3 Intervention for Medical Students: A Large-
Scale Case Study......Page 1078
Clinical Applications......Page 1080
References......Page 1081
Elizabeth Pegg Frates, MD and Joji Suzuki, MD......Page 1082
Key Points......Page 1084
References......Page 1086
90.1 Alcohol......Page 1088
90.2 Opioids......Page 1089
90.4 A Revival of Addiction Treatment in America......Page 1090
90.5 Summary......Page 1091
References......Page 1092
91.1 Health Consequences of Smoking......Page 1094
91.5 Behavioral Smoking Cessation Strategies......Page 1095
91.6.4 Motivational Interviewing......Page 1096
91.7.1 Primary Care Visits......Page 1097
91.8.2 Worksite Programs......Page 1098
91.10.1 Young Adult and Adolescent Smokers......Page 1099
91.11.1 Exercise......Page 1100
91.12 Summary and Conclusions......Page 1101
References......Page 1102
92.1 Epidemiology......Page 1106
92.2.1 Pharmacology of Alcohol......Page 1107
92.2.2 Stages of Addiction......Page 1108
92.3.1 Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition (DSM V) Criteria for
Diagnosis......Page 1109
92.3.3 Special Populations: Elderly......Page 1110
92.4 Medical Comorbidities......Page 1112
92.5.1.2 Inpatient versus Outpatient Setting......Page 1113
92.5.2 Maintenance of Sobriety and Relapse
Prevention......Page 1114
92.5.2.2 Behavioral Treatments......Page 1115
92.6 In Summary......Page 1117
References......Page 1118
93.2 Risk Factors for Opioid Use Disorders......Page 1120
93.3 Diagnosis of Opioid Use Disorder (DSM-5 criteria......Page 1121
93.5.2 Disadvantages......Page 1123
93.7 Naltrexone and XR-Naltrexone......Page 1124
93.8 Integration of Psychosocial Support in Treatment......Page 1127
References......Page 1128
94.2.1 Prenatal Exposure......Page 1130
94.2.4.2 Cannabis Use Disorder......Page 1131
94.2.4.4 Psychiatric Comorbidity......Page 1132
94.3.2 Cannabis Use Disorder Treatment......Page 1133
94.3.4 Use of Cannabis for Psychiatric Conditions......Page 1135
Clinical Applications......Page 1136
References......Page 1137
Emily Wu, MD and John Torous, MD......Page 1142
95.3 Smartphone Technology in Substance Use Disorders......Page 1143
95.5 Smartphone-Based Intervention in Smoking Cessation
Treatment......Page 1144
95.6 Smartphone-Based Intervention in Pathological
Gambling Treatment......Page 1145
Clinical Applications......Page 1146
References......Page 1147
96.1 Behavioral Couples Therapy (BCT......Page 1150
96.3 Cognitive Behavioral Coping Skills Therapy (CBT......Page 1151
96.8 Brief Interventions......Page 1152
96.11 American Society of Addiction Medicine’s (ASAM’s)
Levels of Care......Page 1153
References......Page 1155
Arthur S. Leon, MS, MD, FACSM......Page 1158
Key Points......Page 1160
References......Page 1162
98.1 Skeletal Muscle Function......Page 1164
98.6 Muscle Fiber Change......Page 1165
98.8 Apoptosis......Page 1166
98.12 Reduced Anabolic Hormone Activity......Page 1167
98.13 Reduced Blood Supply......Page 1168
98.17 Reduced Oxidative Stress......Page 1169
98.21 Skeletal Muscle Hypertrophy......Page 1170
98.25 Adequate Food Energy Intake......Page 1171
98.27 Adequate Vitamin D Blood Levels......Page 1172
98.28 Food-Derived Antioxidants......Page 1173
References......Page 1174
Key Points......Page 1178
99.6 Alzheimer Disease (AD......Page 1179
99.9 Traumatic Brain Injury (TBI......Page 1180
99.14 Vitamin D......Page 1181
99.16 Conclusions......Page 1182
References......Page 1183
100.1 Defining Successful Aging......Page 1184
100.3 Life-Course Approach to the Study of Aging......Page 1185
100.5.1 Exercise or Physical Activity......Page 1186
100.5.2 Cognitive Training and Stimulation......Page 1187
100.5.4 Social Engagement and Volunteerism......Page 1188
100.7 Role of Health care Practitioners in the Promotion
of Successful Aging......Page 1189
100.8 Summary......Page 1190
References......Page 1191
101.1 Introduction......Page 1194
101.2 Benefits of Physical Activity for Older Adults......Page 1195
101.3.3 Balance Training for Older Adults......Page 1196
101.4.4 Health Contract or Plan of Action—Making
a Commitment......Page 1197
101.5.2 Step 2—Making Physical Activity Part of
Your Life......Page 1198
101.6.2 Question: How Much Physical Activity Do
I Need......Page 1199
101.6.6 Question: Will Physical Activity Help to Reduce
My Risk for Specific Diseases and Conditions......Page 1200
101.6.9 Question: Do I Need Special Clothing and
Equipment......Page 1201
References......Page 1202
Dee W. Edington, PhD......Page 1204
102.1 Chapters and Authors......Page 1206
103.2 Integrated Models of Population Health......Page 1208
103.5 Emerging Trends and Technologies......Page 1209
References......Page 1210
104.2 Best Business Practices......Page 1212
104.3 The Power of Lifestyle and Lifestyle Medicine......Page 1213
104.4.1 Differentiating Stakeholders and Finding
the Right Partners......Page 1214
104.5 Conclusion......Page 1215
References......Page 1216
105.2 Why......Page 1218
105.4 Shared Accountability......Page 1220
105.6 USPM Program Outcomes......Page 1221
105.6.1 Client Case Study Results......Page 1222
105.6.2 Intel-GE Validation Institute Recognition of
U.S. Preventive Medicine......Page 1224
Clinical Applications......Page 1225
References......Page 1226
106.1 Overview......Page 1228
106.4 Health Risk Assessment......Page 1229
106.7 Tobacco......Page 1230
106.9 Physical Activity......Page 1231
106.13 Technology......Page 1232
Clinical Applications......Page 1233
References......Page 1234
107.1 Introduction......Page 1236
107.2 Healthy Places: Pioneering Organizations and
Individuals......Page 1237
107.3 Building a Theoretical Framework Connecting Health
and Place......Page 1238
107.4 Co-Producing Healthy Change......Page 1240
References......Page 1243
108.1 Introduction......Page 1246
108.6 Controlled Motivation......Page 1247
108.11 Help Patients Strengthen their Willpower “Muscle......Page 1248
108.13 Holding Compassion......Page 1249
108.16 Motivational Interviewing......Page 1250
References......Page 1251
Alyssa B. Schultz, PhD......Page 1254
109.2 The Future of Health Promotion: The Settings Approach......Page 1256
109.4 Advanced Definitions of Health......Page 1257
109.7 Behavior Change......Page 1258
109.10 Conclusion......Page 1259
Steven J. Petruzzello, PhD......Page 1260
110.1 Windows into the Thinking Mind......Page 1262
110.2 Windows into the Feeling Mind......Page 1264
110.4 “Looking through Strained-Glass Windows”: The
Impact of Stress on the Body/Mind......Page 1266
References......Page 1269
111.2 Definitions of Voluntary Exercise Behavior......Page 1272
111.3 Prevalence of Voluntary Exercise Behavior......Page 1273
111.4 Twin Studies on Voluntary Exercise Behavior......Page 1276
111.5 Family Studies on Voluntary Exercise Behavior......Page 1283
References......Page 1284
112.1 Introduction and Organization of the Chapter......Page 1288
112.2 A Brief History of Exercise Neuroscience......Page 1289
112.3 Exercise and Aging: Normal vs Pathologic......Page 1290
112.5 Neurotransmitters......Page 1292
112.6 Neurotrophic Factors......Page 1293
112.9 Angiogenesis......Page 1294
112.11 Attenuation of Glucocorticoids......Page 1295
112.12 How Does Physical Activity Counteract Normal and
Pathological Cognitive Aging......Page 1296
112.13 Cognitive Reserve—Epidemiological Evidence......Page 1297
112.16 Brain-Derived Neurotrophic Factor (BDNF......Page 1298
112.19 Physical Activity and Cognition in Relation to APOE
Genotype......Page 1299
112.20 Benefits of Physical Activity in Children and Young
Adults: An Investment Hypothesis......Page 1300
112.21 Additional Considerations: Exercise Intensity and
Modality vs. Skillful Movement......Page 1301
Clinical Applications......Page 1302
References......Page 1303
113.1.1 Agoraphobia......Page 1308
113.2.1 Psychotherapeutic Treatment of Anxiety Disorders......Page 1309
113.2.4 Complementary Treatment Methods and
Add-Ons......Page 1310
113.3.1 Physical Activity and the Prevalence and
Incidence of Anxiety Disorders......Page 1311
113.3.2.3 Endurance Training and Anxiety......Page 1312
113.3.3.2 Biological Mechanisms......Page 1313
References......Page 1314
114.1 Prevalence and Burden of Depression......Page 1318
114.1.2.3 Meta-Analyses Examining the
Efficacy of Exercise in Reducing
Depressive Symptoms......Page 1319
114.1.3.3 Intervention Duration......Page 1320
114.1.4.3 Cancer......Page 1321
114.1.5.4 Endocannabinoids......Page 1322
114.1.7 Future Directions......Page 1323
References......Page 1324
David A. Sleet, PhD, FAAHB......Page 1328
115.1 Introduction......Page 1330
115.3.1 Costs......Page 1331
115.4 Trends and Variations......Page 1332
115.6 Injury or Accident......Page 1333
115.9 Axioms in Injury Prevention......Page 1334
115.10 How Lifestyle Medicine Practitioners Can Help
Prevent Injuries......Page 1335
Clinical Applications......Page 1336
References......Page 1337
116.1 Traffic Injury and Lifestyle......Page 1340
116.2 Epidemiology......Page 1341
116.3.1 Alcohol-Impaired Driving......Page 1343
116.3.2 Occupant Protection......Page 1345
116.3.7 Automated Enforcement: Speed and Red
Light Cameras......Page 1346
116.5.2 Drug-Impaired Driving......Page 1347
References......Page 1348
117.2 Guideline Development......Page 1352
117.3.1 Determining when to Initiate or Continue
Opioids for Chronic Pain......Page 1353
References......Page 1354
118.1 Introduction......Page 1356
118.2.2 Indications of Deteriorating Neurological
Function......Page 1357
118.3.2 Key Recommendations in CDC’s Pediatric
Mild TBI Guideline......Page 1358
118.5 Next Steps......Page 1361
References......Page 1362
119.2 Epidemiology......Page 1364
119.3 Risk Factors......Page 1365
119.4 Evidenced-Based Strategies......Page 1367
119.5 How to Incorporate Effective Fall Prevention Activities
into Primary Care......Page 1368
Clinical Applications......Page 1369
References......Page 1370
120.1 Introduction......Page 1374
120.2 The Epidemiology of Suicide......Page 1375
120.3.1.4 Older Adults......Page 1377
120.4 Prevention Strategies......Page 1378
120.5 Role of Lifestyle Medicine Practitioners......Page 1380
Clinical Applications......Page 1381
References......Page 1382
121.1 Introduction......Page 1386
121.4 The Invisibility of People with Disability......Page 1387
121.5 Public Safety......Page 1388
121.7 Call to Action......Page 1389
Clinical Applications......Page 1390
References......Page 1391
Part XX: Public Policy and Environmental Supports for Lifestyle Medicine......Page 1392
122.1 Introduction......Page 1394
Clinical Applications......Page 1399
References......Page 1400
123.2 Community-Based Approaches to Promoting
Physical Activity......Page 1402
123.3.1 Schools......Page 1404
123.3.2 Worksites......Page 1405
123.3.4 Public Recreation Facilities and the Built
Environment......Page 1406
123.4.2 Costs/Benefits and Funding......Page 1407
Clinical Applications......Page 1408
References......Page 1409
124.1 Introduction......Page 1412
124.3.1 Disparities/Inequities in Healthy Eating......Page 1413
124.5.2 Food Labels......Page 1414
124.5.4 Behavioral Economics......Page 1415
124.5.6 Healthy Eating Recommendations......Page 1416
124.6 Summary......Page 1417
References......Page 1418
125.1 Introduction......Page 1420
125.1.1 Strategic Alliances......Page 1421
125.1.3 Charleston, West Virginia......Page 1422
125.2.1 Portland, Oregon......Page 1423
125.2.3 Making the Most of Your Engagement......Page 1424
125.3.2 Know the Neighborhood Environments......Page 1425
Clinical Applications......Page 1426
References......Page 1427
126.1 Introduction......Page 1428
126.2.2 Children and Adolescents......Page 1429
126.4.3 Obesity and Cancer......Page 1431
126.5 Economic Impact of Obesity......Page 1432
126.6 Public Health Implications......Page 1433
126.7.2 The Food Environment......Page 1434
126.8 The Need for Healthcare Professional Involvement......Page 1436
References......Page 1437
Index......Page 1442
A one-year phone follow up data collection ascertained the success of the inpatient program at changing behaviors and effecting outcomes. The easiest measure to collect was self-reported weight. Out of around 150 patients, only two weighed more than wh......Page 0

Citation preview

Lifestyle Medicine

Lifestyle Medicine Third Edition

Edited by

James M. Rippe, MD

CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 ©  2019 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed on acid-free paper International Standard Book Number-13: 978-1-138-70884-6 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe.

Library of Congress Cataloging‑  i n‑ P ublication Data Names: Rippe, James M., editor. Title: Lifestyle medicine / [edited by] James M. Rippe. Other titles: Lifestyle medicine (Rippe) Description: Third edition. | Boca Raton : Taylor & Francis, 2019. | Includes bibliographical references. Identifiers: LCCN 2018043101| ISBN 9781138708846 (hardback : alk. paper) | ISBN 9781315201108 (General eISBN) | ISBN 9781351781008 (pdf) | ISBN 9781351780995 (epub) | ISBN 9781351780988 (mobi/kindle) Subjects: | MESH: Primary Prevention | Health Promotion | Health Behavior | Healthy Lifestyle Classification: LCC RA427 | NLM WA 108 | DDC 610--dc23 LC record available at https://lccn.loc.gov/2018043101 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com

Dedication

To my beautiful wife, Stephanie Hart Rippe, and our wonderful children Hart, Jaelin, Devon, and Jamie who make my life worth living.

Contents Preface.............................................................................. xiii Acknowledgments........................................................... xvii About the Editor................................................................ xix Contributors...................................................................... xxi

Part I Lifestyle Management and Prevention of Cardiovascular Disease James M. Rippe, MD Chapter 1: The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease..................................... 3 James M. Rippe, MD and Theodore J. Angelopoulos PhD, MPH

Chapter 10: Effects of an Active Lifestyle on Water Balance and Water Requirements................................... 135 Gethin H. Evans, BSc, PhD, Ronald J. Maughan, BSc, PhD, and Susan M. Shirreffs, BSc, PhD

Part III  Physical Activity   Edward M. Phillips, MD Chapter 11: Implementation of the Exercise Prescription...................................................................... 147 Rachele M. Pojednic, PhD, EdM, Caroline R. Loveland, MS, and Sarah Tierney Jones, BS Chapter 12: What Physicians Need to Know, Do, and Say to Promote Physical Activity..................................... 153 Mary A. Kennedy, MS

Chapter 2: Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease..................................................... 19 James M. Rippe, MD and Theodore J. Angelopoulos, PhD, MPH

Chapter 13: Physical Fitness Evaluation.......................... 163 Peter Kokkinos, PhD and Jonathan Myers, PhD

Chapter 3: Physical Activity and Fitness in the Prevention of Cardiovascular Disease............................... 37 Robert F. Zoeller Jr., PhD

Chapter 14: Exercise Prescription for Apparently Healthy Individuals and for Special Populations............. 177 Paul G. Davis, PhD, ACSM-CEP

Chapter 4: Clinical Strategies for Managing Dyslipidemias..................................................................... 53 Ulf G. Bronas, PhD, ATC, FSVM, FAHA, Mary Hannan, MSN, APN, AGACNP-BC, and Arthur S. Leon, MS, MD, FACSM Chapter 5: Lifestyle Management and Prevention of Hypertension...................................................................... 65 Ulf G. Bronas, PhD, ATC, FSVM, FAHA, Mary Hannan, MSN, APN, AGACNP-BC, and Arthur S. Leon, MS, MD, FACSM

Part II  Nutritional Aspects of Lifestyle Medicine   James M. Rippe, MD Chapter 6: The Concept of Nutritional Status and Its Measurement..................................................................... 77 Johanna T. Dwyer, DSc, RD and Regan L. Bailey, PhD, RD, MPH, CPH Chapter 7: Dietary Guidelines for Americans, 2015–2020: National Nutrition Guidelines....................... 101 Elizabeth B. Rahavi, RDN, Jean M. Altman, MS, and Eve E. Stoody, PhD

Part IV  Behavioral Medicine   Elizabeth Pegg Frates, MD Chapter 15: Behavior Change.......................................... 193 Elizabeth Pegg Frates, MD and James E. Eubanks Jr., DC, MS Chapter 16: Applying Psychological Theories to Promote Healthy Lifestyles.............................................. 197 Maryam Gholami, PhD, Cassandra Herman, MS, Matthew Cole Ainsworth, MPH, Dori Pekmezi, PhD, and Sarah Linke, PhD, MPH Chapter 17: Motivational Interviewing and Lifestyle Change............................................................................. 207 Peter Fifield, EdD, LCMHC, MLADC, Joji Suzuki, MD, Samantha Minski, PhD, and Jennifer Carty, PhD Chapter 18: Transtheoretical Model................................ 219 James O. Prochaska, PhD and Janice M. Prochaska, PhD

Chapter 8: Nutrition and Cardiovascular Disease............111 James M. Rippe, MD

Chapter 19: The Impact of Positive Psychology on Behavioral Change and Healthy Lifestyle Choices......... 229 Shelley H. Carson, PhD, Andrea Cook, PhD, Stephanie Peabody, PsyD, Sandra Scheinbaum, PhD, and Leslie Williamson, BA

Chapter 9: Optimal Nutrition Guidance for Older Adults...... 125 Alice H. Lichtenstein, DSc

Chapter 20: The Intention–Behavior Gap........................ 241 Mark D. Faries, PhD and Wesley C. Kephart, PhD vii

viii  Contents Chapter 21: Cognitive and Behavioral Approaches to Enhancing Physical Activity Participation and Decreasing Sedentary Behavior...................................... 253 Barbara A. Stetson, PhD and Patricia M. Dubbert, PhD Chapter 22: Enhancing the Nutrition Prescription Using Behavioral Approaches......................................... 269 Jonas Sokolof, DO, Margaret Loeper Vasquez, MS, RD, LDN, Jenny Sunghyun Lee, PhD, MPH, CHES, CWP, CHWC, BCLM, Daniel B. Clarke, MBA, and P. Michael Stone, MD, MS, IFMCP Chapter 23: Behavioral Approaches to Manage Stress............................................................................... 281 Elise Loiselle, RN, MSN, FNP-C, Darshan Mehta, MD, and Jacqueline Proszynski, BS Chapter 24: Health Coaching and Behavior Change...... 299 Karen L. Lawson, MD, ABIHM, NBC-HWC, Margaret Moore, MBA, ACC, Matthew M. Clark, PhD, Sara Link, MS, NBC-HWC, and Ruth Wolever, PhD Chapter 25: Digital Health Technology for Behavior Change............................................................................. 311 Jeffrey Krauss, MD, DipABLM, Patricia Zheng, MD, Courtenay Stewart, DO, and Mark Berman, MD, FACLM

Part V  Women’ s Health  Paulette Chandler, MD, MPH Chapter 26: Breast Health: Lifestyle Modification for Risk Reduction................................................................. 331 Beth Baughman DuPree, MD, FACS, ABOIM and Jodi Hutchinson, PA-C Chapter 27: Sports and Physical Activity for Women and Girls........................................................................... 341 Elizabeth A. Joy, MD, MPH, FACSM

Part VI  Endocrinology and Metabolism    Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU Chapter 28: Impact of Lifestyle Medicine on Dysglycemia-Based Chronic Disease............................. 355 Michael A. Via, MD and Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU

Chapter 31: Implementing Nutritional Lifestyle Treatment Programs in Type 2 Diabetes......................... 393 George Guthrie, MD, MPH, CDE, CNS, FAAFP, FACLM

Part VII Lifestyle Issues in the Prevention and Treatment of Cancer   Cindy D. Davis, PhD and Sharon Ross, PhD, MPH Chapter 32: Diet and Cancer Prevention......................... 409 Cindy D. Davis, PhD and Sharon Ross, PhD, MPH Chapter 33: Lifestyle Approaches Targeting Obesity to Reduce Cancer Risk, Progression, and Recurrence..........419 Debora S. Bruno, MD, MS and Nathan A. Berger, MD Chapter 34: Physical Activity and the Prevention and Treatment of Cancer........................................................ 431 Case H. Keltner, MPH and Heather R. Bowles, PhD Chapter 35: Nutrition Therapy for the Cancer Patient.......441 Sandeep (Anu) Kaur, MS, RDN, RYT-500 and Elaine Trujillo, MS, RDN

Part VIII  Obesity and Weight Management   John P. Foreyt, PhD Chapter 36: Epidemiology of Adult Obesity.................... 455 R. Sue Day, MS, PhD, Nattinee Jitnarin, PhD, Michelle L. Vidoni, MPH, PhD, Christopher M. Kaipust, MPH, and Austin L. Brown, MPH, PhD Chapter 37: Exercise Management for the Obese Patient.............................................................................. 473 John M. Jakicic, PhD, Renee J. Rogers, PhD, and Katherine A. Collins, MS, CBDT Chapter 38: Dietary Management of Overweight and Obesity............................................................................. 483 Nina Crowley, PhD, RDN, LD, Katherine R. Arlinghaus, MS, RD, LD, and Eileen Stellefson Myers, MPH, RDN, LDN, CEDRD, FADA, FAND Chapter 39: Pharmacological Management of the Patient with Obesity......................................................... 491 Magdalena Pasarica, MD, PhD and Nikhil V. Dhurandhar, PhD Chapter 40: Surgery for Severe Obesity......................... 505 Robert F. Kushner, MD and Lisa A. Neff, PhD

Chapter 29: Lifestyle Medicine and the Management of Prediabetes.................................................................. 367 Karla I. Galaviz, PhD, MSc, Lisa Staimez, PhD, MPH, Lawrence S. Phillips, MD, and Mary Beth Weber, PhD, MPH

Chapter 41: Adiposity-based Chronic Disease a New Diagnostic Term............................................................... 517 Michael A. Via, MD and Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU

Chapter 30: Lifestyle Therapies for the Management of Diabetes....................................................................... 383 Marion J. Franz, MS, RD, CDE

Chapter 42: Future Directions in Obesity and Weight Management.................................................................... 529 Theodore K. Kyle, RPh, MBA

Contents 

ix

Part IX  Immunology and Infectious Disease   Gregory A. Hand, PhD, MPH, FACSM, FESPM

Chapter 56: Contraception.............................................. 687 Karen Carlson, MD and Sadia Haider, MD, MPH

Chapter 43: Exercise, Inflammation, and Respiratory Infection........................................................................... 539 Wesley D. Dudgeon, PhD, David C. Nieman, DrPH, FACSM, and Elizabeth Kelley, MS, ACSM-RCEP

Chapter 57: Prevention, Screening, and Treatment of Sexually Transmitted Infections....................................... 697 Karen Carlson, MD

Chapter 44: Chronic Exercise and Immunity................... 547 Melissa M. Markofski, PhD, Paul M. Coen, PhD, and Michael G. Flynn, PhD Chapter 45: HIV and Exercise.......................................... 555 Jason R. Jaggers, PhD and Gregory A. Hand, PhD, MPH, FACSM, FESPM Chapter 46: Exercise, Aging, and Immunity.................... 563 Jeffrey A. Woods, PhD, Yi Sun, PhD, and Brandt D. Pence, PhD

Part X  Pulmonary Medicine   Nicholas A. Smyrnios, MD, FACP, FCCP Chapter 47: Respiratory Symptoms................................ 573 Jeremy B. Richards, MD and Richard M. Schwartzstein, MD Chapter 48: Asthma......................................................... 589 David E. Ciccolella, MD and Gilbert E. D’Alonzo, DO Chapter 49: Occupational and Environmental Lung Diseases........................................................................... 611 Sunkaru Touray, MBChB, MSc, Emil Tigas, MD, and Nicholas A. Smyrnios, MD, FACP, FCCP Chapter 50: Venous Thromboembolic Disease............... 621 Joseph Gallant, MD and Ryan Shipe, MD Chapter 51: Influenza....................................................... 631 Gail Scully, MD, MPH Chapter 52: Indoor Air Quality......................................... 639 Anthony C. Campagna, MD, FCCP and Dhruv Desai, MD

Part XI  Obstetrics and Gynecology   Amanda McKinney, MD, FACLM, FACOG, CPE Chapter 53: Antenatal Care—Nutrition and Lifestyle to Improve Conception and Pregnancy Outcomes......... 653 Amanda McKinney, MD, FACLM, FACOG, CPE Chapter 54: Exercise in Pregnancy................................. 663 Kristin Bixel, MD and Christie Mitchell Cobb, MD Chapter 55: Breast-Feeding............................................ 673 Julia Head, MD, Stephanie-Marie L. Jones, MD, Marcie K. Richardson, MD, and Angela Grone, MD, FACOG

Chapter 58: Menstrual Disorders and Menopause......... 707 Amanda McKinney, MD, FACLM, FACOG, CPE Chapter 59: Risk Reduction and Screening for Women’s Cancers............................................................ 715 Amanda McKinney, MD, FACLM, FACOG, CPE and Jo Marie Tran Janco, MD

Part XII Cardiovascular Rehabilitation and Secondary Prevention  Kathy Berra, MSN, NP-BC, FAANP, FPCNA, FAHA, FAAN and Barry A. Franklin, PhD Chapter 60: Medication Dosing and Adherence in Secondary Prevention..................................................... 735 Ozlem Bilen, MD and Nanette K. Wenger, MD, MACC, MACP, FAHA Chapter 61: Using Digital Health Technology to Promote Cardiovascular Disease Risk Reduction in Secondary Prevention......................................................741 Neil F. Gordon, MD, PhD, MPH, FACC, Richard D. Salmon, DDS, MBA, Mandy K. Salmon, ChBE, and Prabakar Ponnusamy, MS Chapter 62: Psychosocial Risk Factors as Modulators of Cardiovascular Outcomes in Secondary Prevention..................................................... 751 Joel W. Hughes, PhD, FAACVPR and David Ede, Jr., BS Chapter 63: A Patient’s Perspective on the Keys to Longevity 40 Years after Undergoing Coronary Artery Bypass Surgery..................................................... 761 Joseph C. Piscatella, BA Chapter 64: Lipid Management in Secondary Prevention........................................................................ 767 Paul D. Thompson, MD and Antonio B. Fernandez, MD Chapter 65: Complementary Effects of Lifestyle Modification on Cardioprotective Medications in Primary/Secondary Prevention........................................ 771 Xisui Shirley Chen, MD and Philip Greenland, MD Chapter 66: Counseling Cardiac Patients to Facilitate Behavior Change............................................................. 781 Lola A. Coke, PhD, ACNS-BC, CVRN-BC, FAHA, FPCNA, FAAN, Nancy Houston Miller, RN, BSN, FAHA, FPCNA, FAACVPR, and Kathy Berra, MSN, NP-BC, FAANP, FPCNA, FAHA, FAAN



x  Contents Chapter 67: Extreme Exercise and High Intensity Interval Training in Cardiac Rehabilitation....................... 787 Kathy Berra, MSN, NP-BC, FAANP, FPCNA, FAHA, FAAN and Barry A. Franklin, PhD Chapter 68: Counseling Coronary Patients About Their Body Weight: Implications Regarding the Obesity Paradox.............................................................. 801 Sergey Kachur, MD, Carl J. Lavie, MD, FACC, FACP, FCCP, FESPM, and Richard V. Milani, MD Chapter 69: Vitamins and Supplements: Evidence in the Prevention and Treatment of Cardiovascular Disease............................................................................. 811 Jenna M. Holzhausen, PharmD, BCPS and Aaron D. Berman, MD, FACC Chapter 70: Intensive Cardiac Rehabilitation: Evolution, Preliminary Outcomes, Considerations, and Future Directions...................................................... 825 Jenna Brinks, MS, FAACVPR and Amy Fowler, BS Chapter 71: Alternative Models to Improve the Delivery and Impact of Cardiac Rehabilitation................ 833 Randal J. Thomas, MD, MS, Robert Scales, PhD, and Regis Fernandes, MD, FACC, FASE Chapter 72: Primordial/Primary Prevention: Implications and Challenges for Families and Children..... 841 Laura L. Hayman, PhD, MSN, FAAN, FAHA, FPCNA and James M. Muchira, MSN, PhD candidate

Part XIII  Lifestyle Components of Pediatric Medicine   Stephen R. Daniels, MD, PhD Chapter 73: Pediatric Lifestyle Medicine......................... 851 Jonathan R. Miller, PhD, Richard Boles, PhD, and Stephen R. Daniels, MD, PhD Chapter 74: Life Course Approach to Prevention of Chronic Disease............................................................... 861 Katherine A. Sauder, PhD and Dana Dabelea, MD, PhD Chapter 75: Cardiovascular Risk and Physical Activity in Children........................................................... 873 Lars Bo Andersen, Dr Sc and Robert G. Murray, PhD Chapter 76: Cardiovascular Risk and Diet in Children....... 887 Jessica L. Hildebrandt, MS, RD and Sarah C. Couch, PhD, RD

Chapter 79: Identification and Management of Children with Dyslipidemia.............................................. 921 Julie A. Brothers, MD and Stephen R. Daniels, MD, PhD Chapter 80: Diagnosis, Management, and Treatment of Systemic Hypertension in Youth, Updates from the 2017 American Academy of Pediatrics Clinical Practice Guideline............................................................ 937 Carissa M. Baker-Smith, MD, MS, MPH, FAAP, FAHA and Samuel Gidding, MD Chapter 81: Prevention of Osteoporosis in Children and Adolescents.............................................................. 951 Heidi J. Kalkwarf, PhD

Part XIV  The Practice of Lifestyle Medicine    George Guthrie, MD, MPH, CDE, CNS, FAAFP, FACLM Chapter 82: Definition of Lifestyle Medicine.................... 961 George Guthrie, MD, MPH, CDE, CNS, FAAFP, FACLM Chapter 83: Health Provider Core Competencies in Lifestyle Medicine............................................................ 969 Liana Lianov, MD, MPH, FACPM, FACLM Chapter 84: Lifestyle Medicine Clinical Processes......... 977 Ingrid Edshteyn, DO, MPH Chapter 85: Sleep as Medicine and Lifestyle Medicine for Optimal Sleep............................................. 995 Virginia F. Gurley, MD, MPH Chapter 86: Emotional Health and Stress Management.................................................................. 1003 Neil Nedley, MD and Francisco E. Ramirez, MD, BS, SC Chapter 87: High-intensity Therapeutic Lifestyle Change........................................................................... 1019 John Kelly, MD, MPH Chapter 88: Physician Health Practices and Lifestyle Medicine......................................................................... 1033 Erica Frank, MD, MPH, FACPM and Debora Holmes, MES

Part XV  Substance Abuse and Addiction     Elizabeth Pegg Frates, MD and Joji Suzuki, MD

Chapter 77: Sleep and Obesity Prevention in Children and Adolescents............................................... 901 Jill Landsbaugh Kaar, PhD and Stacey L. Simon, PhD

Chapter 89: Introduction to Addiction Section.............. 1047 Joji Suzuki, MD, Elizabeth Pegg Frates, MD, and Irena Matanovic

Chapter 78: Childhood Obesity....................................... 909 Jaime M. Moore, MD and Matthew Allen Haemer, MD, MPH

Chapter 90: History of Alcohol and Opioid Use and Treatment in the United States...................................... 1051 Sanchit Maruti, MD, MS and Steven A. Adelman, MD

Contents  Chapter 91: Behavioral Approaches to Enhancing Smoking Cessation........................................................ 1057 Joseph T. Ciccolo, PhD, CSCS, Nicholas J. SantaBarbara, MS, and Andrew M. Busch, PhD Chapter 92: Alcohol Use Disorders: Diagnosis and Treatment....................................................................... 1069 Chwen-Yuen Angie Chen, MD, FACP, FASAM and Sara C. Slatkin, MD Chapter 93: Diagnosis and Treatment of Opioid Use Disorders........................................................................ 1083 Joseph R. Volpicelli, MD Chapter 94: Cannabis Use Disorder and Treatment....... 1093 Christina Aivadyan, MS and Deborah Hasin, PhD Chapter 95: Smartphone-Based Technologies in Addiction Treatment....................................................... 1105 Emily Wu, MD and John Torous, MD Chapter 96: Psychosocial Interventions for Treatment of Substance Use Disorders.........................1113 Saria El Haddad, MD

Part XVI  Lifestyle Medicine in Geriatrics   Arthur S. Leon, MS, MD, FACSM Chapter 97: Lifestyle Medicine and the Older Population: Introductory Framework..............................1123 Arthur S. Leon, MS, MD, FACSM and Charlotte A. Tate, PhD Chapter 98: Reducing Aging-associated Risk of Sarcopenia......................................................................1127 Arthur S. Leon, MS, MD, FACSM Chapter 99: Aging-Associated Cognitive Decline and its Attenuation by Lifestyle..............................................1141 Arthur S. Leon, MS, MD, FACSM Chapter 100: Aging Successfully: Predictors and Pathways.........................................................................1147 Debra J. Rose, PhD Chapter 101: Role of Physical Activity in the Health and Wellbeing of Older Adults........................................1157 Andiara Schwingel, PhD and Wojtek J. Chodzko-Zajko, PhD

Part XVII  Health Promotion     Dee W. Edington, PhD Chapter 102: Health Promotion Introduction................ 1169 Dee W. Edington, PhD Chapter 103: Health Promotion: History and Emerging Trends.............................................................1171 Michael Parkinson, MD, MPH, FACPM

xi

Chapter 104: The Employer’s Role in Lifestyle Medicine..........................................................................1175 Dexter Shurney, MD, MBA, MPH Chapter 105: Why, How, and What in Leveraging the Value of Health................................................................1181 Ron Loeppke, MD, MPH, FACOEM, FACPM Chapter 106: International Health & Lifestyle.................1191 Wayne N. Burton, MD, FACP, FACOEM Chapter 107: The Community as a Catalyst for Healthier Behaviors........................................................ 1199 Jane Ellery, PhD and Peter Ellery, PhD, MLA Chapter 108: Motivation as Medicine............................ 1209 Jennifer S. Pitts, PhD Chapter 109: Future Directions of Health Promotion: Role of the Physician......................................................1217 Alyssa B. Schultz, PhD

Part XVIII  Exercise Psychology    Steven J. Petruzzello, PhD Chapter 110: My, How Those Seedlings Have Grown: An Update on Mind/Body Interactions in the Exercise Domain.................................................. 1225 Steven J. Petruzzello, PhD, Allyson G. Box, BS, and Dakota G. Morales, MS Chapter 111: Genetic Influences on Regular Exercise Behavior......................................................................... 1235 Matthijs D. van der Zee, MSc, Nienke Schutte, PhD, and Marleen H.M. de Moor, PhD Chapter 112: The Influence of Physical Activity on Brain Aging and Cognition: The Role of Cognitive Reserve, Thresholds for Decline, Genetic Influence, and the Investment Hypothesis..................................................................... 1251 Maureen K. Kayes, MS and Bradley D. Hatfield, PhD, FACSM, FNAK Chapter 113: Physical Activity and Anxiety................... 1271 Katharina Gaudlitz, MSc, Brigitt-Leila von Lindenberger, MSc, and Andreas Ströhle, MD Chapter 114: Physical Activity and Depression............. 1281 Kayla N. Fair, DrPH and Chad D. Rethorst, PhD

Part XIX  Injury Prevention   David A. Sleet, PhD, FAAHB Chapter 115: Injuries and Lifestyle Medicine................. 1293 David A. Sleet, PhD, FAAHB



xii  Contents Chapter 116: Traffic Injury Prevention: Strategies That Work....................................................................... 1303 Ann M. Dellinger, PhD, MPH, David A. Sleet, PhD, FAAHB, and Merissa A. Yellman, MPH

Part XX Public Policy and Environmental Supports for Lifestyle Medicine     Gregory W. Heath, DHSc, MPH FAHA, FACSM

Chapter 117: Review and Implementation of the CDC Guideline for Prescribing Opioids for Chronic Pain.......1315 LeShaundra Cordier, MPH, CHES and Helen Kingery, MPH

Chapter 122: Lifestyle Medicine in an Era of Healthcare Reform— Seven Years of Healthcare Disruption: 2010– 2017................................................... 1357 Aaron F. Hajart, MS, ATC, FACNA, Sandra Weisser, MSEd, ATC, Gary B. Wilkerson, EdD, ATC, and Gregory W. Heath, DHSc, MPH, FAHA, FACSM

Chapter 118: Improving the Care of Young Patients with Mild Traumatic Brain Injury: CDC’s EvidenceBased Pediatric Mild TBI Guideline............................... 1319 Kelly Sarmiento, MPH, Angela Lumba-Brown, MD, Matthew J. Breiding, PhD, CDR, US, Wayne Gordon, PhD, ABPP/Cn, David Paulk, PA-C, EdD, DFAAPA, Kenneth Vitale, MD FAAPMR, and David A. Sleet, PhD, FAAHB Chapter 119: Older Adult Falls: Epidemiology and Effective Injury Prevention Strategies............................ 1327 Ann M. Dellinger, PhD, MPH, David A. Sleet, PhD, FAAHB, and Jeanne Nichols, PhD, FACSM Chapter 120: Prevention of Suicidal Behavior............... 1337 Alex E. Crosby, MD, MPH, Deborah M. Stone, ScD, MSW, MPH, and Kristin Holland, PhD, MPH Chapter 121: Unintentional Injuries to Disabled Persons: An Unrecognized Yet Preventable Problem...... 1349 Louis Hugo Francescutti, MD, PhD, MPH, David A. Sleet, PhD, FAAHB, Linda Hill, MD, and Henry Xiang, MD, MPH, PhD

Chapter 123: Policy and Environmental Supports for Physical Activity and Active Living................................ 1365 Elizabeth A. Dodson, PhD, MPH and Gregory W. Heath, DHSc, MPH, FAHA, FACSM Chapter 124: Policy and Environmental Supports for Healthy Eating................................................................ 1375 Charlene Schmidt, PhD, MS, RDN, Emily Maddux, MS, MPH, RD, LDN, and Elizabeth Hathaway, PhD, MPH Chapter 125: Building Strategic Alliances to Promote Healthy Eating and Active Living................................... 1383 Risa Wilkerson, MA, Elizabeth A. Baker, PhD, MPH, Matt M. Longjohn, MD MPH, Shewanee D. Howard-Baptiste, PhD, Kara C. Hamilton, PhD, and Kori Hahn, BS, MS Chapter 126: Obesity and Health.................................. 1391 James M. Rippe, MD and Theodore J. Angelopoulos, PhD, MPH Index������������������������������������������������������������������������������ 1405

Preface There is no longer any serious doubt that daily habits and actions profoundly impact both short- and long-term health and quality of life. The scientific and medical literature that supports this concept is now overwhelming. Thousands of studies provide evidence that regular physical activity, maintenance of a healthy body weight, not smoking cigarettes, as well as following sound nutrition, stress reduction, and other health promoting practices all profoundly impact health. Conversely, an inactive lifestyle, obesity, high levels of stress, and cigarette smoking or exposure to cigarette smoke and other pollutants all significantly and negatively impact health. Since the publication of the second edition of Lifestyle Medicine (CRC Press, 2013), this literature has continued to grow stronger and even more robust. The field of lifestyle medicine has continued to expand around the globe, and multiple new initiatives in the area of lifestyle medicine have sprung up in the last few years. Because the field of lifestyle medicine has grown and expanded, it is necessary for our Lifestyle Medicine text to continue to grow and expand in order to serve the needs of an increasing number of individuals who are incorporating lifestyle medicine practices in various components of health care. The text also serves other physicians and other health care professionals in their practices. Serving all these providers is the goal of the third edition of Lifestyle Medicine. This edition has been thoroughly rewritten and updated, and incorporates a number of new sections which address the needs and concerns of lifestyle medicine practitioners and other physicians throughout the world. The evidence-base for lifestyle medicine procedures and practices is based on the enormous strength of the literature and underscored by its incorporation into virtually every evidence-based clinical guideline addressing the prevention and treatment of metabolic diseases. For example, the following guidelines and consensus statements from various prestigious medical organizations all provide significant emphasis on lifestyle medicine principles and practices as key components of the prevention and treatment of disease: • JNC VIII Guidelines for Hypertension, Prevention and Treatment • ACC/AHA Guidelines for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure • NCEP (ATP IV) Guidelines for Blood Cholesterol • Institute of Medicine Guidelines for Obesity Treatment • ACC/AHA Scientific Consensus Statement on the Treatment for Blood Cholesterol • Guidelines from the American Diabetes Association for the Management of Diabetes • Dietary Guidelines for Americans 2015–2020

• American Heart Association Nutrition Implementation Guidelines • Guidelines from the American Academy of Pediatrics for the Prevention and Treatment of Childhood Obesity • Guidelines from the American Academy of Pediatrics for the Treatment of Pediatric Blood Pressure • Guidelines from the American Academy of Pediatrics for the Treatment of Lipids • Guidelines from the American Heart Association and the American Academy of Pediatrics for the Prevention and Treatment of the Metabolic Syndrome • American Heart Association Strategic Plan for 2020 • Joint Statement from the American Heart Association and American Cancer Society for the Prevention of Heart Disease and Cancer • Presidential Advisory from the AHA and American Stroke Association • AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults • ACC/ADA/AHA Scientific Statement on Preventing Cancer, Cardiovascular Disease and Diabetes • Physical Activity Guidelines Advisory Committee Report of 2018 Unfortunately, despite the widespread recognition in these evidence-based guidelines and consensus statements about the important role of lifestyle measures and practices in the prevention and treatment of metabolic diseases, little progress has been made in improving the habits and practices of the American population. In fact, in some instances, risk factors for chronic diseases have actually continued to increase in the past decade. For example, consider the following: • Cardiovascular disease, which remains the leading killer of both men and women in the United States, resulting in over 37% of all mortality each year, has multiple lifestyle factors as underlying risk factors. • Over 80% of the adult population in the United States does not get enough physical activity to result in health benefits. • Over two-thirds of the adult population in the United States is either overweight or obese • The prevalence of pediatric obesity has tripled in the past 20 years. • Less than one-third of the adult population consumes adequate levels of fruits and vegetables and follows other simple evidenced-based nutritional practices related to good health. • Over 15% of individuals still smoke cigarettes. • Over 40% of the adult population in the United States has high blood pressure. xiii

xiv  Preface

• The choice of an inactive lifestyle increases the risk of an individual developing heart disease by as much as smoking a pack of cigarettes a day does. • Obesity is the leading cause of osteoarthritis in women and the second leading cause in men. • Cigarette smoking is the leading cause of cancer in the United States and obesity is the second leading cause. There is now a wide body of scientific evidence that positive lifestyle factors dramatically lower risk factors for chronic disease and promote good health. For example, in the Nurses’ Health Study, 80% of all heart disease and over 91% of all diabetes in women could be eliminated if they would adopt a cluster of positive lifestyle practices, including maintenance of a healthy body weight (BMI of 19–25 kg/m 2), regular physical activity (30 minutes or more on most days), not smoking cigarettes, and following a few simple nutritional practices such as increasing whole grains and consuming more fruits and vegetables. The U.S. Health Professionals Study showed similar dramatic reductions of risk in men from these same positive lifestyle factors. Importantly, if individuals adopted only one of these positive factors, their risk of developing coronary artery disease would be cut in half. Unfortunately, numerous studies have shown that less than 5% of adults in the United States follow most or all of these healthpromoting practices. The power of daily lifestyle practices and habits has also been shown in multiple large, randomized controlled trials. For example, in the Diabetes Prevention Program, individuals with baseline glucose intolerance who increased physical activity and lost 5–7% of their body weight also reduced their risk of developing diabetes by 58%. In the LOOK AHEAD Trial, individuals who lost 7% of their body weight significantly reduced risk factors for heart disease and diabetes. Importantly, in both of these studies, over 90% of initial weight loss was maintained over four years for individuals who continued to follow the program and received periodic follow-up from health professionals. Levels of physical activity remained high in both of these studies in follow-up periods of up to four years. Because the literature to relating lifestyle practices and habits has continued to grow deeper and more complex, the challenge for physicians and other health care professionals to keep abreast of this ever-expanding field and incorporate these findings into modern medical practice has become even more daunting. To further complicate the challenge, the literature relating lifestyle and health is spread over a wide variety of disciplines, journals, and textbooks. The need to provide comprehensive evidencebased summaries concerning lifestyle and health in a textbook that spans the field of lifestyle medicine has clearly become even more evident in the five years since the publication of the second edition of our textbook. Another goal for the third edition of Lifestyle Medicine has been to address this need. With the first edition of Lifestyle Medicine in 1999 we coined the term “lifestyle medicine” and summarized key findings across multiple disciplines that existed in the

late 1990s. Following the publication of the first edition of Lifestyle Medicine, a number of initiatives took place, including the launch of a peer-reviewed academic journal in lifestyle medicine (the American Journal of Lifestyle Medicine; SAGE Publications). A consensus statement on the core principles of lifestyle medicine was published in the Journal of the American Medicine Association based on recommendations from representatives from major medical groups, including the American Medical Association, the American College of Physicians, the American Academy of Pediatrics, the American College of Sports Medicine, the American College of Preventive Medicine, and others. In addition, an academic medical society in lifestyle medicine, the American College of Lifestyle Medicine, has been established for physicians and other health care workers. This organization has more than doubled its membership each year for the past five years and has launched a number of important initiatives in the education and practice of lifestyle medicine. Other professional groups have increasingly embraced the concept of lifestyle medicine. These include the American Heart Association, which now has a council entitled the “Council on Lifestyle and Cardiometabolic Health.” The American Academy of Family Practice and the American College of Preventive Medicine now offer education tracks for individuals interested in adding lifestyle medicine as a key component of their medical practices. All of these advances are welcome and will enhance the likelihood of formal adoption of lifestyle medicine practices within the medical community. Unfortunately, however, at the current time, less than 30% of physicians routinely counsel their patients on weight management, physical activity, and proper nutrition. This is a squandered opportunity, since more than 75% of the adult population sees a primary care physician at least once per year. This gap between evidence and application represents an enormous mandate and opportunity to underscore the links between lifestyle habits and practices and health outcome. So what is “lifestyle medicine?” In the first edition of our textbook we defined it as “the integration of lifestyle practices into the modern practice of medicine both to lower the risk factors for chronic disease and/or, if disease is already present, serve as an adjunct in its therapy. Lifestyle medicine brings together sound, scientific evidence in diverse health-related fields to assist the clinician in the process of not only treating disease but also promoting good health.” While this definition was put forth over almost two decades ago, it has largely stood the test of time. Other organizations have offered very similar definitions of lifestyle medicine, and these definitions serve as the defining principle behind the third edition of Lifestyle Medicine. The third edition of Lifestyle Medicine is divided into 20 parts related to lifestyle medicine; each part’s chapters have been edited by a leader of that particular discipline. All chapters have been fundamentally rewritten or substantially revised and brought up-to-date with current understandings and practices. There are also many new chapters and several new parts added to reflect modern understandings and particular areas which have emerged

Preface 

as critically important in lifestyle medicine over the past five years. The third edition of Lifestyle Medicine opens with Part I, Lifestyle Management and Prevention of Cardiovascular Disease. I chose to have this as the initial part for a number of reasons. First, I am a cardiologist, and my initial interest in lifestyle medicine came through issues related to lowering the risk of cardiovascular disease. Secondly, the area of cardiovascular medicine has been one of the leaders in adopting lifestyle habits and practices to reduce the risk of disease. These concepts are further articulated in the AHA Strategic Goals for the Year 2020. In addition, the council that I sit on within the AHA has changed its name from the “Council on Nutrition, Physical Activity and Metabolism” to the “Council on Lifestyle and Cardiometabolic Health,” a welcome recognition of the key role that lifestyle plays in the prevention and treatment of heart disease. Within this opening part are state-of-the-art chapters on various aspects of risk reduction incorporating the most recent guidelines promulgated by the American College of Cardiology (ACC) and the American Heart Association (AHA). Part II, is Nutritional Aspects of Lifestyle Medicine. Of course, nutrition plays a very prominent role in healthy lifestyle habits and actions. This section has been entirely updated and includes such new chapters as the one on the Dietary Guidelines for Americans 2015 and one on hydration, which is an important area that is often overlooked in nutrition. Part III is a greatly expanded section on Physical Activity. This Part contains state-of-the- art chapters on exercise prescription in various populations and what physicians should know about prescribing exercise and physical activity. Levels of physical activity remain extremely low in the American population, and I hope that this section will encourage physicians to play a more active role in this area. Physical activity is one of the most powerful tools we have to lower the risk of chronic disease. These chapters further elucidate the findings of the Physical Activity Guidelines for 2018 Advisory Committee report, which documents the expanding list of health benefits of physical activity for both adults and children. Part IV is also a greatly expanded section on Behavioral Medicine. Understandings of how to change behaviors are fundamental to virtually every other aspect of lifestyle medicine. This Part includes not only chapters on theoretical frameworks for how to apply psychological theories to promote healthy lifestyles but also important new chapters on Motivational Interviewing, the Transtheoretical Model of Change, and Positive Psychology. An important new chapter delves into how to address the gap between what people intend to do and what they actually do. This “Intention-Behavior Gap” has not received enough attention in the past, but the state-of-the-art chapter on this topic provides practical advice in this important area. Three chapters focus on how to use behavioral approaches in the areas of physical activity, nutrition, and stress management. The section concludes with a state-of-the-art chapter on the emerging field of health coaching and a chapter on the latest technologies and devices which hold great promise for facilitating behavioral change.

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Part V focuses on specific issues related to Women’s Health and includes chapters on breast health and physical activity. Part VI, Endocrinology and Metabolism, is a thoroughly updated and expanded section which focuses on lifestyle factors particularly in the area of the prevention and management of diabetes and the metabolic syndrome. Part VII, Lifestyle Issues in the Prevention and Treatment of Cancer, represents an important area which has been underestimated in many clinicians’ practices. The chapters are written by leading world experts not only from the Centers from Disease Control but from various universities. These chapters are particularly important since many physicians are unaware of the multiple links between lifestyle practices and a wide variety of cancers. Part VIII, Obesity and Weight Management, has been thoroughly rewritten with state-of-the-art chapters on epidemiology, exercise management, dietary management, pharmacologic management, and surgery for obesity. Also included is a new chapter entitled “Impact of Lifestyle Medicine on Dysglycemia-Based Chronic Disease,” which focuses on recently released statements from the American College of Endocrinology and provides an intriguing new framework for considering obesity-related conditions. The Immunology and Infectious Disease and Pulmonary Medicine sections have both been entirely rewritten and updated. The section on Obstetrics and Gynecology contains a number of new chapters and revisions of other chapters related to how lifestyle impacts on pregnancy and other key issues in obstetrics and gynecology, such as breastfeeding, contraception, sexually transmitted diseases, menstrual disorders, and risk reduction of cancers. Part XII is an entirely rewritten and expanded section on Cardiovascular Rehabilitation and Secondary Prevention, which provides contemporary information on the intersection between traditional cardiac rehabilitation and emerging areas of secondary prevention in cardiovascular medicine. Part XIII, Lifestyle Components of Pediatric Medicine, contains state-of-the-art chapters by world leaders in the application of lifestyle practices to the treatment of the pediatric population. We have increasingly come to understand that many diseases which are manifested in adults have their roots in childhood. Key issues related to cardiovascular risk, obesity, diabetes, lipids, blood pressure, and osteoporosis in children are all highlights of this important section. Increasingly individuals are opting to make lifestyle medicine the cornerstone of their medical practice. For this reason we have included an entirely new section, The Practice of Lifestyle Medicine, which contains chapters by leading practitioners within the American College of Lifestyle Medicine (ACLM). Many of these chapters relate specifically to educational efforts by the ACLM to engage physicians in this area and provide the core competencies needed to practice lifestyle medicine. Part XV is an entirely new section in the area of Substance Abuse and Addiction. It will come as no surprise to members of the medical community that the United States is in the midst of an opioid epidemic, but there are also a variety of other addictions such as alcohol, tobacco, marijuana, and so on which should be part of the knowledge base for every physician. There is also an



xvi  Preface

important chapter in this section on emerging technologies and apps for treating addiction. Individuals over the age of 65 represent the fastest growing portion of the United States population. The expanded section on Lifestyle Medicine in Geriatrics deals with a number of issues that are highly relevant to this segment of the population. In particular, age-related declines in skeletal muscle and cognitive function which are increasingly prevalent in this population have both been demonstrated to be significantly ameliorated by lifestyle practices and habits. There are two new chapters on these topics. In addition, a separate chapter on physical activity in individuals over the age of 65 is presented as well as a general overview on the concept of “successful aging.” This latter concept has changed the way we approach lifestyle measures in people over the age of 65. Rather than focusing on declining physiological and emotional characteristics in this population, there are now data and programs that show how individuals in this phase of life can maintain a healthy lifestyle and benefit from their wealth of experience while slowing down the normal physical and mental declines often experienced with aging. Part XVII, Health Promotion, is an important concept in lifestyle medicine, and this section contains a substantial increase in the number of chapters devoted to this very important topic. This Part focuses largely on different venues where health promotion can be delivered and offers practical, evidence-based advice about successful health promotion programs. The psychological benefits of exercise represent an area of increasing research, interest, and application. The expanded and updated section on Exercise Psychology (Part XVIII) deals with the science that is known about how exercise impacts psychological well-being. New chapters on the role of physical activity to ameliorate anxiety and depression as well as improve or maintain cognitive function are important chapters in this area. Often injuries are not considered in the area of lifestyle medicine. However, injuries have a direct impact on lifestyle for many individuals. These topics are handled in detail in the expanded Part XIX, Injury Prevention. These chapters are largely written by experts from the National Center for Injury Prevention and Control at the Centers for Disease Control. Of course, lifestyle changes do not occur in isolation. Public policy issues play a very important role in how the environment either supports or undercuts individuals’ ability to improve their health through lifestyle

measures. The final section of the book, Public Policy and Environmental Supports for Lifestyle Medicine, deals with this important aspect of lifestyle medicine in considerable detail. The work of generating this comprehensive and up-todate volume in lifestyle medicine involved the hard work and talent of 21 section editors who have devoted enormous energy and talent to the difficult task of organizing and editing parts and ensuring that they are both scientifically accurate and clinically useful. What has resulted from their efforts and those of over 250 distinguished contributors is a textbook which I hope and believe will be clinically useful in guiding health care professionals and providing state-of-the-art summaries and practical applications of modern science and medical understandings related to the interaction between lifestyle practice, medicine, and good health. We have further emphasized clinical utility in the third edition of Lifestyle Medicine by asking each author to list “Key Points” at the beginning of each chapter and “Clinical Applications” at the end of each chapter. These additions, we hope, will respectively be a helpful introduction to each chapter and guidance for applying the information in the chapter to the daily practice of medicine. As in previous editions, we hope this work will help our patients lead happier, healthier, and more productive lives while lowering their risk of chronic diseases and enhancing their quality of life. Over the two decades since the publication of the first edition of Lifestyle Medicine, important and extensive new information has emerged to provide scientific links between daily habits and actions and their ever-expanding impact on short- and long-term health and quality of life. A key consideration remains for those of us in the health care community with respect to applying these understandings to the modern practice of medicine. Lifestyle medicine is, in my view, the single greatest opportunity that we have to improve health outcomes and lower cost. This is crucial to underscoring and advancing the value proposition in the practice of medicine. This is both the challenge and the enormous opportunity in front of all of us who are blessed as gatekeepers to the health of our patients in our country. I hope that this edition of Lifestyle Medicine will continue to support the magnificent efforts of all of those who strive to enhance the health of all their patients. James M. Rippe, MD Boston, Massachusetts

Acknowledgments Textbook writing and editing are collaborative efforts that involve the hard work and passion of numerous contributors. Individuals who have stimulated my thinking about the interaction between lifestyle and health over many years are too numerous to acknowledge all by name. However, I would like to particularly thank a few individuals who have made substantial contributions to the third edition of Lifestyle Medicine. First, my longtime Editorial Director, Beth Grady, who plays a critically important role in all of the major writing and editing projects that emerge from my research organization, deserves special thanks. The third edition of Lifestyle Medicine is one of over 50 books that Beth has managed which have been generated through our organization. In addition to the current textbook, she provides editorial direction to two academic journals which I edit as well as a major intensive-care textbook (Irwin and Rippe’s Intensive Care Medicine, 8th Edition, Wolters Kluwer, 2018). She also helps to coordinate other academic endeavors. Beth possesses superb editorial skills and puts in enormous efforts with unfailing good humor to make all of these complex and difficult projects possible. I would also like to thank 21 section editors who contributed hard work and exceptional editorial skills to ensure scientific accuracy and clinical relevance for each of the sections of this book. I am deeply grateful to all of these individuals. A special thanks goes out to the more than 250 scientists and clinicians who have contributed chapters to this textbook. These individuals, who are internationally renowned experts in the key fields related to lifestyle medicine, have made invaluable contributions to assemble and explain enormous amounts of data in this rapidly emerging discipline. I would also like to express my appreciation to my office support staff, including my Executive Assistant, Carol Moreau, who seamlessly coordinates my schedule

and travel plans to free up the time necessary for such large writing and publishing projects. Our Office Assistant, Deb Adamonis, assists all of us in the multiple daily tasks required to expedite diverse projects in our office, while our Chief Financial Officer, Connie Martell, makes sure that the financial processes are in place for all or our projects to move forward smoothly. The research team at Rippe Lifestyle Institute has always contributed enormous insights to clarify my thinking about a number of aspects of lifestyle medicine, while our Director of Marketing and Client Services, Amy Continelli, coordinates the day-today interactions with multiple research sponsors. I would also like to thank the outstanding editorial team at Taylor & Francis Group/CRC Press. Included in this group are Randy Brehm, Senior Editor, who has been an early key supporter of our textbooks, Jay Margolis, the Project Editor who managed every step of the production process with expertise, patience, and knowledge, Laura Piedrahita, Editorial Assistant, who prepared and organized our files for production while managing communication with hundreds of authors, as well as Rachel Cook, Senior Project Manager at Deanta, who managed the editing, design, and typesetting of the book with great skill. Finally, I am grateful to my family, including my loving wife, Stephanie Hart Rippe, and our four beautiful daughters, Hart, Jaelin, Devon, and Jamie, who continue to love and support me through the arduous process of many major textbooks and journals and the other diverse professional responsibilities that I juggle along with my family life. If there are errors or omissions in Lifestyle Medicine, the responsibility is mine. If there is credit due for this project, it belongs to the numerous people who have made substantial contributions along the way. James M. Rippe, MD Boston, Massachusetts

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About the Editor James M. Rippe, MD , is a graduate of Harvard College and Harvard Medical School. His postgraduate training was at Massachusetts General Hospital. He is currently the founder and director of the Rippe Lifestyle Institute. Over the past 25  years, Dr. Rippe has established and run the largest research organization in the world that explores how daily habits and actions impact short- and long-term health and quality of life. This organization, the Rippe Lifestyle Institute (RLI), has published hundreds of papers that form the scientific basis for the fields

of lifestyle medicine and high-performance health. RLI also conducts numerous studies every year on physical activity, nutrition, and healthy weight management. A lifelong and avid athlete, Dr. Rippe maintains his personal fitness with a regular walk, jog, swimming, and weight training program. He holds a black belt in karate and is an avid wind surfer, skier, and tennis player. He lives outside of Boston with his wife, television news anchor Stephanie Hart and their four children, Hart, Jaelin, Devon, and Jamie.

xix

Contributors Steven A. Adelman, MD Director of Massachusetts Physician Health Services Clinical Associate Professor of Psychiatry University of Massachusetts Medical School Worcester, Massachusetts Matthew Cole Ainsworth, MPH Doctoral Trainee Department of Health Behavior University of Alabama at Birmingham Birmingham, Alabama Christina Aivadyan, MS School of Social Work Columbia University New York, New York Jean M. Altman, MS Nutritionist Office of Nutrition Guidance and Analysis Center for Nutrition Policy and Promotion U.S. Department of Agriculture Alexandria, Virginia Lars Bo Andersen, Dr Sc Professor Faculty of Teacher Education and Sport Western Norwegian University of Applied Sciences Oslo, Norway Theodore J. Angelopoulos, PhD, MPH Professor & Chair Department of Rehabilitation and Movement Sciences University of Vermont Burlington, Vermont Katherine R. Arlinghaus, MS, RD, LD Department of Health and Human Performance University of Houston Houston, Texas Regan L. Bailey, PhD, RD, MPH, CPH Associate Professor of Nutrition Science Purdue University West Lafayette, Indiana Elizabeth A. Baker, PhD, MPH Professor and Chair, Behavioral Science and Health Education Saint Louis University School of Public Health St. Louis, Missouri

Carissa M. Baker-Smith, MD, MS, MPH, FAAP, FAHA Assistant Professor of Pediatrics Division of Cardiology University of Maryland School of Medicine Baltimore, Maryland Christie Mitchell Cobb, MD Partner Little Rock Gynecology & Obstetrics Little Rock, Arkansas Nathan A. Berger, MD Distinguished University Professor Hanna-Payne Professor of Experimental Medicine Professor of Medicine, Biochemistry, Oncology, Genetics and Genome Sciences Director, Center for Science, Health and Society Case Comprehensive Cancer Center Case Western Reserve University School of Medicine Cleveland, Ohio Aaron D. Berman, MD, FACC Clinical Chief, Department of Cardiovascular Medicine Beaumont Hospital Royal Oak, Michigan and Associate Professor, Oakland University William Beaumont School of Medicine Rochester, Michigan Mark Berman, MD, FACLM Head of Health Better Therapeutics, LLC San Francisco, California Kathy Berra, MSN, NP-BC, FAANP, FPCNA, FAHA, FAAN Co-Director The LifeCare Company Nurse Practitioner Cardiovascular Medicine and Coronary Interventions Redwood City, CA Stanford Prevention Research Center Stanford University School of Medicine (Ret) Menlo Park, California Ozlem Bilen, MD Cardiology Fellow Department of Medicine Division of Cardiology Emory University School of Medicine Atlanta, Georgia xxi

xxii  Contributors

Kristin Bixel, MD Division of Gynecologic Oncology Department of Obstetrics and Gynecology Ohio State University Columbus, Ohio Richard Boles, PhD Associate Professor, Pediatrics-Nutrition University of Colorado School of Medicine Aurora, Colorado Heather R. Bowles, PhD Epidemiologist Biometry Research Group Division of Cancer Prevention National Cancer Institute Bethesda, Maryland Allyson G. Box, BS Graduate Student Department of Kinesiology and Community Health University of Illinois Urbana-Champaign Urbana, Illinois

Debora S. Bruno, MD, MS Assistant Professor of Medicine and Oncology Hematology/Oncology Division Department of Medicine Case Western Reserve University School of Medicine MetroHealth Medical Center Cleveland, Ohio Wayne N. Burton, MD, FACP, FACOEM Former Global Corporate Medical Director American Express Company Chicago, Illinois Andrew M. Busch, PhD Hennepin Healthcare University of Minnesota Medical School St Paul, Minnesota Anthony C. Campagna, MD, FCCP PCCM Fellowship, Program Director Department of Pulmonary and Critical Care Medicine Lahey Hospital and Medical Center Burlington, Massachusetts

Matthew J. Breiding, PhD, CDR, US Public Health Service Traumatic Brain Injury Team Lead Division of Unintentional Injury Prevention National Center for Injury Prevention & Control Centers for Disease Control & Prevention Atlanta, Georgia

Karen Carlson, MD Assistant Professor Obstetrics & Gynecology University of Nebraska Medical College Nebraska Medicine Obstetrics & Gynecology Omaha, Nebraska

Jenna Brinks, MS, FAACVPR Business Manager Heart & Vascular Services Beaumont Hospital Royal Oak, Michigan

Shelley H. Carson, PhD Associate Department of Psychology Lecturer in Extension Harvard University Cambridge, Massachusetts

Ulf G. Bronas, PhD, ATC, FSVM, FAHA Associate Professor The University of Illinois at Chicago College of Nursing Department of Biobehavioral Health Science Chicago, Illinois Julie A. Brothers, MD Assistant Professor of Pediatrics and Medical Director Lipid Heart Clinic The Perelman School of Medicine at the University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Austin L. Brown, MPH, PhD Instructor Department of Pediatrics Hematology & Oncology Baylor College of Medicine Houston, Texas

Jennifer Carty, PhD Behavioral Health Fellow University of Massachusetts Medical School Worcester, Massachusetts Paulette Chandler, MD, MPH Assistant Professor of Medicine Harvard Medical School Division of Preventive Medicine Associate Epidemiologist and Associate Physician Phyllis Jen Center of Primary Care Brigham and Women’s Hospital Boston, Massachusetts Chwen-Yuen Angie Chen, MD, FACP, FASAM Primary Care and Population Health in the Department of Medicine Medical Director of Primary Care Chemical Dependency Program Stanford University School of Medicine

Contributors 

Xisui Shirley Chen, MD Division of General Internal Medicine Department of Medicine University of Pennsylvania Perelman School of Medicine Philadelphia Wojtek J. Chodzko-Zajko, PhD Dean Graduate College Shahid and Ann Carlson Khan Professor in Applied Health Sciences University of Illinois at Urbana-Champaign Urbana, Illinois David E. Ciccolella, MD Department of Thoracic Medicine and Surgery Temple Lung Center Louis Katz School of Medicine Temple University Philadelphia, Pensylvannia Joseph T. Ciccolo, PhD, CSCS Assistant Professor of Movement Science and Kinesiology Department of Biobehavioral Sciences Teachers College Columbia University New York, New York Daniel B. Clarke, MBA Executive Chef Spaulding Rehabilitation Hospital Boston, MA University of Massachusetts, Boston, MA (MBA) The Culinary Institute of America Hyde Park, New York Matthew M. Clark, PhD Professor of Psychology Chair for Research Department of Psychiatry and Psychology Mayo Clinic Rochester, Minnesota Paul M. Coen, PhD Translational Research Institute for Metabolism & Diabetes AdventHealth Orlando, Florida Lola A. Coke, PhD, ACNS-BC, CVRN-BC, FAHA, FPCNA, FAAN Associate Professor Johns Hopkins School of Nursing Baltimore, Maryland Katherine A. Collins, MS, CBDT Graduate Student Researcher University of Pittsburgh Department of Health and Physical Activity Healthy Lifestyle Institute Physical Activity and Weight Management Research Center Pittsburgh, Pennsylvania

xxiii

Andrea Cook, PhD Department of Psychology University of California Santa Cruz Santa Cruz, California LeShaundra Cordier, MPH, CHES Communications Team Lead Division of Unintentional Injury Prevention (DUIP) National Center for Injury Prevention and Control (NCIPC) Centers for Disease Control and Prevention (CDC) Atlanta, Georgia Sarah C. Couch, PhD, RD Professor and Vice Chair Graduate Program Director Department of Rehabilitation, Exercise and Nutrition Sciences University of Cincinnati Cincinnati, Ohio Alex E. Crosby, MD, MPH Medical Epidemiologist Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control (NCIPC) Division of Violence Prevention (DVP) Atlanta, Georgia Nina Crowley, PhD, RDN, LD Surgery Program Coordinator Metabolic and Bariatric Surgery Medical University of South Carolina Charleston, South Carolina Gilbert E. D’Alonzo, DO Department of Thoracic Medicine and Surgery Temple Lung Center Louis Katz School of Medicine Temple University Philadelphia, Pennsylvania Dana Dabelea, MD, PhD Conrad M. Riley Professor of Epidemiology and Pediatrics Director Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center Colorado School of Public Health University of Colorado Anschutz Medical Campus Aurora, Colorado Stephen R. Daniels, MD, PhD Chair Department of Pediatrics University of Colorado School of Medicine Pediatrician-in-Chief Children’s Hospital Colorado Aurora, Colorado



xxiv  Contributors

Cindy D. Davis, PhD Director of Grants and Extramural Activities Office of Dietary Supplements National Institutes of Health Bethesda, Maryland Paul G. Davis, PhD, ACSM-CEP Associate Professor Department of Kinesiology The University of North Carolina at Greensboro Greensboro, North Carolina R. Sue Day, MS, PhD Professor of Epidemiology The University of Texas Health Science Center at Houston (UTHealth) School of Public Health Department of Epidemiology, Human Genetics & Environmental Sciences Southwest Center for Occupational and Environmental Health Michael & Susan Dell Center for Healthy Living Houston, Texas Eco J.C. De Geus, PhD Professor Department of Biological Psychology Vrije Universiteit Amsterdam, The Netherlands Ann M. Dellinger, PhD, MPH Division of Unintentional Injury Prevention National Center for Injury Prevention and Control Centers for Disease Control and Prevention Atlanta, Georgia Marleen H.M. de Moor, PhD Assistant Professor Section of Clinical Child and Family Studies, Methods Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam Amsterdam, The Netherlands Dhruv Desai, MD Fellow Department of Pulmonary and Critical Care Medicine Lahey Hospital and Medical Center Burlington, Massachusetts

Patricia M. Dubbert, PhD Associate Director for Research Training Professor (Retired) South Central Veterans Affairs Mental Illness, Research, Education, and Clinical Center Department of Psychiatry University of Arkansas for Medical Science Little Rock, Arkansas Wesley D. Dudgeon, PhD Associate Professor and Chair Department of Health and Human Performance College of Charleston Charleston, South Carolina Beth Baughman DuPree, MD, FACS, ABOIM Adjunct Assistant Professor University of Pennsylvania Medical Director Oncology Service Line Northern Arizona Healthcare VP Holy Redeemer Health System Sedona, Arizona Johanna T. Dwyer, DSc, RD Senior Nutrition Scientist (contractor) Office of Dietary Supplements NIH Bethesda, Maryland David Ede, Jr., BS Graduate Student Department of Psychological Sciences Kent State University Kent, Ohio Dee W. Edington, PhD Professor Emeritus University of Michigan Principal, Edington Associates Ann Arbor, Michigan Ingrid Edshteyn, DO, MPH Associate Physician Department of Medicine Center for Human Nutrition David Geffen School of Medicine at UCLA Los Angeles, California

Nikhil V. Dhurandhar, PhD Professor and Chair Department of Nutritional Sciences Texas Tech University Lubbock, Texas

Saria El Haddad, MD Instructor Harvard Medical School Department of Psychiatry Brigham and Women’s Faulkner Hospital Boston, Massachusetts

Elizabeth A. Dodson, PhD, MPH Research Assistant Professor Brown School and Prevention Research Center in St. Louis Washington University in St. Louis St. Louis, Missouri

Jane Ellery, PhD Project For Public Spaces and School of Kinesiology Ball State University Muncie, Indiana

Contributors 

Peter J. Ellery, PhD, MLA School of Architecture & Built Environment Deakin University—Geelong Waterfront Campus Geelong, Victoria, Australia James E. Eubanks, Jr., DC, MS Research Scholar MD Candidate, Class of 2018 Brody School of Medicine at East Carolina University Department of Physical Medicine and Rehabilitation Greenville, North Carolina Gethin H. Evans, BSc, PhD Principle Lecturer in Healthcare Science School of Healthcare Science Manchester Metropolitan University Manchester, UK Kayla N. Fair, DrPH Postdoctoral Researcher Center for Depression Research and Clinical Care Department of Psychiatry University of Texas Southwestern Medical Center Dallas, Texas Mark D. Faries, PhD Texas A&M AgriLife Extension Service Texas A&M School of Public Health Texas A&M University College of Medicine College Station, Texas Regis Fernandes, MD, FACC, FASE Medical Director, Cardiac Rehabilitation Program Mayo Clinic Scottsdale, Arizona Assistant Professor of Medicine Mayo Clinic School of Medicine Scottsdale, Arizona Antonio B. Fernandez, MD Director Cardiac Intensive Care Unit The Heart and Vascular Institute Hartford Hospital Hartford, Connecticut Peter Fifield, EdD, LCMHC, MLADC Adjunct Faculty Department of Education University of New England Biddeford, Maine Michael G. Flynn, PhD Division Director of Research HCA South Atlantic Charleston, South Carolina

xxv

John P. Foreyt, PhD Professor Department of Medicine and Director Behavioral Medicine Research Center Baylor College of Medicine Houston, Texas Amy Fowler, BS Senior Exercise Physiologist Preventive Cardiology & Rehabilitation Beaumont Health Royal Oak, Michigan Louis Hugo Francescutti, MD, PhD, MPH Professor School of Public Health Department of Emergency Medicine Faculty of Medicine University of Alberta Edmonton, AB, Canada Erica Frank, MD, MPH, FACPM Professor and Canada Research Chair University of British Columbia Founder and President, www.NextGenU.org and Principal Investigator Healthy Doc = Healthy Patient Vancouver, BC, Canada Barry A. Franklin, PhD Director, Preventive Cardiology and Cardiac Rehabilitation Beaumont Health Beaumont Health & Wellness Center Royal Oak, Michigan Marion J. Franz, MS, RD, CDE Nutrition/Health Consultant Nutrition Concepts by Franz, Inc. Minneapolis, Minnesota Elizabeth Pegg Frates, MD Lifestyle Medicine Specialist Health and Wellness Coach Wellness Synergy, LLC and Assistant Professor, Part Time Harvard Medical School Harvard Extension School Boston, Massachusetts Karla I. Galaviz, PhD, MSc Assistant Professor Hubert Department of Global Health Rollins School of Public Health Emory University Atlanta, Georgia



xxvi  Contributors

Joseph Gallant, MD University of Massachusetts Medical School Division of Pulmonary, Allergy, and Critical Care Medicine Worcester, Massachusetts Katharina Gaudlitz, M.Sc Dr. rer. medic Zentrum fuer Angst- und Depressionsbehandlung Zuerich (ZADZ) Switzerland Maryam Gholami, PhD Department of Family Medicine and Public Health University of California, San Diego La Jolla, California Samuel Gidding, MD Chief Division of Pediatric Cardiology Department Nemours Cardiac Center Alfred I. duPont Hospital for Children Wilmington, Delaware Neil F. Gordon, MD, PhD, MPH, FACC INTERVENT International Savannah, Georgia and Centre for Exercise Science and Sports Medicine School of Therapeutic Sciences University of the Witwatersrand Johannesburg, South Africa

George Guthrie, MD, MPH, CDE, CNS, FAAFP, FACLM President American College of Lifestyle Medicine Centre for Family Medicine Florida Hospital Medical Group Florida Hospital Graduate Medical Education University of Central Florida Winter Park, Florida Matthew Allen Haemer, MD, MPH Associate Professor University of Colorado School of Medicine Department of Pediatrics Section of Nutrition Medical Director Lifestyle Medicine Level One Weight Management Program Children’s Hospital Colorado Aurora, Colorado Kori Hahn, BS, MS Master of Science Candidate Department of Health and Human Performance University of Tennessee at Chattanooga Chattanooga, Tennessee Aaron F. Hajart, MS, ATC, FACNA Assistant Dean, Clinical Strategy and Development Office of Clinical Affairs Rutgers New Jersey Medical School Newark, New Jersey

Wayne Gordon, PhD, ABPP/Cn Jack Nash Professor and Vice Chair Department of Rehabilitation Medicine Icahn School of Medicine at Mount Sinai New York, New York

Sadia Haider, MD, MPH Associate Professor Chief, Family Planning and Contraceptive Research Department of Obstetrics and Gynecology University of Chicago Medicine The University of Chicago Chicago, Illinois

Philip Greenland, MD Harry W. Dingman Professor Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago, Illinois

Kara C. Hamilton, PhD Assistant Professor, Department of Health and Human Performance University of Tennessee at Chattanooga Chattanooga, Tennessee

Angela Grone, MD, FACOG Obstetrician/Gynecologist Beatrice Women’s & Children’s Clinic Beatrice Community Hospital and Health Center Beatrice, Nebraska

Gregory A. Hand, PhD, MPH, FACSM, FESPM Professor Department of Epidemiology Robert C. Byrd Health Sciences Center West Virginia University Morgantown, West Virginia

Virginia F. Gurley, MD, MPH AxisPoint Health and HGS Healthcare Lisle, Illinois

Mary Hannan, MSN, APN, AGACNP-BC PhD student Department of Biobehavioral Health Science College of Nursing University of Illinois at Chicago Chicago, Illinois

Contributors 

Deborah Hasin, PhD Professor Department of Psychiatry College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health Columbia University New York, New York Bradley D. Hatfield, PhD, FACSM, FNAK President National Academy of Kinesiology Professor and Chair Department of Kinesiology and Associate Dean for Faculty Affairs School of Public Health Affiliate – Neuroscience and Cognitive Science Program University of Maryland College Park, Maryland Elizabeth Hathaway, PhD, MPH Assistant Professor Exercise Science Department of Health and Human Performance University of Tennessee at Chattanooga Chattanooga, Tennessee Laura L. Hayman, PhD, MSN, FAAN, FAHA, FPCNA Professor Department of Nursing College of Nursing and Health Sciences University of Massachusetts Boston Adjunct Professor of Medicine Department of Medicine Division of Preventive and Behavioral Medicine University of Massachusetts Medical School Boston, Massachusetts Julia Head, MD Clinical Fellow Department of Obstetrics and Gynecology, and Reproductive Biology Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts Gregory W. Heath, DHSc, MPH FAHA, FACSM Guerry Professor, Public Health Program Department of Health and Human Performance University of Tennessee at Chattanooga Chattanooga, Tennessee Cassandra Herman, MS Doctoral Trainee Department of Health Behavior University of Alabama at Birmingham Birmingham, Alabama

Jessica L. Hildebrandt, MS, RD Clinical Dietitian Lifestyle Medicine Program Children’s Hospital Colorado Aurora, Colorado Linda Hill, MD Director Center for Human and Urban Mobility and Director Preventive Medicine Residency and Professor Department of Family Medicine and Public Health School of Medicine University of California, San Diego San Diego, California Kristin Holland, PhD, MPH Lead Behavioral Scientist Division of Violence Prevention (DVP) Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control (NCIPC) Atlanta, Georgia Debora Holmes, MES Chief Editor NextGenU.org Clear Lake, Washington Jenna M. Holzhausen, PharmD, BCPS Clinical Pharmacy Specialist, Critical Care Cardiac Intensive Care Unit Beaumont Hospital Royal Oak, Michigan Shewanee D. Howard-Baptiste, PhD Associate Professor Department of Health and Human Performance University of Tennessee at Chattanooga Chattanooga, Tennessee Joel W. Hughes, PhD, FAACVPR Professor Department of Psychological Sciences Kent State University Kent, Ohio Jodi Hutchinson, PA-C Director of Integrative Medicine Holy Redeemer Health System Meadowbrook, Pennsylvania Jason R. Jaggers, PhD Assistant Professor Department of Health & Sport Sciences University of Louisville Louisville, Kentucky

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xxviii  Contributors

John M. Jakicic, PhD Distinguished Professor and Chair Department of Health and Physical Activity Director Healthy Lifestyle Institute and Director Physical Activity and Weight Management Research Center University of Pittsburgh Pittsburgh, Pennsylvania Jo Marie Tran Janco, MD Clinical Fellow Department of Obstetrics, Gynecology, and Reproductive Biology Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts Nattinee Jitnarin, PhD Principal Investigator National Development and Research Institutes, Inc. Institute for Biobehavioral Health Research Leawood, Kansas Sarah Tierney Jones, BS Exercise Physiologist Simmons University Boston, Massachusetts Stephanie-Marie L. Jones, MD Clinical Fellow Department of Obstetrics, Gynecology and Reproductive Biology Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts Elizabeth A. Joy, MD, MPH, FACSM Medical Director Community Health, Health Promotion & Wellness, Food & Nutrition Intermountain Healthcare Salt Lake City, Utah Jill Landsbaugh Kaar, PhD Assistant Professor Department of Pediatrics University of Colorado Anschutz Medical Campus Aurora, Colorado Sergey Kachur, MD Assistant Professor of Medicine at the University of Central Florida Associate Program Director of the Internal Medicine Residency Program Department of Graduate Medical Education Ocala Regional Medical Center Ocala, Florida

Christopher M. Kaipust, MPH Predoctoral Fellow The University of Texas Health Science Center at Houston (UTHealth) School of Public Health Division of Epidemiology, Human Genetics, & Environmental Sciences Southwest Center for Occupational and Environmental Health Michael & Susan Dell Center for Healthy Living Houston, Texas Heidi J. Kalkwarf, PhD Professor Department of Pediatrics University of Cincinnati College of Medicine Division of Gastroenterology, Hepatology and Nutrition Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Sandeep (Anu) Kaur, MS, RDN, RYT-500 Nutritionist Nutritional Science Research Group Division of Cancer Prevention National Cancer Institute National Institutes of Health Rockville, Maryland Maureen K. Kayes, MS Department of Kinesiology University of Maryland College Park, Maryland Case H. Keltner, MPH MD Candidate Oregon Health & Science University School of Medicine Portland, Oregon Elizabeth Kelley, MS, ACSM-RCEP Lab Manager Health and Human Performance College of Charleston Charleston, South Carolina John Kelly, MD, MPH Oak Haven Lifestyle Medicine Center American College of Lifestyle Medicine Preventive Medicine Loma Linda University, California Mary A. Kennedy, MS Institute of Lifestyle Medicine Harvard Medical School Boston, MA and Exercise Medicine Research Institute Edith Cowan University Joondalup, Western Australia Australia

Contributors 

Wesley C. Kephart, PhD Assistant Professor University of Wisconsin Whitewater Health, Physical Education, Recreation and Coaching Whitewater, Wisconsin Helen Kingery, MPH Division of Unintentional Injury Prevention (DUIP) National Center for Injury Prevention and Control (NCIPC) Centers for Disease Control and Prevention (CDC) Atlanta, Georgia Peter Kokkinos, PhD Professor Veterans Affairs Medical Center Cardiology Department Washington, DC Georgetown University School of Medicine Washington, DC Rutgers University, Department of Kinesiology and Health New Brunswick, NJ University of South Carolina, Department of Exercise Science Columbia, SC Jeffrey Krauss, MD, DipABLM Veterans Affairs Palo Alto Health Care System and Department of Orthopaedic Surgery Stanford University School of Medicine Palo Alto, California Robert F. Kushner, MD Professor Department of Medicine Division of General Endocrinology Northwestern Medicine Chicago Illinois Theodore K. Kyle, RPh, MBA Principal and Founder ConscienHealth Pittsburgh, Pennsylvania Carl “Chip” J. Lavie, MD, FACC, FACP, FCCP, FESPM Medical Director, Cardiac Rehabilitation and Preventive Cardiology Director, Exercise Laboratories John Ochsner Heart and Vascular Institute and Editor-in-Chief Progress in Cardiovascular Diseases Associate Editor and Cardiovascular Section Editor, Mayo Clinic Proceedings Professor of Medicine Ochsner Clinical School-the University of Queensland School of Medicine New Orleans, Louisiana

xxix

Karen L. Lawson, MD, ABIHM, NBC-HWC University of Minnesota Assistant Professor Family Medicine and Community Health Director of Integrative Health Coaching Earl E. Bakken Center for Spirituality and Healing Minneapolis, Minnesota Jenny Sunghyun Lee, PhD, MPH, CHES, CWP, CHWC, BCLM Assistant Professor of Family Medicine Founder & Director, GoodNEWS Lifestyle Medicine and Holistic Wellness Program Director, Community Engagement in PRECISION Pain Research, Osteopathic Research Center Texas College of Osteopathic Medicine University of North Texas Health Science Center Fort Worth, Texas Arthur S. Leon, MS, MD, FACSM Henry L. Taylor Professor Laboratory of Physiological Hygiene and Exercise Science School of Kinesiology University of Minnesota Minneapolis, Minnesota Liana Lianov, MD, MPH, FACPM, FACLM Founder and Principal HealthType LLC and Chair Happiness Science and Positive Health Committee American College of Lifestyle Medicine and Vice-Chair American Board of Lifestyle Medicine Fair Oaks, California Alice H. Lichtenstein, DSc Gershoff Professor of Nutrition Science and Policy Director and Senior Scientist, Cardiovascular Nutrition Laboratory Tufts University JM USDA Human Nutrition Research Center on Aging Boston, Massachusetts Sara Link, MS, NBC-HWC Department of Family Medicine and Public Health University of California, San Diego La Jolla, California Sarah Linke, PhD, MPH Assistant Clinical Professor Department of Family Medicine and Public Health University of California, San Diego and Family Medicine and Public Health La Jolla, California



xxx  Contributors

Ron Loeppke, MD, MPH, FACOEM, FACPM Vice Chairman U.S Preventive Medicine, Inc. Jacksonville, Florida Elise Loiselle, RN, MSN, FNP-C Nurse Practitioner Spaulding Rehabilitation Hospital Massachusetts General Hospital Boston, Massachusetts Matt M. Longjohn, MD MPH Adjunct Assistant Professor of Pediatrics Northwestern University Feinberg School of Medicine; Senior Director, Chronic Disease Prevention Programs, Activate America, YMCA of the USA Caroline R. Loveland, MS Graduate Assistant Department of Nutrition Simmons University Boston, Massachusetts Angela Lumba-Brown, MD Clinical Assistant Professor; Department of Emergency Medicine Clinical Assistant Professor of Pediatrics Stanford University School of Medicine Palo Alto, California Emily Maddux, MS, MPH, RD, LDN Lecturer, Nutrition/Dietetics Department of Health and Human Performance University of Tennessee at Chattanooga Chattanooga, Tennessee Melissa M. Markofski, PhD Assistant Professor Department of Health and Human Performance University of Houston Houston, Texas Irena Matanovic Master of Clinical Psychology degree candidate Harvard Extension School Boston, Massachusetts Ronald J. Maughan, BSc, PhD Visiting Professor School of Medicine St. Andrews University St. Andrews, UK

Sanchit Maruti, MD, MS Assistant Professor of Psychiatry Larner College of Medicine at the University of Vermont Attending Psychiatrist, Inpatient service and Medical Director Addiction Treatment Program University of Vermont Medical Center Burlington, Vermont Amanda McKinney, MD, FACLM, FACOG, CPE Director- Open Learning Academy Executive Director- Institute for Human and Planetary Health Doane University Crete, Nebraska Robert G. McMurray, PhD Professor Emeritus Departments of Nutrition and Exercise and Sport Science University of North Carolina Chapel Hill, North Carolina Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU Professor of Medicine Medical Director, The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health at Mount Sinai Heart and Director, Metabolic Support Division of Cardiology, Endocrinology, Diabetes, and Bone Disease Icahn School of Medicine at Mount Sinai New York, New York Darshan Mehta, MD Medical Director of Medical Education Benson-Henry Institute for Mind Body Medicine Massachusetts General Hospital and Associate Director of Education Osher Center for Integrative Medicine Instructor in Medicine Harvard Medical School Brigham and Women’s Hospital Boston, Massachusetts Richard V. Milani, MD Chief Clinical Transformation Officer Ochsner Health System Vice-Chairman Department of Cardiovascular Diseases John Ochsner Heart and Vascular Institute Ochsner Clinic Foundation New Orleans, Louisiana

Contributors 

Jonathan R. Miller, PhD Assistant Professor Department of Psychiatry University of Colorado School of Medicine Aurora, Colorado Nancy Houston Miller, RN, BSN, FAHA, FPCNA, FAACVPR Co-Director The LifeCare Company Stanford University School of Medicine (Ret) Los Altos, California Samantha Minski, PhD Behavioral Health Fellow Department of Family Medicine and Community Health University of Massachusetts Medical School Worcester, Massachusetts Jaime M. Moore, MD Postdoctoral Fellow University of Colorado School of Medicine Department of Pediatrics, Section of Nutrition Children’s Hospital Colorado Aurora, Colorado Margaret Moore, MBA, ACC Founder/CEO Wellcoaches Corporation Wellesley, Massachusetts Dakota G. Morales, MS Department of Kinesiology and Community Health University of Illinois Urbana-Champaign Urbana, Illinois James M. Muchira, MSN, PhD candidate PhD Program in Nursing (Population Health Track) College of Nursing and Health Sciences University of Massachusetts Boston Boston, Massachusetts Eileen Stellefson Myers, MPH, RDN, LDN, CEDRD, FADA, FAND Private Practice Nashville, TN Jonathan Myers, PhD Director Exercise Research Laboratory Division of Cardiology VA Palo Alto Health Care System Palo Alto California

xxxi

Neil Nedly, MD President Weimar Institute Adjunct Professor of Clinical Medicine Loma Linda University and Owner Nedley Clinic, Depression and Anxiety Recovery Programs Weimar, California Lisa A. Neff, PhD Associate Professor Department of Medicine Division of Endocrinology Northwestern University Feinberg School of Medicine Chicago, Illinois Jeanne Nichols, PhD, FACSM Research Director Exercise and Physical Activity Resource Center (EPARC) Department of Family Medicine and Public Health University of California, San Diego San Diego, California David C. Nieman, DrPH, FACSM Professor and Director Appalachian State University Human Performance Lab North Carolina Research Campus Kannapolis, North Carolina Michael Parkinson, MD, MPH, FACPM Senior Medical Director Health and Productivity UPMC Health Plan and Work Partners Pittsburgh, Parkinson Magdalena Pasarica, MD, PhD Associate Professor of Medicine Director Internal/Family Medicine Clerkship and Medical Director KNIGHTS student-run free clinic Family Medicine Chair of Education FMIG Advisor University of Central Florida College of Medicine Orlando, Florida David Paulk, PA-C, EdD, DFAAPA Professor and Founding Director MSPA Program Murphy Deming College of Health Sciences Mary Baldwin University Fishersville, Virginia Stephanie Peabody, PsyD Academy of Brain Health and Performance Harvard Extension School Cambridge, Massachusetts



xxxii  Contributors

Dori Pekmezi, PhD Associate Professor University of Alabama at Birmingham Department of Health Behavior School of Public Health Birmingham, Alabama Brandt D. Pence, PhD Assistant Professor of Nutrition School of Health Studies The University of Memphis Memphis, Tennessee Steven J. Petruzzello, PhD Department of Kinesiology and Community Health University of Illinois Urbana-Champaign Urbana, Illinois Edward M. Phillips, MD Assistant Professor Physical Medicine & Rehabilitation Harvard Medical School and Director Institute of Lifestyle Medicine Spaulding Rehabilitation Hospital Boston, Massachusetts Lawrence S. Phillips, MD Medical Director Clinical Studies Center Atlanta VA Medical Center Decatur, Georgia and Professor of Medicine Division of Endocrinology and Metabolism Department of Medicine Emory University School of Medicine Atlanta, Georgia Joseph C. Piscatella, BA Founder and President Institute for Fitness and Health Gig Harbor, Washington Jennifer S. Pitts, PhD Founder Institute for Positive Organizational Health and Co-Founder Edington Associates Cambria, California Rachele M. Pojednic, PhD, EdM Department of Nutrition Simmons University Boston, Massachusetts

Prabakar Ponnusamy, MS Chief Technical Officer INTERVENT International Savannah, Georgia James O. Prochaska, PhD Cancer Prevention Research Center Clinical Psychology The University of Rhode Island Pro-Change Behavior Systems, Inc. Prochaska Change Consultants Kingston, Rhode Island Janice M. Prochaska, PhD The University of Rhode Island Pro-Change Behavioral Systems, Inc. Prochaska Change Consultants Mill Valley, California Jacqueline Proszynski, BS Clinical Research Program Coordinator The Benson-Henry Institute for Mind Body Medicine Massachusetts General Hospital Boston, Massachusetts Elizabeth B. Rahavi, RDN Nutritionist Center for Nutrition Policy and Promotion United States Department of Agriculture Alexandria, Virginia Francisco E. Ramirez, MD, BS, SC Director of Research Nedley Clinic Weimar Institute Colfax, California Chad D. Rethorst, PhD Associate Professor Department of Psychiatry University of Texas Southwestern Medical Center Dallas, Texas Jeremy B. Richards, MD Assistant Professor of Medicine Division of Pulmonary, Critical Care, and Sleep Medicine Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts Marcie K. Richardson, MD Assistant Clinical Professor in Obstetrics, Gynecology, and Reproductive Biology Harvard Medical School and Obstetrician Harvard Vanguard Medical Associates/Atrius Health Department of Obstetrics and Gynecology Beth Israel Deaconess Medical Center Boston, Massachusetts

Contributors 

James M. Rippe, MD Founder and Director Rippe Lifestyle Institute Shrewsbury, Massachusetts Renee J. Rogers, PhD Assistant Professor University of Pittsburgh Department of Health and Physical Activity Healthy Lifestyle Institute Physical Activity and Weight Management Research Center Pittsburgh, Pennsylvania Debbie Rose, PhD, FNAK President, National Academy of Kinesiology Professor Director Center for Successful Aging Co-Director Fall Prevention Center of Excellence California State University, Fullerton. Fullerton, California Sharon Ross, PhD, MPH Program Director Nutritional Sciences Research Group Division of Cancer Prevention National Cancer Institute National Institutes of Health Department of Health and Human Services Rockville, Maryland Mandy K. Salmon, ChBE Analyst INTERVENT International Savannah, Georgia Richard D. Salmon, DDS, MBA Chief Operations Officer INTERVENT International Savannah, Georgia Nicholas J. SantaBarbara, MS Doctoral Research Fellow Department of Biobehavioral Science Teachers College Columbia University New York, New York

xxxiii

Robert Scales, PhD Program Director Cardiac Rehabilitation & Wellness Department of Cardiovascular Diseases Mayo Clinic Scottsdale, Arizona and Clinical Professor College of Health Solutions Arizona State University Phoenix, Arizona Sandra Scheinbaum, PhD Founder and CEO Functional Medicine Coaching Academy Chicago, Illinois Charlene Schmidt, PhD, MS, RDN Associate Professor, Nutrition/Dietetics, Department of Health and Human Performance University of Tennessee at Chattanooga Chattanooga, Tennessee Alyssa B. Schultz, PhD Research Scientist Global Health Management Research Core Ann Arbor, Michigan Nienke Schutte, PhD Postdoctoral Researcher Department of Biological Psychology Vrije Universiteit Amsterdam Amsterdam, The Netherlands Richard M. Schwartzstein, MD Ellen and Melvin Gordon Professor of Medicine Harvard Medical School Associate Chief Division of Pulmonary, Critical Care and Sleep Medicine Beth Israel Deaconess Medical Center Boston, Massachusetts Andiara Schwingel, PhD Associate Professor Department of Kinesiology and Community Health University of Illinois at Urbana-Champaign Champaign, Illinois

Kelly Sarmiento, MPH Health Communications Specialist Traumatic Brain Injury Team Division of Unintentional Injury Prevention National Center for Injury Prevention & Control Centers for Disease Control & Prevention Atlanta, Georgia

Gail Scully, MD, MPH Assistant Professor Department of Medicine Division of Infectious Disease University of Massachusetts Medical School Worcester, Massachusetts

Katherine A. Sauder, PhD Assistant Professor Pediatric Nutrition University of Colorado School of Medicine Aurora, Colorado

Ryan Shipe, MD School of Medicine University of St. Andrews St. Andrews, UK



xxxiv  Contributors

Susan M. Shirreffs, BSc, PhD School of Medicine University of St. Andrews St. Andrews, UK Dexter Shurney, MD, MBA, MPH Senior Vice President/Chief Medical Officer Zipongo, Inc. and Former Chief Medical Director Executive Director Global Health and Wellness Cummins, Inc and President-elect American College of Lifestyle Medicine San Francisco, California Stacey L. Simon, PhD Assistant Professor Pulmonary Medicine Children’s Hospital Colorado University of Colorado Anschutz Medical Campus Aurora, Colorado Sara C. Slatkin, MD Internal Medicine The Permanente Medical Group Campbell, California David A. Sleet, PhD, FAAHB Consultant to the National Center for Injury Prevention & Control Centers for Disease Control & Prevention Atlanta, Georgia and Scholar-in-Residence Evidence-Based (EB) Medicine Norcross, Georgia Jonas Sokolof, DO Assistant Attending Physician Department of Neurology Rehabilitation Service Memorial Sloan-Kettering Center Assistant Professor of Clinical Rehabilitation Medicine Weill Cornell Medical College New York, New York Nicholas A. Smyrnios, MD, FACP, FCCP Professor of Medicine Associate Chief, Division of Pulmonary, Allergy, and Critical Care Medicine and Medical Director, Medical Intensive Care Units University of Massachusetts Medical School UMass Memorial Medical Center Worcester, Massachusetts

Lisa Staimez, PhD, MPH Assistant Professor Hubert Department of Global Health Rollins School of Public Health Emory University Atlanta, Georgia Barbara A. Stetson, PhD Associate Professor Department of Psychological and Brain Sciences University of Louisville Louisville, Kentucky Courtenay Stewart, DO Chief Resident Physician Department of Orthopaedic Surgery Physical Medicine & Rehabilitation Division Stanford Health Care Stanford, California Deborah M. Stone, ScD, MSW, MPH Behavioral Scientist Division of Violence Prevention (DVP) Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control (NCIPC) Atlanta, Georgia P. Michael Stone, MD, MS, IFMCP Ashland Comprehensive Family Medicine Ashland, Oregon Eve E. Stoody, PhD Lead Nutritionist Nutrition Guidance and Analysis Center for Nutrition Policy and Promotion U.S. Department of Agriculture Alexandria, Virginia Andreas Ströhle, MD Leitender Oberarzt Department of Psychiatry and Psychotherapy Charité – Universitätsmedizin Berlin Berlin, Germany Yi Sun, PhD Doctoral Student Department of Kinesiology and Community Health Integrative Immunology and Behavior Program University of Illinois at Urbana-Champaign Urbana, Illinois Joji Suzuki, MD Director Division of Addiction Psychiatry Assistant Professor of Psychiatry Harvard Medical School Department of Psychiatry Brigham and Women’s Hospital Boston, Massachusetts

Contributors 

Charlotte A. Tate, PhD Former Dean, College of Applied Health Sciences University of Illinois at Chicago Chicago, Illinois Randal J. Thomas, MD, MS Medical Director Cardiac Rehabilitation Program Mayo Clinic Rochester, MN and Professor of Medicine Mayo Clinic School of Medicine Rochester, Minnesota Paul D. Thompson, MD Co-Chair Heart and Vascular Institute Chief of Cardiology Hartford Hospital Hartford, Connecticut Emil Tigas, MD Assistant Professor of Medicine Division of Pulmonary, Allergy & Critical Care Medicine University of Massachusetts Medical School Worcester, Massachusetts John Torous, MD Psychiatrist and Director of Digital Psychiatry Department of Psychiatry Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts Sunkaru Touray, MBChB, MSc Clinical Fellow in Pulmonary Diseases & Critical Care Medicine Division of Pulmonary, Allergy & Critical Care Medicine University of Massachusetts Medical School Worcester, Massachusetts Elaine B. Trujillo, MS, RDN Nutritionist Nutritional Science Research Group Division of Cancer Prevention National Cancer Institute National Institutes of Health Rockville, Maryland Matthijs D. van der Zee, MSc PhD Student Department of Biological Psychology Vrije Universiteit Amsterdam, The Netherlands

xxxv

Margaret Loeper Vasquez, MS, RD, LDN Director of Nutrition and Food Services Spaulding Rehabilitation Hospital and Clinical Associate Boston University Clinical Associate Framingham State University Boston, Massachusetts Michael A. Via, MD Assistant Professor Department of Medicine Fellowship Director Division of Endocrinology, Diabetes and Bone Disease Mount Sinai Beth Israel Medical Center Icahn School of Medicine New York, New York Michelle L. Vidoni, MPH, PhD Senior Statistician Department of Medical School Center for Clinical and Translational Sciences The University of Texas Health Science Center at Houston (UTHealth) Houston, Texas Kenneth Vitale, MD FAAPMR Physical Medicine and Rehabilitation Subspecialty Certification in Sports Medicine Associate Professor Department of Orthopaedic Surgery University of California, San Diego La Jolla, California Joseph R. Volpicelli, MD Executive Director Institute of Addiction Medicine, Inc. Plymouth Meeting, Pennsylvania Brigitt-Leila von Lindenberger, MSc Department of Psychiatry and Psychotherapy Charite-Universitatsmedizin Berlin Berlin, Germany Mary Beth Weber, PhD, MPH Assistant Professor Emory University Hubert Department of Global Health Rollins School of Public Health, Atlanta, Georgia Sandra Weisser, MSEd, ATC Clinical Operations Manager Office of Clinical Affairs New Jersey Medical School Rutgers The State University of New Jersey Newark, New Jersey



xxxvi  Contributors

Nanette K. Wenger, MD, MACC, MACP, FAHA Professor of Medicine (Cardiology) Emeritus Emory University School of Medicine Consultant Emory Heart and Vascular Center Founding Consultant Emory Women’s Heart Center Atlanta, Georgia

Emily Wu, MD Child and Adolescent Psychiatry Fellow Department of Psychiatry Harvard Longwood Psychiatry Residency Training Program Harvard Medical School Massachusetts General Hospital Boston, Massachusetts

Gary B. Wilkerson, EdD, ATC Graduate Athletic Training Program Department of Health & Human Performance University of Tennessee at Chattanooga Chattanooga, Tennessee

Henry Xiang, MD, MPH, PhD Professor of Medicine Department of Pediatrics The Ohio State University College of Medicine Director of Center for Pediatric Trauma Research Director of Research Core Center for Injury Research and Policy The Research Institute at Nationwide Children’s Hospital Columbus, Ohio

Risa Wilkerson, MA Project Officer Active Living by Design, North Carolina Institute for Public Health University of North Carolina Gillings School of Global Public Health Chapel Hill, North Carolina Leslie Williamson, BA Academy for Brain Health and Performance Center for School Success Lebanon, New Hampshire Ruth Wolever, PhD Director of Vanderbilt Health Coaching: Practice, Research & Education Osher Center for Integrative Medicine Associate Professor Physical Medicine & Rehabilitation and Department of Psychiatry Vanderbilt Schools of Medicine and Nursing Nashville, Tennessee Jeffrey A. Woods, PhD Professor of Kinesiology Department of Kinesiology and Community Health Integrative Immunology and Behavior Program Division of Nutritional Sciences Carle-Illinois College of Medicine University of Illinois at Urbana Champaign Champaign, Illinois

Merissa A. Yellman, MPH Synergy America, Inc. Division of Unintentional Injury Prevention National Center for Injury Prevention and Control Centers for Disease Control and Prevention Atlanta, Georgia Patricia Zheng, MD Assistant Professor Department of Orthopaedic Surgery University of California – San Francisco San Francisco, California Robert F. Zoeller Jr., PhD Professor and Graduate Coordinator Department of Exercise Science and Health Promotion Florida Atlantic University Boca Raton, Florida

I

PA RT

Lifestyle Management and Prevention of Cardiovascular Disease James M. Rippe, MD

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1

CHAPTER

The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease James M. Rippe, MD and Theodore J. Angelopoulos PhD, MPH

Key Points...................................................................................... 3 1.1 Introduction............................................................................ 3 1.1.1  The Pathophysiology of Atherosclerosis......................... 4 1.2  Understanding Risk Factors.................................................... 5 1.2.1  The Concept of Risk Factors.......................................... 5 1.2.2  Relative Risk versus Absolute Risk................................ 5 1.2.3  Primary versus Secondary Prevention........................... 5 1.3  Primordial Prevention and “Ideal” Cardiovascular Health......... 5 1.4  Implementing Risk Factor Reduction Guidelines...................... 6 1.5  The Scientific Basis for Risk Factor Reduction......................... 6 1.6 Evidence-Based Versus Risk-Based Strategies for Prevention of Cardiovascular Disease..................................... 6 1.7  Modifiable Risk Factors........................................................... 6 1.7.1  Tobacco Use.................................................................. 6 1.7.2 Dyslipidemias................................................................ 7 1.7.2.1 Elevated Low Density Lipoprotein Cholesterol and Hyperlipidemia����������������������� 7 1.7.2.2  Low Levels of HDL Cholesterol......................... 7 1.7.2.3 Hypertriglyceridemia........................................ 7 1.7.3 Hypertension................................................................. 7 1.7.4  Diabetes and Glucose Intolerance.................................. 8 1.7.5 Obesity.......................................................................... 9 1.7.6  Inactive Lifestyle........................................................... 9 1.7.7  Poor Nutritional Habits................................................. 10 1.8  Nonmodifiable Risk Factors.................................................. 11

KEY POINTS • Cardiovascular Disease (CVD) remains the leading cause of death and disability in the United States and worldwide. • Multiple risk factors increase the risk of CVD. Many of these risk factors have a significant lifestyle component. • There has been a significant decrease in CVD mortality over the past four decades. Half of this decrease is due to lower risk factors. Increases in several risk factors, however, including obesity and diabetes, threaten to wipe out gains in all other risk factors. • If individuals used the following four positive daily lifestyle measures, the prevalence of CVD could be decreased over 80% and the prevalence of diabetes could be decreased over 90%. The measures are1

1.8.1 Age......................................................................... 11 1.8.2 Gender.................................................................... 11 1.8.3  Family History......................................................... 11 1.9 The Metabolic Syndrome and the Concept of Multiple Risk Factors........................................................................ 11 1.10  Emerging Risk Factors........................................................ 12 1.10.1  High Sensitivity C-Reactive Protein (hs-CRP)............ 12 1.10.2  Other Markers of Inflammation................................ 12 1.10.3  Hemostatic Factors.................................................. 12 1.10.4 Homocysteine......................................................... 12 1.10.5  LDL Subclasses and Particle Size............................ 12 1.10.6  Lipoprotein (a)......................................................... 12 1.11  Other Risk Factors.............................................................. 12 1.11.1  Levels of Antioxidants.............................................. 13 1.11.2 Alcohol.................................................................... 13 1.11.3  Stress and Type A Personality.................................. 13 1.11.4 Depression.............................................................. 13 1.12  Future Trends in Risk Factor Assessment............................ 13 1.12.1  Direct Plaque Imaging............................................. 13 1.12.2  Genomic Approaches............................................... 13 1.12.3  New Risk Factor Scoring Systems........................... 14 1.12.4  Implementation of Risk Factor Reduction Strategies......14 1.13 Conclusions........................................................................ 14 Clinical Applications..................................................................... 14 References.................................................................................. 14

maintain proper weight, 2 do not smoke cigarettes, 3 engage in regular physical activity, and4 follow sound nutritional patterns. • The American Heart Association (AHA) has recommended an emphasis on “primordial prevention,” which means lowering the likelihood of developing risk factors in the first place. • Physician visits are an ideal opportunity to stress the importance of lifestyle habits and practices to reduce the risk of cardiovascular disease.

1.1 INTRODUCTION Cardiovascular disease (CVD) remains the leading cause of death for both men and women in the United States each year.1 Over 37% of all mortality in the United States 3

4  Chapter 1  The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease

comes from cardiovascular disease.1 Although knowledge of many factors contributing to CVD is incomplete, it is clear that many risk factors contribute in significant ways to the ongoing epidemic of cardiovascular disease. Cardiovascular disease is truly a pandemic and represents the most important cause of death worldwide. In 2010, cardiovascular disease resulted in an estimated 16 million deaths and 293 million disability-adjusted life years (DALYs) lost. These represent approximately 30% of all deaths worldwide and 11% of all DALYs lost that year. This disease not only impacts high-income countries but has become increasingly prevalent in both low- and middle-income countries, which have seen an alarming increase in CVD rates. So prominent has been the role of certain lifestyle factors that it has been argued that the world is entering into a new epidemiologic transition. In the past four epidemiologic transitions, the predominant causes of death have been identified starting with pestilence and famine, then receding pandemics, followed by degenerative and man-made diseases, and finally delayed degenerative diseases. It has been argued that the modern world maybe entering a fifth epidemiologic phase highlighted by inactivity and obesity/diabetes, both of which contribute in significant ways to CVD.2 Lifestyle habits and practices constitute a significant contributor to this ongoing epidemic. While progress has been made in some of these areas (e.g., hypertension, total cholesterol, smoking cessation, physical activity), unfortunately, regression has occurred in such areas as obesity and diabetes. 3 The increasing prevalence of these latter two conditions has the potential to wipe out progress made on all the other lifestyle-related risk factors for CVD.3 In addition to its human cost, CVD also represents an enormous financial drain in the United States. It has been estimated that over $150 billion per year is spent on direct medical expenses and other associated costs related to CVD.4,5 Lifestyle factors play a particularly prominent role in the development and pathogenesis of CVD. Indeed, five of the major risk factors for developing CVD relate to lifestyle practices, including the following: the choice of whether or not to use tobacco products, level of physical activity, control of lipids, diabetes, and obesity.6 In this chapter we focus on the rationale for intervening to reduce risk factors for CVD. The next chapter, “Lifestyle Strategies for Risk Factor Reduction, Prevention, and Treatment of Cardiovascular Disease,” will discuss applications of lifestyle interventions in clinical practice to reduce the risk of CVD. Deaths from CVD and stroke have been declining in the United States for the past four decades. For example, between 1963 and 1990 the mortality of coronary heart disease fell by more than 50%.7 Nonetheless, CVD and stroke remain the leading causes of morbidity and mortality in the United States and in most other industrialized countries. The decline in CVD and stroke is a result of not only reduced prevalence of risk factors but also advances in treatment and therapies. However, the increased prevalence of diabetes and obesity, and an aging population, work against reductions in CVD and stroke prevalence and require expanded efforts to reduce lifestyle-related risk factors in order to continue reducing the burden of CVD. Between 1980 and 2000, the decline in the age related death from coronary heart disease (CHD) led to

an estimated decrease of 341,745 deaths.3 About half of this decline resulted from improvements and advances in treatment, while approximately 44% related to risk factor reduction. An estimated 149,635 fewer deaths from CVD came from improved treatment3 of some of its risk factors, while an estimated 59,370 increase in deaths occurred from the higher rates of obesity and diabetes. 3 The increasing prevalence of obesity and diabetes has the potential to completely wipe out the advances in the reduction of other risk factors if the trends of these two lifestyle risk factors are not reversed. Despite advances in reducing certain lifestyle-related risk factors for CVD, these risk factors remain extremely common. For example, the prevalence of hypertension in the United States has continued to increase, with recent data suggesting that more than one-third of American adults have high blood pressure,7,8 The Surgeon General’s Report on Physical Activity and Health documented that over 70% of the adult population in the United States fail to get enough regular physical activity to lower their risk of CVD,9 despite the fact that the 2008 Physical Activity Guidelines for Americans demonstrate multiple health benefits for virtually every population group.10 Overweight and obesity has continued to rise in the United States, with over 68% of the population showing one of these two conditions.11 The epidemic of diabetes in the United States continues to rise, with approximately 9% of the adult population currently suffering from this chronic condition—almost double the rate of 20 years ago.12 After several decades of encouraging declines in cigarette smoking, progress unfortunately appears to have leveled off in this area, with about 20% of the overall population in the United States still smoking.13 Thus, some progress in reducing risk factors has occurred, but enormous challenges and opportunities remain for applying lifestyle measures often, in conjunction with pharmaceutical therapy, to reduce the risk of CVD.

1.1.1 The Pathophysiology of Atherosclerosis As knowledge of the pathophysiology of atherosclerosis has advanced, new understandings have provided crucial linkages to the role of various lifestyle interventions in the reduction of risk of CVD. For example, the role of poor diet (e.g., elevated consumption of saturated fats) and diminished physical activity have been known for years to contribute to atherogenesis.14,15 However, only in the past decade has the significant role of inflammation as an initiating event in the process of atherosclerosis begun to be elucidated. Since multiple related conditions such as CHD, obesity, diabetes, glucose intolerance and the metabolic syndrome have significant overlap; it may indeed be a component of systemic inflammation that unites all of these processes. Fundamental to the understanding of the interplay between lifestyle and atherosclerosis is the evolving concept of the role of various structures and the interaction of components of both normal and diseased arteries (e.g., endothelium, smooth muscle, and intima) as well as how

1.3  Primordial Prevention and “Ideal” Cardiovascular Health  5

various cells in these structures function both in health and disease.16–18 The evolving understanding of the biology of atherosclerosis is beyond the scope of the current chapter. The reader is referred to several recent excellent reviews that discuss current understandings of the atherosclerotic process in detail.18,19

1.2 UNDERSTANDING RISK FACTORS 1.2.1 The Concept of Risk Factors The concept of risk factors is relatively new in the history of medicine. In fact, until the initial findings from the Framingham Study were published in the 1960s, the concept of risk factors for CVD did not formally exist.20 Framingham data showed that factors such as diabetes,21–24 dyslipidemia,25–29 high blood pressure,30–33 and cigarette smoking34–37 each independently and significantly increased the risk of CVD. The concept of CVD risk factors has been expanded to include physical inactivity38 and obesity.39 Other emerging risk factors where lifestyle habits and practices may play a role are under active investigation. Framingham data also demonstrated that risk factors act synergistically and tend to cluster with each other.40 Thus, in the presence of two risk factors, an individual quadruples their chance of developing CVD compared to individuals with no risk factors. Individuals with three risk factors increase their risk of developing CHC between eight- and twenty-fold compared to individuals with no risk factors.41 In addition to the lifestyle-related risk factors identified by the Framingham Study and other observational and interventional studies, other risk factors have been determined, including age, gender, family history of CVD, elevated C-reactive protein (CRP), hemostatic factors, excessive alcohol consumption, hypertriglyceridemia, elevated homocysteine levels, and perhaps stress and other psychological factors such as depression. Numerous studies have demonstrated that reducing risk factors for CVD can significantly decrease its likelihood.42–44 Lifestyle measures are a particularly powerful and effective way of lowering risk factors, since these measures are low-risk and many of them simultaneously affect multiple risk factors.

1.2.2 Relative Risk versus Absolute Risk It is important to differentiate between “relative” and “absolute” risk, since this distinction underlies treatment strategies for risk factor reduction in CVD. Relative risk is a comparison between different risk levels. It compares the likelihood that an individual who possesses a specific risk factor will develop CVD in comparison to an individual without that risk factor. Absolute risk represents the likelihood of developing CVD over a specified period of time. Framingham risk scores, for example, typically assess the absolute risk of developing CVD over a ten-year period. The difference between relative and absolute risk is a critical factor in clinical decision making. For example, a

young individual with abnormal lipids would be treated differently than an older individual with a similar lipid profile, all other things being equal, since while their increased relative risk may be the same, their absolute risk may be quite different.45–47 One way of viewing relative risk may be that it provides an indication of how rapidly an individual may move to absolute risk. Thus, a young individual with high relative risk would be at greater risk of ultimately developing high absolute risk and that fact might motivate the clinician to devise strategies for lowering risk as a means of slowing the early stages of developing CVD. Such interventions as lifestyle measures, which carry multiple benefits and relatively little risk and expense, are attractive means for lowering both relative and absolute risk of CVD.

1.2.3 Primary versus Secondary Prevention It is also important to distinguish between “primary” and “secondary” prevention when approaching risk factor reduction. Primary prevention is based on the goal of preventing or delaying the development of CVD, while secondary prevention focuses on interventions designed to reduce the likelihood of repeat cardiovascular events and/ or mortality in individuals who already have established CVD. More aggressive measures for risk factor reduction are typically indicated in individuals when they are used in secondary prevention (see Chapters 64 and 70). Guidelines for risk factor reduction in primary prevention are available from a variety of sources. Perhaps the most widely used is the Framingham Risk Scoring system.48 Guidelines for interventions for secondary prevention have also been published by the American Heart Association (AHA) and are discussed in detail in Chapter 64 and 70 later in this book.

1.3 PRIMORDIAL PREVENTION AND “IDEAL” CARDIOVASCULAR HEALTH In 2010 the American Heart Association issued a strategic plan through the year 2020 and beyond.49 New to this plan was a concept of “primordial” prevention. The goal of primordial prevention as articulated by the AHA is “that by 2020 to improve the cardiovascular health of Americans by 20% while reducing deaths from cardiovascular and stroke by 20%.” In issuing this statement, the AHA recognized and declared: “Health is a broader, more positive construct than just the absence of clinically evident disease.” It defined “primordial” prevention as a process to avoid adverse levels of risk factors in the first place rather than trying to reduce risk factors when they are already present or treating already established disease. This broader risk factor reduction strategy is completely consistent with the goals and vision of lifestyle medicine and will require careful attention to daily lifestyle habits and actions and their impact on risk factors and overall health.

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The AHA Strategic Plan49 also defined a construct of “ideal” cardiovascular health, which was defined as the following: The simultaneous presence of four favorable health behaviors: absence of smoking within the last year, physical activity at goal, consumption of a “heart healthy” dietary pattern and an ideal body mass index (BMI). Simultaneous presence of four favorable health factors: absence of smoking for at least one year, untreated cholesterol less than 200 mg/dL, untreated blood pressure less than  500 mg/ dL, very high. Overall, 31% of the adult population in the United States has a triglyceride level > to 150 mg/dL.43

1.7.3 Hypertension High blood pressure constitutes a significant increased risk of CVD. The prevalence of hypertension has increased steadily in the United States over the past ten years.87 According to the report of the most recent Joint National Committee on Prevention, Evaluation and Treatment of High Blood Pressure (JNC VII), more than one out of every three adults suffers from high blood pressure.87 This means that more than 50 million individuals have high blood pressure.87 A subsequent report based on data from the most recent National Health and Nutrition Evaluation Survey (NHANES III) places the number even higher at 38% of the population (65 million individuals).88 Even individuals who have normal blood pressure at the age of 55 have a 90% lifetime risk of developing hypertension during their lifetime according to data from the Framingham Heart Study.89 The relationship between blood pressure and the risk of CVD events is independent of other risk factors for CVD. For every 10 mm Hg rise in diastolic blood pressure or 20 mmHg rise in systolic blood pressure above 115/75 mm Hg, the increase in risk of CVD doubles.87

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The JNC VII guidelines create a guideline lower than previously established for normal blood pressure (below 120/80 mmHg) and create a new category of “prehypertension” to replace the old category of “high normal.” The JNC VII classification for blood pressure in adults is found in Table 1.1.87 High blood pressure is also frequently found coexisting with other risk factors for CVD. For example, individuals with high blood pressure have a greater than 40% chance of having elevated blood cholesterol.90–92 This is particularly important since over half of heart disease occurs in individuals with two or more risk factors. JNC VII guidelines recommend a six month trial of lifestyle related measures such as weight loss, smoking cessation, regular exercise, and improved nutrition for individuals with Stage1 hypertension before starting pharmacologic therapy.87 It should be noted that a commission was established to formulate JNC VIII guidelines and made somewhat different recommendations.93 The JNC VIII Guidelines contain the following statement: “There is strong evidence to support treating hypertensive individuals aged 60 or older to a BP goal of less than 150/90 mmHg and hypertensive patients 30–59 years of age to a diastolic goal of less than 90 mmHg; however there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal or in those younger than 30 years for a diastolic goal. So the panel recommends a BP of less than 140/90 mmHg for those groups based on expert opinion.” The goal of the JNC VIII guidelines was to make the blood pressure control recommendations based on evidence from randomized controlled trials. However, these recommendations have not been widely adopted. The JNC VIII guidelines emphasize that while these targets have been articulated, people’s judgment should still prevail in hypertensive therapy.93 Of note, both JNC VII and JNC

VIII recommend lifestyle interventions such as regular aerobic exercise, eliminating salt intake, maintenance of proper healthy weight, and not smoking cigarettes as the cornerstone of any antihypertensive regimen.

1.7.4 Diabetes and Glucose Intolerance The incidence of type 2 diabetes, which represents a major risk factor for CVD, has increased dramatically in both men and women in the United States over the past 20 years. Diabetes now affects over 9% of adults.12 Perhaps of even greater importance is that an estimated 35–40% of adults have impaired glucose tolerance or impaired fasting glucose levels.90 Diabetes is also one of the most common chronic diseases in the world, affecting an estimated 285 million adults in 2010 (6.4% of the global adult population).93 It is estimated that the prevalence of diabetes will grow to more than 430 million individuals (7.7% of the global adult population) by the year 2030.93 Diabetes represents a significant risk factor for CVD. Individuals with diabetes have between two and eight times higher rates of cardiovascular events, compared to nondiabetic controls.91 This risk factor is particularly potent in women with diabetes who increase their risk of developing CVD 3–7 times compared to an increased risk in men of 2–3 times. The increase in diabetes parallels the increase of obesity in the United States.92 It has been estimated that individuals born in the United States in the year 2000 will have a 36% chance of developing diabetes in their lifetime.94 For all of these reasons, prevention, early detection, and treatment of diabetes assumes great importance as a modality for reducing risk of CVD. Typical treatment involves multiple components of lifestyle measures such as weight loss for individuals who are overweight or obese and regular physical activity.

TABLE  1.1  Classification and management of blood pressure for adults aged 18 years or older Management* Initial drug therapy BP classification

Systolic BP, mm Hg*

Diastolic BP, mm Hg*

Lifestyle modification

Without compelling indication

With compelling indications

 35 inches in women confers a significantly increased risk of CVD compared to lower levels of abdominal fat. Adult weight gain also confers additional risk of CVD. According to the Nurses’ Health Study105 and U.S. Men’s Health Professional Study,106 individuals who gained 20 lbs or more during their adult life significantly increased their risk of type 2 diabetes and CVD.

The prevalence of overweight and obesity has increased significantly in the United States and other developed countries over the past 30 years. It is estimated that over two-thirds of the adult population in the United States is now overweight or obese.11 Increases have been particularly prominent in the area of Stage 1 obesity and severe obesity. Between 1980–2004, the prevalence of obesity among adults in the United States doubled. In 2006, it was estimated that 35% women and 33% of men in the United States were obese.95 Numerous studies have demonstrated that obesity constitutes a strong and independent risk factor for CVD in addition to its association with other risk factors such as dyslipidemia, diabetes, and hypertension. The American Heart Association classifies obesity as a major risk factor for CVD because of these associations. The most practical and recognized way of assessing obesity in clinical practice is to determine an individual’s body mass index (BMI). BMI has also been shown in numerous studies to correlate with health risk. BMI classifications, according to the Institute of Medicine,96 are listed in Table 1.2. The linkages between obesity and CVD are not completely understood, although they are probably not only mediated by direct effects on the cardiovascular system (a hyperdynamic state and increased blood flow) but also by systemic inflammation. Adipocytes used to be considered relatively inactive storage depots, but recent studies have shown that, in fact, adipocytes are very metabolically active and generate a variety of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF- a), and C-reactive protein (CRP)97–100 Excess weight is also associated with a variety of novel risk factors, including an atherogenic dyslipidemia (low HDL-C, elevated triglycerides, elevated apoprotein B, and elevated low-density lipoprotein). In addition, obesity is associated with elevations in thrombotic factors such as Plasminogen Activator Inhibitor I and increased levels of fibrinogen.101,102

1.7.6 Inactive Lifestyle Physical activity carries multiple health benefits. 51 Unfortunately, the population in the United States (both children and adults) has become increasingly inactive. Numerous studies have demonstrated that an inactive lifestyle significantly increases the risk of CVD. In one study, fitness level was more strongly associated with heart disease than any other risk factor, including cigarette smoking and hypertension.107 The Physical Activity Guidelines for Americans 2008 lists multiple significant benefits for increased physical activity as demonstrated in Table 1.3. There is strong evidence that regular physical activity lowers the risk of high blood pressure, adverse lipid profiles, type 2 diabetes, the metabolic syndrome, and weight gain. In addition, regular physical activity also reduces overall risk for CVD, risk for stroke and all-cause mortality. The Healthy People 2010 Initiative108 recommended the goal that at least 30% of the population over the age of six should engage in light-to-moderate physical activity of at least 30 minutes per day. This goal has been repeated in the Healthy People 2020 guidelines.109 Clearly, we are falling

TABLE 1.2  Classification of overweight and obesity as recommended by the National Heart, Lung, and Blood Institute guidelines Disease riska relative to normal weight and waist circumference Waist circumference 88 cm (women)

 110 mg/dL HDL cholesterol  than 150 mg/dL

According to the ATP III Guidelines, if an individual has three or more of these five criteria, he or she is considered to have the metabolic syndrome. Individuals with metabolic syndrome are at significantly higher risk for both coronary heart disease and diabetes than the general population. The ATP III Guidelines recommend that an individual with the metabolic syndrome should be treated as though they already have CVD. Data from the Framingham Study demonstrate that 60% of CVD is found in individuals who possess two or more risk factors. Debate is ongoing about the exact mechanism through which metabolic syndrome increases the risk of CVD. Some investigators maintain that the mechanism is through insulin resistance.123 Others have emphasized underlying inflammatory processes as part of the metabolic syndrome which link to increased risk of CVD.124 While the metabolic syndrome and obesity are not synonymous, they are strongly linked to each other. According to Framingham Study data, obese individuals have approximately a 50% chance of having at least two other risk factors for coronary heart disease.41

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12  Chapter 1  The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease

The increased prevalence of obesity in children has drawn attention to its linkage to the increasing prevalence of both diabetes and the metabolic syndrome in children.125 While considerable controversy exists about the criteria for the metabolic syndrome in children, the American Heart Association has recommended careful exploration for other risk factors for CVD in children who are obese. It should also be noted that recent data support that metabolic syndrome also results in a pro-inflammatory state. This is recognized by the most recent definition of the metabolic syndrome by the National Heart, Lung, and Blood Institute.126 This observation is important since a pro-inflammatory state also occurs in diabetes, hypertension, and obesity.

1.10 EMERGING RISK FACTORS Recent research has identified a variety of other risk factors which are associated to a greater or lesser degree with CVD. These risk factors are discussed in this section.

1.10.1 High Sensitivity C-Reactive Protein (hs-CRP) Inflammation has been identified as a key component of arthrosclerothrombosis and provides an important link between plaque formation and acute rupture.127 CRP, which is a marker of inflammation, has been identified as a significant cardiovascular CVD risk marker.128 Numerous prospective studies have demonstrated that hs-CRP independently predicts the risk of CVD.129–134 These data also apply not only to individuals with existing CVD but also to healthy individuals, including both men and women at all age levels. Elevated hs-CRP is not only associated with obesity and diabetes but also found in increased prevalence in individuals who lead sedentary lifestyles or are cigarette smokers.128 These findings carry significant practical implications for counseling individuals concerning a variety of lifestyle measures. Comprehensive meta-analyses of the hazard associated with CVD associated with hs-CRP demonstrated that it may exceed the risks associated with either elevated blood pressure or cholesterol.135 The Emerging Risk Factor Collaboration study showed that hs-CRP is as accurate in predicting future coronary heart disease events as is total HDL cholesterol.136 Individuals with elevated hsCRP and low levels of LDL cholesterol have higher absolute risk of vascular disease than those with low levels of hs-CRP and elevated levels of LDL. For all these reasons, it appears clinically wise to include hs-CRP along with lipid evaluation as a strategy for lowering the risk of CVD.137 Several of the statin medications have been demonstrated to lower CRP in addition to lowering LDL cholesterol, which carries significant implications for combining pharmaceutical therapies along with lifestyle measures.138,139

1.10.2 Other Markers of Inflammation The relationship between CVD and inflammation is an area of active research. A variety of other markers of

inflammation in addition to CRP have emerged as potential risk factors for CVD. Most prominently TNF-α and Interleukin-6 (IL-6) have been associated with increased risk of CVD, but the data supporting these relationships are not as advanced as with CRP.42

1.10.3 Hemostatic Factors Factors that may contribute to thrombogenesis have also been associated with increased risk of CVD. Factors currently under investigation that may contribute to thrombogenesis include Plasminogen Activator Inhibitor I (PAI-1), fibrinogen,140,141 and coagulation Factor VII.

1.10.4 Homocysteine Elevated levels of homocysteine, an amino acid derived from the degradation of methionine, have been associated with increased risk of CVD. Although the epidemiologic evidence is somewhat diverse, on average a 25% lower homocysteine level appears to be associated with approximately 11% lower risk of coronary heart disease in the general population. Homocysteine elevations are typically found in diets that are low in folate. In countries such as the United States, where folate supplementation occurs, prevalence of elevated homocysteine is significantly reduced. While laboratory tests are available to assess homocysteine, studies attempting to reduce the risk of CVD by reducing homocysteine levels have not yielded promising results.142,143 Thus, homocysteine is not currently included as part of a risk factor profile.

1.10.5 LDL Subclasses and Particle Size Laboratory tests are available to determine the amount of cholesterol carried by individual lipoprotein particles which are characterized by their particle size. Some studies have suggested that small, dense LDL particles may be more atherogenic than larger LDL particles.144,145 Of note, small, dense LDL particles have been associated more frequently in obese individuals and individuals with abdominal obesity than normal weight individuals. The data have not established the association between LDL particle size and CVD risk at a level that is useful for risk factor reduction strategies.

1.10.6 Lipoprotein (a) Lipoprotein (a) is an LDL particle linked to a protein by a disulfide bridge. A number of studies have supported the role for LP(a) as a determinant of vascular risk.146 However, it remains uncertain whether LP(a) contributes further sensitivity or specificity to standard risk factor reduction strategies.147

1.11 OTHER RISK FACTORS A variety of other risk factors for CVD have either been identified or postulated to potentially influence the likelihood of its development.

1.12  Future Trends in Risk Factor Assessment  13

1.11.1 Levels of Antioxidants Initial observational studies, including the Health Professional Follow-up Study148 and the Nurses Health Study149 showed an association between high levels of vitamin E and other antioxidants and reduced risk of CVD. Subsequent interventional trials, however, have not corroborated these findings.150 The American Heart Association does not currently advocate antioxidant supplementation as a means of reducing CVD risk.

1.11.2 Alcohol Alcohol consumption exerts a variety of effects on the overall cardiovascular system. A number of studies have demonstrated that moderate alcohol consumption reduces the overall risk of CVD.151 “Moderate” alcohol consumption is typically defined as no more than one to two beers, one to two glasses of wine, or one to two “shots” of distilled spirits daily. Men are typically able to drink higher amounts of alcohol within the moderate range than women because of higher levels of alcohol dehydrogenase—the enzyme in the liver that breaks down alcohol. The mechanism by which moderate alcohol consumption may reduce the risk of coronary heart disease is attributed either to increasing HDL or decreasing platelet aggregation.152 In contrast, alcohol consumption of three alcoholic drinks per day or more has been associated with increased risk of hypertension, overall risk of heart disease, congestive heart failure, a variety of gastrointestinal cancers, and motor vehicle accidents. Thus, a U-Shaped Curve153 relationship exists related to risk of CVD and alcohol consumption. Any individual or population-wide recommendation for levels of alcohol consumption must consider the complexity of this relationship.154

1.11.3 Stress and Type A Personality Some studies have supported the concept that personality type may contribute to the risk of CVD, but these data remain controversial and inconclusive.155,156 In particular, the anger element of Type A personality (a Type A personality is often found in individuals who are highly competitive and ambitious, and perceive a constant struggle with their environment) may increase the risk of CVD. The mechanism by which stress may lead to increased risk of vascular disease is not completely understood but is possibly related to platelet and endothelial dysfunction as well as the induction of ventricular arrhythmias.

1.11.4 Depression Depression has been demonstrated in a number of studies to predict CVD.157,158 This association appears to be an independent one, although depression is also associated with lack of physical activity, hypertension, and smoking.157,158 The mechanism through which depression may increase the risk of CVD includes elevated levels of hsCRP, increased platelet activation, and decreased heart rate variability. Depression occurs in one out of three

patients with heart failure and one out of five patients with coronary heart disease. Whether therapy for depression lowers risk for CVD is uncertain.

1.12 FUTURE TRENDS IN RISK FACTOR ASSESSMENT Some technologic enhancements, both in imaging techniques and genomics, have provided opportunities which may yield more precise and individualized characterizations of atherosclerotic plaque and risk of CVD.

1.12.1 Direct Plaque Imaging High-speed computed tomography (CT Scanning) of the coronary arteries has been demonstrated in several studies to detect pre-clinical atherosclerosis.159 Advances such as volume CT scanning (VCT) may further enhance the precision and predictive value of these technologies. At the current time, these technologies remain investigational. Concern has also been raised about the potential to overinterpret predictive values from imaging techniques such as coronary calcium scoring. In one study, 41% of all future vascular events occurred in individuals with a coronary calcium score lower than 100, and 17% occurred with a coronary calcium score of zero.160 In this study, individuals with high risk scores by Framingham criteria but low coronary calcium scores still remained at high risk of CVD. Another imaging test which has been employed to attempt to assess risk of CVD is ultrasound measurement of the common carotid intima-media thickness (CIMT). With regard to CIMT, a meta-analysis of 14 population-based cohorts reported a consistent and statically significant 9% increase of future vascular risk for each 0.1 mm increase in CIMT thickness.161 This same analysis, however, found that CIMT measurement did not improve clinical accuracy once risk estimates and re classification were utilized to adjust for usual risk factors.162 In addition, Framingham investigators have reported limited usefulness for CIMT in this prediction.163

1.12.2 Genomic Approaches Advances continue to be made in genetic determinants of atherothrombosis. Although this field remains in its early stages of development, progress continues to be made.164–166 Challenges exist because of multiple geneenvironment interactions. Although this remains an area of active research, no genetic markers for atherothrombosis have yet achieved clinical utility. A recent study involving over 55,000 individuals, including 7,814 participants in the Atherosclerosis Risk in Community (ARIC) study, 21,222 in the Women’s Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) and 4,260 participants in the cross-sectional BioImage assessed thus the risk of pulmonary events in individuals who had high genetic risk (top quintile of polygenic scores) compared to low risks (bottom quintile of polygenic scores). Coronary events were 91% higher in the high

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14  Chapter 1  The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease

genetic risk group. Importantly, among participants in the high genetic risk profile, a favorable lifestyle (defined by no current smoking, no obesity, regular physical activity, and a healthy diet) resulted in a 46% lower relative risk of coronary events than those who had an unfavorable lifestyle. While this type of research167 is in its infancy, it suggests that healthy lifestyle practices interact with playing an important role in individuals who are at high genetic risk of CVD.

1.12.3 New Risk Factor Scoring Systems The Framingham Risk Scoring System has contributed in substantial ways to the ability to predict the risk of CVD, but it is limited by not incorporating such risk factors as level of physical activity and obesity. One particularly attractive system has emerged from the New Zealand Guidelines Group, which provides useful information on five- and ten-year risk of atherosclerosis. This area remains one of active research. Another attractive scoring system is the Reynolds Risk Score (www.reynoldsriskscore.com) which has the advantage of including both hs-CRP and family history as part of global risk assessment.168

1.12.4 Implementation of Risk Factor Reduction Strategies One encouraging trend in risk factor reduction is an increased emphasis on more sophisticated and comprehensive approaches to implementation of currently existing risk factor reduction guidelines.50,52,115 Both the Dietary Guidelines for Americans 201550 and the Nutrition Guidelines from the American Heart Association52 make a substantial effort to focus on strategies for implementing existing guidelines.

1.13 CONCLUSIONS The identification of risk factors for coronary heart disease continues to evolve and is an area of great practical relevance to clinicians. Particularly given the high level of modifiable risk factors for CVD, an enormous opportunity exists for physicians and other healthcare workers to counsel patients on lifestyle medicine concepts to lower their risk of CVD. Specific concepts for how to integrate lifestyle measures into clinical practice will be the topic of the next chapter.

CLINICAL APPLICATIONS Action

Available Tools

Comment

Determine risk of CVD in all patients

Multiple risk factor scoring systems are available

See Chapter 2 for more details

Determine “vital signs” of positive lifestyle

Include body mass index (BMI), level of physical activity, nutritional practices, and smoking status in all initial assessments

These are key determinants of lifestyle CVD risk

Discuss smoking cessation with all smokers

Multiple tools available from many sources

Over one-third of smokers are never counseled about cigarette smoking

Counsel all patients on weight management

Obtain weight and BMI on all patients

Forty percent of overweight and obese patients are never counseled on weight management

Counsel all patients on physical activity

U.S. Physical Activity Guidelines

Become familiar with these guidelines and utilize them in counseling

Counsel all patients on nutrition

Dietary Guidelines for Americans 2015, also multiple materials from the American Heart Association

Improved nutrition is a key in reducing the CVD risk

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CHAPTER

Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease James M. Rippe, MD and Theodore J. Angelopoulos, PhD, MPH

Key Points.................................................................................... 19 2.1 Predicting Risk..................................................................... 21 2.2 Assessing Risk...................................................................... 21 2.3 Classifying Interventions for Modifiable Risk Factors............. 21 2.4 Class 1 Interventions............................................................ 21 2.4.1 Lifestyle Approach to Cigarette Smoking Cessation..... 21 2.4.2 Lifestyle Approach to Management of Dyslipidemias.......24 2.4.3 Lifestyle Management of Hypertension....................... 26 2.4.4 Pharmaceutical Measures for Cardiac Protection........ 28 2.5 Class 2 Interventions............................................................ 28 2.5.1 Obesity Prevention and Management.......................... 28 2.5.2 Diabetes/Glucose Intolerance...................................... 29

KEY POINTS • Lifestyle strategies play a significant role in reducing risk factors for cardiovascular disease (CVD). • Lifestyle interventions are key components of the American Heart Association’s strategic plan for 2020 to lower the burden of cardiovascular disease in the United States. • Lifestyle strategies are a key component for both the prevention and treatment of metabolic diseases and are recognized as such by virtually every major national, evidence-based guideline in metabolic diseases. • In addition to annual fasting lipid profile, highsensitivity CRP (hs-CRP) should be obtained, since levels of hs-CRP are the equivalent risk of LDL cholesterol. • Assessment and counseling for factors for CVD should be a part of every health care visit. Cardiovascular disease (CVD) remains the leading killer of men and women in the United States.1 CVD also represents one of the quintessential lifestyle related diseases, since many of the risk factors for it, including cigarette smoking, 2 elevated cholesterol, 3 high blood pressure,4 obesity5 and an inactive lifestyle,6 have significant lifestyle-related components.

2.5.3 Physical Inactivity....................................................... 30 2.5.4 Moderate Alcohol Consumption................................... 31 2.6 Class 3 Interventions............................................................ 31 2.6.1 Nutritional Counseling................................................. 31 2.6.2 Psychological Risk Factors/Counseling........................ 31 2.7 Post Menopausal Estrogen Therapy...................................... 31 2.8 Determinants of Behavior Change......................................... 32 2.9 Establishing A Lifestyle Medicine Emphasis in Clinical Practice.................................................................... 32 2.10 Summary............................................................................ 32 Clinical Applications..................................................................... 32 References.................................................................................. 33

Lifestyle strategies can play a significant role in the reduction of risk factors for CVD as well as in prevention and effective treatment of the disease. In Chapter 1, “The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease,” we focused on the rationale for employing lifestyle strategies for risk factor reduction. The current chapter provides practical strategies for employing these modalities in clinical practice for the prevention and treatment of CVD. Lifestyle interventions also represent an important strategy for physicians and other health care workers to use in assisting patients to lower their risk factors. These interventions are also helpful in preventing CVD and treating individuals with established CVD. The lifestylerelated strategies discussed here are particularly valuable since they carry very little risk and may simultaneously reduce multiple risk factors for CVD. Furthermore, the American Heart Association (AHA) has articulated a vision to pursue “primordial” risk factors, meaning the prevention of risk factors in the first place. Lifestyle measures will be key components of this strategy.7 Lifestyle measures are already incorporated, either prior to or in conjunction with pharmaceutical therapy, as key recommended early intervention steps in most of the major, evidence-based guidelines that are designed to help patients lower the risk of CVD.3,4,8–15 Unfortunately, many health care workers still do not properly emphasize these measures in their daily clinical practices. In addition, 19

20  Chapter 2  Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease

reimbursement models currently provide disincentives for using these strategies, since lifestyle interventions are typically not covered by health insurance plans. Aspects of the Affordable Care Act of 2010,16 particularly the Accountable Care Organizations provision, provide financial models to encourage these low-cost, potentially high-yield lifestyle measures. The challenge for health care professionals will be to understand and utilize these models to aggressively incorporate lifestyle measures into the prevention and treatment of CVD and other lifestyle-related diseases. In addition to the financial disincentives, lack of time may also represent another hurdle. Delivery of those measures related to prevention of CVD recommended by the U.S. Preventive Services Task Force (USPSTF) has been estimated to take the typical clinician a minimum of 1.5 hours per day in non-reimbursable time.17 Thus, it will be important in clinical practice to find ways to deliver proven lifestyle interventions with efficient strategies that are time sensitive. A representative listing of national guidelines that incorporate lifestyle medicine emphasis in the treatment of CVD or as a strategy for lowering risk factors for related metabolic conditions is presented in Table 2.1. Health care professionals can be enormously influential in helping patients take positive lifestyle actions to lower their risk of CVD. Health care providers’ recommendations to make changes in behavior such as cigarette smoking cessation, weight loss, or improved nutrition have all been demonstrated to play important roles in lowering risk factors for CVD. Numerous studies have shown that the public perceives medical professionals as a reliable and credible source of information concerning health-related behaviors.18–24 Often, however, health care workers underestimate how powerful their role as health counselors can be. For example, less than 50% of smokers report receiving advice to quit from their physician, 25 and less than 40% of obese individuals report receiving advice about weight loss. This is unfortunate, since the average adult in the United States visits a physician’s office more than five times per year, and it has been estimated that physicians come in contact with over 75% of adults in the United States in any given year. 26 In addition to physicians, nutritionists, nurses with an interest and background in preventive cardiology or diabetes education, and other health care professionals can play critically important roles in counseling patients on positive lifestyle behaviors to lower their risk of CVD.

It should also be noted that the majority of patients who make lifestyle behavior changes do this without formal participation in an organized program. For example, over 90% of individuals who have stopped smoking have done this without formal smoking cessation programs. 27 Furthermore, the majority of patients who lose weight also do this on their own. Nonetheless, health care professional recommendations and support can be very valuable in motivating patients to start and to maintain the process of behavioral change. It is particularly important that physicians play a proactive role in this area. At the current time, physician office visits represent a missed opportunity to promote behavioral changes. It is hoped that the advent of such organizations as the American College of Lifestyle Medicine, 28 and the lifestyle medicine track in the American College of Preventive Medicine29 will help physicians build the knowledge, basic skills, and confidence needed to make these recommendations. A “blue ribbon” panel of physicians representing most major medical organizations has urged physicians to become involved in lifestyle medicine and outlined a series of competencies in this area. 30 The American College of Lifestyle Medicine, a professional organization dedicated to advancing the field of lifestyle medicine, has doubled its membership each year for the past two years. In 2016, this organization outlined a series of topics and offered certification for those interested in deepening their knowledge of lifestyle medicine and incorporating it into their clinical practices.31 Increasingly, medical organizations in various subspecialties are understanding the power of daily lifestyle habits and practices in both the prevention and treatment of various diseases, including CVD. For example, in 2013, the AHA and the American College of Cardiology (ACC)32 jointly issued guidelines for lifestyle management to reduce cardiovascular risk. In conjunction with this initiative, the study group within the AHA, which had previously been called “The Council on Nutrition, Physical Activity and Metabolism,” changed its name to “The Council on Lifestyle and Cardiometabolic Health.”33 Along with these changes, a number of articles in a series entitled “Recent Advances in Preventive Cardiology and Lifestyle Medicine”34 were published by the AHA in the journal Circulation. Furthermore, the Affordable Care Act,16 including the Accountable Care Organizations provision, mandated that physicians become more active in this area.

TABLE 2.1  Evidence-based guidelines which employ lifestyle measures to reduce the risk of CHD and other metabolic conditions • National Cholesterol Education Program • JNC VII Guidelines for Prevention and Management of Hypertension • Institute of Medicine Guidelines for Management of Obesity • Guidelines for the American Heart Association for the Prevention and Management of Coronary Artery Disease • Guidelines from the American Diabetes Association for the Management of Diabetes • Dietary Guidelines for Americans • American Heart Association Nutrition Implementation Guidelines • Guidelines from the American Academy of Pediatrics for the Prevention and Treatment of Childhood Obesity • Guidelines from the American Academy of Pediatrics for Heart Disease Risk Factor Reduction in Children • Guidelines from the American Heart Association and American Academy of Pediatrics for the Prevention and Treatment of Metabolic Syndrome • Joint statement from the American Heart Association and American Cancer Society on the prevention of heart disease and cancer

2.4  Class 1 Interventions  21

The case for aggressive employment of lifestyle measures in clinical medicine has continued to grow. Multifactorial risk factor reduction programs have been clearly demonstrated to reduce each of these risk factors individually and in groups of risk factors treated together. Epidemiologic studies have shown that positive lifestyle measures, such as not smoking; engaging in at least 30 minutes of physical activity per day; consuming a diet of more fruits, whole grains, fish and vegetables; and maintaining a healthy weight can reduce the incidence of CVD, 35,36 by over 80% and diabetes by over 90%. Of note is the fact that incorporating just one of these healthpromoting practices reduces the risk of developing CVD and diabetes by over 50%.35,36

2.1 PREDICTING RISK A key first step prior to using lifestyle measures to lower risk factors for CVD involves predicting risk. Risk prediction involves understanding the type and strength of evidence underlying risk factor assessment strategies as well as clearly understanding the difference between relative risk and absolute risk (see Chapter 1, “The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease”). Most currently employed, evidence-based frameworks for lowering risk factors for CVD involve assessing absolute risk. For example, lowering absolute risk underlies the strategies for the National Cholesterol Education Program (NCEP) ATP-III Guidelines, 3 the American Diabetes Association Guide of Managing Diabetes,9 and The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).4

2.2 ASSESSING RISK Multiple frameworks are available for assessing risk of CVD. The most widely used and the one recommended by the AHA is the framework developed by the Framingham Heart Study investigators.37 This framework is found in Figure 2.1 and Figure 2.2. Figure 2.1 is used to assess risk for men, and Figure 2.2 is used to assess risk for women. The Framingham framework is based on estimating an individual’s ten-year risk of developing CVD. The higher the ten-year risk, the more intensity of intervention is warranted. It should be noted that there are alternatives to the Framingham score. For example, the Reynolds Risk Score provides a variation to the Framingham score by incorporating whether a parent suffered an MI before the age of 60 years as well as high-sensitivity CRP (hs-CRP) level.38,39 The Reynolds score appears to be a better predictor of individuals in the middle risk category and is comparable to the Framingham risk score for individuals with low or high risk. Other available risk scores include the Systematic Coronary Risk Evaluation Project (SCORE), developed by the European Joint Task Force, utilizing studies in 12 European countries involving 250,000 individuals.40 A

more recent set of guidelines was developed by the New Zealand Guidelines Committee which assesses absolute cardiovascular risk during five years instead of ten.41

2.3 CLASSIFYING INTERVENTIONS FOR MODIFIABLE RISK FACTORS As outlined in Chapter 1, “The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease,” risk factors for CVD can be conveniently divided into “modifiable” and “non-modifiable.” This framework also carries practical implications and is a commonly employed classification strategy.42 In addition, classifications employed by the American College of Cardiology and the American Heart Association divide intervention to reduce risk factors into four categories based on the level of evidence that modifying a particular risk factor will result in lower risk of CVD. The following four classifications are typically employed: • Class 1 Interventions: These interventions involve risk factor reduction strategies that have been proven to reduce risk when used. • Class 2 Interventions: This classification includes risk factors where interventions are likely to lower the incidence of events but proof is less strong than Class 1 interventions. • Class 3 Interventions: This classification includes risk factors that have been clearly associated with increased risk of CVD which, if modified, might lower the likelihood of a coronary event. • Class 4 Interventions: This classification includes risk factors which have been associated with increased risk of CVD which, if modified, are not likely to decrease the risk of CVD or cannot be modified. This framework for classifications is summarized in Table 2.2.

2.4 CLASS 1 INTERVENTIONS 2.4.1 Lifestyle Approach to Cigarette Smoking Cessation Cigarette smoking is the leading cause of preventable death in the United States each year, resulting in an estimated 443,000 deaths.43 More than 40% of deaths from cigarette smoking result from cardiovascular disease.38,44 It has been estimated that over 49,000 of the smoking related deaths are the result of secondhand smoke exposure. Smoking also has an enormous economic impact on the U.S. economy.45 It has been estimated that the United States incurs $96 billion in direct medical expenses and $97 billion in lost productivity annually as a result of cigarette smoking. 2 Smokers lose at least one decade of life expectancy compared to never-smokers. The risk of death from cigarette smoking has continued to increase among women,46 and the increased risks are now identical

2

22  Chapter 2  Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease

Figure 2.1  Coronary heart disease (CHD) score sheet for calculating 10-year CHD risk according to age, total cholesterol (TC) (or low- density lipoprotein cholesterol [LDL-C]), high-density lipoprotein cholesterol (HDL-C), blood pressure, diabetes, and smoking. Score sheet for men based on the Framingham experience in men 30 to 74 years at baseline. Average risk estimates are based on typical Framingham subjects, and estimates of idealized risk are based on optimal blood pressure, TC of 160 to 199 (or LDL- C of 100 to 129 mg/dL), no diabetes, and no smoking.

2.4  Class 1 Interventions  23

2

Figure 2.2  Score sheet for women based on Framingharri experience in women 20 to 74 years of age at baseline. Average risk estimates are based on typical Framingham subjects, and estimates of Idealized risk are based on optimal blood pressure, total cholesterol (TC) of 160 to 199 mg/dL (or low-density lipoprotein cholesterol [LDL-C of 100 to 129 mg/dL), high-density lipoprotein cholesterol (HDL-C) of 55 mg.’ dL. no diabetes, and no smoking. Use of the LDL-C categories is appropriate when fast ng LDL-C measurements are available. Pts. points. From Wilson PW: D’ Agostino RD, Levy D, et al. Predication of coronary heart disease using risk factor categories. Circulation . 1998;97:1837– 1847.

24  Chapter 2  Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease TABLE 2.2  Framework for risk factor reduction interventions. See text for details Class 1 Interventions • Cigarette smoking cessation • Management of dyslipidemias • Management of hypertension • Pharmaceutical measures for cardiac protection Class 2 Interventions • Obesity prevention and management • Diabetes/glucose intolerance management • Physical inactivity Class 3 Interventions • Nutritional counseling • Psychological risk factors/counseling • No alcohol consumption Class 4 • Age • Male gender • Low socioeconomic status • Family history of early onset CVD

between men and women.47 The 1989 Surgeon General’s Report showed that smoking doubles the risk of CVD and increases CVD mortality by 50%.44 Both of these risks increase with age and the number of cigarette smoked. More than one million more deaths worldwide were attributable to tobacco in the year 2000 than in 1990.47 Tobacco use is estimated to be responsible for five million deaths worldwide per year.48 In the United States, cigarette smoking peaked in 1955, reaching 55% of men. The peak for women came ten years later with more than 33% smoking. Since that time cigarette smoking has substantially declined, but the rate of decline has slowed substantially in the past decade. Currently in the United States, 19% of adults smoke.49 Slightly more of these individuals are men than women. Approximately 16.5 percent of women over the age of 18 smoke and approximately 21.6% of men over the age of 18 years old smoke.49 If individuals do not smoke cigarettes by the time they graduate from high school, it is highly unlikely that they will adopt this habit as adults. Smoking rates among high school seniors are slightly above 30%, with more female smokers than males. 50 Smoking also tracks with socioeconomic status. Thirtytwo percent of individuals living below the federal poverty line are smokers. The U.S. Public Health Service has published clinical practice guidelines classifying tobacco dependency as a chronic condition requiring repeated intervention.51 These guidelines recommend that health care professionals ask every patient about tobacco use at every clinic visit. 52 Counseling and behavior therapies are based on the following:

1. Securing social support 2. Providing problem solving skills 3. Social support outside treatment

According to the U.S. Public Health Service guidelines, which support a combination of counseling and pharmaceutical therapy, seven pharmacotherapies reliably increase

long-term smoking abstinence. These are bupropion hydrochloride,53 Varenicline, and five nicotine replacement therapies (nasal spray, gum, patch, inhaler, and lozenges).54 The efficacy of smoking cessation programs ranges from 6% for one year’s success with physician counseling alone, to 18% with self-help programs, to 20–40% with counseling plus pharmacologic intervention.55 All individuals who smoke should, of course, be counseled to cease this deadly habit. A particularly appropriate time to encourage patients to make this effort is after a cardiac event or discovery of existing cardiovascular disease. The Healthy People 2020 Initiative has established a goal for the United States of reducing the national prevalence of cigarette smoking among adults to under 12%. Achieving this ambitious goal will require extensive implementation of evidence-based tobacco control interventions. Some advances in tobacco control have occurred recently in the United States, including implementation of the 2009 Family Smoking Prevention and Tobacco Control Act, which granted the U.S. Food and Drug Administration (FDA) authority to regulate the manufacture, distribution, and marketing of tobacco products.55 Other laws include the Children’s Health Insurance Reauthorization Act, the Prevent All Cigarette Trafficking Act, and the Patient Protection and Affordable Care Act. These laws grant various federal agencies both authority and funding to regulate tobacco products and decrease access to tobacco among youth. In 2010, the U.S. Department of Health and Human Services entered a National Strategic Plan for Tobacco Control, including 21 Action Steps to accomplish this goal.

2.4.2 Lifestyle Approach to Management of Dyslipidemias Average cholesterol levels among adult men and women in the United States have decreased to some degree since the 1960 s but are still considered higher than good health requires. Agrarian societies have very low rates of CVD and exhibit total and LDL cholesterol levels well below those accepted as normal in Western societies. Currently, approximately 45% of all American adults still have cholesterol levels greater than 200 mg/dL, and 16% have levels higher than 240 mg/dL. 56 In addition, both depressed HDL cholesterol levels and elevated triglyceride levels often occur together and result from different metabolic pathways than are typically involved in elevated LDL. These latter two lipid abnormalities are particularly associated with the metabolic syndrome. Various organizations have listed somewhat different recommendations for cholesterol screenings. There is wide agreement that all patients with currently existing CVD should be periodically screened for serum cholesterol levels. The NCEP ATP-III Guidelines recommend that all adults older than 20 years should be routinely screened for serum cholesterol. 3 The American College of Physicians (ACP) provides less aggressive screening recommendations with advice that men between the ages of 35 and 65 be screened and women between the ages of 45 and 65 be screened.57 The USPSTF advocates screening women over the age of 45 and men over the age of 35. 52

2.4  Class 1 Interventions  25

It is important to understand that all of the above-referenced guidelines advocate treatment based on assessment of the patient’s overall risk. The NCEP ATP-III Guidelines utilize not only LDL level but also recommend calculations based on the Framingham risk score (see Figure 2.1 and Figure 2.2). A guideline algorithm presented by the ATP-III Guidelines is presented in Figure 2.3. A variety of lifestyle recommendations are incorporated as first-line treatment in the NCEP ATP-III Guidelines. Nutritional intervention is recommended, including maintaining calories from fat between 25–35%, saturated fat counting for less than 7%, and cholesterol level intake limited to less than 200 mg/day. Complex carbohydrates are recommended at 50–60% of calories and protein at 15%. NCEP ATP-III Guidelines recommend consumption of 20–30 grams of dietary fiber daily—an amount far more than the average American adult currently consumes.3 In 2006 American College of Cardiology and the American Heart Association updated their secondary prevention guidelines for lipid management, including most of the provisions of the NCEP guidelines but also strengthening them for individuals with established coronary heart disease (CHD). The ACC/AHA Guidelines extend the option of levels of less than 70 mg/dL for LDL for all patients with CHD, not just those at very high risk. 58 The guidelines also recommend that patients with triglyceride levels of 200–499 mg/dL should have a non-HDL cholesterol level of less than 130 mg/dL and potentially further

reduction to less than 100 mg/dL. Also in 2006, the AHA listed its nutritional and lifestyle recommendations. 59 A summary of these recommendations and their lifestyle interventions is found in Table 2.3. Within a clinical setting, it may be valuable for patients to receive the services of a registered dietitian to help them adhere to nutritional guidelines recommended by the AHA and NCEP ATP-III. In 2013, the ACC and AHA issued “Guidelines for the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease in Adults.” These Guidelines recommend increased use of statin medications to reduce atherosclerotic cardiovascular disease (ASCVD) events in secondary and primary prevention and also recommend discontinuation of use of specific LDL and HDL treatment targets.60 The four major statin benefit groups where the use of statin medicines, according to this report, were indicated to reduce ACSVD risk were the following: Individuals1 with clinical ASCVD, 2 primary elevations of LDL-C>190 mg/dL, 3 diabetics aged 40 to 75 years with LDL-C 70 to 189 mg/dL and without clinical ASCVD, and4 without clinical ASCVD or diabetes with LDL-C 70 to 189 mg/dL who had a ten-year ASCVD risk >7.5%These Guidelines were immediately criticized for recommending excessive use of statins, particularly in individuals with risk of >7.5%.61,62 This controversy persists as of this writing. A variety of pharmaceutical agents have been demonstrated to lower both total and LDL cholesterol as well as

Figure 2.3  Algorithm for lipid-lowering therapy based on findings from intervention trials. CHD, coronary heart disease; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides. From the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III]: final report. Circulation  . 2002;106:3143– 3421.

2

26  Chapter 2  Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease TABLE 2.3  AHA 2008 diet and lifestyle recommendations for cardiovascular disease risk reduction . Balance caloric intake and physical activity to achieve or maintain a healthy body weight. 1 2. Eat a diet rich in vegetables and fruits. 3. Choose and prepare foods with little or no salt. 4. Minimize your intake of beverages and foods with added sugars. 5. Consume oily fish at least twice a week. 6. Limit your intake of saturated fat to  50% lowering of LDL-C, and moderate intensity is considered lowering of LDL-C by 30–50%. The intensity of statin treatment is initiated depending on the degree of CHD risk according to the four conditions, or “statin benefit groups,” outlined above47 (Table 4.1). The ACC/AHA guidelines do not strongly advocate for the use of pharmacotherapy other than statins, and the initiation of niacin, bile acid sequestrants, cholesterol-absorption inhibitors, fibrates, or omega-3 fatty acids have no higher than a level IIa recommendation,47 but these therapies can have further lipid lowering effects (Table 4.2). The 2013 ACC/AHA guidelines do not recommend for or against specific LDL-C or non-HDL-C goal levels for the prevention of CHD, either primary or secondary. The guidelines did not find evidence of therapies aimed at specific LDL-C or non-HDL-C improved CHD outcomes.47 The 2013 ACC/AHA guidelines recommend evaluating for secondary causes in individuals found to have triglycerides ≥ 500 mg/dL.47 The 2013 ACC/AHA guidelines advocate for the consideration of non-statin therapies for the patients ≥ 21 yo with untreated primary LDL-C ≥ 190 mg/dL after the maximum intensity of statin therapy has been achieved.47 The use of non-statin medications were further outlined in the 2017 Update to the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. This expert consensus provides recommendations for the utilization of non-statin pharmacotherapy for the management of HLD.18 As an update to the 2016 ACC consensus document on the use of non-statins, the 2017 update includes recommendations integrated from recent RCTs on non-statin lipid-lowering medications. The 2017 update supports the

4

56  Chapter 4  Clinical Strategies for Managing Dyslipidemias TABLE 4.1  Risk category and recommended therapy intensity and expected response: 2013 ACC/AHA guidelines47 Patient group

Expected response of statin intensity

Therapy intensity

≤75 yo with clinical CHD

High intensity statin therapy

Daily dose lowers LDL-C on average by approximately 50%

≥75 yo with clinical CHD

Moderate or high intensity statin*

Daily dose lowers LDL-C on average by approximately 30–50% or 50%

≥21 yo with LDL-C ≥ 190 mg/dL

High intensity statin therapy

Daily dose lowers LDL-C on average by approximately 50%

≥21yo with LDL-C ≥ 190 mg/dL on high- dose statin

Additional considerations

-Consider initiation of non-statin drug*

40–75 yo with DM

Moderate intensity statin therapy

Daily dose lowers LDL-C on average by approximately 30–50%

40–75 yo with DM with ≥ 7.5% estimated 10-year CHD risk

High intensity statin therapy

Daily dose lowers LDL-C on average by approximately 50%

40–75 yo with LDL-C 70–189 without CHD, DM and with an estimated CHD risk ≥ 7.5%

Moderate-to-high intensity statin*

Daily dose lowers LDL-C on average by approximately 30–50%

40–75 yo with LDL-C 70–189 without CHD, DM and an estimated CHD risk ≤ 7.5%

Offer treatment with moderate intensity statin therapy

Daily dose lowers LDL-C on average by approximately 30–50%

* = Consider risk reduction, benefits vs. adverse effects, drug-drug interactions, and patient preferences.

TABLE 4.2  Percent changes in blood lipid/lipoprotein levels for each specific class of drugs Class/

LDL-C.

HDL-C. ↑5–15%

TG.

HMG-CoA reductase inhibitors (statins, e.g., atorvastatin)

↓20–63%

↓10–37%

Bile acid sequestrants (e.g., cholestyramine)

↓15–30%

↑5%

±

Fibric acid derivatives (e.g., gemfibrozil)

↓10–15%

↑5–20%

↓20–50%

Niacin. (e.g., sustained-release)

↓5–25%

↑15–35%

↓20–50%

Cholesterol absorption inhibitor (eczetimibe)

↓20%

↑5%

±

↑ = Increase, ↓ = Decrease, ± Variable, if any, Adapted from Gotto.26 For more details and precautions in use of these lipid management drugs, the reader is referred to Bettridge and Morrell.38

use of non-statin therapies, including ezetimibe, PCSK9 inhibitors, or bile acid sequestrants, for patients with clinical CHD with comorbidities and LDL 70–189 mg/ dL or LDL-C ≥ 190 who are already on a statin and have not had a 50% reduction in LDL-C.18 The guidelines also emphasize the importance of clinician-patient discussion on pharmacologic therapy and risk reduction when adding non-statin therapies.18 The American Association of Clinical Endocrinologists and American College of Endocrinology (AACE, ACE) Practice Guidelines for Managing Dyslipidemia and Prevention of CVD of 2017 provided clinicians with additional considerations and criteria for the management

TABLE 4.3  Risk category and treatment goals: AACE/ACE guidelines48 Risk category

Treatment Treatment Treatment goal: LDL-C goal: nongoal: Apo-B (mg/dL) HDL-C (mg/dL) (mg/dL)

Extreme Risk

5 servings/day), and whole grains.10,50 Patients should also eat slowly, chew thoroughly, avoid fatty foods, sweets and sugar-sweetened beverages, and avoid ingestion of liquids within 30 minutes of meals. Unfortunately, many postoperative patients fail to follow the recommended guidelines, particularly regarding fruit and vegetable consumption and avoidance of sweets and caloric beverages.50 For this reason, clinicians should routinely assess patients’ dietary intake during postoperative visits and reinforce recommended dietary goals.

40.7.3 Prevention of Micronutrient Deficiencies after Bariatric Surgery Patients who have undergone bariatric surgery should be counseled that they are at risk for the development of micronutrient deficiencies after surgery. After RYGB, the most common micronutrient deficiencies include those of vitamin B12, vitamin D, calcium, and iron.51,52 Folic acid deficiency has also been reported but is largely preventable with regular use of a standard multivitamin preparation.51

40.7  Nutritional Care 

Sleeve gastrectomy has been reported to produce similar deficiencies as gastric bypass but at a somewhat lower frequency.52 As compared to RYGB, the BPDDS is much more likely to produce deficiencies of the fat-soluble vitamins, including vitamin A.53 Purely restrictive procedures such as LAGB are infrequently associated with specific nutritional deficiencies.54 In many cases, micronutrient deficiencies can be prevented by regular vitamin and mineral supplementation

509

along with appropriate clinical follow up and routine biochemical surveillance. Expert guidelines are available regarding recommended vitamin and mineral supplementation after surgery and the frequency of laboratory screening for deficiency states.10,55 Tables 40.1 and 40.2 summarize these recommendations. Patients who are found to have evidence of specific micronutrient deficiencies will need additional vitamin or mineral supplementation, as indicated.

TABLE 40.1  Recommended micronutrient supplementation after bariatric surgery Supplement

Dose and frequency

Vitamin B1 (thiamine)

a

Folate (Folic Acid)

a400–800 µg daily 800–1000 µg daily for women of childbearing age

Calcium

b

12 mg daily

1200–1500 mg/day from all sources (after RYGB, SG, or LAGB) 1800–2400 mg/day from all sources (after BPD/DS)

b

Vitamin D (in calcium supplement or separate)

3000 IU/day

Elemental iron

a18 mg daily for low risk patients 40–60 mg/day for menstruating females

Vitamin B12

350–500 µg/day orally Or 500 µg every week intranasally Or 1000 µg/month parenteral (IM or SQ)

Zinc

a

16–22 mg/d (after BDP/SD) 8–22 mg/d (after RYGB) a8–11 mg/d (after SG/LAGB) a

2 mg/d (after BPD/DS or RYGB) 1 mg/d (after SG or LAGB)

Copper

a a

Vitamins A, E and K

Vitamin A 5000 IU/D and vitamin K 90–120 µg/d (after LAGB) Vitamin A 5000–10,000 IU/D and vitamin K 90–120 µg/d (after RYGB and SG) aVitamin A 10,000 IU/D and vitamin K 300 µg/d (after DS) aVitamin E 15 mg/d (after LAGB, SG, RYGB, and BPD/DS) a a

Patient subgroups at higher risk requiring additional supplementation are indicated. Adapted from the American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient. See Ref.55 LAGB, laparoscopic adjustable gastric banding; RYGB, Roux-en-Y gastric bypass; SG, sleeve gastrectomy; BPD/DS, BPDDS. a

Obtained from a multiple vitamin-mineral supplements.

b

Calcium should be given in divided doses, calcium carbonate should be taken with meals, calcium citrate may be taken with or without meals.

TABLE 40.2  Recommended laboratory tests and frequency of routine biochemical surveillance Procedure

Recommended frequency of biochemical surveillance

LAGB, RYGB, and SG

1st year: every 3-6 months. Thereafter: annually

CBC, electrolytes, glucose, iron studies, ferritin, vitamin B12, liver function, lipids, 25-hydroxyvitamin D As needed: intact PTH, thiamine, RBC folate, MMA, HCy

BPD/DS

1st year: every 3 months. Thereafter: every 3-6 months

Every 3-6 months: CBC, electrolytes, glucose, iron studies, ferritin, vitamin B12, RBC folate, liver function, albumin, prealbumin, lipids Every 6–12 months: 25-hydroxyvitamin D, vitamin A, vitamin E, vitamin K, INR, intact PTH Every 12 months: urine N-telopeptide, metabolic stone evaluation (24-hour urine calcium, citrate, uric acid and oxalate), zinc and selenium As needed: osteocalcin, carnitine, essential fatty acid chromatography

Recommended laboratory tests

Adapted from the American Association of Clinical Endocrinologists/The Obesity Society/American Society for Metabolic and Bariatric Surgery Medical Guidelines for Clinical Practice for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient. See Ref.10 LAGB, laparoscopic adjustable gastric banding; RYGB, Roux-en-Y gastric bypass; SG, sleeve gastrectomy; BPD/DS, BPDDS; CBC, complete blood count; PTH, parathyroid hormone; RBC, red blood cell; MMA, methylmalonic acid; HCy, homocysteine; INR, international normalized ratio.

40

510  Chapter 40  Surgery for Severe Obesity

40.7.4 Physical Activity Among individuals who have lost weight with nonsurgical treatment approaches, physical activity clearly plays a vital role in long-term maintenance of weight loss. 56,57 Much less is known about the role of physical activity in weight control after bariatric surgery, but it is likely an important factor.

40.7.5 Physical Activity Levels after Bariatric Surgery Numerous studies suggest that self-reported levels of physical activity increase significantly after bariatric surgery.58 However, there is little objective data regarding changes in physical activity levels in the postoperative period, and selfreported increases are likely to be overestimated. In one study, patients reported a large increase in moderate-tovigorous intensity activity after surgery, but accelerometer data suggested that such an increase did not actually occur in most individuals.60 The data suggest that only 6–24% of post-bariatric surgery patients meet national guidelines regarding minimal physical activity levels for general health promotion (i.e. ≥150 min/week or moderate-to-vigorous physical activity in bouts of 10 minutes or more).61,62 Data from the National Weight Control Registry indicate that patients who have lost weight through bariatric surgery tend to be less physically active than individuals who have lost similar amounts of weight through nonsurgical approaches.63

40.7.6 Benefits of Physical Activity in Postoperative Bariatric Surgery Patients In epidemiologic studies of postoperative patients, increased self-reported physical activity has been repeatedly associated with improved weight loss, mood and psychosocial functioning.63,64 Similarly, in a cross-sectional study that used armband accelerometers to measure activity in patients who had undergone RYGB two to five years earlier, higher levels of moderate-to-vigorous physical activity were associated with greater postoperative weight loss.61 However, there are limited data from intervention studies regarding the impact of physical activity training on perioperative outcomes. In a small, randomized controlled trial, bariatric patients who participated in a six month preoperative exercise program (including 80 minutes of supervised aerobic exercise and resistance training three times a week) had greater step counts, more time spent in light and moderate physical activity, improved fitness parameters, and greater BMI reductions at one year postoperatively than patients assigned to usual care.65 In contrast, in a non-randomized, prospective study, participation in a postoperative exercise program (including 75 minutes of supervised aerobic exercise and resistance training three times a week) for three months did not significantly increase weight loss after RYGB surgery.66 However, the intervention did prevent the observed decrease in dynamic muscle strength that was seen in postoperative

patients who did not exercise, and it was also associated with an increase in functional and aerobic capacity. In another small, randomized, controlled trial, investigators randomly assigned 33 obese (BMI ≥ 35.5 kg/m2) postoperative patients to either high-volume exercise (with a goal of expending ≥2000 kcal/week in moderate intensity aerobic exercise) or a usual activity control for 12 weeks.67 Subjects assigned to the exercise intervention reported a greater than three-fold increase in time spent in moderate physical activity and a nearly two-fold increase in recorded step counts. In this small study, intervention group subjects did not have greater weight loss or greater improvements in body composition, fasting glucose or insulin levels, lipids, or blood pressure, as compared to controls. However, they did have significantly greater improvements in physical fitness and glucose levels after an oral glucose challenge. Additional data are needed to further characterize the benefits of exercise in postoperative bariatric surgery patients and to determine the optimal physical activity levels in this group.

40.7.7 Barriers to Physical Activity after Bariatric Surgery Significant weight loss, such as that achieved after bariatric surgery, may enable patients with severe obesity to become more active. However, cognitive barriers to physical activity may persist after bariatric surgery and may influence patients’ activity levels.59 These barriers include reduced awareness of the health benefits of exercise, fear of injury, a lack of confidence in the ability to participate in physical activity, and self-consciousness or embarrassment. Treatment strategies which address these barriers may help patients become more physically active.

40.7.8 Recommendations for Physical Activity after Bariatric Surgery National guidelines suggest that for optimal weight control most overweight individuals will need to accumulate at least 150–300 minutes of moderate physical activity per week, or 30–60 minutes most days of the week.68 In one study of subjects who have successfully maintained large weight losses over time after surgical or nonsurgical treatments, nearly 70% engage in 150 minutes or more of moderate-to-vigorous physical activity per week, and over 30% are physically active for at least 300 minutes per week.57 Other data from the National Weight Control Registry indicate that walking is the preferred form of physical activity in this group of individuals.69 In randomized controlled trials, as well as epidemiologic studies, individuals who use pedometers to reach a specific step-count goal (such as >10,000 steps/day) increase their activity levels more and lose slightly more weight than those who do not use pedometers.70 Regular pedometer use may therefore be a practical and helpful strategy for patients who have had bariatric surgery. However, a recent, randomized controlled trial suggested that the provision of pedometers to bariatric surgery patients may be an ineffective strategy unless it is coupled with ongoing exercise counseling.71

40.7  Nutritional Care 

40.7.9 Behavioral/Psychological Care Bariatric surgical patients experience a variety of psychosocial challenges in the postoperative period. Initially, patients must adjust to the postoperative diet and to their altered relationship with food. As weight loss progresses, patients must adapt to changes in their appearance and their interactions with others. Dramatic weight loss, however desirable to the patient, can lead to unexpected consequences, such as body image issues related to excess skin, unwanted sexual attention from others, and jealousy from friends and loved ones. As a result of these many challenges, mood disorders, disordered eating patterns, and substance abuse are common among postoperative patients.

40.7.10 Mood Disorders Mood disorders are prevalent among candidates for bariatric surgery. For example, in one prospective study utilizing structured clinical interviews to assess mood pre- and postoperatively, clinical depression was present in approximately one-third and anxiety was present in almost 20% of preoperative patients.72 In this population, the prevalence of clinical depression decreased by over 50% in the three years following surgery, but the prevalence of anxiety remained relatively stable. Other studies have reported significant improvements in depressive symptoms that persist for up to five years postoperatively.73–74 Data from the large Swedish Obese Subjects (SOS) study suggest that after dramatic improvements in both depression and anxiety in the first postoperative year, there may be some deterioration of mood over time.75 However, even 10 years postoperatively, the prevalence of mood disorders did not return to baseline levels in this cohort. Data from the Longitudinal Assessment of Bariatric Surgery (LABS) study, a prospective, observational study of patients undergoing bariatric surgery, have provided further information regarding the effect of weight loss surgery on psychiatric disorders.76 At pre-surgery, 30% of patients met the diagnostic criteria for an Axis 1 disorder. The prevalence dropped to 17% and 18% at two and three years after surgery, respectively. The corresponding prevalence rates at baseline and at years two and three for any anxiety disorder was 17.2%, 12.3%, and 7.8%, respectively. Of note, however, was that use of any psychiatric medication or anti-anxiety medication remained relatively stable over time despite the reduced number of patients meeting the diagnostic criteria for any psychiatric disorder. There was no explanation of this discrepancy provided in the report. It is important to note that some studies have yielded discrepant findings. In one small cohort, levels of depression and anxiety did not change significantly after surgery.41 Furthermore, patients who have undergone bariatric surgery may be at an increased risk of suicide, particularly in the first three years after surgery.77–79 In a large, retrospective cohort study, individuals who had undergone gastric bypass surgery were twice as likely to commit suicide as obese control subjects matched for sex, age, and baseline BMI.80 Case studies suggest that patients who commit suicide after bariatric surgery often have a history of recurrent major depression, both before

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and after surgery, and that their depression persists even if they have excellent weight loss results81 These reports highlight the importance of continued attention to psychosocial health in the postoperative period, regardless of weight loss outcomes.

40.7.11 Disordered Eating Data from the LABS study have provided information regarding the effect of weight loss surgery on eating pathology.82 Following a cohort of 183 patients for up to three years postoperatively, investigators found that pathological eating behaviors and eating-related experiences are common prior to bariatric surgery and improve following surgery. For example, pre- and one-year prevalence rates for bulimic episodes declined from 11.6% to 1.3%, loss of control eating declined from 18.3% to 6.2%, picking/ nibbling diminished from 36.0% to 20.2%, and evening hyperphagia reduced from 16.5% to 5.0%. In contrast, hunger increased from one to three years of follow up. Post-surgery eating-related variables associated with poor weight outcomes included loss of control eating, hunger, and the eating disorder examination global score (which combines several factors such as restraint and shape/ weight concerns). It is important to probe for eating pathology since patients may not report these behaviors unless they are prompted by a clinician.

40.7.12 Alcohol Misuse The concern about the potential for development of alcohol dependence or abuse in postoperative patients was previously raised as a possible “addiction transfer” phenomenon.83 Although there is little support for this hypothesis, it does raise the question of whether patients who drink alcohol preoperatively are at increased risk for continued use, and what effect (if any) bariatric surgery may have on development of alcohol use disorder (AUD). In a substudy of LABS, patients completed baseline and follow up assessments of alcohol consumption using the Alcohol Use Disorders Identification Test (AUDIT), a 10-item test. A score of ≥8 (range 0–40) suggests harmful and hazardous alcohol use and possible dependence. After RYGB, there was an increase in the prevalence of AUD at baseline (pre-surgery) (6.6%) to year two (9.6%) and year seven (16.4%).84–86 Five-year cumulative incidence of AUD treatment was 20.8%. Male sex, younger age, smoking, and any or regular alcohol consumption pre-surgery were associated with increased risk for developing AUD. In another comprehensive review of the literature,84 a preoperative history of substance use (including alcohol) was a reliable predictor of postoperative use. The absorption and metabolism of alcohol may be altered after bariatric surgery, and, as a result, postoperative patients may be more susceptible to the intoxicating effects of alcohol.87–90 Patients should therefore be counseled to exercise caution when consuming alcohol after surgery. In addition, clinicians who care for bariatric surgery patients should ask patients about alcohol intake after surgery and remain alert to the possible presence of AUD in this population.91

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512  Chapter 40  Surgery for Severe Obesity

40.7.13 Psychological Counseling and Peer Support in the Postoperative Period Data suggest that patients with postoperative depression experience poorer weight loss than those who are not depressed.73 Similarly, postoperative patients who exhibit disordered eating patterns, such as grazing and loss of control over eating, have poorer weight loss and greater weight regain.92,93 Clearly, patients who are found to have mood disorders, disordered eating behavior, or substance abuse after bariatric surgery should be offered expert psychological counseling and support. It is not known, however, whether such treatment improves weight loss or other outcomes. In epidemiologic studies, attendance at postoperative support groups is associated with improved weight loss outcomes.94–96 There is a lack of data regarding the effects of other types of postoperative psychological support, such as group or individual therapy, on weight loss and other outcomes. Interestingly, patients who exhibit disordered eating patterns may be more receptive to a behavioral intervention after surgery than before surgery. In one small, nonrandomized, prospective study, pre- and postoperative bariatric surgical patients with binge eating or other disordered eating patterns were referred to a 10-week cognitive behavioral therapy program designed to address and improve the maladaptive eating patterns.97 Patients who were referred to the program postoperatively were much more likely to attend the initial session and to complete the program than patients referred preoperatively.

factors that have been associated with variability in postsurgical weight loss, including binge eating, depression, motivation, and coping skills. Eight of the studies assessed outcome at a one-year follow up, and seven used a nonrandomized controlled trial design. They concluded that both psychotherapeutic interventions and support groups provided a modest beneficial effect on post-surgical weight loss with an overall effect size of 0.18. In a subsequent review by Kushner and Sorenson100 in 2014, seven RCTs were identified investigating the efficacy of behavioral, dietary, or exercise counseling for postoperative weight loss. The authors concluded that the lifestyle interventions had either no effect or were only modestly effective in enhancing further weight loss and influencing lifestylerelated behaviors among post-bariatric surgery patients. More recently, additional pilot studies using cognitive behavioral therapy (CBT),101 CBT and dialectical behavioral therapy,102 and acceptance-based therapy103 have been published. However, enhancement of weight loss TABLE 40.3  Etiological factors for weight regain following bariatric surgery Anatomical   LAGB malfunction or mismanagement    Band or port breakage, band too loose  RYGB   Pouch enlargement    Gastrojejunal anastomosis dilation   Gastro-gastro fistula Physiological

40.7.14 Comprehensive Lifestyle Interventions after Bariatric Surgery There are limited data regarding the benefits of comprehensive lifestyle interventions in the postoperative period. Two systematic reviews and meta-analyses on behavioral98 and psychotherapeutic99 interventions in the bariatric surgical population have been published. In the review by Rudolf and Hilbert,98 they identified 15 behavioral management studies published prior to 2012. Eight provided cognitive behavioral therapy and seven included group support attendance. Five of the behavioral studies were conducted as randomized controlled trials (RCT) while all of the group support studies were of retrospective cohort design. Surgical procedures were primarily RYGB or LAGB and weight loss outcomes ranged from three to 36 months postoperatively. Across all of the behavioral studies, patients in the treatment groups showed greater weight loss than patients in the control groups; however, differences did not reach significance in any samples. For the group support studies, the majority found greater weight loss among those who attended support group meetings than in those that did not, though the difference was once again marginal. In the review by Beck et al.,99 they identified nine studies investigating the effect of psychotherapeutic interventions and support groups on weight loss following bariatric surgery that were published prior to 2012. Psychotherapeutic treatment targets the psychological

 Pregnancy  Menopause   Medications which cause weight gain   Smoking cessation  Endocrine disorders: hypothyroidism, Cushing's Syndrome, insulinoma   Intestinal or hormonal adaptation Behavioral  Dietary   unhealthy eating patterns e.g. grazing, nibbling, mindless eating    consumption of energy-dense foods and beverages    loss of dumping syndrome symptoms    loss of control over urges, binges   reduced vigilance   Physical activity    reduced leisure time activity    increased sedentary behaviors    insufficient moderately- and vigorously-intensity exercise    development of physical limitations to exercise

References  513

outcomes has been largely disappointing. Multiple factors appear to influence the varied outcome results, including patient selection, timing and intensity of the intervention, comprehensiveness of counseling provided, and selection of outcome measurements. Further studies will need to be conducted to identify the most suitable targets and patients for intervention.

40.7.15 Weight Regain following Bariatric Surgery Although clinicians commonly see bariatric surgery patients regain some weight postoperatively, the prevalence and incidence of weight regain has not been well-characterized. Follow up data from the LABS study has continued to inform clinical care regarding various aspects of postoperative management, including postoperative weight loss trajectories,104 behavioral variables, and three-year weight change.105 The underlying factors that influence weight regain following bariatric surgery are multifactorial and include endocrine/metabolic alterations, anatomic surgical failure, dietary indiscretion, mental health issues, and physical inactivity.106 The extent and significance of these factors is currently uncertain and likely varies between individuals and the operative procedure performed. Using cross-sectional data, weight regain has been estimated to occur in 20–35% of patients, depending on the procedure performed and duration of time following surgery.47 Table  40.3 provides a categorical list of potential etiologies that should be explored with all patients who present with weight regain. The physiological and behavioral (diet and physical activity) causes are common to surgical and nonsurgical patients. Depending on the patient’s age and gender, a through history should be performed that reviews all of these reasons followed by appropriate counseling.

40.8 CONCLUSION Bariatric surgery is an effective and acceptable treatment for individuals with severe obesity who are at risk for or have complications associated with obesity. Several surgical procedures are available with variable risk and weight loss outcomes. However, regardless of the procedure performed, surgery is considered a tool that is adjunctive to choosing a healthy, calorie-controlled diet and engaging in daily physical activity. For patients who undergo restrictive-malabsorptive or malabsorptive operations, dietary supplementation is necessary to avoid nutritional deficiencies. Patients are at risk for weight regain following surgery due to several biopsychosocial factors. In order to maximize successful outcomes, all patients should be monitored and managed by a multidisciplinary team of healthcare providers knowledgeable in bariatric surgical care.

CLINICAL APPLICATIONS • Bariatric surgery should be considered for patients with BMI of ≥ 40 kg/m 2 or those with a BMI of ≥ 35 kg/m 2 who have comorbid conditions and have failed nonsurgical approaches. • Preoperative assessment and postoperative management should be conducted by a multidisciplinary team of health care providers with attention to medical, dietary, physical activity and mental health aspects of care. • Since obesity is considered a chronic disease, patients who undergo bariatric surgery require longterm management, employing lifestyle behaviors and strategies conducive to maintaining a healthy body weight.

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78. Kalarchian MA, King WC, Devlin MJ, et al. Psychiatric disorders and weight change in a prospective study of bariatric surgery patients: A 3-year follow-up. Psychosom Med 2016;78:373–381. 79. Tindle HA, Omalu B, Courcoulas A, et al. Risk of suicide after long-term ­follow-up from bariatric surgery. Am J Med 2010;123(11):1036–1042. 80. Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med 2007;357(8):753–761. 81. Omalu BI, Cho P, Shakir AM, et al. Suicides following bariatric surgery for the treatment of obesity. Surg Obes Relat Dis 2005;1(4):447–449. 82. Devlin MJ, King WC, Kalarchian MA, et al. Eating pathology and ­experience and weight loss in a prospective study of bariatric surgery patients: 3-year follow-up. Int J Eating Disord 2016;49:1058–1067. 83. Sogg S. Alcohol misuse after bariatric surgery: Epiphenomenon or “Oprah” phenomenon? Surg Obes Relat Dis 2008;3(3):366–368. 84. King WC, Chen JY, Mitchell JE, et al. Prevalence of alcohol use disorders before and after bariatric surgery. JAMA 2012;307:2516–2525. 85. King WC, Chen JY, Courcoulas AP, et al. Alcohol and other substance use after bariatric surgery: Prospective evidence from a U.S. multicenter cohort study. SOARD 2017;13:1392–1404. 86. Li L, Wu LT. Substance use after bariatric surgery: A review. J Psychiatric Res 2016;76:16–29. 87. Klockhoff H, Näslund I, Jones AW. Faster absorption of ethanol and higher peak concentration in women after gastric bypass surgery. Brit J Clin Pharm 2002;54(6):587–591. 88. Hagedorn JC, Encarnacion B, Brat GA, et al. Does gastric bypass alter alcohol metabolism? Surg Obes Relat Dis 2007;3(5):543–548. 89. Woodard GA, Downey J, HernandezBoussard T, et al. Impaired alcohol metabolism after gastric bypass surgery: A case-crossover trial. J Am Coll Surg 2011;212(2):209–214. 90. Maluenda F, Csendes A, De Aretxabala X, et al. Alcohol absorption modification after a laparoscopic sleeve gastrectomy due to obesity. Obes Surg 2010;20(6):744–748. 91. Parikh M, Johnson JM, Ballem N, et al. ASMBS position statement on alcohol use before and after bariatric surgery. SOARD 2016;12:225–230. 92. Kofman MD, Lent MR, Swencionis C. Maladaptive eating patterns, quality of life, and weight outcomes ­following gastric bypass: Results of an Internet survey. Obesity 2010;18(10):1938–1943. 93. Colles SL, Dixon JB, O’Brien PE. Grazing and loss of control related to eating:

Two high-risk factors following bariatric surgery. Obesity 2008;16(3):615–622. 94. Livhits M, Mercado C, Yermilov I, et al. Behavioral factors associated with successful weight loss after gastric bypass. Am Surg 2010;76(10):1139–1142. 95. Orth W, Madan A, Taddeucci R, et al. Support group meeting attendance is associated with better weight loss. Obes Surg 2008;18(4):391–394. 96. Song Z, Reinhardt K, Buzdon M, Liao P. Association between support group attendance and weight loss after Rouxen-Y gastric bypass. Surg Obes Relat Dis 2008;4(2):100–103. 97. Leahey TM, Bond DS, Irwin SR, et al. When is the best time to deliver behavioral intervention to bariatric surgery patients: Before or after surgery? Surg Obes Relat Dis 2009;5(1):99–102. 98. Rudolph A, Hilbert A. Post-operative behavioral management in bariatric surgery: A systematic review and metaanalysis of randomized controlled trials. Obes Rev 2013;14:292–302. 99. Beck NN, Johannsen M, Stoving RK, et al. Do postoperative psychotherapeutic interventions and support groups influence weight loss following bariatric surgery? A systematic review and meta-analysis of randomized and nonrandomized trials. Obes Surg 2012;22(11):1790–1797. 100. Kushner RF, Sorensen KW. Prevention of weight regain following bariatric surgery. Curr Obes Rep 2015;4(2):198–206. 101. Gade H, Friborg O, Rosenvinge JH, et al. The impact of a preoperative cognitive behavioural therapy (CBT) on dysfunctional eating behaviors, affective symptoms and body weight 1 year after bariatric surgery: A randomized controlled trial. Obes Surg 2015;25:2112–2119. 102. Himes SM, Grothe KB, Clark MM, et al. Stop Regain: A pilot psychological intervention for bariatric patients experiencing weight regain. Obes Surg 2015;25:922–927. 103. Bradley LE, Forman EM, Kerrigan SC, et al. A pilot study of an acceptancebased behavioral intervention for weight regain after bariatric surgery. Obes Surg 2016;26:2433–2441. 104. Courcoulas AP, Chirstian NJ, Belle SH, et al. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA 2013;310:2416–2425. 105. Mitchell JE, Christian NJ, Flum DR, et al. Postoperative behavioral variables and weight change 3 years after bariatric surgery. JAMA Surg 2016;151:752–757. 106. Maleckas A, Gudaityte R, Petereit R, Venclauskas L, Veliekiene D. Weight regain after gastric bypass: Etiology and treatment options. Gland Surg 2016;5:617–624.

40

41 CHAPTER

Adiposity-based Chronic Disease a New Diagnostic Term Michael A. Via, MD and Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU

Key Points.................................................................................. 517 41.1 Introduction...................................................................... 517 41.2  Consequences of ABCD.................................................... 518 41.3  Intensive Lifestyle Intervention.......................................... 518 41.4  Sleep Hygiene................................................................... 520 41.5  Stress Reduction.............................................................. 521 41.6  Antibiotic Use and the Microbiome.................................... 522 41.6.1  Antibiotic Use by Humans...................................... 522

KEY POINTS • Adiposity-based chronic disease (ABCD) is a novel diagnostic term that emphasizes dysfunctional adipose tissue that is present in an unfavorable distribution and associated with metabolic disease, cardiovascular risk, and a host of other comorbidities. • An intensive lifestyle intervention can address many of the risks associated with ABCD. This includes healthy dietary patterns, physical activity, sleep hygiene, stress reduction, and community involvement. • Other aspects of lifestyle may affect ABCD, including minimal use of antibiotics, avoidance of endocrine disruptor chemicals, and transculturalization.

41.1 INTRODUCTION The physiologic role of intracellular fat deposition in the regulation of energy metabolism allows for the classification of adiposity-based chronic disease (ABCD) as a distinct entity and diagnostic term, with opportunities for research, clinical applications, and intensive lifestyle interventions.1 Fat deposition occurs in eutopic adipose tissue (adipocytes) with various body distributions, as well as in ectopic sites (non-adipocytes, such as myocytes and hepatocytes). 2 Depending on the deposition location, distribution, and function, intracellular fat directly and indirectly participates in energy metabolism through intermediary metabolism and hormone receptor signal transduction producing states of inflammation, insulin resistance, abnormal food-seeking behavior, and organ

41.6.2  Antibiotic Use in Farming.................................... 522 41.6.3  Endocrine Disruptors.......................................... 522 41.7  Alcohol Moderation......................................................... 523 41.8 Mood.............................................................................. 523 41.9  Community Engagement................................................ 523 41.10 Transculturization........................................................... 524 41.11 Conclusion...................................................................... 524 References................................................................................ 524

dysfunction. For the purpose of clarity and communication, the term adiposity refers to all sites of intracellular fat deposition, constituting a full range of healthy to unhealthy pathophysiological mechanisms. The term ABCD refers to the chronic disease state causally associated with abnormalities of adiposity (Table 41.1). This is distinguished from the term “obesity,” which is currently and strictly defined as having a body mass index (BMI) greater than a defined cutoff (e.g. 30 kg/m 2 or greater for Caucasians). The clinical diagnosis of ABCD may be supported by anthropometrics (e.g. BMI and waist circumference), body composition technologies (e.g. bioelectrical impedance and dual X-ray absorptiometry), and other imaging studies (e.g. computerized tomography, magnetic resonance, and positron emission tomography), 3 as well as serum markers of adipose function, including adipokines, triglycerides, and markers of inflammation (Table 41.2).4,5 Unfortunately, multiple and conflicting health messaging about the definition and the causes of obesity, best lifestyle practices, and unproven therapies only aggravate confusion within the scientific literature,6,7 lay press,8 and popular culture.9,10 Abnormal adiposity poses significant and irrefutable health risks, but sustainable lifestyle interventions, though logically sound and evidence based, are very difficult to implement. This incongruence commonly leads to therapeutic nihilism on the part of both healthcare professionals (HCP) and patients. To some degree, this follows from the widely held belief that obesity is a personal choice rather than a bona fide chronic disease state with hallmark biological and behavioral components. Despite the classification of obesity as a disease several years ago, negative personal and societal connotations remain associated with the word “obesity.”1,6,7 Moreover, limitations in the use of BMI to predict adverse risk, especially among Asian populations,11 as well as acceptance of 517

518  Chapter 41  Adiposity-based Chronic Disease a New Diagnostic Term TABLE 41.1  Defining characteristics of ABCDa Adiposity variable

Metric

Increased mass

Anthropometrics (e.g. weight, BMI) Body composition imaging

Abnormal distribution

Anthropometrics (e.g. WC, WHR)

Abnormal function

Adipokine/cytokine levels (e.g. adiponectin, leptin)

Body composition imaging

a ABCD is differentiated from obesity by the specific excessive distribution and dysfunction of adipocytes. Abbreviations: ABCD – adiposity-based chronic disease; BMI – body mass index; WC – waist circumference; WHR – waist-to-hip ratio. See references,4,5 and.129

TABLE 41.2  Selected energy and inflammation signal networks affected in ABCDa Adipokines

Change in ABCD

Adiponectin

Reduced

Leptin

Elevated

Resistin

Elevated

Visfatin

Elevated

Cytokines  Interleukin-1

Elevated

 Interleukin-6

Elevated

  Tumor necrosis factor-α

Elevated

Other signal molecules

a

  Fibroblast growth factor-21

Elevated

  Glucagon-like peptide 1

Reduced

 Ghrelin

Elevated

  Plasminogen activator inhibitor-1

Elevated

  Mechanistic target of rapamycin

Reduced

ABCD – adiposity-based chronic disease. See reference.5

changing societal norms, may cast doubt on the urgency and severity of risk among patients with obesity.12 To address these concerns, the concept of ABCD emphasizes the unhealthy nature of adiposity extending well beyond simple BMI or body weight, which includes abnormal body fat distribution, anthropometrics, and adipocyte secretome patterns. Changes in production of adipokines, such as leptin, resistin, and adiponectin, are among the most notable alterations of adipocyte function.5 This greater detail allows for more precise therapeutic interventions, particularly structured lifestyle interventions, but also requires a more robust diagnostic coding system for reimbursement and economic incentive for ABCD tactics. Following a laser-focused behavioral intervention to activate patients for change, an intensive lifestyle intervention approach should be implemented for ABCD and continued even as pharmaceutical and procedural interventions are delivered. Given the high prevalence rate of obesity in

modern global populations, and the limited access to other therapeutic options, an intensive lifestyle modification may be the only available option for the majority of patients with ABCD worldwide. Moreover, the effective implementation of structured lifestyle change for patients with ABCD promises to decrease the need for costlier medical and surgical interventions (quaternary prevention). The premise of this chapter is that the decades-long trend of clinical inertia in obesity medicine, stigmatization, and skyrocketing obesity rates within many subpopulations in the United States and worldwide prompts a call-for-action to optimize and formalize lifestyle interventions to mitigate ABCD risk factors and complications.

41.2 CONSEQUENCES OF ABCD The health consequences of ABCD are far-reaching and include metabolic, cardiovascular, orthopedic, gastrointestinal, psychiatric, and oncologic risk (Table 41.3). Prediction of specific ABCD sequelae can be difficult. Not all patients with ABCD develop each of the associated complications. Additionally, the degree of adipose tissue accumulation may not correlate with the severity or the incidence of ABCD-associated complications, especially in conditions characterized by abnormalities in the distribution and function of adipose tissue. Some authors propose the existence of a subset of patients with “metabolically healthy” obesity (MHO), who are not at increased risk for cardiovascular disease or type 2 diabetes (T2D), despite the presence of a BMI above 30 kg/m 2 (highlighting the problem of defining obesity by a simple arithmetical formula).13 Over time, patients with MHO still demonstrate increased rates of T2D, insulin resistance, and cardiovascular disease.14,15 These patients with MHO are also at risk for other ABCD-associated complications (Table 41.3),16 consistent with a more complex networking model that demonstrates emergent properties. 5 More significantly, many ABCD-associated complications instigate adverse lifestyle choices and create vicious cycles of abnormal adiposity. For example, orthopedic injuries, cardiovascular atherosclerotic disease, or depression can prevent regular exercise and favor individual preference for sedentary activity.17–19 Obstructive sleep apnea disrupts healthy sleep hygiene. 20 Dysglycemia syndromes such as T2D, polycystic ovary syndrome (PCOS), and the metabolic syndrome affect hormonal control of energy homeostasis, which may render attempts at weight loss through lifestyle intervention more difficult. 21 In several studies, patients with T2D achieved approximately 50% of the weight loss that was sustained by patients without T2D following identical dietary and exercise protocols. 22,23 Similarly, women with PCOS demonstrate less weight loss than obesity-matched women without PCOS. 24

41.3 INTENSIVE LIFESTYLE INTERVENTION All patients with ABCD should strive for a healthy lifestyle, avoiding or minimizing modern conveniences and living practices that are detrimental to metabolic health.

41.3  Intensive Lifestyle Intervention  519 TABLE 41.3  ABCD-related conditionsa Condition

Relative risk

ABCD component Adiposity Amount

Reference

Characteristic Adipose Distribution

Abnormal Adipocyte Function

Metabolic   Type 2 diabetes

7.7

++++

++++

++++

130

  Polycystic ovary syndrome

1.5

+

++

++

131,132

 Hepatosteatosis

1.9

++

+++

++

133,134

  Obstructive sleep apnea

3.6

+++

++

++

135,136

 Hypertension

2.0

++

++

+

130,137

  Atherosclerotic disease

1.6

++

++

+++

130,138

 Arrhythmia

1.49

+

+++

++

139,140

 Osteoarthritis

1.39

+

+

−

130,141

  Tendon injuries

1.7

++

++

++

142,143

 Gout

2.2

++

+

+

144,145

  Infertility (women)

1.2

+

++

++

146,147

  Hypothalamic hypogonadism (men)

1.6

++

+++

+++

148

1.8

++

+

++

130,149

2.0

++

+++

+++

150

1.5

++

+

+

130,151

Cardiovascular

Orthopedic

Gonadal function

Gastrointestinal  Cholelithiasis Psychiatric  Depression Cancer   Obesity-related (esophageal, colon, pancreatic, prostate, kidney, liver, gall bladder) a

Relative risk compared to non-obese population.

It may be difficult to define specific populations at risk for ABCD, though the vast differences in modern lifestyles and built environments, compared to those of prior generations and even distant ancestors, are suggestive that the current population would benefit from healthy lifestyle interventions. Among the most obvious aspects is the choice of dietary pattern. Any demonstrably healthy dietary pattern is recommended, provided a durable effect can be realized. 25 Enhanced adherence and sustainability will require motivational interviewing and behavioral assessments of food preferences, daily activities and logistics, cultural mores, tastes, religion-based rules, and other idiosyncrasies. 26 HCPs should exercise flexibility and poise to offer up quick alternatives for a successful trajectory when clinical progress has stalled. A dietary pattern that is high in fruits, vegetables, nuts, complex carbohydrates, with controlled amounts of meats, fish, and negligible amounts of

processed foods and sugar-containing beverages provides the greatest benefit to patients with ABCD.6,27 Some of the most widely studied dietary patterns with these attributes include the Mediterranean diet, the New Nordic diet, the Ornish diet, the Dietary Approaches to Stop Hypertension (DASH) diet, among others. 28–31 In the largest published randomized trial, the group of patients assigned to the Mediterranean diet had the greatest amount of weight loss, as well as reduction in T2D, reduction in cardiovascular events, and reduction in mortality compared with low-fat or low-carbohydrate diets. 28 The New Nordic diet, the Ornish diet, and the DASH diet, which overlap substantially with the Mediterranean diet in categorized food content, may have similar benefits. A very useful tactic to enhance adherence is to have at the ready website addresses, electronic and printed materials, and other information modalities for these dietary patterns for every patient. Various wearable technologies that synchronize

41

520  Chapter 41  Adiposity-based Chronic Disease a New Diagnostic Term

with smartphones and access cloud-based software can be trialed and optimized for individual patients.32 In addition to total body adipose content, the localized distribution and function of adipose tissue can be improved with adoption of healthy dietary patterns. In one randomized trial, subjects assigned to the Mediterranean diet demonstrated improvement in insulin resistance by 37%, reduced inflammation by 37%, and increased adiponectin by 43% after one year, suggesting improved adipose function. 33 A population study of 5,079 individuals demonstrated reduced visceral adipose, reduced cardiac adipose tissue, and less hepatic steatosis, but no change in subcutaneous adipose among those who followed dietary patterns that closely resembled the Mediterranean diet. 34 Increased physical activity and exercise should also be incorporated into daily routines. Although the amount and type of exercise has not been fully settled, regular participation in physical activity is important. Many studies and organizations suggest that at least 150 minutes of physical activity divided over five to seven days per week constitutes a reasonable minimum.6 Strength training provides benefit of increased muscle mass, reducing myocyte adipose content, while cardiovascular exercise promotes reduction of visceral adipose accumulation.35 Both of these endpoints are desirable in ABCD. Adipose function, assessed by adipokine production and inflammation, is also greatly enhanced through regular physical activity and exercise.36 In addition to optimizing the choice of dietary pattern and amount of physical activity, many other individual lifestyle factors can impact the risk of ABCD (Table 41.4).1

41.4 SLEEP HYGIENE Sleep affects metabolic regulation. As a defining feature of circadian rhythm, the amount, quality, and timing of sleep cycles affect hypothalamic function, cortisol release, thyroid function, hepatic glucose production, brown fat activation, and insulin resistance. 37 Additionally, pancreatic β-cell function is impaired in states of sleep deprivation.38 This may reflect the responsiveness that β-cells

demonstrate to melatonin secretion, which is itself diminished in disrupted circadian rhythms.39 In the modern era, average sleep duration has been declining. Time spent sleeping by adults has decreased from an average of nine hours per night to seven hours per night over the past 40 years.40 In children, sleep time has reduced an average of 0.75 min/night/year for the past century.41 These trends continue to spread worldwide.40,41 In addition to reduced sleep time, the presence of insomnia, defined as waking in the middle of the night at least three times weekly, is reported among 25–35% of adults.42 In children, no upper limit of healthy sleep has been identified, and a longer duration of sleep is associated with reduced amounts of adiposity, improved quality of life, and improved academic success.43 In a meta-analysis of longitudinal trials in children, longer sleep duration was associated with reduced adiposity by an odds ratio of 1.89.43 For every one hour of sleep duration, the annual rate of BMI increase was reduced by 0.05 kg/m 2 . In adults, between seven and nine hours of sleep are recommended nightly, and eight to 10 hours of sleep are recommended in adolescents.44 As with studies in children, adults exhibit increased adiposity, especially visceral adiposity, in association with shorter sleep duration.45 In one observational trial, an increase in sleep time from lessthan-six to seven-to-eight hours resulted in a reduction of visceral fat gain over six years of follow-up.46 Several randomized trials demonstrate that even short-term sleep restriction for five days causes weight gain in adults. This is attributed to increased calorie consumption by 130% in the sleep-deprived group compared to the control group.47,48 In a crossover study, a 52% increase in consumption of sweets and desserts was observed during times of sleep deprivation.49 These results may be explained by elevation in circulating ghrelin levels and reduction in leptin levels that are observed in periods of sleep restriction. 50 Both of these hormonal markers of adipose dysfunction within ABCD would be expected to increase appetite and exacerbate insulin resistance. 38,50 The importance of adequate sleep combined with other lifestyle interventions has also been demonstrated in a series of cross-sectional trials.45 One observational

TABLE 41.4  Effects of lifestyle intervention on components of ABCD Intervention (Reference)

Adipose amount

Adipose distribution

Adipose function

Dietary pattern28

Moderate

Moderate

Moderate

Physical activity6

Negligible

Moderate

Moderate

Sleep hygiene49,50

Strong

Moderate

Moderate

Stress reduction59,60,63

Mild

Moderate

Strong

Antibiotic use

Mild

–

–

85

Endocrine disruptors

Moderate

Moderate

Strong

88–90

Alcohol moderation

Moderate

Negligible

Moderate

Moderate

NA

Strong

Moderate

NA

Strong

74

Mood

93,95

Community engagement

113

NA: Sufficient data not available.

41.5  Stress Reduction  521

study demonstrated an association of decreased sleep time and increased calorie consumption among obese women, compared to normal weight controls. 51 In another study, an inverse linear relationship between self-reported sleep duration and BMI was observed. 52 Data from the National Health and Nutrition Examination Survey also demonstrate a strong association between reduced sleep time and adiposity. 53 Additionally, patients with obesity demonstrate increased sleep latency and reduced percentage of time in REM sleep.40 A concerted effort to attain sufficient time for sleep is an important part of a healthy lifestyle, especially in the prevention and treatment of ABCD. 37,40 Disordered sleep is disruptive to circadian rhythms and associated with weight gain.40 Obstructive sleep apnea (OSA) is highly prevalent in adults with obesity and disruptive to healthy sleep. In one longitudinal study, a 10% increase in body weight was associated with a sixfold increase risk of OSA. 54 The use of devices that provide continuous positive airway pressure can reduce the cardiovascular impact of OSA and improve symptoms of daytime drowsiness. However, this modality fails to affect proximate, causative metabolic derangements, such as abnormal adipose distribution and function, in patients with OSA. 55 On the other hand, weight loss through intensive lifestyle modification can improve measures of OSA, simultaneously improving overall sleep hygiene. 56

41.5 STRESS REDUCTION The human response to chronic stress is associated with ABCD and involves hypothalamic dysfunction, increased consumption of palatable and calorie-dense foods, and reduced physical activity. 57,58 The hormonal profile with chronic stress includes elevations of cortisol, catecholamines, and insulin as part of an insulin-resistant state. 58 In one cross-sectional study, chronic stress was associated with increased food cravings despite increased leptin levels, suggesting the presence of leptin resistance and adipose dysfunction in response to stress.59 Another study demonstrated that elevated cortisol and increased visceral

fat accumulation are associated with increased stress.60 Interventions to reduce stress are central to any healthy lifestyle (Table 41.5). Given the multiple stressors that are regularly present in everyday life, simple avoidance of stressful situations is often not possible. Modalities to address stress and activities to lessen pathophysiologic effects of stress may be beneficial in ABCD.1 In studies of stress reduction techniques, mindfulness-based stress reduction may reduce cardiovascular events and has been shown to improve markers of inflammation and adipokine levels in patients with obesity.61,62 In one randomized controlled trial, women with obesity or who were overweight were assigned to either a mindfulness group that met once weekly to discuss stress reduction techniques and given recommendations for daily home sessions for 30–45 minutes each.63 The control group met weekly with a dietitian to review nutritional recommendations. By eight weeks, depression and anxiety declined in the mindfulness group, and quality of life improved. These effects persisted at 16 weeks after the end of intervention. Additionally, fasting insulin and systolic blood pressure improved in the mindfulness group compared to controls at both the end of the trial and 16 weeks after its conclusion. Mindfulness techniques of stress reduction are promising lifestyle interventions in ABCD. This approach has also been shown to reduce binge-eating episodes in at-risk patients.64 Another method for stress reduction is through regular participation of low-impact exercises such as yoga. In a randomized trial of women with overweight or obesity, those assigned to the treatment group sustained a 2.4 kg weight loss and a 3.8 cm decrease in waist circumference after 12 weeks of twice weekly 90-minute yoga classes.65 Additionally, self-assessment measures of stress declined, while measures of quality of life and of selfesteem improved with yoga treatment. Another published, randomized trial in men with overweight or obesity demonstrates reduction in weight by 2.2 kg and reduction in perceived stress score.66 These results are similar to earlier observational studies indicating the practice of yoga can improve stress and adipose tissue accumulation over the short term.67

TABLE 41.5  Clinical application for lifestyle interventions Intervention (Reference)

Practical clinical application

Dietary pattern

Mediterranean, DASH, Ornish, New Nordic, or similar dietary pattern

28

Cardiovascular activity for 30 minutes 5x weekly Resistance training 3–5x weekly

Physical activity

6

Sleep hygiene49,50

7–9 hours nightly sleep, regularly

Stress reduction

Mindfulness, low-impact exercise

59,60,63

Minimal use of antibiotics

Antibiotic use

74

Endocrine disruptors

Avoidance, minimize exposure of environmental toxins

Alcohol moderation

0–9 alcoholic beverages per week for women, 0–14 for men

85

88–90

Cognitive behavioral therapy

Mood

93,95

Community engagement

113

Engagement in community outreach programs

41

522  Chapter 41  Adiposity-based Chronic Disease a New Diagnostic Term

41.6 ANTIBIOTIC USE AND THE MICROBIOME 41.6.1 Antibiotic Use by Humans Since their discovery, antibiotics have been critical for the treatment of infectious disease of bacterial or fungal origin. Clear success has led to widespread use and overuse of antibiotics, including dubious medical practices that employ antibiotic use for conditions that may not be bacterial in origin. A 2011 survey found 263 million separate outpatient antibiotic prescriptions had been filled by pharmacies in the U.S. during that year, an annual rate of 0.8 per citizen.68 This trend leads to concerns regarding the development of antibiotic resistance and pathologic metabolic effects. Antibiotic use can affect microflora residing within the gastrointestinal (GI) tract serving as an exemplar of how other lifestyle changes that affect gut microbiota can indirectly lead to ABCD. Hundreds of species of bacteria and fungi are present within the colon of each individual and take part in a complex relationship between the host and other species of microflora.69 These microbes directly affect host energy homeostasis through metabolism of sugars and fiber present in the intestinal chyme to produce short-chain fatty acids that are available for utilization by the host. Approximately 5–10% of the total daily calorie consumption is obtained in this fashion.70 Additionally, through multiple routes of signaling with the host, the GI microflora can influence the degree of insulin resistance, systemic inflammation, metabolic rate, and may affect other health aspects of the host such as mood and cardiovascular function. 69,71,72 While the specific molecular mechanisms for GI microflora-host metabolic interactions continue to be investigated, a number of population studies have been published that associate the use of antibiotics with weight gain and obesity. This is especially evident among infants and children treated with antibiotics. In a study of children born to normal-weight mothers within the Danish National Birth Cohort, the use of any class of antibiotics in early-life was associated with an increased risk of overweight by age seven (odds ratio of 1.54).73 A large, international study demonstrated increased BMI at ages five to eight among boys who were treated with antibiotics within the first year of life.74 In another international cohort involving eight medical centers located in lowresource settings, 1,954 infants followed until age two demonstrated significant weight gain without change in body length among those treated with one or more courses of various classes of antibiotics.75 In this trial, penicillins, cephalosporins, macrolides, and metronidazole had the largest effects on weight gain. There was no associated weight gain observed in those infants given trimethoprim-sulfamethoxazole. Similarly, a post-hoc analysis of a randomized trial designed to investigate use of prophylactic trimethoprim-sulfamethoxazole for vesicoureteral reflux showed no effect on weight with this class of antibiotic.76 Few studies have been conducted regarding the metabolic effect of antibiotics in adults. In one seven-day

study, oral vancomycin significantly altered the species composition of GI microflora of subjects with obesity but did not demonstrate metabolic changes both during this trial or afterward.77 Amoxicillin also had no discernable effect on metabolism. In another trial, 11 patients with obesity, insulin resistance, and with detectable methane on breath testing were treated with neomycin and rifamaxin until methane could no longer be detected, which took an average of 10 days of treatment.78 The bacterium Methanobrevibacter smithii is presumed responsible for methane production, and stool levels of M. smithii were eradicated in eight of 11 subjects after the treatment course. In all subjects, low-density lipoprotein levels declined and insulin sensitivity by oral glucose tolerance testing improved after treatment. This trial suggests a potential cardiometabolic risk benefit with GI microflora manipulation. Though other confounding factors within many of these reported studies may influence the results, the prudent and minimal use of antibiotics in medical practice may help to prevent weight gain, and may influence other aspects of ABCD, especially among infants and children. Certain classes of antibiotics, such as sulfonamides, appear to have neutral effects on weight and may be preferred in appropriate clinical settings. Protocols for the active manipulation of GI microflora to generate beneficial metabolic effects require more study before firm recommendations can be made.

41.6.2 Antibiotic Use in Farming The use of antibiotics outside of the medical field may also play an indirect role in the development of ABCD and lead to sound conjecture about optimal food sourcing as part of healthy lifestyles. Widespread use of antibiotics by livestock farmers yields animals that gain weight faster and require less feed.79 Nutrient changes within food products yielded by this practice have not been formally evaluated. However, changes within the livestock microbiome have been reported.80 These observations of accelerated growth and altered microbiome are suggestive that the nutrient makeup of meat derived from antibiotic treated livestock may be altered, though further study is warranted in this field.

41.6.3 Endocrine Disruptors Multiple classes of industrially produced chemical compounds demonstrate biological properties that affect hormone signaling. A subset of these endocrine disrupting compounds (EDC) has been shown to affect adipose tissue accumulation, distribution, and function.81 In several studies, childhood exposure to bisphenol A, among the more well studied EDC, is associated with weight gain and obesity.82 Exposure to bisphenol A is also associated with reduced adiponectin and increased resistin gene expression in children.83 Exposure to octylphenol, another EDC, is also associated with increased resistin gene expression.84 Visceral adipose accumulation has been associated with exposure to organic pollutants that likely function as EDC.85 As patients with ABCD successfully lose weight,

41.9  Community Engagement 

lipid soluble EDC may be released into the circulation, especially from visceral adipose depots that may concentrate toxins in close proximity to vital organs.86 Many other EDC can affect energy metabolism and mechanisms leading to ABCD, requiring ongoing clinical study.

41.7 ALCOHOL MODERATION High amounts of alcohol intake are associated with adverse health outcomes, including death. In contrast, moderate alcohol consumption, especially consumption of wine, has been demonstrated to improve markers of insulin resistance, cholesterol levels, and systemic inflammation, suggesting improvement in adipose function.87 Recently published trials continue to support the findings that of moderate alcohol intake, defined as 14 drinks per week for men and nine drinks per week for women, is associated with a lower incidence of T2D, and, in many cases, prevention of weight gain.88 In a study of 224 subjects with T2D who were provided either 150 mL of red wine, white wine, or water daily, both of the groups given wine showed reduced insulin resistance measured by fasting insulin levels, with increases in high-density lipoprotein levels in the red wine group.89 Adipose tissue distribution is not affected by moderate alcohol intake.90 The drawbacks of alcohol consumption include the risk of dependence and the potential for cognitive impairment, especially while operating motor vehicles, or simply walking along a busy street. Another concern is the theoretical risk of accelerated hepatosteatosis when patients at high risk for non-alcoholic fatty liver disease consume alcohol regularly.91 The DIONYSOS study appeared to support this claim; however, in this trial, an increase in steatosis was observed only in subjects with obesity that consumed more than 60 g alcohol, or four standard drinks, daily.92 Within the trial, this group was known as the “heavy drinkers.” Moderate alcohol consumption was not associated with increased hepatosteatosis in patients with obesity.

41.8 MOOD Disorders of mood, such as depression and anxiety, have a complex relationship with weight gain and risk of ABCD. Obesity and depression often occur together in the same patient, in part due to common molecular mechanisms including altered hypothalamic-pituitary-adrenal axis signaling, increased oxidative stress, and increased systemic inflammation.93 In a published cohort, an increased prevalence of depression is associated with increased leptin levels, suggesting adipose function is affected in patients with depression.94 The presence of depression is also associated with increased risk for the development of obesity later in life.95–98 Patients with obesity demonstrate a poorer response to antidepressant therapy.99–101 Additionally, many antidepressant medications induce weight gain and adiposity, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors.102

523

Atypical antipsychotics, which may be applied in major depressive disorder, induce intense weight gain, insulin resistance, increased circulating leptin and reduced adiponectin.103 Still, the successful treatment of depression is often accompanied by significant weight loss and improvement in ABCD.104 Moreover, weight loss in patients with ABCD has been shown to reduce depressive symptoms and improve quality of life.105 Aside from pharmacologic therapies, cognitive behavioral therapy (CBT) can improve mood disorders and weight loss efforts. In one trial, patients with depression and obesity randomized to receive modified CBT that included aspects of healthy living had more sustainable weight loss and improved mood compared to standard CBT practices over 48 weeks of observation.106 In another trial, CBT was associated with weight loss among adolescents with obesity and depression.107 Multiple studies in adult patients with obesity and depression demonstrate effectiveness of CBT in addressing both conditions.108 Improvements in adipose function and distribution would be expected in association with weight loss; however, these effects of CBT have not been assessed.107,108 Practically speaking, with proper training, HCPs outside of the specialty of psychiatry can successfully implement CBT for the treatment of ABCD.109

41.9 COMMUNITY ENGAGEMENT Close personal contacts and community involvement exhibit considerable influence on individual behavior patterns and on patterns of weight gain.110 Moreover, efforts within communities to emphasize healthy lifestyle choices can reduce the impact of ABCD. Community programs that engage whole families in healthy dietary patterns, physical activity, and wellbeing have been shown to diminish childhood obesity.111 These programs regularly meet as a group, create and nurture self-encouragement behaviors, and result in better health.112 Improvements in quality of life and reductions in adiposity have been observed with these type of interventions.112 In one randomized trial, a community-based intervention induced weight loss of 7.8%, adiponectin increase by 27%, and leptin decrease by 22% after one year, suggesting improvement in adipose function and an overall decrease in ABCD related risks.113 Several barriers to program efficacy have been observed including the main driver of program avoidance: parental concerns of psychosocial well-being with little regard for other long-term sequelae of ABCD.112 Denial or lack of recognition by parents also presents a significant barrier to program initiation. With any lifestyle intervention, care should be taken to avoid incurring body dissatisfaction, reduced self-esteem, or other detrimental effects to mental health to the target audience.114 Programs that frame their central message as promotion of a healthy lifestyle are more successful than programs that specifically target weight loss.115 The direct involvement of families may be fundamental to this process; implementation of a five-year health and well-being intervention program through

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524  Chapter 41  Adiposity-based Chronic Disease a New Diagnostic Term

elementary schools with minimal parent involvement had no effect on adiposity.116 In contrast, faith-based programs may represent important modes of community outreach for ABCD prevention.117 In one randomized study involving congregations of 20 churches, hourly, weekly meetings emphasized dietary patterns and physical activity achieved in the Diabetes Prevention Project (DPP) was compared to a control intervention that involved just general information.118 The DPP arm showed a 2.4 kg weight loss after six months, compared to a 0.4 kg weight gain by the control group. Several other observational trials of faith-based community intervention programs also show promise of improved weight reduction.119,120 The recognition of community engagement as a means to drive healthy behaviors has prompted the development of online virtual communities with the goal of improved health.121 Though these have received much fanfare, results are inconsistent and depend on perceived emotional support (though levels of support can vary greatly).121 In-person, family-oriented, community engagement is a successful approach to adapting a healthy lifestyle.

41.10 TRANSCULTURIZATION The cultural background of each individual has significant impact on lifestyle choices and response to medical advice. To be sustainable, suggested dietary patterns should be congruent with a patient’s cultural tradition.122 This approach garners community support and promotes durable and successful healthy lifestyle changes. In contrast, recommended dietary patterns at odds with a patient’s own culture will often incur transgressions if they are not adequately addressed.122 Some cultures traditionally place value on weight gain as a marker of wealth, high social standing, and overall well-being. However, the worldwide increased prevalence of adiposity has triggered responses by governments, cultural leaders, international charitable organizations, the World Health Organization, and the United Nations to address non-communicable chronic diseases, including ABCD.123–125 Recommendations to address ABCD among various nations include the identification and education of physicians and cultural leaders within different regions who would serve as agents of change.122 A respectful understanding of local culture can allow adaptation of lifestyle interventions to curtail ABCD and associated complications, with potential for broad impact when implemented globally. In addition to cultural adaptations for lifestyle medicine approaches, ethnic variation can lead to a range of

ABCD phenotypes. Traditional measures of obesity, such as waist-to-hip ratio or BMI do not capture the full risk conferred by adiposity in Eastern Asian and Indian populations.11 As a model of cardiometabolic risk, the distribution, function, and amount of adiposity among these populations are more predictive than BMI alone.126,127 As an example, when matched for age and BMI, Asian patients demonstrate higher circulating leptin and lower adiponectin, emphasizing the importance of adipose function rather than BMI.128

41.11 CONCLUSION The growing and worldwide epidemic of obesity is among the highest intervention priorities in health care. A number of important lifestyle factors have been identified in addition to the individualization of dietary patterns and physical activity. Unfortunately, a slow rate of success coupled with therapeutic inertia on local and national scales require new ways to regard the problem. ABCD is a new diagnostic term that incorporates not only body weight and BMI, which is all that current obesity definitions and interventions rely on, but also healthy and unhealthy distributions and secretory functions of body fat. This broader conceptualization of this metabolic problem permits a better understanding of pathophysiology, analysis of current evidence, and formulation of effective interventions. Future directions in this field may yield the incorporation of body scanning for adipose distribution assessment and broad molecular testing to identify multiple adipokine abnormalities in the pathologic state of ABCD.1 Healthy lifestyle interventions to mitigate ABCD include individualization and adoption of healthy dietary patterns and physical activity programs. Improvements in sleep hygiene, reduction in stress, and treatment of both clinical and subclinical disorders of mood can also impact weight gain, improve adipose tissue function and distribution, and improve overall well-being among patients with ABCD. Judicious and minimal use of antibiotics, especially among infants and children, can also mitigate weight gain and possibly prevent the development of ABCD. Avoidance of EDC wherever possible, populationbased improvements in food sourcing, and moderation of alcohol intake among adults may also be incorporated in a healthy lifestyle. Beyond the individual, the involvement of community and culturally-sensitive medical practices can help to redirect normative trends in clinical practice. When optimized, these important lifestyle factors can significantly reduce ABCD and its associated detrimental effects.

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P, Rossi S, Mita DG, Perrone L, Diano N, Miraglia Del Giudice E. 2017. Bisphenol A is associated with insulin resistance and modulates adiponectin and resistin gene expression in obese children. Pediatr Obes 12:380–387. Lee MJ, Lin H, Liu CW, Wu MH, Liao WJ, Chang HH, Ku HC, Chien YS, Ding WH, Kao YH. 2008. Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor and extracellular signal-regulated kinase pathways. Am J Physiol Cell Physiol 294:C1542–C1551. Dirinck EL, Dirtu AC, Govindan M, Covaci A, Van Gaal LF, Jorens PG. 2014. Exposure to persistent organic pollutants: Relationship with abnormal glucose metabolism and visceral adiposity. Diabetes Care 37:1951–1958. Dirinck E, Dirtu AC, Jorens PG, Malarvannan G, Covaci A, Van Gaal LF. 2015. Pivotal role for the visceral fat compartment in the release of persistent organic pollutants during weight loss. J Clin Endocrinol Metab 100:4463–4471. Brien SE, Ronksley PE, Turner BJ, Mukamal KJ, Ghali WA. 2011. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: Systematic review and metaanalysis of interventional studies. BMJ 342:d636. Traversy G, Chaput JP. 2015. Alcohol consumption and obesity: An update. Curr Obes Rep 4:122–130. Gepner Y, Golan R, Harman-Boehm I, Henkin Y, Schwarzfuchs D, Shelef I, Durst R, Kovsan J, Bolotin A, Leitersdorf E, Shpitzen S, Balag S, Shemesh E, Witkow S, Tangi-Rosental O, Chassidim Y, Liberty IF, Sarusi B, Ben-Avraham S, Helander A, Ceglarek U, Stumvoll M, Bluher M, Thiery J, Rudich A, Stampfer MJ, Shai I. 2015. Effects of initiating moderate alcohol intake on cardiometabolic risk in adults with type 2 diabetes: A 2-year randomized, controlled trial. Ann Intern Med 163:569–579. Golan R, Shelef I, Shemesh E, Henkin Y, Schwarzfuchs D, Gepner Y, HarmanBoehm I, Witkow S, Friger M, Chassidim Y, Liberty IF, Sarusi B, Serfaty D, Bril N, Rein M, Cohen N, Ben-Avraham S, Ceglarek U, Stumvoll M, Bluher M, Thiery J, Stampfer MJ, Rudich A, Shai I. 2017. Effects of initiating moderate wine intake on abdominal adipose tissue in adults with type 2 diabetes: A 2-year randomized controlled trial. Public Health Nutr 20:549–555. Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ. 2001. Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis 21:17–26. Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, Cristanini G, Tiribelli C. 2000. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 132:112–117. Bornstein SR, Schuppenies A, Wong ML, Licinio J. 2006. Approaching the shared biology of obesity and depression: The stress axis as the locus of geneenvironment interactions. Mol Psychiatry 11:892–902. Ubani CC, Zhang J. 2015. The role of adiposity in the relationship between

serum leptin and severe major depressive episode. Psychiatry Res 228:866–870. 95. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG. 2010. Overweight, obesity, and depression: A systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 67:220–229. 96. Kim WK, Shin D, Song WO. 2016. Are dietary patterns associated with depression in U.S. adults? J Med Food 19:1074–1084. 97. Breland JY, Fox AM, Horowitz CR. 2013. Screen time, physical activity and depression risk in minority women. Ment Health Phys Act 6:10–15. 98. Vallance JK, Winkler EA, Gardiner PA, Healy GN, Lynch BM, Owen N. 2011. Associations of objectively-assessed physical activity and sedentary time with depression: NHANES (2005–2006). Prev Med 53:284–288. 99. Khan A, Schwartz KA, Kolts RL, Brown WA. 2007. BMI, sex, and antidepressant response. J Affect Disord 99:101–106. 100. Kloiber S, Ising M, Reppermund S, Horstmann S, Dose T, Majer M, Zihl J, Pfister H, Unschuld PG, Holsboer F, Lucae S. 2007. Overweight and obesity affect treatment response in major depression. Biol Psychiatry 62:321–326. 101. U her R, Mors O, Hauser J, Rietschel M, Maier W, Kozel D, Henigsberg N, Souery D, Placentino A, Perroud N, Dernovsek MZ, Strohmaier J, Larsen ER, Zobel A, Leszczynska-Rodziewicz A, Kalember P, Pedrini L, Linotte S, Gunasinghe C, Aitchison KJ, McGuffin P, Farmer A. 2009. Body weight as a predictor of antidepressant efficacy in the GENDEP project. J Affect Disord 118:147–154. 102. Serretti A, Mandelli L. 2010. Antidepressants and body weight: A comprehensive review and meta-analysis. J Clin Psychiatry 71:1259–1272. 103. Freyberg Z, Aslanoglou D, Shah R, Ballon JS. 2017. Intrinsic and antipsychotic drug-induced metabolic dysfunction in schizophrenia. Front Neurosci 11:432. 104. Jantaratnotai N, Mosikanon K, Lee Y, McIntyre RS. 2017. The interface of depression and obesity. Obes Res Clin Pract 11:1–10. 105. Faulconbridge LF, Wadden TA, Thomas JG, Jones-Corneille LR, Sarwer DB, Fabricatore AN. 2013. Changes in depression and quality of life in obese individuals with binge eating disorder: Bariatric surgery versus lifestyle modification. Surg Obes Relat Dis 9:790–796. 106. Jelalian E, Jandasek B, Wolff JC, Seaboyer LM, Jones RN, Spirito A. 2016. Cognitive-Behavioral therapy plus healthy lifestyle enhancement for depressed, overweight/obese adolescents: Results of a pilot trial. J Clin Child Adolesc Psychol:1–10. 107. Jelalian E, Mehlenbeck R, LloydRichardson EE, Birmaher V, Wing RR. 2006. ‘Adventure therapy’ combined with cognitive-behavioral treatment for overweight adolescents. Int J Obes (Lond) 30:31–39. 108. Lang A, Froelicher ES. 2006. Management of overweight and obesity in adults: Behavioral intervention for long-term weight loss and maintenance. Eur J Cardiovasc Nurs 5:102–114.

109. Liao KL. 2000. Cognitive-behavioural approaches and weight management: An overview. J R Soc Promot Health 120:27–30. 110. Christakis NA, Fowler JH. 2007. The spread of obesity in a large social network over 32 years. N Engl J Med 357:370–379. 111. Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O’Malley C, Stolk RP, Summerbell CD. 2009. Interventions for treating obesity in children. Cochrane Database Syst Rev:CD001872. 112. Kelleher E, Davoren MP, Harrington JM, Shiely F, Perry IJ, McHugh SM. 2016. Barriers and facilitators to initial and continued attendance at communitybased lifestyle programmes among families of overweight and obese children: A systematic review. Obes Rev 18:183–194. 113. Miller GD, Isom S, Morgan TM, Vitolins MZ, Blackwell C, Brosnihan KB, Diz DI, Katula J, Goff D. 2014. Effects of a community-based weight loss intervention on adipose tissue circulating factors. Diabetes Metab Syndr 8:205–211. 114. Gibbs L, O’Connor T, Waters E, Booth M, Walsh O, Green J, Bartlett J, Swinburn B. 2008. Addressing the potential adverse effects of school-based BMI assessments on children’s wellbeing. Int J Pediatr Obes 3:52–57. 115. Smith KL, Straker LM, McManus A, Fenner AA. 2014. Barriers and enablers for participation in healthy lifestyle programs by adolescents who are overweight: A qualitative study of the opinions of adolescents, their parents and community stakeholders. BMC Pediatr 14:53. 116. Waters E, Gibbs L, Tadic M, Ukoumunne OC, Magarey A, Okely AD, de Silva A, Armit C, Green J, O’Connor T, Johnson B, Swinburn B, Carpenter L, Moore G, Littlecott H, Gold L. 2018. Cluster randomised trial of a school-community child health promotion and obesity prevention intervention: Findings from the evaluation of fun 'n healthy in Moreland! BMC Public Health 18:92. 117. Maynard MJ. 2017. Faith-based institutions as venues for obesity prevention. Curr Obes Rep 6:148–154. 118. Sattin RW, Williams LB, Dias J, Garvin JT, Marion L, Joshua TV, Kriska A, Kramer MK, Narayan KM. 2016. Community trial of a faith-based lifestyle intervention to prevent diabetes among African-Americans. J Community Health 41:87–96. 119. Vincent D, McEwen MM, Hepworth JT, Stump CS. 2014. The effects of a community-based, culturally tailored diabetes prevention intervention for highrisk adults of Mexican descent. Diabetes Educ 40:202–213. 120. Islam NS, Zanowiak JM, Wyatt LC, Kavathe R, Singh H, Kwon SC, TrinhShevrin C. 2014. Diabetes prevention in the New York City Sikh Asian Indian community: A pilot study. Int J Environ Res Public Health 11:5462–5486. 121. Reifegerste D, Wasgien K, Hagen LM. 2017. Online social support for obese adults: Exploring the role of forum activity. Int J Med Inform 101:1–8. 122. Mechanick JI, Marchetti AE, Apovian C, Benchimol AK, Bisschop PH, Bolio-Galvis A, Hegazi RA, Jenkins D, Mendoza E, Sanz ML, Sheu WH, Tatti P, Tsang MW, Hamdy O. 2012. Diabetes-specific nutrition algorithm:

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528  Chapter 41  Adiposity-based Chronic Disease a New Diagnostic Term A transcultural program to optimize diabetes and prediabetes care. Curr Diab Rep 12:180–194. 123. Coates JC, Colaiezzi BA, Bell W, Charrondiere UR, Leclercq C. 2017. Overcoming dietary assessment challenges in low-income countries: Technological solutions proposed by the international dietary data expansion (INDDEX) project. Nutrients 9:289. 124. Gostin LO, Abou-Taleb H, Roache SA, Alwan A. 2017. Legal priorities for prevention of non-communicable diseases: Innovations from WHO’s Eastern Mediterranean region. Public Health 144:4–12. 125. Gulland A. 2016. WHO calls for tax on sugary drinks to tackle child obesity. BMJ 352:i475. 126. Joshi SR, Mohan V, Joshi SS, Mechanick JI, Marchetti A. 2012. Transcultural diabetes nutrition therapy algorithm: The Asian Indian application. Curr Diab Rep 12:204–212. 127. Su HY, Tsang MW, Huang SY, Mechanick JI, Sheu WH, Marchetti A. 2012. Transculturalization of a diabetesspecific nutrition algorithm: Asian application. Curr Diab Rep 12:213–219. 128. Gandhi R, Sharma A, Kapoor M, Sundararajan K, Perruccio AV. 2016. Racial differences in serum adipokine and insulin levels in a matched osteoarthritis sample: A pilot study. J Obes 2016:8746268. 129. Lee JJ, Pedley A, Hoffmann U, Massaro JM, Fox CS. 2016. Association of changes in abdominal fat quantity and quality with incident cardiovascular disease risk factors. J Am Coll Cardiol 68:1509–1521. 130. Zheng Y, Manson JE, Yuan C, Liang MH, Grodstein F, Stampfer MJ, Willett WC, Hu FB. 2017. Associations of weight gain from early to middle adulthood with major health outcomes later in life. JAMA 318:255–269. 131. Norman RJ, Davies MJ, Lord J, Moran LJ. 2002. The role of lifestyle modification in polycystic ovary syndrome. Trends Endocrinol Metab 13:251–257.

132. Polak K, Czyzyk A, Simoncini T, Meczekalski B. 2017. New markers of insulin resistance in polycystic ovary syndrome. J Endocrinol Invest 40:1–8. 133. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. 2004. Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology 40:1387–1395. 134. D’Incao RB, Tovo CV, Mattevi VS, Borges DO, Ulbrich JM, Coral GP, Ramos MJ, Meinhardt NG. 2017. Adipokine levels versus hepatic histopathology in bariatric surgery patients. Obes Surg 27:2151–2158. 135. Hamilton GS, Joosten SA. 2017. Obstructive sleep apnoea and obesity. Aust Fam Physician 46:460–463. 136. Salord N, Gasa M, Mayos M, FortunaGutierrez AM, Montserrat JM, Sanchezde-la-Torre M, Barcelo A, Barbe F, Vilarrasa N, Monasterio C. 2014. Impact of OSA on biological markers in morbid obesity and metabolic syndrome. J Clin Sleep Med 10:263–270. 137. Seven E. 2015. Overweight, hypertension and cardiovascular disease: Focus on adipocytokines, insulin, weight changes and natriuretic peptides. Dan Med J 62:B5163. 138. Liberale L, Bonaventura A, Vecchie A, Matteo C, Dallegri F, Montecucco F, Carbone F. 2017. The role of adipocytokines in coronary atherosclerosis. Curr Atheroscler Rep 19:10. 139. Wanahita N, Messerli FH, Bangalore S, Gami AS, Somers VK, Steinberg JS. 2008. Atrial fibrillation and obesity-results of a meta-analysis. Am Heart J 155:310–315. 140. Hatem SN, Redheuil A, Gandjbakhch E. 2016. Cardiac adipose tissue and atrial fibrillation: The perils of adiposity. Cardiovasc Res 109:502–509. 141. Toussirot E, Michel F, Bereau M, Dehecq B, Gaugler B, Wendling D, Grandclement E, Saas P, Dumoulin G. 2017. Serum adipokines, adipose tissue measurements and metabolic parameters in patients with advanced radiographic knee osteoarthritis. Clin Rheumatol 36:2531–2539.

142. Gaida JE, Cook JL, Bass SL. 2008. Adiposity and tendinopathy. Disabil Rehabil 30:1555–1562. 143. Rechardt M, Viikari-Juntura E, Shiri R. 2014. Adipokines as predictors of recovery from upper extremity soft tissue disorders. Rheumatology (Oxford) 53:2238–2242. 144. He CL, Cheng N, Rong YM, Li HY, Li JS, Ding J, Hu XB, Pu HQ, Ren XW, Bai YN. 2017. Risk factors of gout in Jinchang cohort: A Cox regression analysis. Zhonghua Liu Xing Bing Xue Za Zhi 38:897–901. 145. Inokuchi T, Tsutsumi Z, Takahashi S, Ka T, Moriwaki Y, Yamamoto T. 2010. Increased frequency of metabolic syndrome and its individual metabolic abnormalities in Japanese patients with primary gout. J Clin Rheumatol 16:109–112. 146. Maheshwari A, Stofberg L, Bhattacharya S. 2007. Effect of overweight and obesity on assisted reproductive technology—A systematic review. Hum Reprod Update 13:433–444. 147. Dos Santos E, Duval F, Vialard F, Dieudonne MN. 2015. The roles of leptin and adiponectin at the fetal-maternal interface in humans. Horm Mol Biol Clin Investig 24:47–63. 148. Phillips GB, Jing T, Heymsfield SB. 2003. Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction. Metabolism 52:784–790. 149. Sarac S, Atamer A, Atamer Y, Can AS, Bilici A, Tacyildiz I, Kocyigit Y, Yenice N. 2015. Leptin levels and lipoprotein profiles in patients with cholelithiasis. J Int Med Res 43:385–392. 150. I shii S, Chang C, Tanaka T, Kuroda A, Tsuji T, Akishita M, Iijima K. 2016. The association between sarcopenic obesity and depressive symptoms in older Japanese adults. PLoS One 11:e0162898. 151. Ackerman SE, Blackburn OA, Marchildon F, Cohen P. 2017. Insights into the link between obesity and cancer. Curr Obes Rep 6:195–203.

42 CHAPTER

Future Directions in Obesity and Weight Management Theodore K. Kyle, RPh, MBA

Key Points.................................................................................. 529 42.1 Introduction...................................................................... 529 42.2  Removing Barriers to Better Outcomes............................. 530 42.2.1  Entrenched Bias and Stigma................................. 530 42.2.2  Inadequate Resources for Obesity Care................. 530 42.2.3 Payment Systems that Favor Treating Obesity Complications������������������������������������������������������ 530 42.3  More Effective Public Health Strategies............................. 531 42.3.1  A Narrow Focus on Food Policy............................. 531

KEY POINTS • Significant barriers to effective obesity care are slowly falling away to make better outcomes possible. • Largely ineffective prevention programs narrowly focused on individual behaviors will be replaced by more systematic, evidence-based strategies. • Advances in pharmacotherapy are progressing toward providing more targeted options with the potential to deliver efficacy comparable to bariatric surgery. • Research insights into diverse obesity phenotypes promise advances in precision medicine for obesity. • Attention to long-term outcomes will pinpoint patterns of obesity care that will yield better health and longer lives.

42.1 INTRODUCTION For more than four decades, experts in public health and medicine have been calling attention to the health threat of rising obesity prevalence. Pediatric health experts expressed specific concerns about rising pediatric obesity prevalence and the implication for the health of future generations as early as 1974. To address these concerns, the Centers for Disease Control and Prevention established the Division of Nutrition, Physical Activity, and Obesity in 1997. In 2001, Surgeon General David Satcher issued a national call to action to prevent and decrease overweight and obesity.

42.3.2  Accounting for Complex Systems Driving Obesity......531 42.4  Research Priorities............................................................ 532 42.4.1  Advances in Pharmacotherapy.............................. 532 42.4.2  Precision Medicine................................................ 532 42.4.3  Attention to Long-Term Outcomes......................... 533 42.4.4  Translation Science............................................... 533 42.5 Conclusion........................................................................ 533 Clinical Applications................................................................... 533 References................................................................................ 533

Both Presidents George W. Bush and Barack Obama supported vigorous initiatives to reduce the health impact of obesity and overweight on public health. And yet, as outgoing CDC Director Thomas Frieden conceded in late 2016, progress against public health goals to reduce obesity has fallen well short of expectations.1 Data from the National Health and Nutrition Examination Survey for 2016 indicates that obesity prevalence is at record high levels. 2 Despite best efforts from public health policymakers, what had been an epidemic of obesity in the United States and other developed countries has become a global pandemic.3 To date, no country has succeeded in reversing these trends. These developments have unfolded within the context of progress, albeit incomplete, in understanding the biological and behavioral drivers of obesity. In recent years, options for treatment have grown, especially with respect to pharmacotherapy. A growing number of healthcare providers are acquiring skills and credentials for providing evidence-based care for patients affected by obesity. The evidence for benefits of obesity treatment, especially for bariatric surgery, is growing steadily. Yet relatively few people are benefiting from this progress. Many primary care providers do not provide or even recommend effective forms of treatment for obesity. Many patients are either unaware of treatment options that can improve their health, or they do not believe that such treatments are relevant to them. Future directions for progress in reducing the health impact of obesity will depend upon three broad themes: removing barriers to better outcomes, developing public health strategies that work, and research to provide better treatment options. 529

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42.2 REMOVING BARRIERS TO BETTER OUTCOMES Obesity is a chronic disease with growing prevalence caused by complex interactions between biological, social, economic, and environmental factors. And yet, considerable evidence suggests that better outcomes for public and individual health are possible by implementing evidencebased prevention and treatment options that already exist. Improved outcomes will require removing numerous systemic barriers that include deeply entrenched bias and stigma, inadequate clinical resources for delivering effective obesity care, and payment systems that presently favor treating the complications of obesity over preventing those complications.

42.2.1 Entrenched Bias and Stigma Considerable research has shown that many policies and practices related to obesity serve to make life worse for people living with the disease.4 Recent research shows that children with excess weight and obesity face bias, stigma, and bullying from a very early age. Using data from the TRAILS study, Kayla de la Haye and colleagues examined the social networks of children with a mean age of 11.5 They looked at friendship nominations and dislike nominations for children by their peers. They confirmed findings of prior research: heavier kids were less likely to be nominated for friends. But the researchers went further by examining social networks. They found that the heavier kids were more likely to nominate children as friends whom they dislike—further evidence of the social isolation caused by weight bias. Similarly, researchers have documented that weight bias in children is every bit as harsh as racial bias seen in adults.6 The high levels of implicit weight bias they found by themselves foster unhealthy eating behaviors and increased risk that childhood obesity will persist into adulthood. Bullying is pervasive for children and adolescents, and leads to poor health outcomes.7 Screening children at school for obesity singles them out for stigma and bullying while offering no clinical care that can help to reverse the condition. In a recent review, Thompson and Madsen could find no evidence for a benefit for students regarding this policy and significant concerns about the potential for harm.8 Likewise, many other “awareness” campaigns serve mainly to promote stigma while doing nothing to provide access to clinically effective care. Most adults and children with excess weight experience daily reminders about their weight status—even if they avoid the subject of obesity because it is so highly stigmatized. Among adults with obesity, experiences of weight bias and discrimination are common in employment, education, mass media, personal relationships, and healthcare. They lead to poor psychological and physical health outcomes. Bias expressed by healthcare providers significantly impairs the quality of care that people with obesity receive.9 Rising awareness of the problems that weight bias and fat shaming create offers reason for encouragement. In 2017, both the American Medical Association10 and the

American Academy of Pediatrics11 formally resolved to work toward reducing the harm of weight bias in both pediatric, adolescent, and adult medicine. In parallel, popular media is increasingly drawing attention to this problem, characterizing it as fat shaming and thus unacceptable in popular culture12 In combination with increasingly potent social movements favoring body positivity and feminism, these developments provide reasons for encouragement.13 In fact, life might be considerably better for people with obesity if all the energy that goes into concern trolling were redirected. Redirecting it to fight bias and fat shaming, as well as promote and support body positivity, would do more to improve the lives of people affected.

42.2.2 Inadequate Resources for Obesity Care Although both healthcare providers and patients perceive obesity as a disease, clinical practice patterns do not reflect that perception.14 This might come from a lack of appreciation for the biological basis for obesity and a false perception that this disease results almost exclusively from lifestyle and behavioral factors. Perhaps as a result, many physicians incorrectly believe that behavioral interventions are more effective than pharmacologic and surgical therapies for obesity.15 For childhood obesity care, resources are especially scarce. Approximately 5,000,000 children have severe obesity in the U.S. and yet fewer than 50 centers with class 3 programs for obesity care exist to serve these children.16 A recent conference of cross-sector stakeholders found that inadequate payment systems for childhood obesity care present a significant barrier to the sustainability of centers that can meet this need. Most of those centers operate at a financial loss.17 One reason for this gap in clinical care is that most healthcare providers have relatively little training for delivering evidence-based obesity care. Unsurprisingly, they do not express high confidence in providing such care.18 Medical licensure examinations do not yet test prospective physicians for key competencies required to effectively treat obesity.19 However, recent developments point to more healthcare professionals seeking training to provide obesity care. The American Board of Obesity Medicine reports that more than 2,000 physicians have now become board certified in obesity medicine, making it one of the fastest growing fields of medical care. 20 Most of those diplomates come from primary care—family practice, internal medicine, obstetrics, and gynecology. For a wide range of allied health professionals, the Commission on Dietetic Registration now offers board certification in obesity and weight management.

42.2.3 Payment Systems that Favor Treating Obesity Complications Perhaps one of the most important factors that impedes the delivery of evidence-based obesity care is payment systems that either deny or severely restrict coverage for

42.3  More Effective Public Health Strategies  531

obesity, while fully covering treatment for most of its complications. Significant financial resources go toward treating those complications, which include diabetes, cardiovascular disease, many forms of cancer, arthritis, liver disease, and more. A 2014 analysis estimated that direct medical costs amount to $149 billion in the U.S. 21 Waters and DeVol estimate that the total U.S. economic burden of obesity is $1.4 trillion. 22 Even after the passage of the Affordable Care Act, blanket exclusions for coverages of obesity treatment, regardless of medical necessity, remained common, especially in the market for individual and small employer health plans. Most U.S. adults report that they do not believe that their health plan will cover evidence-based obesity care, such as dietary counseling, pharmacotherapy, and bariatric surgery. 23 As a preventive service, the Affordable Care Act mandated coverage of intensive lifestyle therapy to prevent diabetes, but implementation and uptake of such coverage has been exceedingly slow. One study found that utilization of this option under Medicare amounts to less than 1% of the patients with a medical need for it. 24 Coverage of pharmacotherapy for obesity is perhaps the most limited. Gomez and Stanford found that only 11% of policies in only nine states covered these drugs. They reported that only seven state Medicaid programs provided coverage. 25 Possibly because of dramatic health benefits, bariatric surgery coverage is relatively more common than either lifestyle therapy or pharmacotherapy. 26 Since 2006, Medicare has covered this form of obesity care. Nonetheless, restrictions, exclusions, and large co-pay requirements remain common. Relatively few patients seek clinical care for obesity, perhaps because internalized stigma leads most to presume that this is a self-inflicted condition that they must bear the full responsibility for resolving.14 Presumably, those patients who are sufficiently motivated to seek care might be persistent with therapy and avoid the complications of untreated obesity. A recent economic analysis estimated the potential benefits expanded Medicare coverage offers for obesity care. Covering care by qualified professionals, such as registered dietitians, and for obesity pharmacotherapy could result in substantial cost savings for the program over a ten-year horizon. Those savings would result from cost reductions for treating complications of untreated obesity. 27 Thus, improved access to well-established and effective obesity care represents an untapped opportunity for improved outcomes in the health of the population affected by obesity.

42.3 MORE EFFECTIVE PUBLIC HEALTH STRATEGIES More than 40 years ago, editors of the Lancet warned that: We need to be more vigilant in preventing obesity throughout childhood. Probably the obese adult can never be “cured,” but most obesity could, with care, be prevented. 28

Subsequent experience proved that they were right about the need for prevention, and considerable resources have been applied to this effort. In the U.S., two presidents for more than a decade made obesity prevention a national priority. 29,30 And yet, the prevalence of both childhood and adult obesity has grown relentlessly. Meanwhile, obesity has progressed from an epidemic into a global pandemic.31

42.3.1 A Narrow Focus on Food Policy Public health strategies to address obesity focus primarily upon food policy, even in recent publications that purport to present “new thinking”.32 Beyond nutrition, other strategies target the promotion of physical activity, reflecting the theme behind the Obama administration’s Let’s Move! program. Promoting better nutrition and more physical activity might be a reasonable means for promoting generally better health. However, as a strategy for reducing obesity, little evidence can support a claim that either of those strategies will have a discernable effect. The Cochrane review of childhood obesity prevention found mixed evidence for its effectiveness: Although many studies were able to improve children’s nutrition or physical activity to some extent, only some studies were able to see an effect of the program on children’s levels of fatness. When we combined the studies, we were able to see that these programs made a positive difference, but there was much variation between the study findings which we could not explain. Also, it appeared that the findings may be biased by missing small studies with negative findings.33 Consistent with this conclusion, Christina Roberto and colleagues noted in 2015 that progress on obesity prevention has been patchy, scarce, and fitful. 32 Jannah Jones and colleagues suggest that real world implementation of prevention programs in a childcare setting may be inadequate for delivering meaningful outcomes in the community.34

42.3.2 Accounting for Complex Systems Driving Obesity However, it may also be that programs to promote healthy eating and active living are sound in theory, but too narrow in scope to have a meaningful effect on obesity prevalence. The global pandemic of obesity is best understood as the product of complex, adaptive systems interacting in unpredictable ways.35 This framework includes domains of social psychology, individual psychology, individual physical activity, physical activity environment, human physiology, individual physiology, food consumption, and food production. The focus of many obesity prevention programs is to promote physical activity and improved nutrition by individuals. Some governments have implemented policies that would affect the entire population, but the scope of

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these policies has been relatively narrow. Taxes on sugarsweetened beverages, for example, may have an impact on consumption of the taxed beverages, but no impact on obesity prevalence has yet been found.36,37 Likewise, investments in the built environment might promote physical activity, but it is unclear that those investments will yield a reduction in obesity. 38 Finegood, Merth, and Rutter suggest that a systems approach will be necessary to finding more effective strategies than we have seen to date from public health advocates.39 It will require teams from multiple disciplines and multiple sectors. This requirement alone will challenge the status quo of isolated sectors and like-minded professionals that resist challenges from outside their relatively fixed networks for collaboration. More collaboration between industry, academia, government, and non-profits will be essential. A systems approach to public health strategies will also require functional goals and more attention to measuring progress toward those goals.40 These strategies must provide for continuous feedback between activities, outcomes, and new research findings. In short, after four decades of efforts to prevent obesity, progress has been scant. Better results will only come with a new approach that is more grounded in evidence and rigorous, continuous evaluation. More of the same strategies will deliver only more disappointing results.

42.4 RESEARCH PRIORITIES Biomedical research has great potential to provide better therapeutic options for people living with obesity. Advances are likely to come in three areas of focus: pharmacotherapy, precision medicine, and attention to longterm health outcomes.

42.4.1 Advances in Pharmacotherapy Prior to 2013, very little innovation in pharmacotherapy could be found. The FDA approved phentermine for weight loss in 1959. The first significant new drug approval after that came in 1996 with dexfenfluramine. In 1997, it was withdrawn from the market after reports of an unacceptable risk of valvular heart disease.41 The FDA approved two other prescription drugs, sibutramine and orlistat, shortly after dexfenfluramine. Both of those drugs were marketed more for weight loss than for chronic disease management of obesity, and both had disappointing results in market. Sibutramine was withdrawn in 2010.42 Following those failures, two developments marked a significant shift in the environment for obesity drug development. First, the FDA responded to the safety issues raised by dexfenfluramine’s withdrawal by raising the safety threshold for approving new drugs targeted for use in weight loss. Sanofi had completed its full clinical drug development program for rimonabant and obtained approval to market in Europe. But the FDA balked at approving it for the U.S. because of concerns about depression and suicide. Then the agency turned down the next

three drugs it reviewed for obesity—phentermine/topiramate, bupropion/naltrexone, and lorcaserin.43 Most pharmaceutical companies responded by shutting down drug development programs for obesity. Sanofi’s CEO described his company’s decision to abandon the field in 2010: As long as we’re so worried about obesity being a lifestyle choice – that anyone can choose to be fat or thin – then I don’t think we’re going to have an ability to develop drugs. I don’t think right now we have a regulatory environment, a risk/benefit environment that would allow me as a CEO to take the risk of developing a drug for obesity. That harsh environment eased within three years. The FDA began approving obesity drugs again in 2013. By 2014, the agency had approved four new drugs for obesity, evidently shifting its focus from a conservative view of short-term weight loss toward managing obesity as a chronic disease.44 At about the same time, the American Medical Association joined obesity experts in regarding obesity as a complex, chronic disease that requires careful medical management.45 This shift brought renewed investment in developing new obesity drugs, most notably by Novo Nordisk.46 In addition to that company’s long-term investment in developing a broad portfolio of new obesity drugs, many smaller biotech firms are developing highly targeted drugs for obesity. As a result, the future now holds good possibilities for innovative new drugs for managing obesity. The next agent to reach the market may be semaglutide. In a 52-week phase II obesity study, Novo Nordisk reported outcomes of 13.8% weight loss, which is more than the 5–10% weight loss typical of current medications.47 Likewise, other new agents under development show promise for incremental gains in efficacy. In a phase I study of two patients with a rare genetic POMC defect, setmelanotide produced impressive short-term reductions in weight and hunger.48 In patients with other POMC defects, the results were more modest.49 New drug development is unpredictable. But these and other agents under study suggest that future drugs may offer substantial gains in efficacy for carefully selected patients with obesity. 50

42.4.2 Precision Medicine The heritable nature of obesity has long been apparent.51 But more recent advances have brought deeper insight into the biological basis for that heritability. Research is identifying a growing number of single-gene defects that can cause severe obesity in childhood. In addition, multiple genetic traits can interact to explain an individual’s susceptibility to obesity. 52 Other contributing factors interact to cause obesity, including epigenetics, the microbiome, social environment, economic environment, food environment, and adverse life experiences. These many factors can produce many different subtypes of obesity, potentially with different responses to different forms of therapy. 53

References  533

Advances in multiple omics technologies are creating possibilities for more precise diagnosis of a wide array of obesity phenotypes.54 Those advances are opening new possibilities for highly personalized therapies with much more efficacy than current therapies reliably provide. 55

42.4.3 Attention to Long-Term Outcomes Much clinical research for obesity care focuses on weight loss endpoints. Acute weight loss outcomes are important to patients, but even more important are longer-term outcomes such as sustained loss over the longer term, resolution of obesity complications, and prevention of serious adverse outcomes such as heart attacks, strokes, and death. More robust data on long-term outcomes have already come from research on bariatric surgery and intensive behavioral therapy for diabetes prevention. Longer-term studies of outcomes from obesity pharmacotherapy are more recent and have not yet provided a substantial evidence base. However, data on cardiovascular survival benefits of weight-sparing type 2 diabetes drugs illustrate the possibilities for gains with these types of studies.

42.4.4 Translation Science Tremendous progress in understanding the biological basis for obesity has only slowly been translated into clinical practices for the benefit of people who are living with obesity. Some of this slow progress is due to inadequate resources, as discussed previously. Health systems are better equipped to care for the complications of obesity than to deliver evidence-based care to prevent those complications. But integrated models of disease prevention and clinical care are beginning to evolve to surround patients with a more complete approach to obesity management. Active disease management can be integrated with community initiatives to reduce the burden of disease. Achieving this goal will require more healthcare providers trained in obesity care. Perhaps even more importantly, it will require better incentives for health systems to prevent chronic diseases. 56

42.5 CONCLUSION Progress in understanding the biological and environmental basis for obesity has been substantial, even though it is far from complete. Unfortunately, that progress to date

has hardly translated into improved public health outcomes or improved health and quality of life for the growing population of people living with obesity. Nonetheless, prospects for progress are bright. Immediate progress can come from removing barriers to better outcomes. These barriers include pervasive weight bias, stigma, and discrimination. Broadly, this subject is receiving considerable attention, both in the research literature and in popular culture. Progress toward overcoming inadequate resources for obesity care is evident already. For example, obesity medicine has become one of the fastest growing fields of medical care. The formation of the American Board of Obesity Medicine is a key milestone in this success. The third and perhaps most challenging barrier is payment systems that favor treating obesity complications over providing obesity care that could prevent those complications. Improvements in those systems are coming slowly, but they will favor better utilization of evidencebased care that prevents or slows the progression of obesity and its complications. Beyond simply removing barriers to applying current knowledge for reducing the impact of obesity, progress will come from new evidence in two realms: public health strategies and biomedical research for better therapeutic options. After forty years of disappointing efforts to prevent obesity with a near-exclusive focus on dietary behavior and physical activity, the need for more effective public health policies is obvious. The time is ripe for a new approach, one that is more grounded in objective evidence and rigorous, continuous evaluation. Finally, new insights into the biological basis for obesity are already bringing promising new therapies into view. Pharmacotherapy innovation, precision medicine, and clinical care focused on long-term health outcomes have great potential to support a much higher standard of care for people living with obesity.

CLINICAL APPLICATIONS • Better clinical outcomes will result from increased utilization of the full range of emerging clinical therapies–lifestyle, pharmacotherapy, and surgery. • The options for pharmacotherapy are growing and will soon set a higher bar for efficacy. • Future therapies will be more highly targeted to individual patient profiles through precision medicine and rapidly maturing omics technologies.

REFERENCES 1. Kyle TK. CDC: Learning from a Shortfall on Obesity Goals [Internet]. ConscienHealth. 2016 [cited Feb. 12, 2018]. Available from: http:​//con​scien​ healt​h.org ​/ 2016​/12/c​dc-le​a rnin​g-fro​ m-sho​r tfal​l-obe​sity-​goals ​/ 2. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity among adults and youth: United States, 2015–2016. US Department of Health

and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics; 2017 Oct. 3. GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. New England Journal of Medicine. 2017;377(1):13–27. . Puhl RM, Heuer CA. Obesity stigma: 4 Important considerations for public

health. American Journal of Public Health. 2010;100(6):1019–28. 5. de la Haye K, Dijkstra JK, Lubbers MJ, van Rijsewijk L, Stolk R. The dual role of friendship and antipathy relations in the marginalization of overweight children in their peer networks: The TRAILS Study. PloS One. 2017;12(6):e0178130. . Skinner AC, Payne K, Perrin AJ, Panter 6 AT, Howard JB, Bardone-Cone A, Bulik

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CM, Steiner MJ, Perrin EM. Implicit weight bias in children age 9 to 11 years. Pediatrics. 2017;140(1):e20163936. Puhl RM, King KM. Weight discrimination and bullying. Best Practice & Research Clinical Endocrinology & Metabolism. 2013;27(2):117–27. Thompson HR, Madsen KA. The report card on BMI report cards. Current Obesity Reports. 2017;6(2):163–7. Puhl RM, Phelan SM, Nadglowski J, Kyle TK. Overcoming weight bias in the management of patients with diabetes and obesity. Clinical Diabetes. 2016;34(1):44–50. AMA Destigmatize Obesity Resolution [Internet]. Obesity Medicine Association. 2017 [cited Feb. 12, 2018]. Available from: https​: //ob​esity​medic​i ne.o​rg/am​ a-des​tigma​tize-​obesi​t y-re​solut​ion/ Pont SJ, Puhl R, Cook SR, Slusser W. Stigma experienced by children and adolescents with obesity. Pediatrics. 2017:e20173034. Bergland C. Sizeism Is Harming Too Many of Us: Fat Shaming Must Stop [Internet]. Psychology Today. Sussex Publishers; 2017 [cited Feb. 12, 2018]. Available from: https​: //ww​w.psy​cholo​ gytod​ay.co​m /blo​g /the​-athl​etes-​way/2​ 01708​/size​ism-i​s-har​m ing-​too-m​any-u​ s-fat​- sham ​i ng-m​ust-s​top Salam M. Why ‘Radical Body Love’ Is Thriving on Instagram [Internet]. The New York Times. 2017 [cited Feb. 12, 2018]. Available from: https://nyti. ms/2s4oZI7 Kaplan LM, Golden A, Jinnett K, Kolotkin RL, Kyle TK, Look M, Nadglowski J, O’Neil PM, Parry T, Tomaszewski KJ, Stevenin B. Perceptions of barriers to effective obesity care: Results from the National ACTION Study. Obesity. 2018;26(1):61–9. Tsai AG, Histon T, Kyle TK, Rubenstein N, Troy Donahoo W. Evidence of a gap in understanding obesity among physicians. Obesity Science & Practice. 2018;4:46–51. Kyle TK. Childhood Obesity Treatment Programs: A Few to Serve Many [Internet]. ConscienHealth. 2017 [cited Feb. 12, 2018]. Available from: http:​//con​ scien​healt​h.org ​/ 2017​/02/c​h ildh​ood-o​besit​ y-tre​atmen​t-pro​g rams​- serv​e -man​y/ Wilfley DE, Staiano AE, Altman M, Lindros J, Lima A, Hassink SG, Dietz WH, Cook S. Improving access and systems of care for evidence-based childhood obesity treatment: Conference key findings and next steps. Obesity. 2017;25(1):16–29. Bleich SN, Bandara S, Bennett WL, Cooper LA, Gudzune KA. US health professionals’ views on obesity care, training, and self-efficacy. American Journal of Preventive Medicine. 2015;48(4):411–8. Kushner RF, Butsch WS, Kahan S, Machineni S, Cook S, Aronne LJ. Obesity coverage on medical licensing examinations in the United States. What is being tested? Teaching and Learning in Medicine. 2017;29(2):123–8. American Board of Obesity Medicine Surpasses 2,000 Diplomates [Internet]. Business Wire. American Board of Obesity Medicine; 2017 [cited Feb. 12, 2018].

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35. Vandenbroeck IP, Goossens J, Clemens M. Building the obesity system map. Foresight Tackling Obesities: Future Choices (http:// www.foresight.gov.uk). 2007. 36. Colchero MA, Rivera-Dommarco J, Popkin BM, Ng SW. In Mexico, evidence of sustained consumer response two years after implementing a sugarsweetened beverage tax. Health Affairs. 2017;36(3):564–71. 37. Brand-Miller JC, Barclay AW. Declining consumption of added sugars and sugarsweetened beverages in Australia: A challenge for obesity prevention, 2. The American Journal of Clinical Nutrition. 2017;105(4):854–63. 38. Monsivais P, Burgoine T. The built environment and obesity in UK Biobank: Right project, wrong data? The Lancet Public Health. 2018;3(1):e4–5. 39. Finegood DT, Merth TD, Rutter H. Implications of the foresight obesity system map for solutions to childhood obesity. Obesity. 2010;18(S1):S13–6. 40. Committee on Evaluating Progress of Obesity Prevention Effort. Evaluating Obesity Prevention Efforts: A Plan for Measuring Progress. National Academies Press; 2014. 41. Elliot WT, Chan J. Fenfluramine and Dexfenfluramine Withdrawn from Market. AHC Media; 1997. 42. In Brief: Sibutramine (Meridia) Withdrawn [Internet]. The Medical Letter on Drugs and Therapeutics. Medical Letter, Inc.; 2010 [cited Feb. 12, 2018]. Available from: https://secure. medicalletter.org/w1350d 43. Pollack A. F.D.A. Fails to Approve Contrave, a New Diet Pill [Internet]. The New York Times. 2011 [cited Feb. 12, 2018]. Available from: https://nyti. ms/2rX1C3b 44. Kyle TK. Favoring Innovation in Obesity [Internet]. ConscienHealth. 2014 [cited Feb. 12, 2018]. Available from: http:​//con​ scien​healt​h.org ​/ 2014​/ 09/f​avori​ng-in​novat​ ion-i​n-obe​sity/​ 45. Pollack A. A.M.A. Recognizes Obesity as a Disease [Internet]. The New York Times. 2013 [cited Feb. 12, 2018]. Available from: https://nyti.ms/2kt3fCZ 46. Hirschler B. Novo Nordisk Bets on New Obesity Drug Recipes [Internet]. Reuters. Thomson Reuters; 2017 [cited Feb. 12, 2018]. Available from: https​: //ww​w.reu​ ters.​com/a​r ticl​e /us-​novo-​nordi​sk-ce​o/nov​ o-nor​d isk-​bets-​on-ne​w-obe​sity-​d rug-​recip​ es-id​U SKBN​1871Q ​J 47. Holst JJ, Madsbad S. Semaglutide seems to be more effective the other GLP1Ras. Annals of Translational Medicine. 2017;5(24). 48. Kühnen P, Clément K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, Mai K, Blume-Peytavi U, Grüters A, Krude H. Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. New England Journal of Medicine. 2016;375(3):240–6. 49. Collet TH, Dubern B, Mokrosinski J, Connors H, Keogh JM, de Oliveira EM, Henning E, Poitou-Bernert C, Oppert JM, Tounian P, Marchelli F. Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. Molecular Metabolism. 2017;6(10):1321–9.

References  535 50. Valsamakis G, Konstantakou P, Mastorakos G. New targets for drug treatment of obesity. Annual Review of Pharmacology and Toxicology. 2017;57:585–605. 51. Musani SK, Erickson S, Allison DB. Obesity--still highly heritable after all these years. The American Journal of Clinical Nutrition. 2008;87(2):275. 52. Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, Powell C, Vedantam S, Buchkovich ML, Yang J, Croteau-Chonka

DC. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197. 53. Field AE, Camargo CA, Ogino S. The merits of subtyping obesity: One size does not fit all. JAMA. 2013;310(20):2147–8. 4. Piening BD, Zhou W, Contrepois K, 5 Röst H, Urban GJ, Mishra T, Hanson BM, Bautista EJ, Leopold S, Yeh CY, Spakowicz D. Integrative personal omics profiles during periods of weight gain and loss. Cell Systems. 2018;6:157–70.

55. Yanovski SZ, Yanovski JA. Toward precision approaches for the prevention and treatment of obesity. JAMA. 2018;319(3):223–4. 56. Dietz WH, Solomon LS, Pronk N, Ziegenhorn SK, Standish M, Longjohn MM, Fukuzawa DD, Eneli IU, Loy L, Muth ND, Sanchez EJ. An integrated framework for the prevention and treatment of obesity and its related chronic diseases. Health Affairs. 2015;34(9):1456–63.

42

IX PA RT

Immunology and Infectious Disease Gregory A. Hand, PhD, MPH, FACSM, FESPM

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43 CHAPTER

Exercise, Inflammation, and Respiratory Infection Wesley D. Dudgeon, PhD, David C. Nieman, DrPH, FACSM, and Elizabeth Kelley, MS, ACSM-RCEP

Key Points.................................................................................. 539 43.1 Introduction...................................................................... 539 43.2  Chronic Anti-Inflammatory Influence of Exercise Training.......539 43.3  Physical Activity, Fitness, and Chronic Inflammation.......... 540 43.4  Potential Mechanisms....................................................... 540 43.5 URTI Risk Reduction from Regular, Moderate Exercise Training............................................................................ 541

KEY POINTS • Chronic exercise reduces systemic inflammation. • Weight reduction is key in reducing overall inflammation. • Moderate exercise training reduces the risk of URTIs. • Moderate exercise improves immunosurveillance.

43.1 INTRODUCTION Exercise immunology is a relatively new area of scientific endeavor, with the majority of papers published within the past 25 years.1 Most studies have focused on the acute and chronic effects of various exercise workloads on the immune system and immunosurveillance against pathogens. For the practicing physician, two areas of investigation from exercise immunology have the greatest clinical and public health implications: (1) chronic anti-inflammatory influence of exercise training and (2) reduction in risk of upper respiratory tract infections (URTI) from regular, moderate exercise training.

43.2 CHRONIC ANTI-INFLAMMATORY INFLUENCE OF EXERCISE TRAINING Acute inflammation is a normal response of the immune system to infection and trauma. Intense and prolonged exercise similar to marathon race competition causes large but transient increases in total white blood cells

43.6  Moderate Physical Activity and URTI Risk.......................... 541 43.7 Moderate Physical Activity and Enhanced Immunosurveillance......................................................... 543 43.8 Conclusions...................................................................... 543 Clinical Applications................................................................... 543 References................................................................................ 543

(WBC) and a variety of cytokines including interleukin-6 (IL-6), IL-8, IL-10, IL-1 receptor antagonist (IL-1ra), granulocyte colony stimulating factor (GCSF), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1 beta (MIP-1β), tumor necrosis factoralpha (TNF-α), and macrophage migration inhibitory factor (MIF). 2–4 C-reactive protein (CRP) is also elevated following heavy exertion, but the increase is delayed in comparison to most cytokines. Despite regular increases in these inflammation biomarkers during each intense exercise bout, endurance athletes have lower levels when measured during rest in contrast to overweight and unfit adults. For example, mean CRP levels in long-distance runners (rested state) typically fall below 0.5 mg/L in comparison to 4.0 mg/L and higher in obese, postmenopausal women. 3,5 The persistent increase in inflammation biomarkers is defined as chronic or systemic inflammation and is linked with multiple disorders and diseases including atherosclerosis and cardiovascular disease (CVD), metabolic syndrome, diabetes mellitus, sarcopenia, arthritis, osteoporosis, chronic obstructive pulmonary disease, dementia, depression, and various types of cancers.6–8 CRP is the most frequently measured inflammatory biomarker, and individuals with CRP values in the upper tertile of the adult population (>3.0 mg/L) have a twofold increase in CVD risk compared to those with CRP concentrations below 1.0 mg/L.8 An elevated fasting IL-6 concentration is a significant component of the chronic low-grade inflammation that underlies metabolic syndrome, CVD, diabetes, and various cancers.9 Athletes typically have plasma IL-6 concentrations that fall below 1.0 pg/mL in contrast to values above 2.0 pg/mL in older and obese individuals.3,9 539

540  Chapter 43  Exercise, Inflammation, and Respiratory Infection

43.3 PHYSICAL ACTIVITY, FITNESS, AND CHRONIC INFLAMMATION Large population observational studies consistently show reduced WBC, CRP, IL-6, TNF-α, and other inflammatory biomarkers in adults with higher levels of physical activity and fitness, even after adjustment for potential confounders.10–15 The inverse association between physical activity/fitness and inflammation is related in part to the effect of activity on fat mass.12 In most studies, however, adjustment for body mass index (BMI) and adiposity attenuates but does not negate the strength of the relationship between inflammatory biomarkers and physical activity/fitness.12,16 For example, in a study of 1,002 community-dwelling adults (age range: 18–85 years), a general linear model (GLM) analysis adjusted CRP means for frequency of physical activity, BMI, and several other lifestyle and demographic factors.16 BMI had the strongest effect on CRP, followed by gender (higher in females), exercise frequency, age, and smoking status (Figure 43.1). Randomized, controlled, exercise-intervention studies provide equivocal support for the inverse relationship between increased physical activity and reduced systemic inflammation.12,17–23 Nonetheless, data from both large population and randomized, controlled, exercise-intervention study formats support that, in order for reductions in chronic inflammation to be experienced, a large change in a combination of lifestyle factors is needed, including weight loss, near-daily moderate-to-vigorous physical activity of 30–60 minute duration, avoidance of cigarette smoking, and increased intake of fruits and

vegetables. 23,24 For example, if an obese, older individual adds three weekly 30-minute walking sessions to their lifestyle, reductions in chronic inflammation are unlikely to be experienced unless the exercise workload is increased in combination with significant weight loss and improved diet quality.

43.4 POTENTIAL MECHANISMS When successful, exercise training may exert antiinflammatory influences through a reduction in visceral fat mass25 and the induction of an acute anti-inflammatory environment with each bout of exercise that over time becomes chronic. 26,27 Exercise-induced antiinflammatory adaptations are, in turn, associated with the improved management of chronic diseases associated with low-grade inflammation, including obesity, insulin resistance, cardiovascular disease, and atherosclerosis. 28 These effects may be mediated in part through musclederived peptides or myokines, such as IL-6, but this proposed mechanism needs further testing. 29 Contracting skeletal muscles release myokines (e.g., IL-6, IL-8, IL-15) that may exert both direct and chronic anti-inflammatory effects. The first identified and most studied myokine is IL-6. During prolonged and intense exercise, IL-6 is produced by muscle fibers and stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra and IL-10.30 IL-6 also inhibits the production of the proinflammatory cytokine TNF-α and stimulates lipolysis and fat oxidation. 30 With weight loss from energy restriction and exercise, plasma levels of IL-6 fall, skeletal muscle

Figure 43.1  The relative influence of aerobic exercise frequency and other lifestyle and demographic factors on C-reactive protein. Means are adjusted statistically after weighting for each factor through a general linear model. (From Shanely, R.A. et al., Scand. J Med. Sci Sports. 2013; 23:215–23.)

43.6  Moderate Physical Activity and URTI Risk  541

TNF-α decreases, and insulin sensitivity improves.31,32 Thus, IL-6 release from the exercising muscle may help mediate some of the health benefits of exercise including metabolic control of type 2 diabetes.31,32 There is evidence, however, that the magnitude or presence of muscle IL-6 release is a product of the intensity and/or duration of exercise. Muscle IL-6 release is very low during moderate, prolonged physical activity. For example, during a 30-minute brisk walk on a treadmill, plasma IL-6 concentrations increased from 1.3 to 2.0 pg/mL in female subjects. 33 The increase in IL-6 during brisk walking is probably insufficient to mediate anti-inflammatory and other beneficial health effects, and additional research is needed to determine the relative contribution of myokines compared to other exercise-induced factors. Conversely, there is a more pronounced, acute, exercise-induced increase in IL-6 after prolonged, heavy exertion (e.g. typically above 5, 10, and 50 pg/mL following 1, 2 h, and marathon-race running bouts, respectively) may indeed orchestrate anti-inflammatory influences, lipolysis, and improved insulin sensitivity, but this amount of physical activity is beyond levels achievable by most overweight/obese individuals. Recent studies investigating the effects of short bursts of activity on cytokine release via interval training have elicited similar results as those found with prolonged training. High intensity interval exercise (10 × 60 seconds at 85–90%max) elicited increased systemic levels of IL-6 and IL-10 in both lean and obese males. However, moderate intensity interval exercise (70–75%max) of the same duration had no effect. Therefore, the release of IL-6 and other cytokines may be dependent on a combination of intensity and duration.34 A moderate exercise program of near-daily 30-minute walking bouts, without diet control, has small influences on visceral fat, even in long-term studies.35 This is further evidence that the myokine hypothesis does not apply at the activity level attainable by most middle-aged and elderly individuals. Thus, moderate physical activity training must be increased to the highest levels acceptable to an individual (e.g. 60 min/day) and combined with weight loss through tight control of energy intake and improved diet quality to achieve reductions in systemic inflammation.

43.5 URTI RISK REDUCTION FROM REGULAR, MODERATE EXERCISE TRAINING URTI is the most frequently occurring infectious disease in humans worldwide. 36–38 More than 200 different viruses cause the common cold, and rhinoviruses and coronaviruses are the culprits 25–60% of the time. The National Institute of Allergy and Infectious Diseases reports that people in the United States suffer 1 billion colds each year with an incidence of two to four for the average adult and six to ten for children.36 URTI imposes an estimated $40 billion burden in direct and indirect costs on the U.S. economy.37

43

Figure 43.2 J-Curve model on the relationship between exercise workload and URTI risk. Animal and human data support a reduction in URTI risk with moderate activity in contrast to an elevated risk following heavy exertion.

Low- to high-exercise workloads have a unique effect on URTI risk, and they can be modeled using a J-curve relationship.39 (Figure 43.2). Regular physical activity improves immune function and lowers URTI risk while sustained and intense exertion has the opposite effect. Marathon race competitions and heavy exercise training regimens increase URTI risk, but relatively few individuals exercise at this level, limiting public health concerns. The second half of this chapter will review the benefits of regular, moderate activity in improving immunosurveillance against pathogens and lowering URTI risk. This information has broad public health significance and appeal, and provides the clinician with an additional inducement to encourage increased physical activity among patients.

43.6 MODERATE PHYSICAL ACTIVITY AND URTI RISK Several lines of evidence support the link between moderate physical activity and improved immunity and lowered infection rates. Prospective epidemiologic studies have measured URTI incidence in large groups of moderately active and sedentary individuals. Collectively, the epidemiologic studies consistently show reduced URTI rates in physically active or fit individuals. A one-year epidemiological study of 547 adults showed a 23% reduction in URTI risk in those engaging in regular vs. irregular moderateto-vigorous physical activity (Figure 43.3).40 In a group of 145 elderly subjects, URTI symptomatology during a oneyear period was reduced among those engaging in higher compared to lower amounts of moderate physical activity.41 During a one-year study of 142 males aged 33–90, the odds of having at least 15 days with URTI was 64% lower among those with higher physical activity patterns.42 Randomized experimental trials provide important data in support of moderate physical activity in reducing URTI symptomatology. In a randomized, controlled study

542  Chapter 43  Exercise, Inflammation, and Respiratory Infection

Figure 43.3 This one-year epidemiological study of 547 adults showed a 23% reduction in URTI risk in those engaging in regular vs. irregular physical activity. (From Matthews, C.E. et al., Med. Sci. Sports Exerc., 34, 1242, 2002.)

Figure 43.4 The number of URTI symptom days was decreased by approximately half through a walking program (five days/week, 45 min/session, for 15 weeks) by previously sedentary, overweight adult women. (From Nieman, D.C. et al., Int. J. Sports Med., 11, 467, 1990; Nieman, D.C. et al., Med. Sci. Sports Exerc., 30, 679, 1998.)

of 36 women (mean age 35 years), subjects walked briskly for 45 minutes, five days/week, and experienced one-half the days with URTI symptoms (5.1 versus 10.8) during the 15-week period compared to that of the sedentary control group (Figure 43.4).43 Studies comparing the effect of exercise vs. control (sedentary or calisthenics) groups on URTI risk indicated that regular, moderate exercise, such as walking for 30 to 40 minutes, four to five days per week.44–46 was effective in reducing the incidence of URTI in postmenopausal46

Figure 43.5 URTI incidence in three groups of elderly women for 12 weeks: Highly conditioned, walkers, and controls. (From Nieman, D.C. et al., Med. Sci. Sports Exerc., 25, 823, 1993.) Physically inactive controls had the highest URTI incidence during the fall cold season.

Figure 43.6 A one-year randomized study of 115 overweight, postmenopausal women showed that 166 min/ week (approximately four days/week) of moderate exercise lowered URTI risk compared to controls (stretching), especially during the last three months. (From Chubak, J. et al., Am. J. Med., 119, 937, 2006.)

and elderly44,45 women who exercised compared to the control group (Figure 43.5). With increased duration of regular exercise, the risk of colds in the exercisers was more than three times less than that of the control group (Figure 43.6).46 Regular physical activity may lower rates of infection for other types of diseases, but data are limited due to low disease prevalence. For example, women with a high

References  543

frequency of walking experienced an 18% lower risk of pneumonia compared with women who walked the least.47 In the same cohort, women who reported running or jogging more than 2 hours/week had a reduced pneumonia risk compared with women who spent no time running or jogging.47

43.7 MODERATE PHYSICAL ACTIVITY AND ENHANCED IMMUNOSURVEILLANCE During moderate exercise, several transient changes occur in the immune system.33,48–50 Moderate exercise increases the recirculation of immunoglobulins and neutrophils, and natural killer cells, two cells that play a critical role in innate immune defenses. Animal data indicate that lung macrophages play an important role in mediating the beneficial effects of moderate exercise on lowered susceptibility to infection. 51 Stress hormones, which can suppress immunity, and pro- and anti-inflammatory cytokines, indicative of intense metabolic activity, are not elevated during moderate exercise.33 Although the immune system returns to pre-exercise levels within a few hours after the exercise session is over, each session may represent an improvement in immune surveillance that reduces the risk of infection over the long term. Other exercise-immune-related benefits include enhanced antibody-specific responses to vaccinations. For example, several studies indicate that both acute and chronic moderate exercise training improves the body’s antibody response to the influenza vaccine. 52–55 In one study, a 45-minute moderate exercise bout just before influenza vaccination improved the antibody response. 52 These data provide additional evidence that moderate exercise favorably influences overall immune surveillance against pathogens. Taken together, the data on the relationship between moderate exercise, enhanced immunity, and lowered URTI risk are consistent with guidelines urging the general public to engage in near-daily brisk walking.

43.8 CONCLUSIONS Although methodology varies widely and evidence is still emerging, 56 epidemiologic and randomized exercise training studies consistently report a reduction in URTI incidence or risk of 18%–67%. This is the most important

finding for the practicing clinician that has emerged from exercise immunology studies during the past two decades. Animal and human data indicate that during each exercise bout, transient immune changes take place that over time may improve immunosurveillance against pathogens, thereby reducing URTI risk. The magnitude of reduction in URTI risk with near-daily moderate physical activity exceeds levels reported for most medications and supplements, and bolsters public health guidelines urging individuals to be physically active on a regular basis. Regular physical activity should be combined with other lifestyle strategies to more effectively reduce URTI risk. These strategies include stress management, regular sleep, avoidance of malnutrition, and proper hygiene.38,57–60 URTI is caused by multiple and diverse pathogens, making it unlikely that a unifying vaccine will be developed.38 Thus, lifestyle strategies are receiving increased attention by investigators and public health officials, and a comprehensive lifestyle approach is more likely to lower the burden of URTI than a focus on physical activity alone. The anti-inflammatory effect of near-daily physical activity may play a key role in many health benefits, including reduced CVD, type 2 diabetes, various types of cancer, sarcopenia, and dementia.10–19 This is an exciting area of scientific endeavor, and additional research is needed to determine how immune perturbations during each exercise bout accumulate over time to produce an anti-inflammatory influence. As with URTI, multiple lifestyle approaches to reducing chronic inflammation should be employed with a focus on weight loss, high volume of physical activity, avoidance of smoking, and improved diet quality.

CLINICAL APPLICATIONS • Chronic systemic inflammation has been linked to many disease states. • Lifestyle modifications, in this case, chronic physical activity, have been shown to reduce systemic inflammation, and thus should be prescribed for all adults. • URTIs are the most common infection in the world, and in the U.S. alone cost $40 billion annually. • Regular physical activity has been shown to reduce the incidence of URTIs and reduce the duration of symptoms. For these reasons, clinicians are encouraged to prescribe 60 minutes of moderate physical activity per day to all adults.

REFERENCES 1. Shephard RJ. Development of the discipline of exercise immunology. Exerc Immunol Rev. 2010; 16:194–222. 2. Nieman DC, Henson DA, Smith LL et al. Cytokine changes after a marathon race. J Appl Physiol. 2001; 91:109–114. 3. Nieman DC, Dumke CL, Henson DA, McAnulty SR, Gross SJ, Lind RH.

Muscle damage is linked to cytokine changes following a 160-km race. Brain Behav Immun. 2005; 19:398–403. 4. Bernecker C, Scherr J, Schinner S, Braun S, Scherbaum WA, Halle M. Evidence for an exercise induced increase of TNF-α and IL-6 in marathon runners. Scand J Med Sci Sports. 2013; 23:207–214.

5. Arsenault BJ, Earnest CP, Després JP, Blair SN, Church TS. Obesity, coffee consumption and CRP levels in postmenopausal overweight/obese women: Importance of hormone replacement therapy use. Eur J Clin Nutr. 2009; 63:1419–1424. 6. Khansari N, Shakiba Y, Mahmoudi M. Chronic inflammation and oxidative

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stress as a major cause of age-related diseases and cancer. Recent Pat Inflamm Allergy Drug Discov. 2009; 3:73–80. Devaraj S, Valleggi S, Siegel D, Jialal I. Role of C-reactive protein in contributing to increased cardiovascular risk in metabolic syndrome. Curr Atheroscler Rep. 2010; 12:110–118. Pearson TA, Mensah GA, Alexander RW et al. Markers of inflammation and cardiovascular disease: Application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003; 107:499–511. Dekker MJ, Lee S, Hudson R et al. An exercise intervention without weight loss decreases circulating interleukin-6 in lean and obese men with and without type 2 diabetes mellitus. Metabolism 2007; 56:332–338. Hsu FC, Kritchevsky SB, Liu Y et al. Association between inflammatory components and physical function in the health, aging, and body composition study: A principal component analysis approach. J Gerontol A Biol Sci Med Sci. 2009; 64:581–589. Lavoie ME, Rabasa-Lhoret R, Doucet E et al. Association between physical activity energy expenditure and inflammatory markers in sedentary overweight and obese women. Int J Obes (Lond). 2010; 34:1387–1395. Beavers KM, Brinkley TE, Nicklas BJ. Effect of exercise training on chronic inflammation. Clin Chim Acta 2010; 411:785–793. Ford ES. Does exercise reduce inflammation? Physical activity and C-reactive protein among U.S. adults. Epidemiology. 2002; 13:561–568. Borodulin K, Laatikainen T, Salomaa V, Jousilahti P. Associations of leisure time physical activity, self-rated physical fitness, and estimated aerobic fitness with serum C-reactive protein among 3,803 adults. Atherosclerosis 2006; 185:381–387. Brooks GC, Blaha MJ, Blumenthal RS. Relation of C-reactive protein to abdominal adiposity. Am J Cardiol. 2010; 106:56–61. Shanely RA, Nieman DC, Henson DA, Jin F, Knab AM, Sha W. Inflammation and oxidative stress are lower in physically fit and active adults. Scand J Med Sci Sports. 2013; 23:215–23. Church TS, Earnest CP, Thompson AM et al. Exercise without weight loss does not reduce C-reactive protein: The INFLAME study. Med Sci Sports Exerc. 2010; 42:708–716. Arsenault BJ, Cote M, Cartier A et al. Effect of exercise training on cardiometabolic risk markers among sedentary, but metabolically healthy overweight or obese postmenopausal women with elevated blood pressure. Atherosclerosis 2009; 207:530–533. Kelley GA, Kelley KS. Effects of aerobic exercise on C-reactive protein, body composition, and maximum oxygen consumption in adults: A meta-analysis of randomized controlled trials. Metabolism 2006; 55:1500–1507.

20. Stewart LK, Earnest CP, Blair SN, Church TS. Effects of different doses of physical activity on C-reactive protein among women. Med Sci Sports Exerc. 2010; 42:701–707. 21. Thompson D, Markovitch D, Betts JA, Mazzatti D, Turner J, Tyrrell RM. Time course of changes in inflammatory markers during a 6-mo exercise intervention in sedentary middle-aged men: A randomized-controlled trial. J Appl Physiol. 2010; 108:769–779. 22. Stewart LK, Flynn MG, Campbell WW et al. The influence of exercise training on in ammatory cytokines and C-reactive protein. Med Sci Sports Exerc. 2007; 39:1714–1719. 23. Christiansen T, Paulsen SK, Bruun JM, Pedersen SB, Richelsen B. Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: A 12-week randomized intervention study. Am J Physiol Endocrinol Metab. 2010; 298:E824–E831. 24. Herder C, Peltonen M, Koenig W et al. Anti-inflammatory effect of lifestyle changes in the Finnish Diabetes Prevention Study. Diabetologia 2009; 52:433–442. 25. van Hall G, Steensberg A, Sacchetti M, Fischer C, Keller C, Schjerling P et al. Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab. 2003; 88:3005–10. 26. Brandt C, Pedersen BK. The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol. 2010; doi:10.1155/2010/520258. 27. Pedersen BK. The diseasome of physical inactivity—And the role of myokines in muscle—Fat cross talk. J Physiol. 2009; 587(Pt 23):5559–5568. 28. Gleeson M, Bishop N, Oliveira M, Tauler P. Influence of training load on upper respiratory tract infection incidence and antigen-stimulated cytokine production. Scand J Med Sci Sports. 2013; 23:451–457. 29. Pedersen BK. Anti-inflammatory effects of exercise: Role in diabetes and cardiovascular disease. European Journal of Clinical Investigation. 2017; 47(8):600–611 30. Petersen AM, Pedersen BK. The antiinflammatory effect of exercise. J Appl Physiol. 2005; 98:1154–1162. 31. Ryan AS, Nicklas BJ. Reductions in plasma cytokine levels with weight loss improve insulin sensitivity in overweight and obese postmenopausal women. Diabetes Care 2004; 27:1699–1705. 32. Ferrier KE, Nestel P, Taylor A, Drew BC, Kingwell BA. Diet but not aerobic exercise training reduces skeletal muscle TNF-alpha in overweight humans. Diabetologia 2004; 47:630–637. 33. Nieman DC, Henson DA, Austin MD, Brown VA. The immune response to a 30-minute walk. Med Sci Sports Exerc. 2005; 37:57–62. 34. Dorneles GP, Haddad DO, Fagundes VO, Vargas BK, Kloecker A, Romao PR, Peres A. High intensity interval exercise decreases IL-8 and enhances the immunomodulatory cytokine interleukin-10 in lean and overweight-obese individuals. Cytokine. 2016; 77:1–9.

35. Nicklas BJ, Wang X, You T et al. Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: A randomized, controlled trial. Am J Clin Nutr. 2009; 89:1043–1052. 36. National Institute of Allergy and Infectious Diseases. The Common Cold. http:​//www​.niai​d.nih​.gov/​topic​s /com​ monco​ld (Accessed 3 July 2010). 37. Fendrick AM, Monto AS, Nightengale B, Sarnes M. The economic burden of non-in uenza-related viral respiratory tract infection in the United States. Arch Intern Med. 2003; 163:487–494. 38. Monto AS. Epidemiology of viral respiratory infections. Am J Med. 2002; 112(6A):4S–12S. 39. Nieman DC. Is infection risk linked to exercise workload? Med Sci Sports Exerc. 2000; 32(suppl 7):S406–S411. 40. Matthews CE, Ockene IS, Freedson PS, Rosal MC, Merriam PA, Hebert JR. Moderate to vigorous physical activity and risk of upper-respiratory tract infection. Med Sci Sports Exerc. 2002; 34:1242–1248. 41. Kostka T, Praczko K. Interrelationship between physical activity, symptomatology of upper respiratory tract infections, and depression in elderly people. Gerontology 2007; 53:187–193. 42. Kostka T, Drygas W, Jegier A, Praczko K. Physical activity and upper respiratory tract infections. Int J Sports Med. 2008; 29:158–162. 43. Nieman DC, Nehlsen-Cannarella SL, Markoff PA et al. The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections. Int J Sports Med. 1990; 11:467–473. 44. Nieman DC, Henson DA, Gusewitch G et al. Physical activity and immune function in elderly women. Med Sci Sports Exerc. 1993; 25:823–831. 45. Nieman DC. Immune function. In Gisol CV, Lamb DR, Nadel E (eds). Perspectives in Exercise Science and Sports Medicine, Vol. 8: Exercise in Older Adults. Carmel, IN: Cooper Publishing Group, 1995, pp. 435–461. 46. Chubak J, McTiernan A, Sorensen B et al. Moderate-intensity exercise reduces the incidence of colds among postmenopausal women. Am J Med. 2006; 119:937–942. 47. Neuman MI, Willett WC, Curhan GC. Physical activity and the risk of community-acquired pneumonia in US women. Am J Med. 2010; 123:281.e7–281.e11. 48. Nehlsen-Cannarella SL, Nieman DC, Jessen J et al. The effects of acute moderate exercise on lymphocyte function and serum immunoglobulins. Int J Sports Med. 1991; 12:391–398. 49. Nieman DC. Exercise effects on systemic immunity. Immunol Cell Biol. 2000; 78:496–501. 50. Nieman DC, Nehlsen-Cannarella SL. The immune response to exercise. Semin Hematol. 1994; 31:166–179. 51. Murphy DA, Davis JM, Brown AS et al. Role of lung macrophages on susceptibility to respiratory infection following short-term moderate exercise training. Am J Physiol Regul Integr Comp Physiol. 2004; 287:R1354–R1358. 52. Edwards DM, Burns VE, Reynolds T, Carroll D, Drayson M, Ring C. Acute stress exposure prior to influenza

References  545 vaccination enhances antibody response in women. Brain Behav Immun. 2006; 20:159–168. 53. Kohut ML, Arntson BA, Lee W et al. Moderate exercise improves antibody response to in uenza immunization in older adults. Vaccine 2004; 22:2298–2306. 4. Kohut ML, Lee W, Martin A et al. The 5 exercise-induced enhancement of influenza immunity is mediated in part by improvements in psychosocial factors in older adults. Brain Behav Immun. 2005; 19:357–366.

55. Lowder T, Padgett DA, Woods JA. Moderate exercise early after influenza virus infection reduces the Th1 inflammatory response in lungs of mice. Exerc Immunol Rev. 2006; 12:97–111. 56. Fondell E, Christensen SE, Bälter O, Bälter K. Adherence to the Nordic Nutrition Recommendations as a measure of a healthy diet and upper respiratory tract infection. Public Health Nutr. 2011; 14:860–869. 57. Cohen S. Keynote Presentation at the Eight International Congress of Behavioral Medicine: The Pittsburgh common cold studies: Psychosocial

predictors of susceptibility to respiratory infectious illness. Int J Behav Med. 2005; 12:123–131. 58. Spiegel K, Sheridan JF, Van Cauter E. Effect of sleep deprivation on response to immunization. JAMA 2002; 288:1471–1472. 9. Cohen S, Doyle WJ, Alper CM, Janicki5 Deverts D, Turner RB. Sleep habits and susceptibility to the common cold. Arch Intern Med. 2009; 169:62–67. 60. Keusch GT. The history of nutrition: Malnutrition, infection and immunity. J Nutr. 2003; 133:336S–340S.

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44 CHAPTER

Chronic Exercise and Immunity Melissa M. Markofski, PhD, Paul M. Coen, PhD, and Michael G. Flynn, PhD

Key points.................................................................................. 547 44.1 Effect of Chronic Exercise on Leukocyte Number and Function........................................................................... 547 44.2  Effect of Chronic Exercise on Innate Immunity.................. 547 44.2.1  Monocytes and Tissue Macrophages.................... 547 44.2.2  Natural Killer Cells................................................ 548 44.2.3 Neutrophils........................................................... 548 44.3  Effect of Chronic Exercise on Adaptive Immunity............... 549 44.3.1  T and B Lymphocytes........................................... 549 44.4  Excessive Training and Immunity...................................... 549 44.4.1  Th1/Th2 Balance.................................................. 549

KEY POINTS • Acute exercise induces transient changes to circulating immune cells, and some of these changes may be related to the fitness of the individual. • Exercise training may induce beneficial changes to resting immune function. • Participation in regular exercise is encouraged for prevention of many inflammation-related diseases, especially cardiometabolic diseases. Exercise training influences numerous aspects of host defense and indices of immune function. The field of exercise and immune function continues to be an active area of research, and there are documented potential changes in immunity that are induced by regular exercise or strenuous exercise training. The objective of this chapter is to identify practical implications of chronic exercise that are applicable to both fitness exercisers and athletes. The influence of chronic exercise on innate and adaptive immunity will be reviewed along with the effect of excessive exercise training on selected immune parameters and resistance to infection. We will also address the influence of moderate exercise training on inflammation, wound healing, and the efficacy of vaccines.

44.1 EFFECT OF CHRONIC EXERCISE ON LEUKOCYTE NUMBER AND FUNCTION Leukocytes are circulating cells of the immune and lymphatic systems derived from bone marrow hematopoietic

44.4.2  Toll-like Receptors................................................ 550 44.4.3  Excessive Training: URS or URTI?.......................... 550 44.5  Moderate Training and Immunity....................................... 551 44.5.1  Exercise and Inflammation................................... 551 44.5.2  Wound Healing..................................................... 551 44.5.3  Exercise and Efficacy of Vaccines......................... 552 44.6 Conclusion........................................................................ 552 Clinical Applications................................................................... 552 Acknowledgments..................................................................... 552 References................................................................................ 553

stem cells, which are collectively responsible for mounting an immune response. A physically active or regularly exercising person has a lower number of circulating leukocytes at rest, but it can be difficult to partition the specific effects of exercise from the associated health benefits of regular exercise.1–4 Furthermore, regular exercise and physical activity can alter phenotype and influence the function of specific subsets of leukocytes.5,6 These changes potentially mediate the systemic anti-inflammatory effects of chronic exercise as evidenced by lower levels of circulating markers of inflammation (IL-6 and CRP). In this section, we will summarize current literature to support regular exercise eliciting changes in number, function and phenotype of the major leukocyte subsets.

44.2 EFFECT OF CHRONIC EXERCISE ON INNATE IMMUNITY 44.2.1 Monocytes and Tissue Macrophages Monocytes are circulating cells that have both innate and adaptive immune functions.7 Monocytes can respond to infection or tissue damage by traveling to the lymph nodes to become dendritic cells8 or migrating to the site of insult, where they then differentiate into tissue-specific macrophages (e.g. Kupfer cells in liver, macrophages in adipose tissue). Antigen presentation and subsequent cytokine release help to coordinate the responses of the adaptive immune system. However, chronic low-grade activation of the monocyte/macrophage lineage is thought to contribute to the pathophysiology of obesity, insulin resistance,9 and development of atherosclerosis.10 547

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Several researchers highlighted the role of chronic exercise-induced alterations in monocyte phenotype/ inflammatory response as a possible mechanism underlying the anti-inflammatory effects of exercise. In both cross-sectional and longitudinal training studies, subjects who regularly exercised had lower mitogen-stimulated, ex vivo whole blood production of inflammatory cytokines.11,12 The degree to which Toll-Like Receptor (TLR4) is expressed on circulating monocytes may be related to mitogen-stimulated cytokine production.13 This finding may be significant, as monocyte/macrophage TLR4 activation is implicated in the pathophysiology of atherosclerotic plaque development and peripheral tissue insulin resistance. Indeed, exercise training has elicited decreased monocyte TLR4 expression.13–15 Taken together, this emerging evidence implies that regular exercise can reduce expression and reactivity of the innate immune receptor TLR4, an important factor in monocyte/macrophage activation. Major populations of circulating monocytes are phenotypically classified based on cell surface expression of CD14 and CD16. CD14++CD16− cells are classical monocytes, which make up the largest proportion of the circulating monocyte population.16 CD14+CD16+ monocytes are non-classical “inflammatory” monocytes—a subpopulation with a proclivity for production of proinflammatory cytokines. CD14++CD16+ monocytes are called intermediate monocytes, but a range of methodologies employed in measuring this subpopulation makes it difficult to compare the influence of exercise on intermediate monocytes. Circulating inflammatory monocyte percentage is elevated in patients with subclinical atherosclerosis and obesity.17 This is significant, as inflammatory monocytes adhere robustly to activated endothelial cells.18 and may be precursors to CD16+ macrophages found distributed throughout atherosclerotic lesions and adipose tissue.19,20 Regular exercise training can reduce the inflammatory monocyte population, 21,22 thus providing another potential mechanism by which exercise reduces inflammation. Adipose tissue macrophages are the most dominant immune cell in adipose tissue. There is evidence that adipose tissue macrophages in obese persons are more pro-inflammatory than in lean persons. 23 Furthermore, activation of adipose tissue macrophages is associated with obesity and peripheral tissue insulin resistance, 24 which may be abated by regular exercise. Bruun et al. reported that a 15-week hypocaloric diet and exercise intervention reduced macrophage-specific markers and inflammatory cytokines in adipose tissue. 25 These effects were concomitant with improved insulin sensitivity. There is strong evidence in support of the concept that regular exercise can reduce monocyte/macrophage inflammation, possibly through modulation of TLR4 expression and/or altering the phenotype of circulating monocyte subpopulations. However, more studies need to be conducted to clarify the effect of regular exercise on adipose tissue macrophage recruitment and activation. This body of work is clinically important, as activation of the monocyte/macrophage lineage is implicated in the pathophysiology of diseases such as diabetes and cardiovascular disease.

44.2.2 Natural Killer Cells Natural killer cells are cytotoxic lymphocytes and a major constituent of the innate immune system. They protect against certain tumors and virally infected cells by releasing granules containing proteases and porins that induce apoptosis in the target cell. Yan et al. reported that the proportion of NK cells (CD16+CD56+) in isolated peripheral blood mononuclear cells was higher in older subjects who exercised regularly than those who did not, 26 but the NK activity against K562 target cells was not different between these subject groups. Further, there were no differences in either NK cell number or activity between exercisers and non-exercisers in the young and middle-aged groups. In another study, there were no differences in the expression of NKG2D or NKG2A receptors, but young athletes had a greater NK cell activation and degranulation in response to cells from the K562 and .221 cell lines, though not .221-AEH, when compared with young non-athletes. 27 The differences reported between studies may be attributable to differences between recreationally trained individuals and athletes, and the length of time a person has engaged in habitual exercise. For example, endurance-trained older women had greater NK cell activity compared to sedentary older women, but 12 weeks of moderate aerobic exercise did not alter NK cell activity or number in the previously sedentary women. 28 Another factor to consider is infection history, as there is emerging evidence that latent infections may blunt NK cell mobilization in response to an exercise bout in trained adults. 29 The results of NK cell exercise/physical activity studies are varied, with exercise reported to suppress, 30 increase, 31–34 or not change the cytotoxic activity or number of natural killers cell.11,35–38 Despite many published studies in which the effect of exercise training on NK cells has been examined, it appears that a consensus has not been reached. Variables such as age of participants, length of training, and infection history contribute to the reported variability of results. Furthermore, there may be a need for a more specific NK subset classification, including differentiation status and activation/inhibitory receptors.

44.2.3 Neutrophils Neutrophils are polymorphononuclear cells and are the most abundant leukocyte subtype. Neutrophils are the first responders of the innate immune system and migrate to the site of infection or injury within minutes. In athletes, resting circulating neutrophil number is similar to sedentary individuals. 39,40 However, an exercise training program lowered neutrophil number in overweight women with multiple risk factors for cardiovascular disease.41 Furthermore, the decrease in neutrophil number was correlated with improvements in insulin sensitivity. It may be that in the context of chronic inflammation, such as is evident with CVD, exercise training can impact the neutrophil number. In athletes, however, it appears that regular intense exercise may reduce neutrophil function. 28,42,43

44.4  Excessive Training and Immunity  549

44.3 EFFECT OF CHRONIC EXERCISE ON ADAPTIVE IMMUNITY 44.3.1 T and B Lymphocytes T and B cells are the primary circulating cells of the adaptive immune system. T cells are involved in cell-mediated immunity and B cells are primarily responsible for producing antigen specific antibodies (humoral immunity). There are aging-related changes in adaptive immunity—immunosenescence refers to the natural decline in immune function that occurs with aging and is believed to contribute to age-associated morbidity.44 Regular exercise may impact the number, function, and ex vivo proliferative response of T cell populations in older adults, and, as such, may be an important modality for maintaining immune health as one grows older. The ex vivo lymphocyte proliferative response to mitogen (PHA) was significantly higher in older runners than non-runners.45,46 Koizumi et al. reported that exercise training increased the absolute numbers of T cells and T-helper cells in older adults (2003), and a six-month aerobic exercise training intervention increased T-cell proliferation in response to mitogen. 38 However, others have reported that ex vivo lymphocyte responses are not affected by shorter exercise interventions or resistance training. Ex vivo T-cell proliferation did not change after 12 weeks of exercise training. 28 Resistance training for 10 to 12 weeks did not alter proliferative response to mitogens, 36,47 and a 12-month moderate resistance exercise program for elderly women did not alter circulating numbers of lymphocytes. 37 Currently, there is a lack of consensus on the effects of regular exercise on ex vivo lymphocyte proliferative response. An emerging area of research in the adaptive immune system is the potential elements of an acute exercise response that can be attributed to infection history or latent virus infection. Specifically, subjects who are seropositive for cytomegalovirus (CMV) will have a higher acute aerobic exercise response to total lymphocytes, KLRG1+CD28-CD4+ and CD8+ T cells, and CD45RA+CCR7-CD8+ T cells than CMV negative subjects.48,49 Interestingly, when young and older subjects completed the same relative intensity, acute, aerobic exercise bout, the CMV+ young and older subjects had the same redeployment of total CD8+ T cells as well as CD45RA+CCR7+ and KLRG1-CD28+ CD8+ subsets, but the CMV- older adults had an impaired response. 50 Infection history of some viruses may protect an athlete from subsequent illnesses, 51 and not controlling for infection history could account for some of the conflicting results often reported in the literature.

44.4 EXCESSIVE TRAINING AND IMMUNITY Excessive training can result in a wide range of negative clinical signs and symptoms. This symptom complex is quite often referred to as overtraining syndrome (OTS), but the reader will also frequently see “overtraining” or

reference to the short-term condition “overreaching.” Clinical symptoms of overtraining syndrome are many and include: lethargy, fatigue, mood disturbances, underperformance, immune suppression, and poor healing of cuts and scratches. The etiology of OTS is not fully understood, and in addition to training load, other variables such as micro- and macronutrient intakes, recovery, and sleep quality may also contribute to risk and development of OTS. As noted above, resting immunity is not substantially different between athletes and healthy, sedentary individuals, but it appears that intensive training could negatively affect several immune measures. Changes in NK cell activity and T-cell function have been observed after intensified training programs, but it is unclear whether the changes in the immune system induced by hard training are to blame for a higher incidence of infection in athletes.38 Nevertheless, the collective toll of excessive training on the immune system would appear to render athletes more susceptible to infection. The immune variable that responds most consistently to repeated, hard exercise is the mucosal secretion or secretion rate of immunoglobulin A (IgA), considered a first line of defense against infection. IgA has also been more strongly and consistently linked to infection risk in athletes than other measurable aspects of immunity.52 The influence of intensive training on salivary IgA is discussed in detail below.

44.4.1 Th1/Th2 Balance CD4+ T-helper cells can be divided into several distinct subpopulations, including Th1, Th2, Th17, and T-regulatory (Tregs) cells. Specifically, Th1 cells are part of cell-mediated immunity and produce TNF and INFγ; Th2 cells release IL-4, -5, and -10, and respond to parasites; Th17 produce IL-17 and seem to have a large role in autoimmune disorders; and Tregs suppress the activity of other immune cells and maintaining discrimination between self and non-self antigens during an immune response, thereby preventing autoimmune diseases. In some respects, the ratio of T cell subsets cells may be a better indicator of health than the absolute numbers. For example, the ratio of Thelper1/Thelper2 (Th1/Th2) cytokines is often used as an index of inflammatory signaling. The Th1/Th2 distribution has been consistently shown to be influenced by intensive training, with a shift toward Th2 dominance. 53 A pronounced shift in cytokine production, typical of the Th2 anti-inflammatory milieu, could render the vigorous exerciser more susceptible to infection. 52,54 However, moderate training appears to induce a positive, subtle shift toward a Th2 cytokine profile, balancing the Th1/Th2 response and inducing the antiinflammatory influences of regular exercise. 54 Treg and Th17 cells are not well studied in an exercise or physical activity context. In the limited research available, Yeh et al. reported an increased Treg function in both healthy, middle-aged adults55 and subjects with Type2 diabetes56 after 12 weeks of Tai Chi training. In response to a strenuous acute aerobic exercise event, athletes had a decrease in absolute numbers of Tregs and an

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increase in Th17 cells. Furthermore, there was a decrease in percent circulating Treg cells that remained depressed below pre-race levels 10 days after the event. 57 Treg and Th17 cells both have a role in regulating inflammation and need further examination in a physical activity context.

44.4.2 Toll-like Receptors High-intensity bouts of exercise have also been linked to down-regulation of TLR4-cell surface expression.58 Oliveira and Gleeson found that cycling for 90 minutes (75% VO2peak) resulted in a transient reduction in TLR4 that was sustained for one to four hours after exercise. 58 Toll-like receptors help orchestrate the innate immune response to a wide range of pathogens, which led the Oliveira and Gleeson to conclude that post-exercise TLR4 depression could contribute to post-exercise immune depression. This premise, however, was based on a single bout of exercise and there is a lack of research examining the response of sustained, intensified training on TLR down-regulation. Therefore, while it is possible that regular bouts of hard exercise might transiently reduce TLR expression and increase susceptibility to infection, moderate intensity, long-term exercise reduces TLR4 expression in hyper-inflammatory groups (sedentary, overweight/ obese, and elderly). Reduced TLR4 expression is generally viewed as a positive adaptation due to its potential to influence systemic inflammation. Thus, there is likely a differential response to repeated bouts of intense exercise where the goal is improved performance, which could lead to immune depression and long-term, moderate exercise programs where the goal is to improve fitness, which can lead to overall health improvement.

44.4.3 Excessive Training: URS or URTI? Athletes who train hard are frequently reported to have an increased incidence of upper-respiratory symptoms (URS) related to upper-respiratory tract infection (URTI). 59 Elite athletes are believed to have a higher incidence of URTI than fitness exercisers or sedentary individuals. These findings, along with the fact that several indices of immune function are suppressed by heavy exercise, led to the assertion that heavy exercise lowers immune defenses and increases URTI risk. Two important factors remain unclear in this regard. First, whether or not excessive training suppresses immune function to the extent possible to result in an increased susceptibility to infection has not been determined. 38 There is a general consensus that several immune parameters are depressed following prolonged or severe exercise, most notably and consistently mucosal immunoglobulin A, but it is not known whether the immune depression is causative of an increased incidence of URTI. Second, it is not clear whether the URTIs reported by athletes in the majority of studies are pathogen-based or a result of local airway irritation or inflammation.60 Problematically, most of the studies in which the incidence of URTI has been assessed in conjunction with heavy training largely relied on self-report. Researchers from a small number of studies have called that practice into question, largely

due to a lack of the presence of an infectious pathogen in the sputum of athletes reporting symptoms of URTI.60 However, most researchers also acknowledge that the ability to detect these pathogens in sputum is far from an exact science. It is interesting to note that the daily use of an anti-inflammatory throat spray, one week before and two weeks after a half-marathon, did not influence the number of reported URTI episodes in a relatively small group of runners (n = 25 treatment; n = 20 controls), but may have influenced the severity scores (trend).61 Thus, while evidence is mounting that regular, modest exercise reduces the risk of URTI 28 and prolonged, intense or excessive exercise training increases the risk of URTI, 59 there is considerable controversy in this area that prevents us from making concrete conclusions about the links between hard exercise and illness. No increase in the rate of infectious episodes was found in marathon runners when runners with a prerace infection were removed from the cohort,62 casting further doubt on the relationship between hard exercise and URTI. Thus, while there is conflicting data on the relationship between infection risk and hard training, the conflict is difficult to rectify when considering feasibility and research design issues. Logistically, the excessive time and cost make it difficult to include quantitative cellular immune measures in large cohort studies of infection incidence and prevalence. There are some larger-scale studies in which salivary IgA has been measured and negatively correlated with URTI incidence.35 Gleeson et al.52 monitored 80 athletes for several months, with training and illness logs recorded and blood and saliva samples obtained. These authors identified a sub-group of “illness-prone” subjects who had higher training loads, higher levels of multi-antigen-stimulated anti-inflammatory cytokines— illustrating a Th2 dominant response—and lower salivary S-IgA secretion and flow rates. In addition, the highest quartile of IL-10 producers had higher training loads, higher production of inflammatory and anti-inflammatory cytokines, lower IgA, and higher URTI incidence than the lowest quartile. The authors suggested that IL-10 might be a useful predictor of infection risk in physically active individuals. 52 There is clearly an increase in upperrespiratory symptoms associated with hard training. Further research is required to document what proportion of these illnesses are pathogen-based or linked to airway inflammation/irritation. A relatively new area of research is related to the relationship between the microbiome and overall health. Much of this research specifically relates to gut microbiota, as the results from numerous studies link gut microbiota to health concerns such as obesity and diabetes.63,64 Studies of gut microbiota and health include the potential for dietary supplements to reduce the risk of various infections in athletes. The wide range of the types of supplements, doses, and subject populations in this new research area make it difficult to define an optimal regime for intestinal microbiota health in an athlete. However, there is some evidence that altering gut microbiota may reduce infection risk or length of symptoms in athletes. Highly-trained male and female athletes who received a multi-species probiotic had a lower incidence of URTI, but no improvement in athletic performance.65 Other

44.5  Moderate Training and Immunity  551

researchers have also found a decrease in URTI infection incidence and length of symptoms in athletes taking probiotics, but the benefit may be dependent on the type of probiotic.66–68 Additionally, more work is needed to determine if a sex difference exists in the responses to probiotics.69

44.5 MODERATE TRAINING AND IMMUNITY 44.5.1 Exercise and Inflammation Evidence of the role that inflammation plays in the development and exacerbation of chronic disease has grown substantially. Inflammation or inflammatory biomarkers have been clearly linked to cardiovascular disease,70 type 2 diabetes,71 osteoporosis72 and several other chronic diseases not previously believed to have an inflammatory etiology. For example, cardiovascular disease was long believed to be a disease of lipid storage; however, it is now clear that inflammation plays a major role in the pathophysiology of atherosclerosis and CVD.73 Exercise is known to provide substantial benefits for the prevention and management of chronic diseases. There is growing evidence that exercise has antiinflammatory effects, but it is not clearly known how much of the benefit of exercise is due to contribution of an anti-inflammatory effect or to other actions of exercise. Regardless of the relative contribution, inflammatory biomarkers are significantly lower in segments of the population with moderate-to-high levels of physical activity.74 Not surprisingly, intervention studies provide less consistent support of an anti-inflammatory effect of exercise. Small subject numbers, different exercise modes and intensities, supervised vs. unsupervised exercise, and different choice of biomarkers all likely contribute to these inconsistencies. Nevertheless, there is fairly strong intervention literature to support the observation that exercise training has anti-inflammatory effects in serum or circulating cells,6,15,21 muscle,75,76 and, to a lesser extent, adipose tissue. 25,77 Inflammatory biomarkers and inflammation have been linked to the risk of several chronic diseases, including type 2 diabetes. High levels of inflammation are linked to peripheral tissue insulin resistance, impaired insulin receptor function, and severity of diabetic complications. TLR4 activation has also been shown to mimic several features of the diabetic state, but regular exercise reduces nuclear factor kappaB (NFκB) and TLR4 expression in diabetic subjects.78,79 Thus, it appears that the ability of exercise to ameliorate the symptoms of chronic disease may be linked, in part, to its anti-inflammatory effects. It seems reasonably clear that increasing physical activity level or engaging in an exercise training regimen can exert anti-inflammatory effects. An issue that remains unresolved is whether exercise training can exert an anti-inflammatory effect in the absence of changes in body fat.77,80 The literature in this area is mixed, but there are several examples of exercise providing an independent anti-inflammatory effect. In one review by Beavers, Brinkley, and Nicklas,74 the authors identified 19 studies

in which self-reported physical activity level was linked to biomarkers of inflammation, and an additional nine studies during which the fitness level was measured. These authors concluded that accounting for obesity “…attenuated, but did not negate, the strength of the relationship between inflammatory biomarkers and physical activity.” However, in an analysis of 1,703 adults (55–74 years), BMI was associated with more serum markers of inflammation than self-reported vigorous activity.81 The conflicting results of these studies underscore the differences that may be attributed to type and intensity of exercise. There are few studies in which an exercise intervention with and without body weight losses has been compared. The few in which comparisons were made do not allow for consensus, and it is difficult to control for the changes attributed to exercise training, changes in dietary patterns, and small changes in visceral fat.6,77,82 In summary, moderate exercise has anti-inflammatory effects. It is possible that there is an intensity threshold but evidence in support of low-intensity exercise exerting anti-inflammatory effects suggests the need for further study. It appears that exercise can exert anti-inflammatory effects in the absence of significant changes in body fat, but the lack of controlled studies in which exercise and diet have been studied alone and in combination preclude definitive conclusions. Exercise is known to exert antiinflammatory effects in persons with type 2 diabetes and a concomitant improvement in diabetic state and amelioration of symptoms without significant body fat changes. Thus, while some mechanisms remain to be determined, the anti-inflammatory effect of exercise has important health implications.

44.5.2 Wound Healing Aging and chronic conditions are known to slow the rate at which wounds heal. Bed sores are fairly common in older, institutionalized patients and are difficult and expensive to treat. Thus, it is important to examine potential lowcost interventions such as exercise on wound healing. The influence of exercise training or physical activity levels on wound healing has been studied in a relatively small number of investigations, but the limited available information is promising. As such, the inability of aging macrophages to produce angiogenic proteins could be modified by exercise training, and the anti-inflammatory effect of exercise training could also play a role in enhanced wound healing. Emery et al.83 divided 28 older adults into an exercise and non-exercise group and found a significantly improved healing rate of an experimental wound in the exercised group, compared with the non-exercise group. Although this research was limited by a fairly small number of subjects, the exercise effect in Emery’s study was substantial, with 55% of the subjects in the exercised group showing complete healing at day four compared with 0% on the non-exercised group. In an intent-to-treat intervention study of patients with venous leg ulcers, 77% of those randomized into an exercise intervention healed after 12 weeks, compared to 53% in the usual care group.84 Furthermore, subjects who completed at least 75% of their exercise sessions were more likely to heal and had

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a faster rate for wound healing. More work is needed to determine if simple, cost-effective interventions, such as exercise training, can alter the rate at which wounds heal. However, the paucity of literature on the topic prevents us from making solid conclusions regarding practical strategies for clinicians or patients.

44.5.3 Exercise and Efficacy of Vaccines Aging is associated with a decline in immune function,85 an increase in susceptibility to infections,86 and it can also result in low-grade chronic inflammation.87 Aging-related immunosenescence contributes to the increased incidence and severity of infectious disease among older adults, who experience a greater mortality rate from influenza infection and generally exhibit reduced vaccine efficacy compared to young adults.88,89 Exercise training may improve immune competence among older adults who have been administered an influenza vaccine. Several cross-sectional studies in which physically active older adults were compared to sedentary controls have shown a greater influenza vaccine response.45,90,91 A cross-sectional comparison of older, physically active, moderately active, and sedentary groups showed that physical activity was associated with greater response to influenza immunization. The older physically active group developed greater flu specific IgG and IgM titers two weeks post immunization, compared to moderate activity and sedentary groups.91 Peripheral blood mononuclear cell proliferation in vitro was also lower in the sedentary group. Keylock et al. demonstrated that physically active, highly fit, elderly individuals have higher antibody responses to the fluzone vaccine and a Th2 skewing of the antibody response to tetanus toxoid when compared to sedentary, low-fit, older adults.90 Taken together these studies suggest that lifestyle factors, including regular exercise, may influence immune response to influenza immunization. A number of longitudinal studies have also been conducted to examine the role of exercise training on influenza vaccine response. Kohut et al. reported that a 10-month exercise intervention in older adults resulted in a greater increase in the influenza-specific antibody titer and IFN-γ production following flu vaccine.92 These researchers also identified psychosocial factors such as depression and sense of coherence as potential mediators of response to influenza vaccine. In a larger trial, 144 sedentary, older adults were randomized to either a 10-month aerobic training (n = 74) or a flexibility and balance program (n = 70).38 The intervention resulted in a significant increase in seroprotection, determined as a Hemagglutination Inhibition (HI) titer of >40, 24 weeks after vaccination (30–100%). This is significant as it suggests that an enhanced vaccine response following exercise training can be maintained over a period greater than the length of a typical flu season. However, and possibly more significantly, there was no difference in the incidence of URTI between the two groups, although the aerobic exercise group exhibited reduced overall illness severity and less sleep disturbance.

The mechanisms responsible for mediating the effects of exercise on vaccine efficacy are not fully understood. However, immunosenescence in aging is associated with an elevation in the ratio of memory T cells to naive T cells, potentially reducing the ability of the adaptive immune system to respond to novel antigens. Exercise training has been previously shown to reduce the memory to naive T-cell ratio. 38 Exercise may prolong antibody response, potentially by restoring the naive T cell level and subsequent ability to respond to novel antigen exposure.

44.6 CONCLUSION It is clear that regular, moderate, or extreme exercise has the potential to alter indices of immune function. While it appears that regular exercise may offer some protection against upper-respiratory tract infection, provide antiinflammatory actions, and enhance the response to vaccines, many unanswered questions remain. For example, excessive training (overtraining) has been linked to an increased risk of URTI, but researchers have questioned the reliability of both self-report of URTI and the direct method to detect pathogens in sputum. The ability of exercise to improve the course of chronic disease via anti-inflammatory and other immune changes is an exciting avenue for researchers. These studies will help to close the gap between the myriad benefits of exercise training and the available mechanisms to explain the benefits. Despite the gaps in our knowledge, it is clear that athletes can train effectively without excessive illness and that fitness exercisers adapt in primarily positive immunological fashion to regular, moderate exercise.

CLINICAL APPLICATIONS • Regular exercise shifts circulating T cells toward a more anti-inflammatory profile, and reduces proinflammatory cell surface receptors on monocytes. • Excessive training may increase the risk of developing an URTI, possibly in part by alterations in salivary IgA secretion and flow rate. • Participation in regular exercise may improve wound healing and response to vaccine. • High inflammation is implicated in many diseases, and people who regularly exercise have lower proinflammatory immune cells. An anti-inflammatory effect of exercise training at least partially explains the lower chronic disease rate observed in people who regularly exercise.

ACKNOWLEDGMENTS This research was supported (in whole or in part) by HCA and/or an HCA affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA or any of its affiliated entities.

References  553

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45 CHAPTER

HIV and Exercise Jason R. Jaggers, PhD and Gregory A. Hand, PhD, MPH, FACSM, FESPM

Key Points.................................................................................. 555 45.1 Introduction...................................................................... 555 45.2  HIV Epidemic.................................................................... 556 45.3  Virology and Infection....................................................... 556 45.3.1  Primary HIV Infection............................................ 556 45.3.2  Asymptomatic (Active Latency).............................. 556 45.3.3 Symptomatic........................................................ 556 45.4  Symptomatology of HIV Infection...................................... 556 45.4.1  Psychological Consequences................................ 556 45.4.2  Physical Consequences......................................... 557 45.4.3  Antiretroviral Therapy............................................ 557 45.4.4  Toxic Side Effects.................................................. 557

KEY POINTS • Investigations have continuously reported significant health improvements by modest changes in activity. • Future research is necessary to determine successful motivational- and behavioral-changing interventions aimed at increasing physical activity for this population. • Routine physical activity has shown to reduce daily stress and circulating cortisol in as little as three weeks among people living with HIV/AIDS. • Light-to-moderate intensity levels are sufficient to achieve short-term health benefits as long as the individual stays consistent with their exercise plan. • There is no evidence to indicate that exercise performed at low-, moderate-, or high-intensity will negatively impact immune function or disease progression in HIV-infected individuals.

45.1 INTRODUCTION Living with HIV has become more of a management of chronic conditions in recent years than the battle of opportunistic infections from a depleted immune system, as it was in the first two decades of the epidemic. Even faster have been the changes in patient symptomatology. With rapid advances in medical science, the pharmacological regimens designed to block viral replication and prevent

45.5  Treating the Side Effects................................................... 558 45.5.1  Treatment of HIV-related Symptoms...................... 558 45.5.2  Exercise as Medicine for Managing Art Toxicities.......558 45.5.3  Cardiorespiratory Fitness (VO2peak)......................... 559 45.5.4  Blood Lipids.......................................................... 559 45.5.5  Body Composition................................................. 559 45.5.6  Immune System.................................................... 559 45.5.7  Psychological Improvements with Exercise........... 560 45.5.8  Recommendations for Exercise............................. 560 45.6 Conclusion........................................................................ 560 Clinical applications................................................................... 561 References................................................................................ 561

the spread of infection have quickly gone from a multi-pill daily routine to a single combo-pill. Many people can now live decades longer and well into old age, but also must be more health conscious to offset negative consequences from antiretroviral therapy (ART) side effects. Although the advances in ART have increased life expectancy, the treatment is not without consequence. Early into treatment, chief complaints are often psychological in nature, which over time either subside or become more tolerable. However, studies have shown that there are many physiological consequences, such as increased lipids and risk for cardiovascular disease (CVD) and diabetes.1–3 On top of medication related side effects, there is still an ongoing social stigmatization that comes with living with HIV. Even researchers still struggle to not only recruit eligible participants for HIV specific studies but maintain their participation throughout the study duration. This, in turn, makes it more difficult to determine solid results due to a lack of longitudinal clinical trials and interventions with large datasets. Due to increased life expectancy and only slight reductions in new infections, we have also begun to experience increased prevalence rates. Healthy lifestyle choices, such as diet and exercise, have now become that much more important with this population. Exercise alone has shown to have positive impacts on health across all populations, regardless of disease or health status, on both psychological and physiological outcomes. Research from our lab and others have also demonstrated significant improvements to the health and quality of life for people living with HIV/AIDS (PLWHA).

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45.2 HIV EPIDEMIC Statistics reported by the Centers for Disease Control (CDC) indicate that the number of new HIV cases reported within the United States declined by 10% between 2010 and 2014.4 The trend of new cases has varied between specific populations with higher incidence rates often observed among minority male populations and gay males in their mid-20s and 30s. A large number of new cases also derive from lower socioeconomic backgrounds. On a global level there is even more concern for both prevention and treatment in underdeveloped countries. Different populations and cultures are plagued by more negative health outcomes and life expectancy. Newborns with HIV in third-world countries are a continuing problem, as well as the need for access to proper care and treatment. Even within the United States, the population primarily affected by the HIV epidemic will vary depending on geographical location as well as access to adequate healthcare. More rural parts of the country may require patients to drive hours to the closest healthcare provider able to serve their health needs. Regardless of location, it’s imperative for all PLWHA to have access to specialists and the medications necessary to maintain a non-detectable viral load to help reduce the spread of infection.

45.3 VIROLOGY AND INFECTION 45.3.1 Primary HIV Infection The stage known as primary HIV infection (PHI) is best defined as the time between acute viral transmission lasting anywhere from two to six weeks until the onset of antibody production.5 Current evidence indicates a massive CD4+ cell depletion occurring at mucosal sites within two to three days following viral transmission. Using polymerase chain reaction (PCR) techniques, Piatak and colleagues indicated that viral reproduction was capable of reaching 106 or 107 viral particles/mL of plasma within the first two weeks of transmission.6,7 At the onset of viral infection, symptoms generally appear anywhere within a few days to a couple of weeks. The majority of persons newly infected (70%) experience mild forms of symptoms generally associated with common colds, the flu, or stomach viruses. Due to the initial symptoms being mild in nature and the fact the PHI is short in duration, the initial infection often goes unnoticed until more severe symptoms appear, causing the person to seek medical attention. It is believed that the severity of the initial symptoms and how the immune system reacts are indications for disease progression.

45.3.2 Asymptomatic (Active Latency) Following PHI, there is a sharp increase in viral load as the virion is being disseminated throughout the entire body and spreading the infection to nearby peripheral and distal sites. Generally, within two to four weeks, the sudden peak in viral load begins to regress, which is believed to be the result of the primary immune response involving cell-mediated immunity in addition to antibody

production. 5,8–10 The appearance of HIV antibodies detected within plasma begins a period of clinical latency also referred to as seroconversion. With more advanced measurement techniques, it has been shown that during this stage of clinical latency the virus is actually in a state of active reproduction. Even though it appears to be in a state of inactivity, there is continued infection of nearby cells and ongoing production of viral strands.

45.3.3 Symptomatic The widespread use of ART has successfully increased the lifespan of PLWHA, with AIDS-related deaths declining annually. Instead, PLWHA are more likely to reach a stage of “accelerated aging,” referring to the increased risk of developing chronic disease(s) known to primarily affect uninfected aging populations. Recent evidence indicates PLWHA are being diagnosed with and/or dying from CVD, diabetes, and other metabolic disorders with an early age of onset.1,2,11 This is mainly due to the toxic effects of certain classes of antiretrovirals, which can be found in Table 45.1.

45.4 SYMPTOMATOLOGY OF HIV INFECTION 45.4.1 Psychological Consequences PLWHA are burdened with multiple psychosocial stressors at all stages of illness. Immediately upon diagnosis, patients must face life-changing issues such as managing the illness, affording appropriate healthcare, and the daily struggles that accompany living with the stigmatization of HIV. In addition to these personal stressors, various environmental factors could potentially exacerbate the levels of stress already experienced such as living in a lower socioeconomic status, facing unemployment, reduced access to health care, and many others. The patients’ ability to cope TABLE 45.1  Common antiretroviral side effects Toxic side effect from ART

Drug class(es)

Decreased BMD

All

Cardiac Conduction Impaired

PI, NNRTI

Cardiovascular Disease

PI, NRTI

Diabetes Mellitus

PI, NRTI

Dyslipidemia

All

Gastrointestinal Disturbances

PI, NRTI

Lactic Acidosis

NRTI

Lipodystrophy

All

Psychiatric Disturbances

NRTI, NNRTI, INSTI

Neurological Disturbances

All

Key to Abbreviations: ART= antiretroviral therapy; BMD = bone mineral density; INSTI = integrase strand transfer inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor

45.4  Symptomatology of HIV Infection  557

with these burdens ultimately depends on their psychological state, social support network, and their stage of HIV disease. Many of the psychological complications experienced by PLWHA are known to be treatable, and therefore it is imperative for caregivers and health care providers to learn to recognize the signs of these conditions so they may refer them to a specialist for further evaluation. Effective treatment for depression, a common psychiatric condition among PLWHA, has been shown to result in fewer physical symptoms, better sleep quality, and improvements in health-related quality of life.12,13 Many studies of various chronic diseases have investigated consequences of distress among patients and reported positive associations with mood disturbance, poor treatment adherence, and negative health outcomes.14–16 Similar findings have been reported among HIV-related investigations.12,13,17 Although distress has been identified as an important measure to manage mental health, and self-reported symptoms have become a common method used to indicate health status, the literature on self-reported symptom distress within the HIV population is scarce. Generally, a level of distress is experienced when symptoms are present, and emerging data have shown a negative impact of psychological distress on HIV disease progression.18 Increases in symptom distress have potentially negative consequences to both physical and psychological health, which have been recently discovered with a growing body of evidence supporting the psychoneuroimmunology (PNI) framework as discussed by McCain et al.19 Recent investigations have begun to show consistent reports of psychological distress and disturbances impairing immune function 20 as well as cytokine-induced changes in neurotransmitter and neuroendocrine function, which have been shown to correlate with onset of depression and/or fatigue. 21 The burden of frequent symptoms is known to negatively affect disease management and mental health. 22 Identifying factors that are associated with increased symptom distress may provide possible strategies to lessen the burden of HIV infection and related symptoms while also improving treatment adherence. A few emerging themes in managing psychological stressors is mindful meditation and motivational interviewing. These techniques could prove beneficial with populations such as HIV patients and should be further explored to assist with the psychological burden. Recent updates to primary care guidelines by the Infectious Diseases Society of America (IDSA) suggest including depression and posttraumatic stress disorder screening as part of a patient’s initial evaluation and at periodical intervals thereafter. 23 Women have also been shown to have increased rates of sexual and/or domestic abuse and twice the risk of depression, indicating increased needs for services able to accommodate these needs as well. 23

45.4.2 Physical Consequences All clinical populations face a large variety of diseaserelated physical and psychological symptoms, but prevalence rates of self-reported symptoms are generally over 50% among PLWHA, ranging from a single symptom to

multiple concurrent symptoms. 24–26 Common physical symptoms reported include diarrhea, loss of appetite, nausea, muscle weakness, peripheral neuropathy, fever, dry skin, and persistent cough. These are often experienced in conjunction with antiretroviral side effects for those placed on an ART regimen. As a result, the management of multiple symptoms has become a daily task for PLWHA in an effort to maintain an optimal quality of life. 25,27,28 and ultimately leads to a chronic state of deconditioning leading to functional aerobic impairment. As was the case before the discovery of antiretrovirals, the association between the number of self-reported symptoms and disease status still allows for the use of reported symptom frequency as an indicator of disease progression and health-related quality of life. This has been able to assist health professionals with monitoring how well a patient is responding to current ART regimens. 25,29 Symptoms lasting anywhere between a few days to a few weeks increase the burden of disease among individuals, often resulting in negative lifestyle habits. The side effects and symptoms of HIV infection often have many patients turning to self-medication either by altering their daily ART regimen or seeking additional alternative treatments that may include illegal narcotics. Although the discovery of ART has led to an increased lifespan and decreased reports of AIDS and AIDS-related deaths, many scientists have reported a complex variety of symptoms and side effects associated with ART regimens, creating a metabolic syndrome affect.

45.4.3 Antiretroviral Therapy The timing for initiating treatment varies depending on viral infection as well as the patient’s primary healthcare provider, but generally it is recommended that patients begin an antiretroviral regimen if symptomatic, or asymptomatic but with a CD4 cell count 500 cells/µL.3,23 Options for treatment can range from early, aggressive intervention to postponing ART until a measurable increase in disease progression has been observed. Recommendations were released by the International AIDS Society-USA Panel in early 2012 (Table 45.2), stating the decision as to when patients should start treatment needs to be established after weighing “the benefits of treatment on morbidity and mortality against its risks, including toxicity, resistance, drug interactions, and the costs and inconvenience of lifelong treatment.”3 More recently, certain ART medications, such as Truvada, have also been recommended as a form as prevention for high-risk individuals, such as the partner of a person with HIV. It is still too early to draw any formative conclusions about long-term use for someone not carrying the HIV virus.

45.4.4 Toxic Side Effects The majority of side effects associated with ART are physiological in nature and directly alter metabolic processes, resulting in increased circulating blood lipids,

45

558  Chapter 45  HIV and Exercise TABLE 45.2  2010  Recommendations of the International AIDS Society—USA panel to initiating antiretroviral therapy Measure

Recommendation

Specific conditions

ART is recommended regardless of CD4 cell count

  *Symptomatic HIV Disease

psychotropics, and ergot alkaloids (vasoconstrictors). It has also become evident that when an individual begins an ART regimen their risk of developing cardiovascular disease or diabetes increases every year.

45.5 TREATING THE SIDE EFFECTS

  *Pregnant women

45.5.1 Treatment of HIV-related Symptoms

  * HIV-1 RNA > 100,000 copies/ml

Additional medications are generally prescribed for viral symptoms and treatment related side effects. Common prescription medications taken in addition to ARTs may include appetite stimulants, psychoactive drugs, soporific agents, antidiabetic drugs, analgesics, antibiotics, biophosphonates, calcitonin, or hormone replacements. Some of the more common antidepressants and anxiolytics may be prescribed among those beginning an ART regimen to assist with maintenance of drug adherence. Studies have consistently shown beneficial results in adherence to ART when patients are treated with antidepressants, as well. The use of additional prescription medications in response to disease and ART side effects has not always yielded beneficial results. Each ART can have different interactions with other pharmaceuticals that could further exacerbate symptoms or even prevent the ART’s primary mechanism of action from working, without the patient’s knowledge. 23 For example, in the treatment of anxiety in which someone is taking a daily valium or Klonopin to treat their anxiety in addition to starting ART, the mechanism responsible for inhibiting serotonin reuptake may no longer be effective due to specific antiretroviral mechanisms. In fact, there are some PI medications, such as ritonavir, that metabolize antianxiety or antidepressant medications completely. Because of the unpredictable reactions that an antiretroviral may have on new prescriptions, or even over-the-counter medications, new treatment strategies are imperative. A complementary treatment that may help address ART toxicities in viral-related side effects is exercise training. Similar metabolic abnormalities within the general population respond positively to prescribed dosages of routine exercise designed to increase fitness. These exercise-induced changes include decreases in total cholesterol and triglycerides, decreased fat mass, increased lean tissue mass, decreased waist circumference, and increased insulin sensitivity. 30–36

  *Rapid decline in CD4 cell count   *Active hepatitis B or C virus coinfection   *Active or high risk for CVD   *HIV-associated nephropathy   *Symptomatic PHI   *Risk for secondary HIV transmission   *Asymptomatic, CD4 cell count 75 years of age.70 However, 16 weeks of aerobic exercise in older adults did not change salivary IgA levels, although exercise did increase plasma IgA as well as plasma IgG and IgM antibodies as seen in other studies,71 suggesting that duration, intensity, or mode of exercise may play a major role in determining immunological outcomes. This is partially supported by a study that included both endurance and resistance exercise components in a training program for older adults and which resulted in significant increases in both salivary IgA concentrations and secretion rates compared to the pre-exercise intervention time point.72

Several studies have examined some of the aforementioned measures in rodent models of aging, which allow for a more in-depth look at potential mechanisms by which exercise might cause these changes. However, results from these studies have not always been consistent with those undertaken in humans for reasons that are not yet clear. A training program involving eight weeks of treadmill running failed to elicit a higher antibody response to herpes simplex virus in mice, although other markers of immune function including lymphocyte production of cytokines were increased by exercise training. 54 A similar study, which subjected rats to 10 weeks of treadmill training, demonstrated no increase in antibody or other responses to administration of KLH when these rats were compared to sedentary control animals.73 Despite these challenges, mechanistic studies in older rodents have shed some light as to possible causes for the changes in antibody responses to vaccination and infection seen in older adults. Blockage of β-adrenergic receptors via nadolol ablated the exercise-induced increase in antibody- and cell-mediated immune function seen in response to herpes simplex virus infection in mice.74 Similarly, blockage of endogenous opioid activity, which is increased with exercise, decreased antibody response to albumin injection compared to exercised mice that received a placebo implantation.75 Although these studies provide some insight into possible causes for exerciseinduced increases in immune responses in older adults, much more work remains to be done on this front before a satisfactory mechanism for these changes can be provided.

46.7 CONCLUSION Overall, in healthy older adults, regular aerobic exercise appears to reduce chronic low-level inflammation and augment both cell- and antibody-mediated immune responses. The benefits of regular exercise on the immune system and other systems should persuade practitioners to suggest regular exercise to otherwise healthy older adults. Unfortunately, at this time, the mechanism(s) responsible for the beneficial effects on the aged immune system are unknown.

CLINICAL APPLICATIONS • Aging is associated with chronic, low-grade inflammation, a condition referred to as “inflammaging.” • “Inflammaging” is associated with increased morbidity and mortality among the aged • Aging-induced changes in the immune system, including reduced innate and adaptive immune response, is referred to immunosenescence. • Immunosenescence results in poor vaccine efficacy and defense against microbial infection. • Regular, moderate-intensity exercise training may improve both these age-associated conditions of inflammaging and immunosenescence. • While the mechanisms are largely unknown, exercise-induced changes in body fat, parasympathetic activity, and/or the gut microbiome may be responsible.

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X PA RT

Pulmonary Medicine Nicholas A. Smyrnios, MD, FACP, FCCP

571

47 CHAPTER

Respiratory Symptoms Jeremy B. Richards, MD and Richard M. Schwartzstein, MD

Key Points.................................................................................. 573 47.1 Introduction...................................................................... 573 47.2  Objective Assessment of Respiratory Symptoms............... 574 47.2.1  Objective Dyspnea Scales..................................... 574 47.2.2  Pulmonary Function Tests..................................... 574 47.2.2.1 Spirometry............................................. 574 47.2.2.2  Lung Volume Testing.............................. 575 47.2.2.3  Diffusion Limitation of Carbon Monoxide.... 575 47.2.2.4  Pulse Oximetry...................................... 575 47.3 Dyspnea........................................................................... 576 47.3.1 Definition.............................................................. 576 47.3.2  Physiology of Dyspnea.......................................... 576 47.3.3  Qualities of Dyspnea............................................. 577 47.3.4  Essentials of the History........................................ 578 47.3.4.1  Timing: Acute vs. Chronic Dyspnea......... 578 47.3.4.2  Timing: Night vs. Day............................. 579 47.3.4.3 Position.................................................. 579 47.3.5  Palliative Management.......................................... 580 47.4 Cough............................................................................... 580

KEY POINTS • Dyspnea is the result of a complicated, multisystem pathophysiology that results in the sensation of breathlessness. • Understanding the pathophysiologic mechanisms that result in dyspnea can guide the clinical evaluation and diagnostic testing in a patient with shortness of breath. • The history and physical exam are critical in identifying causes of dyspnea and guide the appropriateness and necessity of further diagnostic testing. • For patients with a clear chest X-ray and who do not smoke cigarettes or take an ACEI, upper airway cough syndrome (UACS), asthma, and GERD cause the majority of cases of chronic cough. • Wheezing is caused by turbulent flow due to narrowing of intra- and/or extrathoracic airways; intrathoracic airway narrowing results in expiratory wheezing, while extrathoracic narrowing causes inspiratory wheezing. • Apnea is defined as cessation of breathing for ≥10 seconds, and hypopnea is defined as a reduction of airflow for ≥10 seconds with a ≥4% decrease in oxygen saturation.

47.4.1  Definition and Physiology...................................... 580 47.4.2  Clinical Causes of Cough....................................... 581 47.4.3  Acute Cough......................................................... 581 47.4.4 Subacute and Chronic Cough with Clear Chest X-Ray��������������������������������������������������������� 581 47.4.5  Chronic Cough with an Abnormal Chest X-Ray...... 582 47.5 Hemoptysis....................................................................... 583 47.5.1  Definition and Physiology...................................... 583 47.5.2 Etiology................................................................. 583 47.6 Wheezing.......................................................................... 584 47.6.1  Definition and Physiology...................................... 584 47.6.2 Etiology................................................................. 584 47.7  Nocturnal Respiratory Symptoms: Snoring and Apnea....... 585 47.7.1  Definition and Physiology...................................... 585 47.7.2 Etiology................................................................. 585 47.7.3  Essentials of the History........................................ 586 47.8 Conclusion........................................................................ 587 Clinical Applications................................................................... 587 References................................................................................ 587

47.1 INTRODUCTION Shortness of breath, cough, and wheezing are among the most common symptoms experienced by patients seeking medical care. As in most areas of medicine, the evaluation of patients with respiratory symptoms largely depends on a comprehensive and insightful history obtained by the physician. Information offered spontaneously by patients is the starting point in the evaluation of any problem, but knowledge of the pathophysiology and differential diagnoses underlying the symptoms allow the physician to probe further, to determine which areas of the physical examination require special attention, and ultimately to narrow if not eliminate the radiographic and laboratory testing required to confirm the diagnosis. We must also remember that, as with pain, many patients do not spontaneously tell healthcare providers about breathing discomfort, and it is important to directly inquire about this symptom. Often there is confusion between respiratory symptoms and signs. For example, patients are described as being “short of breath” as part of the physical examination. In fact, symptoms can only be described by the patient. Physicians may speculate that a patient is experiencing respiratory discomfort based on observing physical signs such as recruitment of accessory muscles

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of ventilation, tachypnea, or an inability to speak in full sentences. Nevertheless, symptoms characterize what patients are experiencing and can only come from them. The timing of respiratory symptoms and conditions that precipitate or alleviate the discomfort can clarify the impact of the symptom on the patient. Understanding the “language of dyspnea,” developed from descriptive research of patients with a variety of respiratory diseases, can help clinicians understand the significance of their patients’ symptoms. This chapter focuses on the physiologic and clinical significance of several common respiratory symptoms. The clinical utility of quantitative dyspnea scales, the multidimensional nature of breathing discomfort, and the consequences of dyspnea are briefly discussed. The role for and utility of pulmonary function tests (PFTs) are briefly reviewed below, but a more complete description is beyond the scope of this discussion. Clinical and pathophysiologic details of specific disease states such as asthma and chronic obstructive pulmonary disease (COPD) will be addressed in other chapters. This chapter does cover how specific elements of the physical examination, in concert with reported symptoms, can narrow the differential diagnosis.

47.2 OBJECTIVE ASSESSMENT OF RESPIRATORY SYMPTOMS Respiratory symptoms can be due to a variety of pathophysiological processes involving disparate organ systems. A general understanding of the use of PFTs is helpful in developing a preliminary, physiologically based approach to respiratory symptoms. We will also comment briefly on some of the common pitfalls associated with the use of pulse oximetry.

47.2.1 Objective Dyspnea Scales There are several quantitative scoring systems designed to assess the severity and impact of dyspnea in patients with respiratory disease. Examples of such scales include the Medical Research Council (MRC) dyspnea questionnaire, the modified MRC (mMRC), the COPD assessment test (CAT), the oxygen cost diagram (OCD), the COPD Clinical Questionnaire (CCQ), the multidimensional dyspnea profile (MDP), and other scoring systems. These scales assess different components of the sensation of breathless.1,2 The scoring systems demonstrate relatively similar performance with regard to assessing symptom severity in clinical practice, such that one scale is not clearly superior to another.3 Assessing dyspnea severity using a quantitative scale can be useful to characterize baseline symptom burden, but following dyspnea scales in response to therapeutic interventions is of less certain clinical utility. 2 The majority of available dyspnea scales assess patientreported perceptions of functional disability attributable to dyspnea (e.g. MRC, mMRC, CAT) or more general perceptions of healthcare-associated quality of life attributed

to dyspnea (e.g. CCQ, OCD). As dyspnea manifests as a constellation of symptoms not solely defined by perceived functional limitation, multidimensional assessment using the MDP instrument has been increasingly used in clinical and research settings.4,5 MDP measurements, as compared to other objective dyspnea scales, have demonstrated adequate sensitivity to detect changes in symptoms of dyspnea over time. 2 In addition, the MDP gives us insight into the relationship between the sensations of breathing discomfort and the affective or emotional responses associated with this frequently debilitating symptom. Anxiety, fear, and frustration are commonly associated with certain types of dyspnea. 5 Quantitative dyspnea scales can be used for any patients with respiratory disease but may be of most use for patients with COPD as a component of determining the Global Initiative for Obstructive Lung Disease (GOLD) stage of disease severity, which has prognostic and therapeutic value for this patient population.6

47.2.2 Pulmonary Function Tests Pulmonary function testing refers to maneuvers in which spirometry, lung volumes, inspiratory and expiratory pressures, and/or diffusion limitation of carbon monoxide (DLCO) are measured. Confusion regarding PFTs arises from imprecise use of the term “pulmonary function tests” in clinical practice to refer to measurements of spirometry alone. It is more precise to consider PFTs to include spirometry, lung volume, and DLCO measurements. PFTs can provide objective data regarding a patient’s specific respiratory impairment and can provide important insight into the cause of respiratory symptoms. Not all respiratory symptoms are best assessed by PFTs, but several common symptoms are due to diseases that may be diagnosed by PFTs. For example, the diagnosis of COPD, which may affect between 4 and 10% of adults in the United States,7 is dependent on spirometric measurements. COPD is typically suspected based on clinical symptoms, but further evaluation by measuring spirometry confirms or excludes the actual diagnosis. When obtaining PFTs, a trained respiratory therapist or technologist can influence the quality of data obtained; the instructions, prompts, and encouragement provided to the patient prior to and during the test significantly affect the patient’s respiratory maneuvers. Normal values for PFTs are determined from predictive equations developed from large, descriptive studies and incorporate an individual patient’s age, gender, race and height.8

47.2.2.1 Spirometry Spirometry refers to measurements of the flow and volume generated when a patient performs a forced vital capacity (FVC) exhalation; these tests are critical for assessment of airway resistance. To perform a FVC exhalation, the patient takes in as big a breath as possible to completely fill the lungs with air (to total lung capacity or TLC), and then forcibly exhales as rapidly as possible until no more air can be emptied from the lungs (to the residual volume

47.2  Objective Assessment of Respiratory Symptoms  575

or RV). In addition to measuring the FVC, determining the volume of air the patient is able to exhale in one second (FEV1) is important in diagnosing obstructive airways diseases. If a patient has increased airways resistance and is unable to generate high flows from total lung capacity, the FEV1 relative to the FVC will be reduced. Patients may develop increased airways resistance due to airway narrowing from airway inflammation, mucus accumulation, and smooth muscle hypertrophy (e.g. as a consequence of chronic asthma) or from loss of tethering of the airways leading to airway collapse during active exhalation (e.g. COPD). Increased airways resistance causes obstruction of airflow during exhalation, which results in a decreased FEV1 out of proportion to the FVC. Therefore, the ratio of the FEV1 to the FVC (FEV1/FVC) will be reduced in such patients. In patients with severe airways resistance, expiratory time is insufficient to permit exhalation of a full vital capacity and RV may be elevated. An elevated RV is referred to as “air trapping.” Obstructive airways diseases are conditions that decrease the FEV1/FVC ratio. COPD and asthma are by far the most common causes of obstructive airways disease. Bronchiectasis, tracheobronchomalacia, and sarcoidosis are much less common causes. While a reduced FEV1, FVC, and a preserved (or increased) FEV1/FVC ratio suggest a restrictive pulmonary disease, lung volumes (particularly TLC) must be measured separately to confirm restrictive disease.

47.2.2.2 Lung Volume Testing Lung volumes may be measured by one of two methods. Plethysmography refers to measuring lung volumes based on the change of pressure and volume of a known quantity of air in a closed container (a so-called “body box”) to calculate lung volumes via Boyle’s Law. Helium dilution refers to the measurement of lung volumes based on the differential exhaled helium concentration and the helium concentration in a closed, external container. Since helium is an inert gas that does not cross the alveolar-capillary basement membrane, the concentration of helium after the gas has equilibrated between the patient’s lungs and the external container of helium provides a measurement of a patient’s lung volumes. This technique is used to measure functional residual capacity (FRC), or relaxation volume at the end of a passive exhalation. Once this volume is known, other volumes (TLC and RV) can be determined with spirometric determinants of the change in volume as the patient goes through various maneuvers. Helium dilution may underestimate lung volumes in patients with poor ventilation (e.g. patients with large bullae) or patients with global hypoventilation (e.g. patients with severe COPD and air trapping). A TLC measurement below 80% of predicted is consistent with restrictive disease. When FRC is greater than the predicted value, one should consider reduced elastic recoil of the lung as a potential cause, most commonly due to emphysema. Specifically, a TLC of >120% of predicted is consistent with hyperinflation. Gas-trapping and an elevated RV will commonly also be present in such patients.

47.2.2.3 Diffusion Limitation of Carbon Monoxide The DLCO measures the transfer of carbon monoxide (CO) across the alveolar-capillary basement membrane. DLCO is considered a surrogate for oxygen transfer across the basement membrane and into the circulation. A patient performs the DLCO maneuver by inhaling air with a small, known concentration of CO to TLC and holding his breath for 10 seconds to allow sufficient time for diffusion of CO into alveoli and for transfer of CO across the alveolar-capillary basement membrane. The amount of CO transferred into the blood stream is determined by the difference in the quantity of CO in inhaled air (which is known) minus the quantity of CO in exhaled air (which is measured). The severity of the reduction is expressed as the percent predicted. A DLCO between 60 and 79% of predicted is consistent with a mild reduction in DLCO, between 40 and 59% is a moderate reduction, and 5 apneas and/or hypopneas

per hour of sleep (the “apnea-hypopnea index” [AHI]). Polysomnography (i.e. a “sleep study”) must be performed to accurately measure the AHI. The clinical syndrome of OSA is the combination of an AHI of ≥5 with daytime symptoms due to chronic nocturnal hypoventilation. Daytime symptoms associated with the OSA syndrome include fatigue, somnolence, and morning headache. These symptoms are common even in patients without nocturnal hypoventilation, but clinical suspicion of OSA syndrome is increased in patients with concomitant obesity, snoring, and/or comorbid conditions such as hypertension, coronary artery disease, and cerebrovascular disease. Cognitive issues (specifically difficulty concentrating), erectile dysfunction, enuresis, and depression may also be associated with the OSA syndrome, due to end-organ damage from the systemic consequences of chronic nocturnal hypoventilation and cyclical hypoxemia. The severity of daytime somnolence can be assessed and quantified by the Epworth Sleepiness Scale (ESS).60 The ESS asks patients to rank their sleepiness in eight scenarios, such as “sitting quietly after a lunch without alcohol” or “in a car, while stopped for a few minutes in traffic” (see Table 47.10).60 Patients with a high score (≥9) have increased daytime sleepiness, but the ESS has not been validated as an independent predictor of the OSA syndrome. There are multiple pathophysiologic mechanisms in the OSA syndrome that account for the epidemiologic association between OSA and cardio- and cerebrovascular disease (see Table 47.11). Essential hypertension occurs in at least 50% of patients with the OSA syndrome.61 Congestive heart failure, arrhythmias, coronary artery disease, and myocardial infarction and cerebrovascular disease, including stroke, are all associated with and likely due to systemic physiologic derangements caused by OSA.62 The “obesity-hypoventilation syndrome” (OHS) is the combination of chronic hypoventilation with chronic hypercapnia and obesity. Right ventricular dysfunction, due to elevated pulmonary arterial pressures and left heart dysfunction, is commonly present in patients with OHS. Of note, certain cerebral pathologies, particularly abnormalities involving areas of non-voluntary respiratory control, may result in a rare condition called central sleep apnea syndrome. Central sleep apnea is not associated with obesity, while OSA and obesity are clearly directly correlated.

47.7.2 Etiology While snoring can be a normal finding, it may be associated with the OSA syndrome. As noted previously, extrathoracic airways, including the hypopharynx, are prone to collapse during inspiration due to the combination of positive atmospheric pressure outside the airway and negative intraluminal pressure during inspiration. Snoring is more likely to occur in obese patients, as the hypopharynx is already narrowed from increased soft tissue fat. Conditions that reduce the muscle tone of the surrounding tissue (e.g. alcohol, sedative agents) further increase the risk of hypopharyngeal obstruction and snoring. Rapid

47

586  Chapter 47  Respiratory Symptoms TABLE 47.10  Epworth sleepiness scale How likely are you to doze off or fall asleep in the following situations, in contrast to just feeling tired? This refers to your usual way of life in recent times. Even if you have not done some of these things recently try to work out how they would have affected you. Use the following scale to choose the most appropriate number for each situation: 0 = would never doze 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing Situation

Chance of Dozing

Sitting and reading Watching TV Sitting, inactive in a public place (e.g. a theater or a meeting) As a passenger in a car for an hour without a break Lying down to rest in the afternoon when circumstances permit Sitting and talking to someone Sitting quietly after a lunch without alcohol In a car, while stopped for a few minutes in the traffic

TABLE 47.11  Mechanisms of end-organ damage in the OSA syndrome Pathophysiologic mechanism

Systemic effects

End-organ consequences

Increased sympathetic tone due to apneas/ hypopneas

Increased systemic vascular resistance

Hypertension Cardiovascular disease Cerebrovascular disease

Increased systemic inflammation due to intermittent hypoxemia

Accelerated atherosclerosis

Coronary artery disease Cerebrovascular disease Peripheral vascular disease

Systemic oxidative stress due to cyclical hypoxemia and reoxygenation

Atherosclerotic changes Tissue ischemia

Cardiovascular disease Cerebrovascular disease

Endothelial dysfunction (uncertain mechanism)

Increased thrombogenesis

Coronary artery disease Cerebrovascular disease

eye movement (REM) sleep is associated with decreased muscle tone, and snoring occurs most commonly during this phase of sleep. The tongue is a major component of the anterior wall of the hypopharynx, and movement of the tongue can contribute to upper airway obstruction. When the tongue falls posteriorly, obstruction is worsened. Given the lack of bony support to maintain hypopharyngeal patency, intact glossal and pharyngeal muscle tone is necessary to keep the airway from collapsing. Patients who sleep in the supine position are more likely to snore or develop more severe obstruction because of the propensity of the tongue to be pulled posteriorly by gravity. Children with large tonsils or adenoids may present with snoring, although significant airway obstruction is unusual.

47.7.3 Essentials of the History Snoring, unlike many symptoms, is less likely to be reported by patients than by bed-partners. It may be

valuable to distinguish between nasal and mouth snoring, as nasal snoring is generally not considered indicative of a pathologic process. If possible, the physician should ascertain whether the patient has been observed to experience apneas, either central (when there is no evidence of airflow or chest wall movement) or obstructive (no airflow but preserved chest wall motion). Loud snoring or loud snorts (which may occur at the end of the obstructive episode) indicates intermittent airway obstructions. Additional questions are focused on daytime symptoms of the OSA syndrome as outlined above. The chronicity of snoring, changes in weight, and/ or drug and alcohol use are also important components of the history. For example, a middle-aged, non-obese woman whose snoring dates back to adolescence and who has otherwise been clinically well is likely to have a benign condition. Alternatively, a middle-aged man with a 20-pound weight gain over the last year and six months of snoring should be questioned about symptoms of the OSA syndrome. The definitive diagnosis of OSA requires the presence of associated daytime symptoms and an AHI of ≥5.

References  587

AHI can only be measured by formal polysomnography, which requires a patient to spend a night in a sleep laboratory. There is no role for PFTs or chest imaging in diagnosing OSA, but these studies may be helpful in searching for associated conditions.

47.8 CONCLUSION Respiratory symptoms are extremely common in clinical practice. As the lungs and upper airways have fairly limited ways to respond to pathologic changes, the challenge for clinicians is to understand the nuances of descriptions of the sensations and the sounds that patients report, and to ask probing questions that elicit these subtle distinctions. Understanding the physiology underlying respiratory symptoms can help a physician perform a focused yet thorough history and physical exam, determine what further testing is needed, and recommend targeted and effective interventions. Additionally, and importantly, having a better understanding of the physiology of respiratory

symptoms augments one’s intellectual enjoyment when caring for patients with these symptoms.

CLINICAL APPLICATIONS • Treatment of dyspnea is primarily dependent on treating the underlying disease process, but palliative interventions with both pharmacologic or non-pharmacologic interventions can provide symptomatic relief. • Cough, like dyspnea, is most effectively treated when the cause is found and treated specifically. • Hemoptysis is classified as massive (≥600cc of blood over 24 hours) or non-massive. • Snoring is of uncertain clinical significance, but a patient or bed-partner complaining of snoring should prompt questions regarding signs or symptoms of obstructive sleep apnea. • Obstructive sleep apnea syndrome is the combination of an AHI of >5 and symptoms of daytime somnolence and fatigue.

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48 CHAPTER

Asthma David E. Ciccolella, MD and Gilbert E. D’Alonzo, DO

Key Points.................................................................................. 589 48.1 Introduction...................................................................... 589 48.2  Clinical Features............................................................... 590 48.3 Pathophysiology............................................................... 590 48.3.1  Variable Airflow Obstruction.................................. 590 48.3.2  Airway Inflammation............................................. 590 48.3.3  Airway Hyperresponsiveness................................. 591 48.3.4 Management........................................................ 591 48.3.5  Monitoring Disease Activity................................... 592 48.4 Treatment......................................................................... 593 48.4.1  Environmental Control........................................... 593 48.4.2  Indoor Allergens.................................................... 594 48.4.3  Outdoor Allergens................................................. 594 48.5  Pharmacologic Therapy.................................................... 595 48.5.1  Chronic Controllers............................................... 595 48.5.2  Long-Acting Beta-2 Agonist.................................. 596 48.5.3  Long-Acting Muscarinic Antagonists..................... 596 48.5.4  Biologic Therapies................................................ 596 48.5.5 Omalizumab......................................................... 596 48.5.6 Mepolizumab........................................................ 597

KEY POINTS • Asthma is an inflammatory disease of the airways characterized by intermittent symptoms, including chest congestion, cough, and wheezing. These symptoms are associated with airway responsiveness and variable airflow obstruction. • Airway narrowing leading to increased airway resistance, and airflow obstruction in asthma occurs through three major mechanisms: • Airway smooth muscle contraction. • Increased airway lumen debris. • Airway wall thickening from inflammation, edema, and over time, fibrosis. • The goals of asthma therapy are as follows: • To prevent symptoms and help the patient achieve normal lung function and activity, especially during exercise. • To prevent exacerbation of asthma, no matter how mild. • To minimize the need for emergency department visits or hospitalizations.

48.5.7 Reslizumab......................................................... 597 48.5.8 Benralizumab..................................................... 597 48.5.9  Bronchial Thermoplasty...................................... 597 48.5.10  Quick-Relief Medications.................................... 598 48.6 Management of Asthma according to Severity and Control Classification........................................................ 598 48.6.1  Other Issues in Long-Term Asthma Management..... 600 48.6.2  Asthma Complications........................................ 600 48.6.3  Allergy Testing and Immunotherapy.................... 601 48.6.4  Exercise and Asthma.......................................... 602 48.6.5  Occupational Asthma.......................................... 603 48.6.6 Obesity............................................................... 604 48.6.7 Stress................................................................. 604 48.6.8  Food Hypersensitivity.......................................... 604 48.6.9  Medication-Induced Asthma............................... 604 48.6.10  Gastroesophageal Reflux.................................... 605 48.6.11  Pregnancy and Asthma....................................... 605 Clinical Applications................................................................... 606 References................................................................................ 606

• To meet patient and family expectations for asthma care. • To provide optimal pharmacotherapy with minimal adversity. • A comprehensive asthma management plan includes both environmental control and medication therapy.

48.1 INTRODUCTION Asthma is an inflammatory disease of the airways characterized by intermittent symptoms, including chest congestion, cough, and wheezing. These symptoms are associated with airway responsiveness and variable airflow obstruction. In 2016, approximately 20.4 million adults representing 8.3% of the population in the United States had asthma.1,2 Despite the constant development of new medications to treat asthma over the last decade, this disease remains a large burden to the healthcare system, accounting for up to 6.2% of physician outpatient visits and emergency department visits of 1.7 million. Asthma remains a

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frequent cause of absenteeism from both school and work. Most concerning is that approximately 3,615 deaths occurred in the United States in 2015, representing about 11 per million population. 3 The prevention and treatment of asthma are highly dependent upon a variety of interventions, both pharmacologic and non-pharmacologic. The daily habits and activities of patients with asthma play an important role in disease management and prevention. Minor alterations in lifestyle practices can make substantial differences in the long-term health of the asthmatic patient. This chapter focuses on the traditional asthma topics of pathogenesis, diagnosis, and treatment. In addition, the environmental issues important to asthma are discussed. Asthma symptom prevention and enhanced control of disease are stressed, and the effects of exercise, occupation, stress, and pregnancy on asthma are discussed.

48.2 CLINICAL FEATURES Clinical symptoms of asthma are dyspnea, cough, chest congestion and tightness, and noticeable wheezing. Milder cases of asthma may only be recognized by a cough, which is worse at night, or dyspnea during or following exertion. Many of the more severe attacks of asthma begin with some or all of the symptoms above occurring for several days before the patient seeks medical help; however, a minority of patients have a rapid onset of severe symptoms over just a few minutes or hours. Very severe attacks may lead to respiratory failure requiring tracheal intubation and mechanical ventilation to avoid death. An asthma patient may be able to identify a certain trigger that destabilizes his or her asthma. Often symptoms occur during exercise, viral infection, exposure to furry or feathered animals, or exposure to environments laden with dust, mold, smoke, or other noxious fumes or chemicals. Changes of weather, emotions such as laughing or crying, and menses may destabilize the asthmatic patient. There are certain patients who have attacks following the ingestion of aspirin or other medications. Eczema, hay fever, rose fever, or a family history of asthma is often associated with asthma, but their presence is not required for its diagnosis. The asthmatic will often have a normal physical examination when asthma is not active. However, when patients are having asthma symptoms the physical examination often reveals an increase in respiratory rate with a prolonged expiratory time and wheezing. On forced expiration, wheezing is accentuated and coughing generally occurs. During more severe asthma attacks, the patient will often use the accessory muscles of ventilation, their chest appears to be hyperinflated, and they may be diaphoretic and not able to speak in full sentences. These clinical features of asthma have been used to develop a clinical classification of asthma severity based on the frequency of these symptoms and nighttime awakenings, interference with activities, lung function impairment, and the frequency of exacerbations (Figure 48.1). 2

48.3 PATHOPHYSIOLOGY 48.3.1 Variable Airflow Obstruction Airway narrowing leading to increased airway resistance, and airflow obstruction in asthma occurs through three major mechanisms: • Airway smooth muscle contraction. • Increased airway lumen debris. • Airway wall thickening from inflammation, edema, and over time, fibrosis. 2 Damaged epithelial cells detach from the mucosal surface of the asthmatic airways. Airway wall thickening occurs in patients with persistent asthma resulting from an unimpeded inflammatory process. The effects of inflammation accumulate over time, leading to smooth muscle hypertrophy, epithelial basement membrane thickening, connective tissue deposition, and proliferation and hypertrophy of mucus-producing glands). All of these factors contribute to progressive airflow obstruction, which is further decreased by the presence of thick, tenacious mucus, ineffective mucociliary clearance, and edema in the walls of the bronchi, especially during an acute asthma exacerbation. Episodic smooth muscle contraction further leads to the variability of symptoms in asthma.

48.3.2 Airway Inflammation Multiple mechanisms produce airway inflammation, and they involve a variety of interactions between proinflammatory and inflammatory mediators. The asthmatic inflammatory cell matrix is made of eosinophils, activated T-helper type 2 lymphocytes, mast cells, neutrophils, macrophages (Figure 48.2). Both immune and nonimmune factors can activate the disease process. When an asthmatic is exposed to a specific activating allergen, the release of a variety of mediators occurs via high-affinity immunoglobulin E (IgE) receptors, which are found on bronchial mast cells, and low-affinity IgE receptors on macrophages and eosinophils. Lymphocytes control these processes. Both antibody-mediated and cell-mediated immune systems are involved. There are increased levels of pro-inflammatory cytokines such as IL-4, IL-5, IL-13. The chemical mediators from these activated cells can directly contract airway smooth muscle, stimulate mucus secretion, enhance vascular permeability, and result in airway edema, all of which contribute to airflow obstruction. Furthermore, some mediators actually attract other inflammatory cells and activate them, and these activated cells further damage the airway. Part of the inflammatory reaction causes a disruption of airway epithelial cell wall integrity, which allows increased permeability to inhaled allergens and other triggering substances and decreases mucociliary clearance of airway debris, enhances cholinergic-mediated airway hyperreactivity, and predisposes asthma patients to bacterial and viral infections. The loss of epithelial integrity exposes nerve endings, which

48.3  Pathophysiology 

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48

Figure 48.1  Classification of asthma severity. (Adapted from National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program: Expert Panel Report 3 [EPR 3]. Guidelines for the Diagnosis and Management of Asthma. NIH Publication no. 08-4051, Full Report 2007.)

partially explains the enhanced cholinergic-mediated airway hyperreactivity found in asthma. Inflammation can be acute or chronic. The acute inflammatory response involves early recruitment of cells to the airway. This is followed by an evolving inflammatory reaction, as recruited and resident cells are activated and produce a complex pattern of inflammation. Chronic inflammation can lead to permanent airway damage.

48.3.3 Airway Hyperresponsiveness Airway hyperresponsiveness is a hallmark of asthma. As depicted in Figure 48.2, airway inflammation induces airway hyperresponsiveness. This hyperresponsiveness, along with the inflammatory changes of the airways, contributes further to airflow obstruction. Certain triggers may not only activate but also propagate inflammation and drive airway responsiveness to a more severe state. The magnitude of airway hyperresponsiveness seems to correlate with the activity of airway inflammation. Furthermore, airway hyperresponsiveness seems to correlate with the clinical symptoms and signs of asthma.

Hyperresponsiveness is assessed by measuring airflow before and after the inhalation of increasing doses of inhaled methacholine or histamine 4 (Figure 48.3). Hyperresponsive airways will develop obstruction at lower cumulative doses of these chemicals than normal airways. This increased “twitchiness” of the airways is thought to protect the lungs from the detrimental effects of irritating inhalants. Airway hyperresponsiveness is not unique to asthma. Hyperresponsive airways are found in other airway inflammatory diseases, like chronic bronchitis and sarcoidosis. The treatment of asthma, by improving airway inflammation, does diminish airway responsiveness but may not eradicate airway responsiveness, suggesting that additional factors are involved.

48.3.4 Management The National Asthma Education and Prevention Program (NAEPP) 2007 Guidelines recommend a written asthma action plan for all asthmatics based on signs and symptoms, changes in PEFR, or both. 2 Written asthma action

592  Chapter 48  Asthma

48.3.5 Monitoring Disease Activity

Inflammatory Stimuli

Cell Activation/Mediator Release: Eosinophils Mast cells Macrophages T Lymphocytes

Neutrophils

Bronchial Epithelial Cells

Asthmatic Inflammation

Airway Hyperresponsiveness

Airway Obstruction

AsthmaSymptoms Figure 48.2  Steps involved in the asthmatic inflammatory cascade. These include the introduction of inflammatory stimuli to cell activation and mediator release, to asthmatic inflammation and bronchial hyperresponsiveness, and finally clinical asthma.

Dose-response curves of methacholine challenge 100 90

Percent FEV1

80 70 60 50 40

pre-challenge

Normal control PC22 - Provocation concentration producing 20% fall In FEV1 (A) (B)

Individuals with hyperactive airway disease

30 20 10 0

2.5 0.025 0.25 10.0 25.0 Melthacholine dose (mg/mL)

Figure 48.3  Asthmatics have hyperresponsive airways that are overly sensitive to immunologic or non-immunologic stimuli. Bronchial provocation testing can serve as a useful tool to measure the severity of bronchial hyperresponsiveness and helpful to confirm the diagnosis of asthma.

plans may be particularly helpful for those with poorly controlled asthma, moderate-to-severe persistent asthma, or a history of severe exacerbations. Action plans are useful in clarifying the roles of the medications and the medication plan, especially in less knowledgeable patients, and for adjusting treatment according to symptoms and peak flow as needed. The more chronic and severe the asthma, the greater is the importance of a written asthma action plan.

The goals of asthma therapy are as follows: (1) to prevent symptoms and help the patient achieve normal lung function and activity, especially during exercise; (2) to prevent exacerbation of asthma, no matter how mild, (3) to minimize the need for emergency department visits or hospitalizations; (4) to meet patient and family expectations for asthma care; and (5) to provide optimal pharmacotherapy with minimal adversity. 2 To ensure that these goals are met, periodic assessment and ongoing monitoring of asthma daytime and nocturnal symptoms, short-acting beta agonist use for symptom relief and symptom interference of daily activities, and measurement of airflow obstruction by spirometry and peak expiratory flow are recommended. 2 Both physician assessment and patient self-assessment are part of the asthma monitoring process. Measurements of airflow are known not to be strongly related to asthma symptoms but provide a more objective and additional measure to evaluate asthma control. Spirometry is recommended at least every one to two years and especially at initial assessment, after treatment has stabilized symptoms and peak flow, and during progressive or prolonged worsening of asthma. 2,5 The patient performs spirometry by taking a deep breath and forcefully exhaling air from the lungs through a spirometer until all airflow has ceased.6,7 As shown in Figure 48.4, airflow obstruction is shown by a decrease in the forced expiratory volumes, the forced vital capacity (FVC), and the forced expiratory volume in one second (FEV1) and a decreased FEV1/FVC ratio. The main factors for determining normal ranges for these parameters are age, height, and gender. Abnormalities in these parameters are typically based on the appropriate reference population using 95% confidence intervals and not fixed values for the normal range. The FEV1 is the most important airflow measurement, and usually, the asthmatic has a reduction in the FEV1. These measurements are generally taken before and after a bronchodilator. The asthmatic typically shows significant improvement in these airflows following a beta-2 agonist treatment, indicating reversible airways disease. This is determined by an increase in either FVC or FEV1 by 12% or more and having a minimum absolute change of 200 mL pre-/ post-bronchodilator in the same parameter. The asthmatic can also measure airflow from large airways as peak expiratory flow rate (PEFR) in L/min at home on a daily basis, using one of the multiple available handheld plastic Peak Flow meters. The patient should determine a personal best PEFR using the highest of three measurements on the same peak flow meter when they are optimal. Peak flow monitoring can be considered in asthmatics who have a history of frequent or severe exacerbations, who are poor perceivers of airflow obstruction or worsening asthma, or who have moderate or severe persistent asthma. 2 The airflow obstruction of asthma waxes and wanes with variations in the degree of inflammation and smooth muscle constriction. With these changes, there are alterations in FEV1 and PEFR (Figure 48.4). There are variable needs for the use of medication to relieve symptoms.

48.4  Treatment  9

Post Bronchodilator

5

8

Flow (L/s)

Volume (L)

Post Bronchodilator

7

4 3

Pre Bronchodilator

2

593

Pre FEV1 2.71 L Post FEV1 3.07 L (13% increase)

Pre FEV1 2.71 L Post FEV1 3.07 L (13% increase)

6 5

Pre Bronchodilator

4 3 2

1

1 0

0

1

2

3

4

5 6 Time (s)

7

8

9

10

0

0

1

2

3

4

5

Volume (L)

Figure 48.4  Spirometry pre-/post-bronchodilator in the asthmatic. Administration of an inhaled bronchodilator improves airflow significantly. The left panel depicts the volume-time curve and shows improvement in FEV1. The right panel shows the flowvolume curve and improvement in peak expiratory flow over exhaled lung volume. The dependent portion of the curve is also curvilinear (not straight) consistent with airflow obstruction.

As the asthmatic becomes better controlled with therapeutic interventions, overall airflow improves, variability in airflow decreases, and the need for short-acting beta-2 agonist medication to relieve symptoms substantially decreases, leading to an overall improvement in quality of life. This translates into better sleep at night and improved resistance to asthma exacerbation during exposure to environmental challenges such as exercise or cigarette smoke. It is important to teach patients to recognize symptom patterns that indicate inadequate asthma control. Spirometry and peak flow both measure asthma control based on the degree of airflow obstruction, but it would be helpful to have (more directly measured) biomarkers of airway inflammation, such as quantifying eosinophils in expectorated sputum and measured fraction of exhaled nitric oxide (FENO).8 Sputum quantification for eosinophilia obtained by either spontaneous or hypertonic saline has limited utility for the diagnosis of asthma because other illnesses may have sputum eosinophilia, and some asthmatics may have a non-eosinophilic pattern. However, it may be helpful for monitoring or guiding treatment in adults.9 The presence of sputum eosinophilia during tapering of inhaled steroids or oral steroids is associated with an increased risk for asthma exacerbation.10 Accordingly, treatment of asthma guided by percent of sputum eosinophils has been shown to reduce exacerbations.11 However, the use of sputum eosinophil counts and clinical parameters to guide therapy in severe asthmatics is recommended only in specialized centers experienced in this technique.12,13 Nitric oxide is produced by inflammatory cells and other cells in the airway. The fraction of exhaled nitric oxide, which is easily measured even with handheld devices, correlates with eosinophilia and is elevated in non-smokers with eosinophilic asthma but also in other illnesses such as allergic rhinitis, eosinophilic bronchitis, and hypersensitivity pneumonitis.9 In adult asthmatics, unlike in children and young adults, FENO-guided treatment did not show a reduction in exacerbations as

compared to guideline-based treatment.13,14 Accordingly, the International ERS/ATS guidelines 2014 for severe asthma do not recommend using FENO for guiding therapy in adults, more so because of increased cost with an uncertain benefit.12 In summary, currently minimally invasive biomarkers sputum eosinophil count-guided and FENO-guided therapies are not recommended for the routine management of the typical asthmatic, and further studies are needed to better define who will benefit from these types of monitoring.9,12

48.4 TREATMENT 48.4.1 Environmental Control Environmental control measures, such as allergen avoidance, should always be included in asthma management strategies. 2 Generally, a comprehensive approach to control of allergen or irritant exposure is needed since single measures for avoidance of allergens is not effective. Exposure of asthma patients to certain irritants or allergens increases asthma symptoms and often precipitates exacerbations. As a team, the physician and patient should do try to identify those allergens and irritants causing asthma symptoms. The common inhalant allergens that are known to cause asthma exacerbations are animal allergens; house dust mites; cockroaches; indoor and outdoor fungi; and outdoor plant allergens such as tree, grass, and weed pollens. The NAEPP guidelines 2007 recommend environmental control at each step and have a questionnaire to help determine environmental factors and other factors that worsen asthma symptoms. 2,15 A history of likely sensitivity to seasonal allergens from the questionnaire and positive skin testing or allergen immunoassay IgE blood testing to assess the sensitivity to perennial allergens can be helpful in identifying these allergens.15 Generally, seasonal allergens in early spring are trees; late spring, grasses; late summer to autumn,

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weeds; summer and fall, Alternaria, Cladosporium, mites; and in cold months in temperate climates, animal dander. 2 Allergy skin or allergen immunoassay for allergen-specific IgE blood testing is the only way to reliably determine sensitivity to year-round indoor allergens. Certain environmental exposure rules should be followed. If an asthmatic knows what irritants, foods, or allergens destabilize his or her disease, they should avoid these exposures. Exposure to tobacco smoke should be avoided.16,17 Asthmatic patients should avoid beta-blocker therapies, if possible, but these do have an established benefit in cardiovascular disease and should be utilized on an individual basis.18,19 Asthmatics should avoid foods and drinks that contain sulfite preservatives such as shrimp, dried fruit, processed potatoes, sauerkraut, beer, and wine, which can cause exacerbations in a small percentage of asthmatics.10 Aspirin and other non-steroidal anti-inflammatory agents should be avoided, especially by patients who have nasal polyps.21,22 Finally, rhinosinusitis and gastroesophageal reflux, which have been implicated as asthma destabilizers, should be controlled.23,24

48.4.2 Indoor Allergens Perhaps the most important step in controlling allergeninduced asthma is to reduce exposure to relevant indoor and outdoor allergens. Major indoor allergens that are of particular importance are animal pet dander, dust mites, mold, mice, and cockroaches. All warm-blooded pets can cause allergic reactions. Although of unproven effectiveness, if there are pets in the patient’s home and the patient is sensitive to that animal, then the patient should be encouraged to remove the animal from the house but to keep in mind that it can be months for allergen levels to decrease. 2 Otherwise, we would encourage keeping the animal out of the bedroom by keeping the bedroom door closed, and if possible depending on expense, remove any carpets and cloth-covered furniture from the home. The bedroom should be kept clean and all air ducts that lead into it should be covered with a filter. 25 House dust mite allergen is a major environmental factor in asthma. 2 House dust mites are universal in areas of high humidity, which include most of the United States. In addition to high humidity, mites depend upon human dander for survival. Dust mites thrive in mattresses, pillows, carpets, upholstered furniture, and soft toys. In patients who are house dust mite sensitive and demonstrate a clinical picture consistent with allergy to the mite allergens, there are a variety of desirable control measures that should be considered. 2 Mattresses and pillows should be encased in allergen-impermeable covers. The sheets and blankets on the patient’s bed should be washed weekly in hot water, which must be >130˚F to kill mites. Indoor humidity should be maintained at less than 50%, and carpets, upholstered furniture, and stuffed animals should be removed from the area. Although there are a variety of chemical agents available for killing mites and denaturing the antigens, they are not as effective as the environmental control measures described earlier.

Molds are fungi which proliferate in humid environments, especially homes that have dampness problems. Creating a drier environment by fixing old water leaks and eliminating water sources reduces mold growth. Reducing indoor humidity to less than 50% substantially limits mold growth. If cockroach infestation is present in the home, it is very important to institute chemical control measures to reduce this antigen load. 2 Asthma severity seems to increase with increasing levels of cockroach antigen. Food should be kept out of bedrooms, and food and garbage should be kept in closed containers. When chemical agents are used to control infestation, the home should be well ventilated and the patient should not return to the home until the odor has substantially dissipated. A variety of measures can be taken to reduce allergens in the home by modifying indoor air. Vacuuming carpets twice a week, preferably with a vacuum loaded with a high-efficiency particulate air filter; can reduce house dust accumulation, but the patient should not be in the room when the vacuuming is occurring. Air-conditioning and the use of a dehumidifier are helpful. Humidifiers and evaporative coolers are not recommended for use around dust mite-sensitive patients with asthma. Indoor air cleaning devices should not substitute for the measures previously described. High- particulate air filters and electrostatic precipitating filters have been shown to reduce certain animal dander, mold spores, and the particulates from tobacco smoke. However; these devices do not have an impact on house dust mite and cockroach allergens, which are heavy particulates and do not remain airborne, and thus are not affected by air filtering.

48.4.3 Outdoor Allergens A variety of tree, grass, and weed pollens and seasonal spores contribute to the outdoor allergen loads that affect many asthmatic patients. By staying indoors with windows closed, generally in an air-conditioned environment, patients with outdoor allergen problems can be relatively protected. Pollen and spore counts are highest during the midday and afternoon, at periods of brightest sunlight. For the asthmatic who has a significant outdoor allergen problem, conducting outdoor activity shortly after sunrise or before sunset can result in a reduced pollen exposure. Allergen immunotherapy can be helpful in certain allergic asthmatic patients. 2,27,28 According to the NAEPP Expert Panel Report 3, subcutaneous immunotherapy can be considered for patients who have prominent allergies, as with allergic rhinoconjunctivitis, and who have mild to moderate persistent asthma (steps 2 to 4). 2,13 However, it is preferable to have clear evidence of a relationship between asthma symptoms and exposure to the allergen in question. Finally, symptoms should be nearly perennial and difficult to control with pharmacotherapy alone. The whole concept of allergen immunotherapy is under constant debate, in terms of long-term benefit. If allergen immunotherapy is started, it should be given under the careful guidance of a well-trained immunotherapist who is capable of treating any life-threatening reaction

48.5  Pharmacologic Therapy 

that may occur. 29 The immunotherapy should be directed at a single or only a very few antigens. There is a paucity of data support for use of multiple-allergen mixes. The responses to therapy may be specific to the allergen extracts and regimens used and it has been recommended to use those allergen extracts shown to have efficacy in clinical trials.13 Finally, the optimal duration of allergen therapy is not clear but typically is three to five years, and a recognizable favorable improvement in asthma should occur early in treatment.

48.5 PHARMACOLOGIC THERAPY The pharmacologic treatment of asthma includes two broad categories of drugs: bronchodilators that relax airway smooth tissues and anti-inflammatory drugs that reduce the influx of inflammatory cells and the release of chemical mediators from these cells. Bronchodilators include short- and long-acting beta-2 receptor agonists (beta agonists), methylxanthines, and anticholinergics. Anti-inflammatory agents include glucocorticoids, cromolyn, leukotriene blockers, omalizumab, and anti-IL-5 monoclonal antibodies. In the chronic management of asthma, pharmacologic therapy is given by the oral or inhalation route, but inhalation therapy seems to be the preferred because of the higher concentration of medication directly delivered to the lungs, often with greater efficacy and lower risk of adverse effects.30 The inhalation of medication can be performed through a small-volume nebulizer or a metereddose inhaler. An inhaler is sometimes attached to a tube spacer device, in order to reduce certain oropharyngeal adverse effects and, for some patients, enhance aerosol drug delivery into the lungs. 2 Medications are characterized into two general treatment classes: long-term control medications, which are used to achieve and maintain control of chronic asthma, and quick-relief medications, or relievers, which treat acute symptoms during an asthma exacerbation (Table 48.1). 31 The most effective medications for long-term controller therapy are those that have clearly demonstrated antiinflammatory effects. The U.S. National Asthma Education and Prevention Program (NAEPP 2007) Guidelines for Asthma recommend the use of these medications for asthmatics based on severity using a step therapy approach from 1–6. There are also more recently updated Global Initiative for Asthma guidelines in 2018 (GINA 2018) which use step therapy from 1–5.

48.5.1 Chronic Controllers Corticosteroids are the most potent and effective antiinflammatory medications available for the management of asthma. The inhaled form of medication from a metered-dose inhaler is used for the long-term control of asthma. Systemic corticosteroids, administered orally, are used to gain control of asthma following a period of destabilization and are avoided for long-term control.

595

TABLE 48.1  Long-term control and quick-relief therapies for asthma Long-term control

Quick-relief

Inhaled Corticosteroids

Short-acting beta-2 agonists

Cromolyn

Systemic Corticosteroids

Leukotriene Modifiers

Ipratropium bromide

Long-Acting Bronchodilators • Long-acting beta-2 agonists • Theophylline • Tiotropium Systemic Corticosteroids   Anti-IgE Therapy • Omalizumab   Anti-IL-5 Ab and –IL-5-Receptor Ab • Mepolizumab • Reslizumab • Benralizumab* Immunotherapy * IL-5 Receptor Ab.

However, some patients with severe chronic disease may require systemic corticosteroid therapy on a regular basis. Corticosteroids reduce airway inflammation and airway hyperresponsiveness.32–35 Glucocorticoids also prevent asthmatic exacerbations and bronchial wall remodeling, known to occur with chronic inflammation and to be responsible for the development of fixed airflow obstruction later in life. There are many different products and delivery devices for the administration of inhaled corticosteroids, and their inhalation doses vary. 2 The lowest daily dose of an inhaled corticosteroid should be used in order to control the disease. Leukotriene receptor blockers and synthesis inhibitors are another group of anti-inflammatory agents. These are oral therapies that block or inhibit the production of leukotrienes, which are by-products of the arachidonic acidmetabolic pathways and are potent bronchoconstrictors and inflammatory stimulants in humans.36 Leukotrienes are released from a variety of inflammatory cells, such as lymphocytes, eosinophils, and mast cells, and not only induce bronchoconstriction but increase vascular permeability, mucous secretion, and other inflammatory cells. When these additional cells enter the airway, they are activated and release other powerful chemicals that propagate the inflammatory state even further. 36 There are three agents currently being used in the United States; they are montelukast and zafirlukast (which are leukotriene receptor blockers) and zileuton, a 5-lipoxygenase inhibitor. Zileuton acts earlier in the arachidonic acid/leukotriene pathway and could have greater effects. Zileuton is taken twice a day and requires liver function monitoring. Leukotriene-pathway agents improve lung function, diminish asthma symptoms, and reduce the need for the use of short-acting inhaled rescue beta agonists.37–40 Their efficacy has been shown in patients with

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mild to moderate asthma and the improvements seen are modest in nature when compared to inhaled corticosteroid therapy (but some studies show no difference).41,42 These agents have been shown to reduce bronchoconstriction caused by exercise, aspirin, and inhaled allergen exposure. 38,43–46 Theophylline, a methylxanthine compound, acts as a modest bronchodilator and may also improve asthma through certain anti-inflammatory effects and reductions in bronchial reactivity.47,48 When theophylline is administered in a sustained-release oral therapy form, it has a long duration of action and can further control asthma when used in combination with inhaled corticosteroid therapy.49,50 However, theophylline is rarely used in asthma treatment because it has a narrow therapeutic margin of safety, multiple medication interactions, and weak bronchodilating effect which has placed it as a third-line controller therapy for chronic asthma. Some patients may adhere better to an oral regimen than an inhaler administered regimen. For each patient using theophylline, the dose would be titrated to a therapeutic level, but more importantly, to minimize the potential for drug toxicity. The target level for theophylline has been recommended to be approximately 5–15 mg per liter. 2,51,52 Theophylline levels may be affected by several factors, including smoking, which decrease the level, and medical conditions that increase the level, such as heart failure, cor pulmonale, cirrhosis, hypoxia, hypothyroidism, febrile illness, pregnancy. Levels can also be affected by the addition of drugs inhibiting metabolism (clarithromycin, ciprofloxacin) or the removal of drugs increasing metabolism (rifampin, phenobarbital, phenytoin, carbamazepine). After the patient is on a stable dose of theophylline, drug levels should be checked at least once a year provided that the patient remains stable and has no changes in health or other medications.

48.5.2 Long-Acting Beta-2 Agonist In addition to anti-inflammatory therapy, long-acting inhaled beta agonist (LABA) is used as add-on controller therapy to inhaled corticosteroids. Patients with moderate-to-severe asthma generally require at least two or three controller medications to optimize their pharmacologic therapy. 2 Inhaled beta-agonists, which are more selective for the beta-2 receptor, are preferred. Long-acting beta agonist inhalers can have a duration of action of at least 12 hours, far longer than that of the short-acting beta agonists that are needed by inhalation for the acute control of symptoms. 53

48.5.3 Long-Acting Muscarinic Antagonists Tiotropium is an example of the long-acting muscarinic antagonist class of medication. The standard dose of 2.5 mcg is delivered by mist inhaler and approved in the United States for the maintenance treatment of asthma. In the GINA 2018 guidelines, Tiotropium is currently included as an optional addition for patients who have persistent symptoms or exacerbations not well controlled

with inhaled corticosteroids and LABA despite adequate inhaler technique, medication compliance, and other controller options.13 It moderately improves lung function and moderately increases time to severe exacerbation requiring corticosteroids. 54,55 However, if the patient is using a short-acting beta-2 agonist several times a day, then stopping the LABA should be considered. In a metaanalysis in 2018, the addition of a LAMA to inhaled steroids resulted in lower asthma exacerbations but was no different than a LABA. 56 However, triple therapy (inhaled steroids+LABA+LAMA) did not further reduce exacerbations, but spirometry was improved compared to inhaled steroids and LABA. 56

48.5.4 Biologic Therapies Patients who continue to have asthma symptoms that are not controlled despite high-dose inhaled corticosteroids in addition to one or more non-corticosteroid controller medications may be candidates for injectable biologic monoclonal antibody therapies such as anti-Immunoglobulin E(anti-IgE) (e.g., omalizumab), or anti-interleukin5(anti-IL-5) agents such as mepolizumab, reslizumab, and benralizumab.

48.5.5 Omalizumab Omalizumab is a subcutaneously injected recombinant humanized monoclonal IgG antibody that binds to circulating IgE antibody that is used for the treatment of patients with moderate-to-severe persistent allergic asthma and sensitivity to perennial allergens such as dust mites, animal dander, cockroaches, or molds. 57–60 Other controller medications such as corticosteroids do not inhibit IgE production. Recommendations from the NAEPP 2007 guidelines, however, consider omalizumab for perennial allergen-associated severe persistent asthmatics, in steps 5 (inadequately controlled on highdose inhaled corticosteroids and LABAs) or 6 (requiring oral corticosteroids on a daily or alternate day basis). 2 The injectable medication is a recombinant humanized monoclonal IgG antibody that binds to IgE antibody. Omalizumab prevents IgE binding to high-affinity receptors on mast cells, basophils, and other cells, and leads to decreased mediator release from these cells. 2 Patients on omalizumab have been able to reduce the dose of their inhaled steroids and frequency of exacerbations, including those requiring hospitalization. 57,61–68 However, in patients already on therapy for asthma, omalizumab does not improve spirometry, that is FEV1.60,68 There is also little to no effect on bronchial hyperresponsiveness, but it does decrease some airway inflammatory markers.62,63,69,70 In a recent multicenter “real life” retrospective study in severe allergic asthmatics, response to omalizumab as measured by improvement in symptoms and a >40% reduction in exacerbation rate suggested that omalizumab may be similarly effective in patients with high (>300) or low eosinophil (60% of predicted since more severe asthmatics were excluded from the sham-controlled trial.13,86 Although bronchial thermoplasty may be of benefit in certain severe asthmatics, further studies are needed on the long-term efficacy and safety of bronchial thermoplasty in other severe asthma populations.13 The European Respiratory Society/American Thoracic Society (ERS/ATS) 2014 Task Force on severe asthma recommends that bronchial thermoplasty be done in an IRB-approved registry or clinical study.12

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48.5.10 Quick-Relief Medications In order to achieve immediate relief of bronchoconstriction and the discomforting symptoms associated with asthma, quick-relief medications, such as fast-acting/short-acting beta-2 agonists and anticholinergics are employed. Shortacting beta-2 agonists relax airway smooth muscle within minutes and improve airflow. These agents are the drugs of choice for treating acute asthma symptoms and exacerbations. 2 They are also used for preventing exercise-induced bronchospasm. 2 Inhaled anticholinergic therapy, such as ipratropium bromide, can also be used as a bronchodilator in this setting, but a beta agonist should be used first. Ipratropium bromide may provide some additional benefit during a moderate-to-severe asthma exacerbation and it may also be considered as an alternative for those who absolutely cannot tolerate beta agonists. 2 Systemic corticosteroid therapy can speed the resolution of airflow obstruction and reduce the rate of relapse of treated severe asthma. 2 Therefore, systemic corticosteroid therapy is used in more serious asthma exacerbations as part of the quick-relief medical plan. Because short-acting beta-2 agonist therapy like albuterol should only be used for the symptomatic relief of asthma, the use of this medication can also serve as a marker of asthma stability. The more albuterol necessary to control symptoms, the greater the airway

inflammation that is present, and the stronger is the need for optimization of inhaled anti-inflammatory therapy. Using a short-acting beta-2 agonist inhaler at the rate of one or more canisters per month has been associated with an increase in asthma morbidity and mortality.87 Seventy to 80% of chronic asthma patients in this country should be able to be controlled to a level of mild episodic asthma. Mild episodic asthmatics have two or fewer mild asthmatic attacks a week. Therefore, if more than four puffs of a short-acting beta agonist are used weekly, then enhanced asthma control is necessary. A well-controlled asthmatic should only need one or two canisters of a short-acting beta-2 agonist per year, not counting the therapy that would be used to prevent exercise-induced bronchospasm.

48.6 MANAGEMENT OF ASTHMA ACCORDING TO SEVERITY AND CONTROL CLASSIFICATION As shown in Figure 48.5 a stepwise approach has been proposed for the pharmacologic therapy of asthma. 2 The amount and frequency of medication are dictated by asthma severity in those patients not currently on

Figure 48.5  Stepwise approach for managing asthma. Abbreviations: EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist; LTRA, leukotriene receptor antagonist; SABA, inhaled short-acting beta2agonist. § Theophylline is less desirable due to need to monitor serum concentration levels. ‡‡ Zileuton is less desirable because of limited studies and need for liver function monitoring. §§ Before oral corticosteroids are introduced, a trial of high-dose ICS + LABA + either LTRA, theophylline, or zileuton. (Adapted from: Asthma Care Quick Reference, National Heart, Lung and Blood Institute. National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR 3). Guidelines for the Diagnosis and Management of Asthma. NIH Publication no. no. 12-5075, Revised September 2012.)

48.6  Management of Asthma according to Severity and Control Classification   599

medication (Figures 48.1 and 48.5). The level of severity is determined by assessment of both impairment and risk components. 2 According to the Expert Panel 3, the level of severity is based on the most severe impairment or risk category. The components of impairment based on the last two to four weeks include symptom frequency, medication use (short-acting beta agonist), and lung function measurement by spirometry. The risk assessment includes frequency of exacerbations of asthma requiring systemic corticosteroids over the last year. However, there is not enough information to correlate the frequency (specific number of exacerbations) and severity of exacerbations with the various step classification levels of asthma severity. The guidelines suggest that patients with a risk component of two or more exacerbations per year would be considered as having persistent asthma despite impairment levels that would not indicate this degree of severity. Once the severity level is assessed, the suggested step level of therapy can be determined (Figure 48.5). Therapy is directed toward treating airway inflammation. Therefore, controller therapies are emphasized, with anti-inflammatory therapy considered the mainstay.

Patients should be evaluated within at least two to six weeks after starting therapy. Once the patient returns for a follow-up appointment or for a patient already on longterm controller therapy, the asthma control is assessed to adjust the current therapy (Figure 48.6). Determination or measurement of asthma control is based on impairment and risk components. 2 According to the NAEPP guidelines Expert Panel Report 3, the level of control is based on the most severe impairment or risk category. The components of impairment include symptom frequency, medication use (short-acting beta agonist), and lung function measurement by either FEV1 or peak flow. The impairment component is based on the last two to four weeks, and if a longer period, it is recommended to use an overall assessment by the patient as to whether their asthma is better or worse. There are also validated questionnaires that can be used to assess impairment, but these do not assess the lung function component or even risk category. The three validated questionnaires include the Asthma Therapy Assessment Questionnaire (ATAQ), Asthma Control Questionnaire (ACQ), and the Asthma Control Test (ACT). The ACT can be administered quickly, and

Figure 48.6  Classification of asthma control. Adapted from National Heart, Lung and Blood Institute. National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR 3). Guidelines for the Diagnosis and Management of Asthma. NIH Publication no. 08-4051, Full Report 2007.

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the score is based on the answers to five questions assessing symptoms, interference with activities, and beta agonist use over the past four weeks.88 Based on these parameters, asthma control is determined to be well controlled, not well controlled, or very poorly controlled. After control has been achieved, then therapy is reduced or stepped down. Step-down therapy (Figure 48.5) is essential if one is to identify the minimum medication necessary to maintain disease control. During this process, it is helpful that airflow is monitored and correlated with asthma symptoms and signs and the intermittent use of an inhaled short-acting beta-2 agonist. Patients may relapse if inhaled corticosteroids are completely discontinued. Patients with intermittent symptoms are treated with a beta-2 agonist, which has a quick onset and short duration of action. Albuterol by metered-dose inhaler or nebulizer, used on an as-needed basis, is the quick-relief therapy of choice, but other medications can be used. 2 However, when any one of these medications is being used on more than two occasions per week for the relief of asthma, then the patient no longer has episodic asthma and must be classified as having a more persistent form of asthma. Persistent asthma is most effectively controlled with the daily long-term use of a controller medication. The clinician must treat each individual patient, paying attention to the needs and circumstances of the patient in his or her stepwise treatment process. In order to initially gain disease control, it is often necessary to initiate anti-inflammatory therapy at a more aggressive level than that required in the long run by the patient’s actual clinical disease severity. 2 This often helps establish quicker control, and then therapy can be reduced. Many times a short course of systemic corticosteroid therapy is used to gain control, along with a reasonable, perhaps more intermediate, daily dose of inhaled corticosteroids. Once asthma is controlled, oral therapy is quickly reduced and stopped. Within a brief period of time, inhaled corticosteroid may even be reduced to a lower daily dose. With reduced inflammation, asthma symptoms and signs should improve, PEFR should increase, the variability in airflow over each 24-hour time period should decrease, and finally, the dependency on the rescue use of inhaled albuterol should decrease. Enhanced control should eliminate nocturnal awakenings and activity limitation. Most patients with moderate-to-severe chronic asthma require not only a higher daily dose of inhaled corticosteroid therapy but a second- or third-line controller medication. These medications include the preferred long-acting inhaled beta agonist like salmeterol or formoterol, or alternatively a leukotriene modifier or perhaps a sustained-release theophylline. However, before going to daily doses of an oral corticosteroid at step 6, you may consider a trial of high-dose inhaled corticosteroids, a long-acting beta-2 agonist, and either a leukotriene modifier or sustained-release theophylline to enhance disease control, thereby improving the asthmatic’s overall quality of life. A long-acting beta-2 agonist or theophylline may be especially helpful in controlling nocturnal breakthrough symptoms.89 Based on established guidelines, patients at step 5 or 6 may also be candidates for biological agents. The most severe persistent asthmatics may also require continuous systemic steroid therapy.

This group of patients should see an asthma specialist on a regular basis. With regular follow-up visits, the clinician may be able to reduce inhaled corticosteroid therapy by 25% every three months until an optimal daily dose is achieved and disease control is maintained. A chronic asthmatic who is completely withdrawn from inhaled corticosteroid therapy often relapses.90 Therefore, there should be an excellent reason why inhaled corticosteroid therapy or other anti-inflammatory controller therapy is completely discontinued. If the asthma is not well controlled, then the following factors must be considered before increasing therapy:

1. Patient medication adherence and inhaler technique should be checked on the initial visit and then periodically based on the clinician’s evaluation of patient skill and understanding. 2. Environmental control issues must be carefully reviewed for adherence and technique (See discussion above). 3. Review of the following comorbid conditions: Allergic bronchopulmonary aspergillosis, GE reflux, smoking, obesity, obstructive sleep apnea, rhinosinusitis, paradoxical vocal cord dysfunction, and chronic stress or depression.

48.6.1 Other Issues in Long-Term Asthma Management To enhance compliance with anti-inflammatory medication regimen, it is often helpful to patients to try to integrate the medication frequency into their lifestyle or their ability to adhere to the regimen. For patients who are uncontrolled or even controlled on their current regimen, it is important to determine if they are taking their medication as prescribed, especially inhaled corticosteroids, because it is not uncommon to find that patients dosed on a twice-daily regimen will remember their morning dose but tend to forget their evening dose. This may also depend on their work schedule, whether they work days, evenings, or nights. To improve patient adherence to their inhaled corticosteroid dose regimen, it may be better to determine if it is easier for the patient to take the medication (e.g., inhaled corticosteroids) all in the morning or evening instead of two divided doses (Table 48.2).

48.6.2 Asthma Complications Complications from asthma can occur acutely or chronically. An acute asthmatic attack is associated with a variety of complications, including pneumothorax, pneumomediastinum, a variety of cardiac arrhythmias, lung atelectasis, and respiratory failure. Rarely, death can occur. The young and the elderly are at particular risk for death because the severity of their disease is either not appreciated or is ignored. Asthma death can be sudden in onset, possibly associated with laryngospasm. However, most asthmatic deaths are slow in evolution to the point

48.6  Management of Asthma according to Severity and Control Classification   601 TABLE 48.2  Referral to asthma specialist for consultation or co-management

1. Patient has had a life-threatening asthma exacerbation. 2. Patient has needed more than two bursts of oral corticosteroids in one year or required hospitalization. 3. Patient is not meeting the goals of asthma therapy after three to six months of treatment or is unresponsive to therapy. 4. Diagnosis unclear 5. Conditions complicating asthma or its diagnosis (e.g., sinusitis, nasal polyps, aspergillosis, severe rhinitis, VCD, GERD, COPD, psychosocial problems). 6. Further diagnostic studies needed) is needed (e.g., allergy skin testing, rhinoscopy, complete pulmonary function studies, provocative challenge, bronchoscopy). 7. Consideration for immunotherapy. 8. Patient requires step 4 care or higher, or even consider referral for step 3 care. 9. Patient education and guidance on complications of therapy, problems with adherence or allergen avoidance. 10. Confirmation of possible occupational or environmental inhalant or ingested substance contributing to asthma. Adapted from National Heart, Lung and Blood Institute. National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR 3). Guidelines for the Diagnosis and Management of Asthma. NIH Publication no. 08-4051, Full Report 2007.

TABLE 48.3  Factors associated with increased risk of asthma exacerbations or mortality

1. Severe airflow obstruction, as detected by spirometry 2. Two or more ED visits or hospitalizations for asthma in the past year; past intubation or ICU admission, especially in past five years 3. Patients feeling in danger or frightened by their asthma 4. Patient characteristics: female, nonwhite, nonuse of ICS therapy, and current smoking 5. Psychosocial factors: depression increased stress, socioeconomic factors 6. Attitudes and beliefs about taking medications

Adapted from National Heart, Lung and Blood Institute. National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR 3). Guidelines for the Diagnosis and Management of Asthma. NIH Publication no. 08-4051, Full Report 2007.

at which respiratory failure occurs, as a multitude of metabolic problems develop.91 Table 48.3 shows the factors that have been implicated in asthma exacerbation and mortality. With poorly controlled asthma over a long period of time, irreversible airflow obstruction develops.92,93 Recurrent airway infection is associated with fixed airflow obstruction.94 In a few patients, allergic bronchopulmonary aspergillosis occurs, often with mucoid airway impaction and secondary bacterial infection. Allergic bronchopulmonary aspergillosis associated with asthma is characterized by episodes of severe recurrent asthmatic exacerbations.95 Fever can be associated with this condition, as can chest pain, and mucus impaction causes transient infiltrates to develop on the chest x-ray, usually in the upper lung fields. Associated blood eosinophilia and an increased serum IgE level are associated with allergic bronchopulmonary aspergillosis, but a positive skin prick test and serum precipitating antibodies to the fungus Aspergillus fumigatus are confirmatory for this particular form of chronic asthma. This condition generally requires high doses of inhaled corticosteroids each day, often with oral corticosteroid therapy.

48.6.3 Allergy Testing and Immunotherapy The discovery of IgE as the antibody responsible for allergic reactions has led to the development of certain allergy immunoassay blood tests that can measure the amount of allergen-specific IgE.15 Obtaining a total IgE is not useful for determining the absence or presence of allergy due to the large variation and does not tell you the specific allergen. Allergy skin testing is less expensive and more

sensitive than allergy immunoassay tests, often providing results within one hour. There are two types of skin tests. The epicutaneous test is the main skin test for evaluating allergy and is often referred to as the scratch or prick technique. Also, there is an intracutaneous or intradermal test. These skin tests are generally easy to perform and cause little patient discomfort. The results are dependent in part on the use of standardized extracts and the expertise of the tester. When the skin test is positive, the patient can see the positive skin test, which encourages patient compliance with environmental control measures. Measurement by allergy immunoassay does not require expertise in technique for the ordering physician; no allergen extracts are necessary; there is no risk of an allergic systemic reaction; and an allergy immunoassay can be performed on patients who are taking medications that often suppress the skin test reaction (e.g., antihistamines, montelukast, prednisone, and tricyclic antidepressants). A positive allergy test, however, does not indicate that the allergy is causing the patient’s symptoms. However, when a positive result is found with skin testing or allergy immunoassay, the clinician is obliged to look for clinical significance of the positive allergy test in the context of the patient’s medical history. If this relationship is clear, the allergen cannot be avoided, and symptoms are difficult to control with pharmacologic therapy (NAEPP 2007 steps 2–4, mild to moderate persistent asthma), then immunotherapy can be considered.2 Evidence is strongest for house dust mites, animal dander, and pollens.2 However, immunotherapy should not be used until environmental control has been maximized. Allergen immunotherapy should be administered by a physician in the office or the hospital where facilities are available to treat the serious adverse

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reactions that can occur as a result of this form of therapy.96 It is better to use immunotherapy for a single allergen—the more allergens that are being treated for, the higher the incidence of failure.2 Although multiple-allergen mixes are used for immunotherapy, only a few studies clearly support this practice.97 Allergy immunotherapy is typically administered for three to five years. There are controlled studies and a meta-analysis that support the use of immunotherapy in the treatment of asthma and that do show some benefit for asthma symptoms, bronchial reactivity, and reduced medication use. 2,98–100 Immunotherapy is felt to reduce not only the frequency of symptoms but the extent of symptoms and to minimize the need for bronchodilator medications in the control of asthma. Immunotherapy is most effective for some types of seasonal pollens (tree, grass, weed) and house dust mites, with some success in pet allergy, particularly cat in controlled studies.98–100 Immunotherapy is not a cure but may reduce asthma and allergic rhinitis symptoms and signs. The success of immunotherapy is dependent upon identifying the correct allergens. There are certain risks associated with immunotherapy.96 The most common reaction to an allergy shot is swelling, erythema, and pruritus at the site of the injection. This type of a reaction is usually short-lived and can be minimized by using topical anti-inflammatory therapy in the form of a cream or an oral antihistamine. The most serious reaction from an allergy shot is anaphylaxis. Anaphylaxis can occur quickly after the injection. Therefore, immunotherapy should be performed in the presence of a physician experienced in treating anaphylaxis. Sufficient time should be allowed for the reaction to occur if it will develop, so most patients have to stay in a physician’s office for a period of 15 to 30 minutes after each injection so anaphylaxis can be treated. Less serious reactions include nasal congestion and sneezing, asthma itself, difficulty swallowing and talking because of a swollen tongue or larynx, and lightheadedness. With these reactions, there is often an increase in heart rate and perhaps even a slight change in blood pressure.

48.6.4 Exercise and Asthma Exercise-induced asthma (EIA) or bronchoconstriction (EIB) is a transient airway narrowing and airflow obstruction that occurs during or after exercise.4,101 Nearly 90% of persistent asthmatics have ElB, and patients with allergic rhinitis and even normal relatives of asthmatics can demonstrate this phenomenon. As with asthma, the common symptoms are a cough, wheezing, chest tightness, shortness of breath, and what the patient describes as an inability to take in a full breath of air during or following exercise. Symptoms start several minutes after exercise has stopped and usually improve within one hour, even without medication. The airflow decline is seen between five and 20 minutes after exercise and resolves in about 60 minutes. EIB can seriously and adversely affect athletic performance if not recognized and controlled. EIB is thought to be associated with the exchange of heat and water that occurs in the airways during exercise

in which minute ventilation is increased. The main factors affecting the severity of EIB during exercise are the amount of minute ventilation attained and sustained as well as the inspired air-water content and temperature. Because of the high minute ventilation, there is a cooling and drying effect on the airway that somehow influences airway inflammation in a way that expresses itself more intensely.4,101,102 During exercise, the airways cool down as minute ventilation increases. This cooling and drying effect of the airways sets the stage also for rapid rewarming of the airways that occurs with resting. The high-flow ventilation may dry the surfaces of the airways and cause an increase in osmolarity, which may trigger the release of inflammatory mediators. Effective control of chronic asthma includes the control of asthma during and following exercise. It is realistic to believe that if chronic asthma is controlled, patients can participate in exertional, even athletic, activities at a reasonable level to maintain body conditioning and enjoy themselves. This is important because the lifestyle changes of reduced exercise may increase the risk of asthma.103 There are certain interventions that should be followed to control exercise-induced bronchospasm. Exercise-induced bronchospasm can be diagnosed simply for many patients. After an exercise challenge (e.g., running one mile at a moderate pace) airflow is measured sequentially at 5, 15, and 30 minutes. The patient with EIA often has a fall in airflow within this time period. When airflow falls, especially when associated with symptoms consistent with asthma, the diagnosis can be made. This evaluation can be done by a physician or under the guidance of a physician by instructed individuals such as trainers or coaches. Patients who are known to have asthma should be screened for EIB breakthrough. Also, individuals who may be at high risk for EIB should be screened. We have found that as many as 14% of high-performance athletes will have bronchial hyperresponsiveness, including bronchoconstriction associated with exertion. There is also a substantial rate of unrecognized EIB among urban varsity athletes. In one study, it was reported that during screening for asthma and EIB, approximately 10% of 238 students had a history of treated asthma and that another 9% had unrecognized EIB during screening. This suggests that active screening for EIB, especially for students residing in poverty areas, may be indicated.104 The prevention and control of EIB can be accomplished by both non-pharmacologic and pharmacologic approaches. For some athletes, it is important to choose a sport that does not require sustained exercise, perhaps baseball, golf, or even weightlifting. When exercise is performed, it is good to avoid cold, dry environments. However, in cases when exercise is performed in colder environments, a mask or scarf covering the mouth may help reduce exercise-induced bronchospasm.105 A warm (but not too warm) and moist environment can often be helpful in minimizing EIB. Finally, it is not only the type of sport that one plays but the position selected. For example, a football lineman is at less risk than a running back. The use of an extended warm-up session and special breathing techniques that help minimize hyperventilation and promote relaxation can be helpful. There are some reports that a warm-up period before exercise results in a

48.6  Management of Asthma according to Severity and Control Classification   603

refractory period or reduction in EIB in more than 50% of individuals for up to two hours.102,106,107 The athlete should begin warming up slowly to loosen the muscles and elevate the heart rate. With the beginning of a light sweat, the patient can perform the exercise at or close to his or her maximum exertion for up to five minutes and then take a rest. More accomplished athletes can continue this warm-up process recurrently for 30 to 40 minutes. Another strategy is to do brief bouts of exercise for two to three minutes followed by three to five minutes of rest. These repetitive exertional challenges should occur over a 30- or 40-minute period. It is important for the individual athlete to find out which warm-up protocol works best for him or her. Just as important as warming up appropriately is concentrating on breathing maneuvers during and following exercise. Symptoms can be reduced by breathing warm, humid air rather than cold, dry air. Therefore, swimmers are likely to tolerate their disease better than football players. Certain athletes have learned to breathe through their nose instead of their mouth. This is a difficult technique to master. When athletes learn how to breathe through their nose, especially during periods where heavy breathing is unnecessary, the air that is brought into their lungs is humidified and heated. By breathing deeper and more slowly, the cooling and drying effect of the hyperventilation phenomena can be minimized. The post-exercise period is also very important. The cool-down phase after a workout or competition should consist of taking deep, slow breaths. Cooling down in a warmer environment, but not too warm, can be helpful. Often, drug therapy is necessary to prevent EIB. There are numerous inhaled beta agonist medications that can be used shortly before, during, or even after exercise to prevent or relieve asthma symptoms.2 Beta agonists administered by inhalation will prevent EIB in more than 80% of patients. Administering a short-acting inhaled beta agonist such as albuterol approximately 15 to 30 minutes before exercise provides protection for two to three hours. When asthma breaks through, these medications can be safely administered by a metered-dose inhaler. The inhaled longacting beta-2 agonists (formoterol, salmeterol) can be helpful for controlling the frequent need for short-acting beta-2 agonists. Salmeterol has been shown to prevent EIB for 10 to 20 hours and is valuable for prolonged prevention when the athlete will re-expose himself or herself to the exercise challenge over this time period.108 Long-acting beta-2 agonists should not be used alone as daily prophylaxis of EIB, as the duration of effect is reduced and may be masking suboptimally controlled asthma.2 Other therapies can be used in addition to the beta agonist. If available, inhaled cromolyn can be taken approximately 30 minutes to 1 hour prior to exercise, often in addition to the preexercise use of the short-acting inhaled beta agonist for further control in those patients who fail single preventative therapy.109 Administered in a single dose at least two hours before exercise, the leukotriene receptor antagonists can decrease EIB in more than half of patients for a period of 12 hours or more.2,110 Most EIB occurs in the chronic asthmatic, making control of chronic asthma with inhaled corticosteroids, leukotriene receptor antagonists and long-acting beta

agonists crucial. Inhaled corticosteroids can decrease airway responsiveness over the long term and decrease EIB. When chronic asthma is controlled, the frequency and severity of EIB are reduced.111

48.6.5 Occupational Asthma It has been estimated that occupational factors account for approximately 9–15% of cases of asthma in adults of working age, including new onset or recurrent disease.112 A variety of substances in the workplace have been implicated in the development of asthma, including a large variety of animal proteins, flour and grain dust, wood dust, cotton dust, chemical compounds such as isocyanates and hydrides, metal salts, and even pharmaceuticals.112 The workers most commonly reported for occupational asthma include paint sprayers, bakers and pastry makers, animal handlers, nurses, chemical workers, welders, food processing workers, and timber workers.112 The causes of occupational asthma can be grouped into immunologic and non-immunologic (e.g., smoke, aerosols, fumes) causative agents. Up to 90% of cases have been of the immunologic type. Some causative agents can produce occupational asthma through both immunologic and non-immunologic mechanisms, such as toluene diisocyanate resulting from airway damage and sensitization. The immunologic agents can be divided into high- and low- molecular weight substances (Table 48.4). The high-molecular-weight agents are complete sensitizing agents, while the low-molecular-weight agents need to combine with a protein to form a sensitizing agent. The high-molecular-weight agents are usually mediated through IgE. TABLE 48.4  Select causes of allergic and non-allergic occupational asthma Allergic High-Molecular-Weight Substance

Occupations

Animal Protein

Laboratory workers

Papain

Brewers, lens workers

Wheat Flour

Bakers, millers

Trypsin

Plastic/pharmaceutical workers

Soybean dust

Farmers, food workers

Vegetable Gums

Printers, food workers

Low-Molecular-Weight Substance  Platinum

Jewelers, refiners

  Trimellitic anhydride

Plastic and epoxy resin workers

  Phthalic anhydride

Plastic and epoxy resin workers

Non-Allergic Isocyanates

Spray painters, foundry workers

Polyvinylchloride

Meat wrappers

Western Red Cedar

Carpenters

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It is extremely important to recognize occupational asthma as soon as possible because the likelihood of complete resolution of symptoms decreases over time. 2 Occupational asthma is suspected when either the patient or the clinician realizes that there is a relationship between asthma symptoms and work exposure. There is often a time delay between exposure to the offending agent and the development of symptoms of occupational asthma. Many times, the patient will improve on the days that he or she is away from the workplace, particularly during vacations. Sometimes, coworkers have similar symptoms, and sometimes asthma can occur during the night. Serial peak flow measurements at work and away from work can help diagnose occupational asthma.112 There are also some allergens available, which are not well standardized, for skin prick testing or blood tests for specific IgE for highmolecular weight agents but only a few for low-molecular-weight agents. Occupational asthma can usually be diagnosed without using specific bronchial provocation testing. although occasionally a specific bronchial provocation challenge, done in a specialized laboratory with a suspected allergen or irritant from the workplace, can be helpful.112 The management of occupational asthma can be difficult, and the patient may have to be referred to an occupational asthma specialist. Diagnosing patients early and avoiding further exposure to the causative agent will give the worker the best opportunity for a complete recovery. Often, the employee must avoid the triggering substance. If impossible, the employee should be moved to an area of low or occasional exposure with increased health monitoring. The use of respiratory protection by wearing a ventilator mask can be helpful. Many times, the patient must completely avoid exposure to the irritating agent; therefore, a new job position may be necessary. The outcome of any intervention for patients with confirmed occupational asthma depends on factors such as age and the type of agent.112 Unfortunately, some patients will have persistent asthma despite the removal of the inciting substance. A variety of chemicals, dust, and other particulates can sensitize the airways and induce chronic asthma.113 This is different than allergen- or irritantinduced asthma, in which these substances aggravate preexisting asthma but do not actually initiate the disease process. A single high-intensity exposure to a nonimmunologic irritant can produce the syndrome known as reactive airways dysfunction syndrome (RADS), in which asthma-like symptoms occur in minutes and may last for years.

48.6.6 Obesity Asthma is more common and more difficult to control in obese patients.13,114 Some obese patients with asthma have prominent respiratory symptoms and little eosinophilic inflammation. These symptoms need to be distinguished from those of obese patients who have respiratory symptoms due to deconditioning, chest restriction, and obstructive sleep apnea.13,114 Because of the potential contributors to dyspnea and wheeze in obese patients, it is important to confirm the diagnosis of asthma with objective

measurement of variable airflow obstruction. There are various strategies for weight reduction. However, as part of a lifestyle change, the addition of exercise twice a week or a weight loss program in obese asthmatics can improve asthma control, pulmonary function, and inflammatory markers.115

48.6.7 Stress Asthma is not a psychosomatic illness. However, there is emerging evidence that stress plays an important role in precipitating asthma exacerbation and may act as a risk factor for the increased prevalence of this disease.116 Since emotional upset does contribute to the asthma symptom picture, a variety of psychological interventions may be necessary to enhance overall asthma care. In some cases, a patient may need help to distinguish asthma flares and panic attacks. Stress exacerbation of asthma may involve enhanced generation of pro-inflammatory cytokines, but more importantly, psychosocial factors associated with stress influence the asthmatic’s personal sphere and often lead to a poor outcome.117 Conflict that develops between the patient, the family, and the medical staff often interferes with appropriate asthma care. It is true that the poorly controlled chronic asthmatic can despair, and his or her disease can have a significant negative effect on personal relationships, family life, and self-image. Enhanced asthma control, and careful discussion of these issues with the patient and family, can help the overall asthma care process. The asthmatic who needs psychosocial assistance should take advantage of appropriate professional counseling with a psychologist, psychiatrist, social worker, or other licensed practitioner. 2 There are a variety of psychologically oriented approaches to asthma care that can be helpful, including family counseling, educational seminars, and even psychotherapy. Ignoring one’s asthma symptoms and neglecting to use medication can seriously adversely affect overall asthma control. Asthma education is associated with enhanced confidence in the patient’s management of chronic asthma. 2

48.6.8 Food Hypersensitivity Food allergens may rarely precipitate asthma symptoms alone but more commonly are associated with extrapulmonary involvement such as skin and gastrointestinal signs and symptoms. 2,118

48.6.9 Medication-Induced Asthma The ingestion of aspirin in sensitive individuals may result in nasal congestion, eye irritation, facial flushing, and an asthma exacerbation, which usually occurs rapidly after ingestion, often within 30 minutes.119 Approximately 4–20% of asthmatics are sensitive to aspirin and related compounds, especially non-steroidal anti-inflammatory agents.120,121 Severe and even fatal asthma exacerbations have been associated with aspirin ingestion. Adult patients with severe persistent asthma who have nasal polyps should be carefully instructed not to use any aspirin or aspirin-like

48.6  Management of Asthma according to Severity and Control Classification   605

medication. Some safe alternatives to aspirin to consider include salsalate and acetaminophen celecoxib, but highly sensitive patients may even react to these.2,21,122,123 Nasal polyposis and chronic rhinosinusitis occur in nearly 90% of patients with aspirin sensitivity (Samter’s syndrome).124 The prevalence of aspirin sensitivity increases with age and the severity of the asthma. There is no known familial predilection to aspirin sensitivity. It is not known to be associated with atopy. The mechanism seems to be related to altered arachidonic metabolism and to inhibition of the enzyme cyclo-oxygenase (COX-1), in which arachidonic acid metabolites are passed through the leukotriene pathway resulting in increased production of the leukotrienes C4, D4, and E4 (the slow reacting substance of anaphylaxis).126 Therefore, medications that interfere with leukotriene synthesis or leukotriene receptor antagonists are helpful in the management of aspirin-induced asthma. Patients are treated according to asthma guidelines, but usually, a leukotriene modifying agent is added, which may also diminish nasal symptoms.43,44,126 The treatment of aspirin-induced asthma also includes either avoiding all NSAIDs that inhibit COX-1 enzyme or performing aspirin desensitization and maintaining daily aspirin therapy.2 Tartrazine or yellow food dye No. 5 can induce asthma symptoms in some individuals. This food coloring is found in a number of foods and in some medications. Beta blockers, including a variety of eye drop preparations, can induce asthma symptoms and should be avoided in asthmatic patients. 2,127,128 The more cardioselective agents may be better tolerated by the asthmatic, but in order to be safe, an asthmatic should avoid beta-blocker therapy, unless this form of medication is unavoidable for the cardiac or ophthalmologic condition.129 The NAEPP Asthma Guidelines 2007 suggest avoiding non-selective beta blockers. 2 However, many patients who have mild to moderate airflow obstruction are able to tolerate selective beta blockers, and the NAEPP guidelines recommend using them only after careful consideration in patients with cardiac disorders. 2 Fortunately, there are satisfactory alternatives to beta blockers for most of these patients.

48.6.10 Gastroesophageal Reflux Gastroesophageal (GE) reflux results from some of the acidic liquid contents of the stomach being regurgitated into the esophagus. This fluid substance is irritating to the esophagus. The GE reflux material does not have to be aspirated into the lungs to induce asthma. Reflux of the acidic fluid into the esophagus likely destabilizes asthma by enhancing the cholinergic autonomic nervous system influence or microaspiration, or both. GE reflux should be suspected in patients with poorly controlled asthma, particularly those who have nocturnal symptom breakthroughs. 2 Reflux symptoms do not have to be present, which makes the diagnosis difficult. However, when GE reflux is symptomatic, patients usually complain of “heartburn” or sometimes note food regurgitated into the throat. 2 A patient who has a hiatal hernia is at particular risk for GE reflux. Treatment of patients with symptomatic GE reflux has been associated with improvement in some aspects

of their asthma.130,131 If GE reflux symptoms are present, medical management includes (1) avoidance of eating food and drinking liquids within three hours prior to bedtime; (2) sleeping with the head of the bed elevated by using six- to eight-inch blocks; (3) eating smaller, and if necessary, more frequent meals; (4) using appropriate pharmacologic therapy such as H2 receptor blockers or proton pump inhibitors; (5) cessation of alcohol, cigarettes, and caffeinated foods. 2 Also, theophylline can reduce the lower esophageal sphincter tone and predispose the asthmatic to GE reflux. Patients, especially with nocturnal symptoms and/or regurgitation, are more likely to show improvement in their asthma with treatment. 2,132 However, studies have indicated that treatment of asthmatics without GE reflux symptoms did not improve their asthma.133 If the medical management as described above fails or the patient has other disturbing symptoms, then further evaluation by a gastroenterologist and other treatment options should be considered. Some patients may have further diagnostic interventions like an esophago-gastroduodenoscopy, and others may have to be referred to a surgeon for evaluation.

48.6.11 Pregnancy and Asthma Asthma is the most common medical condition during pregnancy occurring in 4–8% of pregnant women.134 The risk of asthma exacerbation during pregnancy is higher for women especially in the second trimester.13,135 As a general rule, one-third of all pregnant asthma patients improve, one-third remain the same, and one-third have worsening disease during pregnancy. 2,13,136 Whatever way the asthma changes during the first pregnancy, it is likely that similar symptoms will occur with subsequent pregnancies. Patients with more severe and difficult-tocontrol asthma generally have worse symptoms during pregnancy. It is important for every asthma patient who becomes pregnant to be carefully managed medically during obstetrical care. Asthma may also have an effect on pregnancy complications.137 Uncontrolled asthma is a risk for the fetus. One large study showed that asthmatic patients had an increased risk of infant mortality, preterm birth, and low birth weight infants than non-asthmatics.137 Those with more severe asthma have a higher risk of complications.137 However, this study did not find an increased risk of congenital defects.137 A mother whose asthma is well controlled and free of complications imposes no additional risk to the fetus. The goals of asthma treatment during pregnancy are to prevent acute exacerbations and to optimize lung function, which should provide maximum benefit to the health of the mother and the fetus. 2,138 If asthma medications are necessary during pregnancy, one must keep in mind the benefit of keeping asthma under control against the small potential risk for adverse effects from the asthma medications during pregnancy. The majority of asthma medications that are used in practice present little to no risk during pregnancy, although prospective well-designed and well-controlled clinical trials do not exist for most

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medications that are used during pregnancy.139 In one study, inhaled corticosteroids, beta-2 agonists, theophylline, or montelukast were not associated with an increased frequency of fetal abnormalities.13,139 For prescription drug labeling, the U.S. FDA has had a five-category medication classification system (A-D and X) related to their potential for adverse effects on pregnancy but recently has begun to phase it out and replace it with a requirement for information from human and animal studies on known possible maternal or fetal risks, medication dose adjustments, and risk/benefit considerations. These medication classifications are based on animal and human data and also risk-benefit. The best category is A, but there are no asthma medications in this group. Both systemic and inhaled corticosteroids can be used during pregnancy. The inhaled steroid budesonide has long been listed as category B and preferred during pregnancy because of the large amount of safety data obtained from the medical birth registry in Sweden. 2 However, patients who are doing well on other inhaled corticosteroids could be continued. Inhaled beta agonist therapy with albuterol, which has the most safety data during human pregnancy, should be used for symptom breakthrough. 2 During pregnancy, the leukotriene inhibitors montelukast, and zafirlukast are not preferred therapy for mild persistent asthma. The Merck Pregnancy Registry, although small and unpublished, has not shown an increase in perinatal complications. Allergy immunotherapy can be continued through pregnancy but should not

be altered. Furthermore, allergen immunotherapy should not be started during pregnancy. Inhaled therapy should be selected over systemic therapies during pregnancy. Over-the-counter medications should be avoided. The obstetrician and primary care physician should work together to create the safest treatment regimen for the pregnant asthmatic patient. When questions arise, the local asthma expert, generally an allergist or pulmonary specialist, should be consulted.

CLINICAL APPLICATIONS • Asthma is diagnosed by identifying reversible airflow obstruction, either at baseline or in response to a bronchoprovocation challenge test, that is consistent with the clinical syndrome. • Mild asthmatics may be managed with an occasional dose of a short-acting bronchodilator, although persistent asthma almost always requires an anti-inflammatory controller medication. • Exercise-induced bronchospasm is present in most asthmatics and can be treated or prevented with a variety of agents. • Certain special features such as occupation, stress, obesity, gastroesophageal reflux, medications, and pregnancy can make asthma more difficult to control and should be looked for and managed in parallel with asthma.

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106. Edmunds AT, Tooley M, Godfrey S. The refractory period after exercise-induced asthma: Its duration and relation to the severity of exercise. Am Rev Respir Dis. 1978;117:247–254. 107. de Bisschop C, Guenard H, Desnot P, et al. Reduction of exercise-induced asthma in children by short, repeated warm ups. Br J Sports Med. 1999;33:100–104. 108. Kemp JP, Dockhorn RJ, Busse WW, et al. Prolonged effect of inhaled salmeterol against exercise-induced bronchospasm. Am J Respir Crit Care Med. 1994;150:1612–1615. 109. Spooner CH, Spooner GR, Rowe BH. Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction. Cochrane Database Syst Rev. 2003;(4):CD002307. 110. Philip G, Villaran C, Pearlman DS, et al. Protection against exercise-induced bronchoconstriction two hours after a single oral dose of montelukast. J Asthma. 2007;44:213–217. 111. Vathenen AS, Knox AJ, Wisniewski A, et al. Effect of inhaled budesonide on bronchial reactivity to histamine, exercise, and eucapnic dry air hyperventilation in patients with asthma. Thorax. 1991;46:811–816. 112. Nicholson PJ, Cullinan P, Taylor AJ, et al. Evidence based guidelines for the prevention, identification, and management of occupational asthma. Occup Environ Med. 2005;62:290–299. 113. Pisati G, Baruffini A, Zedda S. Toluene diisocyanate induced asthma: Outcome according to persistence or cessation of exposure. Br J Ind Med. 1993;50:60–64. 114. Boulet LP. Asthma and obesity. Clin Exp Allergy. 2013;43:8–21. 115. Freitas PD, Ferreira PG, Silva AG, et al. The role of exercise in a weight-loss program on clinical control in obese adults with asthma. A randomized controlled trial. Am J Respir Crit Care Med. 2017;195:32–42. 116. Wright RJ. Epidemiology of stress and asthma: From constricting communities and fragile families to epigenetics. Immunol Allergy Clin North Am. 2011;31:19–39. 117. Busse WW, Kiecolt-Glaser JK, Coe C, et al. NHLBI Workshop summary. Stress and asthma. Am J Respir Crit Care Med. 1995;151:249–252. 118. Sampson HA. 9Food allergy. J Allergy Clin Immunol. 2003;111:S540–7. 119. Pleskow WW, Stevenson DD, Mathison DA, et al. Aspirin-sensitive rhinosinusitis/ asthma: Spectrum of adverse reactions to aspirin. J Allergy Clin Immunol. 1983;71:574–579. 120. Jenkins C, Costello J, Hodge L. Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ. 2004;328:434. 121. Hedman J, Kaprio J, Poussa T, et al. Prevalence of asthma, aspirin intolerance, nasal polyposis and chronic obstructive pulmonary disease in a population-based study. Int J Epidemiol. 1999;28:717–722. 122. Gyllfors P, Bochenek G, Overholt J, et al. Biochemical and clinical evidence that aspirin-intolerant asthmatic subjects tolerate the cyclooxygenase 2-selective analgetic drug celecoxib. J Allergy Clin Immunol. 2003;111:1116–1121. 123. Settipane RA, Schrank PJ, Simon RA, et al. Prevalence of cross-sensitivity with

References  609 acetaminophen in aspirin-sensitive asthmatic subjects. J Allergy Clin Immunol. 1995;96:480–485. 124. Samter M, Beers RF, Jr. Intolerance to aspirin. Clinical studies and consideration of its pathogenesis. Ann Intern Med. 1968;68:975–983. 125. Szczeklik A. The cyclooxygenase theory of aspirin-induced asthma. Eur Respir J. 1990;3:588–593. 126. Dahlen B, Nizankowska E, Szczeklik A, et al. Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional therapy in aspirin-intolerant asthmatics. Am J Respir Crit Care Med. 1998;157:1187–1194. 127. Odeh M, Oliven A, Bassan H. Timolol eyedrop-induced fatal bronchospasm in an asthmatic patient. J Fam Pract. 1991;32:97–98. 128. Schoene RB, Abuan T, Ward RL, et al. Effects of topical betaxolol, timolol, and placebo on pulmonary function in asthmatic bronchitis. Am J Ophthalmol. 1984;97:86–92. 129. Dunn TL, Gerber MJ, Shen AS, et al. The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in

asthmatic subjects. Am Rev Respir Dis. 1986;133:264–268. 130. Littner MR, Leung FW, Ballard ED,2nd, et al. Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms. Chest. 2005;128:1128–1135. 131. Kiljander TO, Junghard O, Beckman O, et al. Effect of esomeprazole 40 mg once or twice daily on asthma: A randomized, placebo-controlled study. Am J Respir Crit Care Med. 2010;181:1042–1048. 132. McCallister JW, Parsons JP, Mastronarde JG. The relationship between gastroesophageal reflux and asthma: An update. Ther Adv Respir Dis. 2011;5:143–150. 133. American Lung Association Asthma Clinical Research Centers, Mastronarde JG, Anthonisen NR, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009;360:1487–1499. 134. Kwon HL, Belanger K, Bracken MB. Asthma prevalence among pregnant and childbearing-aged women in the United States: Estimates from national

health surveys. Ann Epidemiol. 2003;13:317–324. 135. Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during pregnancy: Incidence and association with adverse pregnancy outcomes. Thorax. 2006;61:169–176. 136. G luck JC, Gluck PA. The effect of pregnancy on the course of asthma. Immunol Allergy Clin North Am. 2006;26:63–80. 137. Kallen B, Rydhstroem H, Aberg A. Asthma during pregnancy—A population based study. Eur J Epidemiol. 2000;16:167–171. 138. National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program Asthma and Pregnancy Working Group. NAEPP expert panel report. Managing asthma during pregnancy: Recommendations for pharmacologic treatment-2004 update. J Allergy Clin Immunol. 2005;115:34–46. 139. Lim A, Stewart K, Konig K, et al. Systematic review of the safety of regular preventive asthma medications during pregnancy. Ann Pharmacother. 2011;45:931–945.

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49 CHAPTER

Occupational and Environmental Lung Diseases Sunkaru Touray, MBChB, MSc, Emil Tigas, MD, and Nicholas A. Smyrnios, MD, FACP, FCCP

Key Points.................................................................................. 611 49.1  Work-Related Asthma....................................................... 611 49.1.1 Epidemiology...................................................... 611 49.1.2  Clinical Presentation and Diagnosis.................... 612 49.1.3  Prevention and Treatment................................... 612 49.1.4  Chronic Obstructive Pulmonary Disease.............. 612 49.1.5 Epidemiology...................................................... 612 49.1.6  Clinical Presentation and Diagnosis.................... 612 49.1.7  Prevention and Treatment................................... 613 49.1.8  Non-pharmacologic Therapy............................... 613 49.1.9  Pharmacologic Therapy...................................... 613 49.1.10  Asbestos-Related Lung Disease........................ 613 49.1.10.1 Epidemiology..................................... 614 49.1.11  Clinical Presentation and Diagnosis..................... 614 49.1.12 Silicosis.............................................................. 614 49.1.13 Epidemiology...................................................... 614 49.1.14  Clinical Presentation and Diagnosis..................... 614 49.1.15  Prevention and Treatment................................... 615 49.1.16 Berylliosis........................................................... 615 49.1.17 Epidemiology...................................................... 615

KEY POINTS • Work-related asthma is responsible for about 15– 20% of adult asthma and is associated with high morbidity, disability, and costs. • Chronic Obstructive Pulmonary Disease is a leading cause of morbidity and mortality globally, especially among non-smokers with occupational exposure to noxious fumes from the combustion of biomass fuel. • Silica, coal, asbestos, and beryllium are important causes of occupational lung disease among workers in the mining, automotive, and construction industries. • Hypersensitivity pneumonitis is an immunologically mediated lung disease caused by exposure to a variety of inducing agents. The cornerstone of treatment is avoidance of exposure and in some cases corticosteroids. • High-altitude illness is a group of clinical syndromes that occur among travelers to altitudes above 2,500 meters. It is caused by the physiologic responses to a low barometric pressure at an altitude that results in a low inspired oxygen tension and arterial oxygen

49.2  Clinical Presentation and Diagnosis.................................. 615 49.3  Treatment and Prevention................................................. 616 49.3.1  Coal Mine Dust Lung Disease................................ 616 49.3.2 Epidemiology........................................................ 616 49.4  Clinical Presentation and Diagnosis.................................. 616 49.5  Prevention and Treatment................................................. 616 49.5.1  High-Altitude Illnesses.......................................... 616 49.5.2 Acute Mountain Sickness and High Altitude Cerebral Edema��������������������������������������������������� 617 49.5.3  High Altitude Pulmonary Edema............................ 617 49.5.4  Prevention and Treatment..................................... 617 49.5.4.1  Controlled Ascent................................... 617 49.5.4.2 Acetazolamide........................................ 617 49.5.5  Hypersensitivity Pneumonitis................................ 618 49.5.6 Epidemiology........................................................ 618 49.6  Clinical Presentation and Diagnosis.................................. 618 49.6.1  Treatment and Prevention..................................... 618 Clinical Applications................................................................... 618 References ................................................................................ 618

content. Treatment consists of descent, supplemental oxygen, and occasionally medication.

49.1 WORK-RELATED ASTHMA 49.1.1 Epidemiology Asthma affects about 8% of the adult U.S. population, and it is estimated that about 15– 20% of patients with asthma have work-related asthma (WRA).1  Work-related asthma is a chronic inflammatory lung disease characterized by the presence of reversible airway narrowing following exposure to airborne dust, gases, or fumes in the work environment. Work-exacerbated asthma (WEA) is a subset of WRA, which describes asthma that worsens in individuals with a preexisting diagnosis of asthma occurring in the context of exposure to triggers in the work environment. 2  Work-related asthma is grouped into Sensitizer-Induced Asthma (SIA) and Irritant-Induced Asthma (IIA) based on the mechanism of disease. SIA is an immune-mediated inflammatory reaction to compounds known to be sensitizers, of which there 611

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are over 200. Diisocyanates are the most common cause of SIA in many industrialized areas.1  Other sensitizers include proteins, polysaccharides, animal dander, castor beans, latex, and vegetable gum. WRA is caused by the activation of T-lymphocytes resulting in cytokinemediated airway inflammation. IIA, on the other hand, is thought to be caused by a direct irritant effect of inhaled chemical compounds on the bronchial wall that results in the activation of inflammatory pathways that cause reversible airway obstruction. It is less common than SIA.

49.1.2 Clinical Presentation and Diagnosis Sensitizer-induced symptoms are variable and can occur at any time during the workday or toward its end. Symptom remission or improvement typically occurs during weekends and holidays when the patient is away from the work environment. Making a confident diagnosis of WRA first requires establishing a diagnosis of asthma on the basis of a consistent history, associated with reversible airway obstruction on spirometry (defined as a reduced FEV1/ FVC ratio below the lower limit of normal that increases by 12% and 200 ml with the administration of a bronchodilator).3  In patients without airway obstruction, bronchial hyperresponsiveness demonstrated on bronchial provocation testing with either methacholine or histamine supports the diagnosis. Chest imaging in the form of a chest x-ray is recommended to exclude parenchymal lung disease that may be causing symptoms. Once a diagnosis of asthma is established, the next step involves demonstrating an objective association between work-environment exposures and worsening lung function as determined by an objective demonstration of airflow obstruction measured by Peak Expiratory Flow Rate (PEFR) or FEV1 on spirometry. The recommended minimum monitoring period should be two weeks at and away from work during which asthma treatment should be kept constant. Worsening of symptoms during work that improves when the patient is away from work is consistent with a diagnosis of work-related asthma. In patients who are unable to continue employment due to symptom limitation, referral to specialized centers for bronchoprovocation testing using occupational inhalational agents is recommended. 4 , 5 

49.1.3 Prevention and Treatment Primary prevention of work-related asthma involves employee education, avoidance of exposure to sensitizing agents; and where this is not possible, substitution of known sensitizing agents with non-sensitizers. Periodic medical surveillance using respiratory questionnaires with or without spirometry and immunologic tests are recommended secondary preventative measures.4  Pharmacotherapy is an adjunct to sensitizer and irritant avoidance in the treatment of work-related asthma and follows recommended guidelines, including the use of short-acting beta agonists (SABA) on an “ as-needed basis”  for symptom relief, with the addition of an inhaled corticosteroid (ICS) inhaler in moderate cases. An inhaled − adrenergic (LABA) bronchodilator long-acting beta 2  can be added to the regimen as a “ step-up”  therapy in

refractory moderate-severe cases. Oral steroids are used for severe acute exacerbations, while immunotherapy has been tried in a few small studies with variable efficacy.6 , 7 

49.1.4 Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by irreversible airway obstruction.8 –  10  Smoking is the most important risk factor, with more than two-thirds of COPD cases linked to the long-term effects of cigarette smoking.11 

49.1.5 Epidemiology COPD affects about 10% of the general population, with a prevalence that increases with age and smoking.9 , 10  Globally, 65 million people are affected, and COPD kills over 3 million people annually.12 , 13  In the United States, it is the third most common cause of death, affecting about 16 million people and causing over 120,000 annual deaths.14 , 15  Healthcare costs from COPD are estimated to be over $50 billion annually.15 

49.1.6 Clinical Presentation and Diagnosis A diagnosis of COPD should be considered in any patient presenting with a chronic cough, shortness of breath, and sputum production in the context of a smoking history and suspected or established biomass fuel exposure. The latter should be considered in patients originating from low- and middle-income countries in sub-Saharan Africa, parts of South America, and in Asia.16  COPD is a heterogeneous disease with different phenotypes that include chronic bronchitis and emphysema most prominently. Chronic bronchitis manifests as a cough and sputum production on most days for three months in two consecutive years. Patients with an emphysema phenotype have an abnormal and permanent dilatation of airspaces distal to the terminal bronchioles. Emphysema is associated with the destruction of the alveolar walls. Symptoms common to these two major phenotypes include wheezing, fatigue, and loss of appetite. Spirometry is required to make the diagnosis of COPD. A post-bronchodilator FEV1/FVC less than 0.70 confi rms the presence of persistent airfl ow limitation and identifi es the presence of COPD in patients with appropriate symptoms and predisposing risks.10 The use of an FEV1/FVC ratio of 0.7 as a diagnostic criterion is independent of reference values and is a simple, easily reproducible measure that can be used in a physician’ s office. Physical examination findings are nonspecific and rarely aid in the diagnosis except in advanced cases where chest wall deformities such a barrel-shaped chest may be present.17 The disease course is variable, with extended periods of chronic daily symptoms punctuated by periods of acute exacerbations during which there is a sustained worsening of the patient’ s condition, from the stable state and beyond normal day-to-day variations that necessitate a change in regular medication.18  Once a diagnosis of COPD is made, a combined assessment is performed to determine symptom burden, degree

49.1  Work-Related Asthma 

of airflow limitation, and the risk of acute exacerbation. To assess symptoms, the modified Medical Research Council (MMRC) or COPD assessment test (CAT) score can be used. Next, the FEV1 is used to classify the degree of airflow obstruction based on the GOLD criteria. Finally, the number of acute exacerbations and hospitalizations in the preceding year is determined. Using these variables, presented in Figure 49.1, patients are categorized into one of four groups (A, B, C, and D). The GOLD criteria present a framework on which treatment is instituted.

49.1.7 Prevention and Treatment The therapeutic objectives in COPD management include symptom control, prevention of acute exacerbations, and improvement of exercise tolerance. This is usually achieved with a combination of non-pharmacologic and pharmacologic interventions.

49.1.8 Non-pharmacologic Therapy Smoking cessation is the most effective non-pharmacologic intervention in preventing COPD and slowing its progression. All patients should be offered tobacco cessation counseling. Assessing medication adherence and training in good inhaler technique are integral parts of patient education.19 , 20  Pulmonary rehabilitation is a multidisciplinary program that aims to improve exercise capacity, reduce symptoms, and improve overall quality of life in patients across the spectrum of disease severity and has been shown to improve dyspnea, health status, and exercise tolerance.19  It is therefore recommended that all patients with COPD be considered for pulmonary rehabilitation as part of a multimodality treatment regime.

613

Age-appropriate pneumococcal vaccination should be offered to all patients in accordance with established guidelines. The pneumococcal polysaccharide vaccine (PPSV23, Pneumovax) is recommended for patients under age 65 years; while the pneumococcal conjugate vaccine (PCV13, Prevnar) is recommended for patients aged 65 years and older.21 

49.1.9 Pharmacologic Therapy Bronchodilators are the first-line pharmacologic drug class for symptom control and have been shown to improve lung aeration and exercise tolerance. In patients with low risk of acute exacerbation and fewer symptoms (Category A), the use of a short-acting beta agonist (SABA) alone or in combination with a short-acting muscarinic antagonist (SAMA) is appropriate for use as a reliever medication on an as-needed basis. For low-risk patients with high symptom scores (Category B) and high-risk patients (Categories C and D), maintenance therapy is indicated for symptom control. This involves the use of long-acting bronchodilators such as beta agonists (LABA) or a long-acting muscarinic antagonists (LAMA) singly or in combination. Patients in categories C and D may also benefit from the addition of an inhaled corticosteroid (ICS) as combination therapy in refractory cases. ICS use as monotherapy is discouraged, and recent evidence suggests a better outcome in patients on LAMA/LABA compared to an ICS/LABA, with a lower incidence of pneumonia in patients with moderate-to-severe COPD and higher dyspnea scores (Categories C and D).10 , 22 

49.1.10 Asbestos-Related Lung Disease Asbestos-related lung disease is a group of lung diseases caused by exposure to naturally occurring asbestos fibers

Figure 49.1   GOLD COPD Assessment Tool. Source  :  Global Initiative for Chronic Obstructive Lung Disease , ©  2017 

49

614  Chapter 49  Occupational and Environmental Lung Diseases

comprised of magnesium silicate minerals. These fibers have desirable physical properties for industrial use, such as high tensile strength, flexibility, and resistance to chemical and thermal degradation, hence their prior extensive use in the construction, automotive, and textile industries. 23  Chrysotile (also known as white asbestos) is the most common and only type of asbestos currently used in manufacturing in the United States, while the more toxic amphibole fibers, including crocidolite, amosite, and tremolite are still used in parts of sub-Saharan Africa, South America, and Asia. 24  Asbestos fibers are highly carcinogenic and are known to cause lung cancer and malignant mesothelioma. Asbestos is considered one of the most important occupational carcinogens. 24 

49.1.10.1 Epidemiology The use of asbestos has been banned in many countries, including the United States. Therefore, exposure is limited to certain occupations such as construction workers, car mechanics, and plumbers working on old homes and buildings where asbestos was used. 25  Global asbestos exposure is unknown, although it is estimated that worldwide over 40,000 people die of malignant mesothelioma each year. 24 

49.1.11 Clinical Presentation and Diagnosis Individuals exposed to asbestos are mostly asymptomatic, and the latency period can be as long as 20– 30 years between initial exposure and the development of the clinically apparent disease. In patients who develop clinical disease, benign asbestos pleural plaques are a common finding, the development of which suggests prior exposure and is reported to be prevalent in about 60– 70% of individuals with an average cumulative exposure of about 32 years. 26 , 27  The diagnosis is usually incidental and made during chest imaging for other reasons. Chest x-ray may show a diffuse pleural thickening in the lower portions of the chest, sparing the apices and costophrenic angles, which may be calcified in about 5–  15% of cases. 28 , 29  Chest CT has a higher sensitivity and specificity and can detect noncalcified pleural plaques. Malignant pleural mesothelioma (MPM) is a dreaded consequence of asbestos exposure that typically occurs in older (median age 60) men. Patients with MPM present with nonspecific symptoms of dyspnea, cough, chest pain, and constitutional symptoms including fever, chills, night sweats, malaise, and weight loss. Pleural effusions may be present and are usually an exudate with an eosinophilic cellular profile. Unfortunately, thoracentesis has a low sensitivity for diagnosing MPM, hence a surgical pleural biopsy using a video-assisted thoracoscopic approach is the gold standard for diagnosis.30  Treatment of MPM involves multimodality treatment, including surgery in patients who are good candidates for resection and chemoradiation therapy. In non-operable cases, chemotherapy, palliative radiation, and tunneled pleural catheters have been employed for symptomatic relief. Asbestos-associated pulmonary fibrosis (asbestosis) is a less common form of asbestos-related lung disease

which may be difficult to distinguish from other causes of pulmonary fibrosis. Chest CT may show honeycombing and upper lobe involvement in advanced stages of the disease. The presence of pleural plaques suggests prior asbestos exposure and raises suspicion for asbestos-associated pulmonary fibrosis but is not confirmatory. Such patients should be referred to specialists familiar with asbestosrelated lung disease for periodic monitoring of disease progression and the development of asbestos-associated malignancies.31 , 32 

49.1.12 Silicosis Silicosis is a fibrotic lung disease caused by inhalation of free crystalline silicon dioxide or silica and is recognized as one of the most important occupational diseases worldwide. Silicon dioxide or silica is the most abundant mineral and occurs in crystalline and amorphous forms.33  The most common free crystalline forms of silica in workplaces are quartz, tridymite, and cristobalite.33 

49.1.13 Epidemiology Silica exposure is highest among individuals employed in construction work involving masonry, heavy construction, painting, and in iron and steel foundries. Metalworking occupations that involve sandblasting, grinding, or buffing of metal parts are also considered high-risk jobs. 33  Global disease burden is difficult to estimate due to lack of disease surveillance in lower- and middle-income countries (LMICs); however countries like China and South Africa have reported significant silica exposure, suggesting that the disease burden in these parts of the world may be high. In the United States, about 127,000 miners are reportedly exposed, with a higher rate of disease in African Americans compared to white workers with the same dust exposure.34 , 35 

49.1.14 Clinical Presentation and Diagnosis Acute silicosis is characterized by rapid onset of symptoms including dyspnea, cough, weight loss, fatigue, and sometimes pleuritic pain and fever following acute exposure to silica. 36  Lung examination may reveal crackles. Chest x-ray may be normal in the acute phase or may demonstrate bilateral consolidation and ground-glass infiltrates. Diagnosis of acute silicosis requires a high clinical index of suspicion and is contingent on establishing an occupational exposure to silica and the absence of other differentials. Chronic silicosis is characterized by two clinical syndromes on two ends of a disease spectrum, namely, simple silicosis (SS) and progressive massive fibrosis (PMF). In simple silicosis, a chest x-ray may show upper lobe predominant ground-glass opacities; while in progressive massive fibrosis, there are mass-like areas of dense consolidation. Pulmonary function tests may reveal a mixed obstructive and restrictive ventilatory defect and a decreased DLCO. Bronchoscopy (when performed) is classically described as demonstrating a milky lipoproteinaceous bronchoalveolar

49.2  Clinical Presentation and Diagnosis  615

lavage effluent, requiring the exclusion of other potential causes, including malignancy, pulmonary alveolar lipoproteinosis, and atypical infections such as Pneumocystis jirovecii  and Norcardiosis. A diagnosis of silicosis can be established on the basis of a documented history of significant silica exposure, consistent chest imaging findings of diffuse nodular and patchy consolidative opacities, and supportive BAL findings in the absence of other causes (Figure 49.2).

49.1.15 Prevention and Treatment The Occupational Safety and Health Administration (OSHA) recommends limiting exposure to silica using a combination of respiratory protection, medical surveillance, and good record-keeping. Half-face particulate respirators with N95 or better filters are considered appropriate for silica at concentrations of 50 microgram/m3  or fewer; powered respirators are recommended for exposures above this limit.37 

49.1.16 Berylliosis Beryllium is a naturally occurring element that is extracted from ores and processed into metal, oxides, alloys, and composite materials used in the aerospace, automotive, and mining industries.38  Berylliosis manifests as two clinical syndromes at opposite ends of a disease spectrum. Beryllium sensitization occurs in acutely exposed individuals, while chronic beryllium disease is an inflammatory lung disease affecting individuals who are chronically exposed to beryllium.

49.1.17 Epidemiology It is estimated that about 134,000 current workers in government and private industry are potentially exposed to beryllium in the United States.38 

49.2 CLINICAL PRESENTATION AND DIAGNOSIS Acute exposure to beryllium presents with nonspecific respiratory symptoms, including a cough, rhinorrhea, and dyspnea. This is associated with a delayed hypersensitivity reaction resulting in chronic granulomatous inflammation affecting the lungs, a condition known as beryllium sensitization (BeS). About 8% of individuals with BeS, may progress to chronic beryllium disease, characterized by progressive dyspnea, non-productive cough, fatigue, and exercise intolerance as lung tissues are destroyed by chronic granulomatous inflammation.38  Patients may have constitutional symptoms, including fever, night sweats, and weight loss. Physical examination findings are nonspecific, although bibasilar crackles and digital clubbing may be present. Extrapulmonary manifestations are rare and include uveitis and cardiac conduction abnormalities. Chest x-ray has a low sensitivity for diagnosing berylliosis in the acute setting, as it may be normal in BeS and early phases of CBD. Chest computed tomography has a higher sensitivity and may demonstrate hilar adenopathy, upper lobe predominant reticulonodular infiltration in a peribronchovascular pattern that is indistinguishable from sarcoidosis. It has been reported that about 6% of patients undergoing diagnostic evaluation for a clinical suspicion of sarcoidosis were ultimately diagnosed with berylliosis, highlighting the importance of a detailed occupational history to assess for exposure.39 –  41  Pleural effusion is an uncommon manifestation of BeS and CBD. Pulmonary function tests may be normal in the early stages of the disease, while in advanced cases airflow obstruction, restriction, or a mixed pattern on spirometry may be present. A  reduced diffusion capacity for carbon monoxide (DLCO) may also be present in advanced cases. The diagnosis of beryllium sensitization is made on the basis of a positive blood beryllium lymphocyte proliferation test (BeLPT) in a patient with a history of beryllium exposure.

Figure 49.2  Touray Occupational Environmental Lung Disease Silicosis.

49

616  Chapter 49  Occupational and Environmental Lung Diseases

Chronic beryllium disease is diagnosed when either blood or bronchoalveolar lavage fluid BeLPT is positive in a patient with a documented history of beryllium exposure. Other features supportive of the disease include consistent radiographic abnormalities and lung pathology demonstrating non-caseating granulomas with lymphocytic infiltration.

49.3 TREATMENT AND PREVENTION Disease prevention involves the avoidance of inhalation and dermal exposures to beryllium by employing the use of personal protective equipment, administrative changes such as the exclusion of workers from specific areas to prevent nonessential contact, and regular screening of employees involved in activities with exposure to beryllium. Patients with respiratory symptoms suspicious for berylliosis should be referred to a pulmonologist for diagnostic evaluation and treatment, which generally consists of systemic corticosteroids. Methotrexate can be used as a second-line agent in corticosteroid-refractory cases.

49.3.1 Coal Mine Dust Lung Disease Coal mine dust lung disease (CMDLD) refers to a broad spectrum of lung diseases caused by exposure to coal mine dust. It includes disease entities such as coal workers’  pneumoconiosis (CWP), progressive massive fibrosis (PMF), Caplan Syndrome, and Chronic Obstructive Pulmonary Disease (COPD).42 , 43 

49.3.2 Epidemiology Coal is the second largest energy source worldwide, accounting for over 25% of global energy supply and more than one-third of the fuel used to generate electricity. Consequently, the number of individuals exposed to coal particles is considerable, with China, the United States, and India being the top consumers accounting for over 70% of total global consumption. Coal production in the United States is largely concentrated in a few states, including Wyoming, West Virginia, Kentucky, Pennsylvania, and Texas, accounting for over 70% of production.44  Most coal workers are men; therefore, CMDLD disproportionately affects men, with about 38% of coal miners showing radiographic features of interstitial lung disease. Diagnosis of CMDLD is made clinically on the basis of a combination of an appropriate exposure history, radiological or pathological findings consistent with the diagnosis, and a lack of alternative explanations for the patient’ s lung disease.43 

49.4 CLINICAL PRESENTATION AND DIAGNOSIS Coal workers’  pneumoconiosis (CWP) is caused by the accumulation of coal dust in the lungs and classically presents as the occurrence of upper lobe predominant

small rounded opacities that may also be found in all lung zones.43  Most cases are asymptomatic and are detected incidentally as part of surveillance programs or in the context of a diagnostic workup for other conditions. Progressive massive fibrosis (PMF) is a progressive form of CMDLD found in miners with greater dust exposure. A recent study found PMF in about 63% of coal miners with a mean coal mining tenure of 27 years in Kentucky and Virginia.45  It may present with breathlessness, cough, and the production of sputum that has been variably described as mucoid, mucopurulent, and rarely discolored as if mixed with black ink (melanoptysis). Clinical exam findings are nonspecific, and the average interval from a normal chest radiograph to massive fibrosis can be as long as 12 years.46  Spirometry findings include a restrictive, obstructive, or mixed pattern of impairment, and a reduced DLCO depending on the severity of lung fibrosis. An association between CWP and rheumatoid arthritis called Caplan syndrome, originally described by Anthony Caplan, describes the occurrence of multiple well-defined opacities on chest radiographs of rheumatoid arthritis patients.47  CMDLD has also been associated with chronic obstructive pulmonary disease and other pulmonary infections which account for significant morbidity in patients with CWP.

49.5 PREVENTION AND TREATMENT In the United States, environmental controls are mandated by federal law. Coal dust exposure can be minimized using ventilation systems, water sprays, and other dust capture devices as part of a continuous monitoring program. There is no specific medical therapy that has proven effective in reversing CMDLD. Management involves periodic medical monitoring with periodic chest radiographs and spirometry.42  Patients with CMDLD should be offered vaccinations against viral and bacterial pathogens, and smoking cessation counseling should be offered to patients who smoke.

49.5.1 High-Altitude Illnesses It is estimated that more than 30 million people each year travel to and from recreational areas with altitudes in excess of 2,500 meters. This presents unique challenges for travelers to these areas, and therefore a good understanding of common problems that arise from exposure to high altitude is important in order to prevent the development of high-altitude illnesses.48  High-altitude illnesses (HAI) are a group of pulmonary and cerebral conditions that occur in the context of a rapid initial ascent to altitudes at a rate that exceeds the body’ s ability to acclimatize to changes in oxygen tension. The fraction of oxygen in inspired air is constant at 0.21 regardless of altitude, but for each unit change in altitude, there is a non-linear change in the barometric pressure of oxygen that affects the alveolar partial pressure and consequently, oxygen availability to tissues. The physiologic response to this change in oxygen tension is called acclimatization and

49.5  Prevention and Treatment 

is characterized by changes in the heart rate, respiratory rate, chemoreceptor sensitivity to hypoxia, and pulmonary vasoconstriction. These act in concert to restore normal oxygen levels in tissues, but when the rate of altitude change exceeds the body’  s homeostatic capacity, acute hypoxemia ensues, resulting in distinct clinical syndromes primarily affecting the lung and brain. Risk factors for the development of HAI include preexisting cardiopulmonary disease, heavy exertion at altitude, low-altitude residence before ascent, and obesity.49 

49.5.2 Acute Mountain Sickness and High Altitude Cerebral Edema Acute mountain sickness (AMS) is the most common presentation of HAI that typically occurs about 6– 12 hours after ascent to altitudes above 2,500 meters (8,000 feet). It is diagnosed when an unacclimatized traveler develops a headache, with one of the following symptoms: nausea, anorexia, vomiting, insomnia, dizziness, or fatigue. It occurs in about 10– 40% of climbers at 3,000 meters, while more than 50% of climbers experienced symptoms at altitudes greater than 4,000 meters. 50  High-altitude cerebral edema (HACE) is considered an end-stage form of acute mountain sickness and is characterized by the presence of ataxia and altered mental status in an unacclimatized climber and can occur in the absence of acute mountain sickness or pulmonary edema.

49.5.3 High Altitude Pulmonary Edema High altitude pulmonary edema (HAPE) is a rare lifethreatening form of noncardiogenic pulmonary edema that develops two to four days following rapid ascent above 2,500 meters (8,000 feet).

617

49.5.4 Prevention and Treatment 49.5.4.1 Controlled Ascent Controlled exposure to hypobaric hypoxia remains the most effective non-pharmacologic means of preventing HAI. Gradual ascent that allows for acclimatization is the most effective preventive strategy. The ideal rate of ascent is variable, but it is generally recommended that at altitudes above 3,000 meters, daily ascent should not exceed 300– 500 meters above the previous night with a rest day after every 1,000 meters (or every 2– 3 days).48 , 51 

49.5.4.2 Acetazolamide The use of acetazolamide, a carbonic anhydrase inhibitor, has been shown to be effective in preventing HAI by inhibiting bicarbonate excretion in the kidneys, which results in an increase in serum bicarbonate and a concomitant increase in minute ventilation in response to elevated PCO2 . The benefit of acetazolamide for the prevention of AMS/HACE has been demonstrated in multiple trials, and it remains the primary pharmacologic agent of choice. 52 , 53  In patients who develop AMS, rest and descent to a lower altitude are recommended. Given that AMS and HACE are considered two extremes of a continuum, physicians must be vigilant to look out for symptoms of HACE. The Lake Louise Scoring system is a screening tool that can detect AMS/HACE in high-altitude climbers. A score of 3– 5 is consistent with AMS, while a score greater than 6 indicates severe AMS/HACE, and such patients should be treated with acetazolamide. The recommended dose is 125– 250 mg twice a day. Common side effects include paresthesia, loss of appetite, and nausea. Because acetazolamide is sulfonamide, patients with sulfa allergies should not take this medication (Table 49.1).

TABLE 49.1   Source  :  “  The Lake Louise Consensus on the Definition and Quantification of Altitude Illness”  in Sutton JR, Coates G, Houston CS (Eds),  Hypoxia and Mountain Medicine  . Queen City Printers, Burlington, Vermont, 1992 .  Acute Mountain Sickness 

Headache and  at least one  of the following symptoms:  • gastrointestinal (anorexia, nausea or vomiting) • fatigue or weakness • dizziness or lightheadedness • difficulty sleeping

High-Altitude Cerebral Edema 

The presence of a change in mental status and/or ataxia in a person with acute mountain sickness OR the presence of both mental status changes and ataxia in a person without Acute Mountain Sickness

High-Altitude Pulmonary Edema 

The presence of at least two  of the following symptoms • dyspnea at rest • cough • weakness or decreased exercise performance • chest tightness or congestion AND At least two  of the following signs: • crackles or wheezing in at least one lung field • central cyanosis • tachypnea • tachycardia

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618  Chapter 49  Occupational and Environmental Lung Diseases

49.5.5 Hypersensitivity Pneumonitis Hypersensitivity pneumonitis (formerly extrinsic allergic alveolitis) is an immune-mediated inflammatory disease of the lung that occurs due to exposure to an inducing agent called a hypersensitivity-pneumonitis inducer (HP inducer). Exposure typically occurs in an occupational or recreational setting, which has given rise to an extensive list of diseases, including farmer’ s lung, bird fancier’ s lung, and hot-tub lung. It is characterized by a lymphocytic inflammation of the lung due to the accumulation of activated T-lymphocytes in the lung tissues.

49.5.6 Epidemiology The incidence of HP is about one per 100,000 in the United Kingdom, with a mean age of 57 and an almost equal sex distribution. Incidence in the United States is unknown. 54  In the United States, identified risk factors are quite extensive and include bird and hot-tub exposure, contaminated humidifiers, and exposure to mold or fungi in plants and water systems.55 , 56  Lung fibrosis on chest CT has been associated with poorer outcomes with about 25% of patients with fibrotic HP dying or requiring lung transplantation during a five-year follow-up period. 57 

49.6 CLINICAL PRESENTATION AND DIAGNOSIS HP presents with intermittent dyspnea, wheezing, cough, and constitutional symptoms, including fevers, chills, and malaise with a temporal relationship to an antigen exposure. 58 , 59  Chest CT is crucial in the diagnostic evaluation of patients in whom a diagnosis of HP is being entertained. Classical features include an upper lobe predominant centrilobular diffuse micronodular ground-glass opacification and mosaic attenuation (reflecting coexistent small airways disease).60 , 61  HP is classified into acute (inflammatory) HP, with a symptom duration less than six months and chronic (fibrotic) HP, with symptom duration greater than six months. 56  Chronic HP is characterized by fibrotic changes in high-resolution computed tomography images or lung biopsy and is associated with a poorer outcome. 56 

Diagnosis of HP requires a high index of suspicion in a patient presenting with the aforementioned clinical symptoms and diagnostic imaging. Once the diagnosis is considered, a detailed history looking for potential exposure to an HP-inducing antigen is crucial, although these are identified in only about 50% of cases. 56 , 59  A detailed occupational and social history should be obtained to identify any potential exposures in the work environment or during recreational activities.62  Pulmonary function tests and referral to a pulmonologist are recommended for further diagnostic evaluation, including bronchoscopy with bronchioalveolar lavage and/or lung biopsy. Cases of HP are best managed with a multidisciplinary team comprised of pulmonologists, chest radiologists, and pathologists. Specific IgGs have been employed as a screening tool, but these tests are performed only in a few specialized centers.

49.6.1 Treatment and Prevention The cornerstone of HP treatment involves identification of the offending antigen and avoidance. However, given that an inducing agent remains unidentified in half of patients with HP, consideration of treatment with inflammatory suppression agents in symptomatic patients may be indicated. Prednisone has been used in this scenario, while mycophenolate and azathioprine have been used as second-line agents.

CLINICAL APPLICATIONS • A diagnosis of work-related asthma should be suspected in any patient with asthma that is difficult to control. • COPD should be considered as a diagnosis in any patient with dyspnea from parts of the world where there is significant exposure to biomass fuel or coal mining (even among non-smokers). • Employees involved in industries with exposure to silica, coal, asbestos, and beryllium should undergo periodic surveillance for pneumoconiosis using history, lung function testing, and chest imaging. • Travelers to high altitudes should receive information on high-altitude illnesses and be counseled on how to prevent, recognize, and treat symptoms of these syndromes.

REFERENCES  1. Tarlo, S. M. et al.  Diagnosis and management of work-related asthma: American College Of Chest Physicians Consensus Statement. Chest  134, 1S– 41S (2008). 2. Henneberger, P. K. et al.  An official American Thoracic Society statement: Work-exacerbated asthma. Am J Respir Crit Care Med  184, 368– 378 (2011). 3. Horak, F. et al.  Diagnosis and management of asthma— Statement on the 2015 GINA Guidelines. Wien Klin Wochenschr  128, 541– 554 (2016).

4. Tarlo, S. M. & Lemiere, C. Occupational asthma. N. Engl. J. Med.  370, 640– 6 49 (2014). 5. American Thoracic Society. American Thoracic Society - Selected Specialized Clinical Tests In EOH Evaluation (2016). Available at: http:​//www​.thor​acic.​org/p​ rofes​siona​ls/cl​i nica​l-res​ource​s /env​i ronm​ ental​-and-​occup​ation​al/cl​i nica​l-tes​ts.ph​p (Accessed: 24 October 2017). 6. Pereira, C. et al.  Specific immunotherapy for severe latex allergy. Eur Ann Allergy Clin Immunol  35, 217– 2 25 (2003).

7. Leynadier, F., Herman, D., Vervloet, D. & Andre, C. Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers. J Allergy Clin Immunol  106, 585– 590 (2000). 8. Tan, W. C. et al.  Characteristics of COPD in never-smokers and ever-smokers in the general population: Results from the CanCOLD study. Thorax  70, 822– 829 (2015). 9. Oh, Y.-M. et al.  Characteristics of stable chronic obstructive pulmonary disease

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49

50 CHAPTER

Venous Thromboembolic Disease Joseph Gallant, MD and Ryan Shipe, MD

Key Points.................................................................................. 621 50.1  VTE Introduction/Overview................................................ 621 50.2 Epidemiology.................................................................... 621 50.3 Pathophysiology............................................................... 622 50.4  Embolization to the Pulmonary Vasculature....................... 622 50.5  Risk Factors...................................................................... 623 50.5.1 Immobility............................................................. 623 50.5.2 Obesity................................................................. 623 50.5.3 Smoking............................................................... 624

KEY POINTS • Venous thromboembolism (VTE) is a common, morbid, and costly disease process with a multitude of risk factors. • Risk factors for the development of venous thromboembolic disease are commonly present in combination rather than isolation. • The role of modifiable risk factors for VTE such as immobility, obesity, and smoking is an area of growing interest. • More study is needed to define the impact of modification of these risk factors with respect to VTE or VTE recurrence in individual patients.

50.1 VTE INTRODUCTION/ OVERVIEW Venous thromboembolic disease (VTE) in the form of deep venous thrombosis (DVT) and pulmonary embolism (PE) is a common, costly, and morbid problem encountered by both generalists and specialists in a variety of medical and surgical fields. As our understanding of the many risk factors for the development of VTE has grown, and as our approach to diagnosis and treatment has become more complex, it has become necessary to adopt an increasingly broad and multidisciplinary approach to management of these patients. There is growing evidence that application of the principles of lifestyle medicine should become a central component of comprehensive management of patients with VTE. Critically important to an understanding of the development of VTE and the management of this patient population is the concept of risk factor synergy or interaction.

50.5.4 Diagnosis.............................................................. 625 50.5.5 Treatment............................................................. 626 50.5.6  Massive PE........................................................... 626 50.6  Distal DVT......................................................................... 627 50.7  Isolated Subsegmental PE................................................. 627 50.8  Malignancy-Associated Thromboembolism....................... 627 Clinical Applications................................................................... 627 References................................................................................ 627

This concept describes the observation that the presence of specific combinations of individual (and often relatively weak) risk factors engenders an overall risk that is potentially much greater than the sum of their individual contributions.1 While it is true that many risk factors for the development of VTE have a non-modifiable genetic basis, other risk factors may exist as a consequence of an otherwise healthy or necessary risk exposure (such as OCP use or surgical immobilization). The application of the principles of lifestyle medicine can further reduce the overall risk of developing VTE due to their influence over several important risk factors that are synergistic, common, and modifiable. While the precise pathophysiological mechanisms underlying the interactions of these modifiable risk factors are not fully understood, we do know that getting adequate levels of physical activity, making smart nutritional choices for maintenance of a healthy weight, and avoiding cigarette smoking will be increasingly important in the overall management of patients with DVT and subsequent PE.

50.2 EPIDEMIOLOGY Accurately assessing the true incidence of VTE disease is challenging due to the unknown number of asymptomatic DVT or PE cases that are suspected to occur each year. Asymptomatic PE alone is believed to complicate up to 50% of all confirmed cases of DVT.2 Estimates suggest a combined incidence rate of one in 1,000 people per year, with the rate of diagnosis of PE being approximately half that of DVT (60 vs. 124/100,000).1,3 CDC data are in agreement, reporting 300,000 to 600,000 new cases of VTE each year in the United States alone. As many as 80% of these new cases of VTE will occur in the context of at least one, and often more than one, known risk factor.4 621

622  Chapter 50  Venous Thromboembolic Disease

The morbidity and mortality of VTE are also difficult to quantify precisely and likely varies significantly with underlying patient comorbidities, characteristics of the VTE itself, and access to treatment. 5 Pulmonary embolism is associated with the majority of directly attributable mortality. Population data collected over the last several decades demonstrates an overall mortality rate of untreated PE as high as 30%, improving to 8% with prompt recognition and treatment. The highest mortality rates are observed in patients presenting in cardiogenic shock due to massive PE (up to 65%) or mobile thrombus within the atria (up to 27%). It is estimated that up to 100,000 deaths annually in the United States are due to complications of VTE.6 Both PE and DVT contribute to the morbidity and the societal costs associated with VTE. Much of the cost comes from the impact of chronic thromboembolic pulmonary hypertension, VTE recurrence, and peripheral vascular dysfunction due to damage to the valves in the deep leg veins. Using data obtained from nearly 27,000 U.S. cases of DVT and PE from 1997 to 2004, it has been estimated that average annual individual healthcare costs are estimated to increase from approximately $7,000 U.S. (pre-event) to $17,500 and $25,000 in cases of DVT and PE, respectively.7 In this data set, the presence of postthrombotic syndrome was also a strong driver of additional medical costs and was not limited to the time of the inciting event. The relatively high pre-VTE annual medical expenditure in this cohort was thought to be due to preexisting comorbid diseases in this population (compared to less than $1,000 in annual healthcare costs in age-matched “healthy” controls). The aggregate annual economic burden of VTE in the United States, including the longitudinal cost of therapy and management of side effects, has been estimated to be between $7 billion to $10 billion per year.6 The costly, morbid, and frequently mortal nature of VTE is reason enough to explore all reasonable avenues of risk reduction and therapy optimization. As we will see later in this chapter, application of the principles of lifestyle medicine may be an inexpensive and efficacious adjunct to the growing technological arsenal of diagnosis and therapy.

50.3 PATHOPHYSIOLOGY The development of VTE is dependent on the local interaction of venous stasis, vascular endothelial injury, and intrinsic hypercoagulability in the paradigm attributed to Virchow in 1856.8 Though a detailed exploration of the hematological mechanisms of clot formation is beyond the scope of this text, there are several key ideas to understand as they pertain to the development of DVT and subsequent PE. The risk of thrombosis can be thought of as proportional to the cumulative impact of multiple risk factors, all in some way related to the presence of the three commonly observed physiological derangements noted above.9 It has also been observed that while venous stasis is likely the most important contributor to DVT (and by extension PE), stasis in the complete absence of endothelial disruption or

hypercoagulable state is likely insufficient for clot formation. While global stasis in the context of absent muscular contraction (such as during general anesthesia) has been linked to thrombosis, autopsy and physiological studies have also demonstrated that the local effect of eddy currents in venous sinuses adjacent to the valves of the large veins creates a microenvironment of relative hypoxia and increased viscosity which further enhances the propensity to clot.8,10 It has been theorized that this low-oxygen tension environment further contributes to clot formation as it promotes the downregulation of antithrombotic proteins that are otherwise expressed in greater concentrations on the endothelial surface of such valves.11 A similar imbalance in pro and anticoagulants is also seen in locations of decreased endothelial cell surface to blood volume, such as is found in large vessels such as the femoral and iliac veins, and may explain the higher rates of clot formation in those areas.12 The prothrombotic effect associated with inherited or acquired defects in expression of the constituents of the fibrinolytic and clotting pathways is magnified at such sites.13

50.4 EMBOLIZATION TO THE PULMONARY VASCULATURE A perfect understanding of the frequency of embolization of these lower extremity clots is impossible, given the suspected frequency of asymptomatic DVT, though data derived predominantly from the surgical literature have provided some insight into features impacting the likelihood of progression.14 While it is true that the development of de novo thrombosis of the large veins in the periphery is dependent upon the factors noted above, the likelihood of embolization of these clots to the pulmonary vasculature has been linked only to the proximity of the clot to the central circulation.15 Based on these data, it is suspected that nearly all venous thrombotic events are asymptomatic until they reach the proximal veins (cephalad to the popliteal circulation.16,17 In a consecutive series of 189 patients with suspected lower extremity DVT, only 11% had distal calf DVT only, and more than 90% had continuous clot extension from the calf to the proximal veins.14 It has been estimated that nearly half of the patients with symptomatic proximal DVT will have imaging evidence of pulmonary emboli at the time of diagnosis, and one-third will be diagnosed with concurrent PE, even in the absence of chest or respiratory symptoms.18,19 The majority of these datasets were generated decades ago. With the now-widespread use of the MDCT scan, our ability to detect small PE is significantly improved. It may be reasonable to expect that a higher sensitivity test would only increase our estimate of the frequency of asymptomatic embolization. The natural history of untreated DVT, therefore, is suspected to be one of eventual progression and ultimately distal migration. The risk of such an event is believed to be highest immediately following the development of thrombosis, and this risk declines over a several-month period as the stabilization effects of partial resorption and endothelization of distal clots progresses. 20

50.5  Risk Factors 

50.5 RISK FACTORS It is likely that truly idiopathic VTE or PE is rare and that the majority of VTE occurs in the context of at least one, and often multiple, risk factors. 21 The risk factors that predispose the patient to clot can be divided generally into two groups: inherited (including anatomical variations and genetic clotting disorders) or acquired (e.g., undergoing surgery or presence of comorbid disease such as cancer). 22 Though these risk factors might appear varied and unrelated, the final common pathway of clotting is the perturbation of the local vascular microenvironment such that some or all of Virchow’s triad is satisfied. 23 There are several published datasets that enhance our understanding of both the relative individual strength of risk factors and the interplay of acquired and innate risks when present concurrently. 24 Describing the effect of a single risk factor is straightforward: surgery with general anesthesia and the presence of malignancy are implicated in as many as one-third of all cases, and are likely the most important single risk factors for the development of VTE.21,25–27 Delineating the synergistic effects of multiple concurrent risk factors is more complex, but more reflective of real patients and real risk. Using the example of surgery: in one of the largest casecontrol studies of VTE (the MEGA study, 4311 cases), it was observed that the combination of surgical immobility of non-malignant medical illness (including renal or liver disease, heart failure, and CVA) increased the OR for the development of VTE by 10.9 (95% CI 4.2–28).28 The addition of any of the inherited thrombophilias to that combination increased the OR to as high as 88. For the purposes of this text, we will focus primarily on the complex synergistic interaction between several pertinent lifestyle-related health choices: risk of immobility or a sedentary lifestyle, obesity, and smoking will also be further reviewed.

623

Immobility not related to airline travel is less well described. As the modern office becomes more decentralized, and Americans spend more and more time with their computers for both work and recreation, there has been an increase in individual case reports and case series describing the development of significant DVT related to elective, non-flight-related immobility.35 In one of the largest series of its kind, 61 consecutive patients with VTE were surveyed and tested for underlying thrombophilia. Multiple risk factors were present in the majority of patients. Prolonged seated immobility was the second most common risk factor after a family medical history of thrombosis. This study defined “prolonged” as sitting a cumulative eight hours in a 24-hour period (with at least three hours unbroken), 10 hours in a 24-hour period (with at least two hours unbroken), or 12 hours in a 24-hour period (with at least one hour of continuous sitting). Thirty-four percent of patients with a new diagnosis of DVT demonstrated this finding.36 A follow-up case-control study attempted to describe the odds ratio specifically associated with workrelated immobility. Ninety-seven consecutive patients with radiographically confirmed VTE (both DVT and PE) were administered a questionnaire almost identical to that used in the Aldington case series. These patients were then matched to controls from the same center admitted over the same time period. Following univariate analysis, authors found that immobility due to work or recreation carried an odds ratio of 2.2 (CI 1.0–5.0) for the development of VTE. While this was an important observation, the effect was modest, especially when compared to the effect of recent surgery or family history of VTE in this same dataset (OR 70.6 and 5.7, respectively). 37 Interestingly, the total duration of hours spent sitting, irrespective of frequency or duration of breaks, had a direct relationship with an increasing risk of VTE. This final conclusion underscores the risks associated with a sedentary lifestyle, as it highlights the challenge of simply instituting preventative regimens.

50.5.1 Immobility Interest in the development of VTE due to prolonged nonsurgical immobility has existed since it was first observed that there was a sixfold increase in the risk of fatal PE in patients who sat for prolonged periods of time in air raid shelters during the London Blitz of World War II. 29 More recently, it was reported that rates of incidence of distal DVT in patients requiring cast immobilization without surgery may be high as 19% (35/188).30 The risk associated with airline travel is likely the most intensely scrutinized, though it remains controversial. Estimates from prospectively obtained data sets indicate the risk of DVT may be twice that of non-flyers.31 The overall incidence of PE may be as low as 4.8 per million patients traveling more than 6,000 miles, but it is believed that we underestimate the true incidence of minimally symptomatic and nonembolizing distal clots.32 Additionally, it has been suggested that it is not only the lack of movement while flying but concurrent mild hypoxemia (cabin PaO2 of 72 mmhg) that promotes coagulation. 33,34 Given the frequency of multiple risk factors present in the same patients, it is also challenging to attribute the risk of immobility itself during activities such as airline travel.

50.5.2 Obesity The development of atherosclerotic arterial disease and the development of venous thromboembolism have significant epidemiological overlap. The risk of VTE attributable to specific cardiovascular risk factors such as hypertension, hyperlipidemia, and diabetes, however, has been inconsistently demonstrated or even refuted. 38 The same cannot be said for obesity and smoking. Multiple population-based, retrospective and even prospective studies have observed the link between these important lifestyle-related risk factors, development of VTE, and cardiovascular disease.38– 40 In parallel with the rapid rise of the obesity epidemic in Americans, there has been increasing interest in understanding the role that obesity plays in the development of DVT and PE. Although obesity has been theorized for decades to exert a pro-coagulant effect in the model of Virchow’s triad, it is only in the last few decades that we have seen significant data in support of this association.41,42 Several meta-analyses and large-population cohort studies have supported the link between increasing BMI and the risk of VTE. The largest of these meta-analyses includes

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data from 21 case-control and cohort studies and represents 63,552 patients diagnosed with PE or DVT over the last five decades. Obesity, defined as BMI > 30kg/m 2 carried an OR of 1.84 (95% CI, 1.55 to 2.18; I 2 = 69.2%; P = 0.01) for the development of VTE. The average BMI in the cohort of patients who developed VTE was 1.7 kg/m 2 higher than their matched controls.43 Though focused on a homogenous population, data published in 2010 from the Copenhagen City Heart Study also found obesity to be an independent risk factor for the development of VTE.44 Based on their evaluation of more than 360,000 patient-years and nearly 1,000 individual cases of VTE, they observed that a BMI of 30 to 35 carried an HR of 1.65 (1.17–2.34, P = 0.005) for the development of DVT or PE. Their data set also suggested the possibility of graded risk with rising BMI, as the subset of patients with BMI over 35 kg/m2 had an HR of 2.1 (1.39–3.16, P = 12 months total) was associated with a lower prevalence of hypertension, diabetes, and cardiovascular disease.35 These authors estimated that for every 29 women who breastfed for more than one year, one case of postmenopausal hypertension could be prevented. They also estimated that for every 40 women who breast-fed for over one year, one case of hyperlipidemia could be prevented. Parous women who had never breast-fed were 28% more likely to develop cardiovascular disease than women who had breast-fed for 7–12 months. In the Nurses’ Health Study, women

55

676  Chapter 55  Breast-Feeding

who had breast-fed for two years had a 37% decreased risk of coronary heart disease compared to parous women who had never breast-fed.37 Some studies demonstrate that breast-feeding can impact a woman’s future chance of cancers, including breast, ovarian, and uterine. In 2002, a meta-analysis in the Lancet38 analyzed data from 47 studies comprising 50,302 women with breast cancer and 96,973 women without. They showed a decrease in the relative risk of breast cancer of 4.3% for every 12 months of breast-feeding, with an additional relative risk reduction of 7% for each birth. Other evidence has been mixed, however, and many studies may be limited by recall bias. The Nurses’ Health Study looked at the risk of epithelial ovarian cancer in women who breast-fed for over 18 months compared with parous women who had never breast-fed39 and found a significant difference. It has been postulated that this may be related to the presence of antibodies to epithelial mucin (MUC1 antibodies); these antibodies have been associated with a more favorable prognosis in women with ovarian cancer.40 Formation of these antibodies may be precipitated by episodes of mastitis in women who have ever breast-fed.41 A meta-analysis to assess the association between breast-feeding and endometrial cancer shows a durationdependent decreased risk. This is thought to be due to the low estrogen levels during lactation. In addition to the hormonal influence, the strong exfoliation of breast tissue during lactation and the massive epithelial apoptosis at the end of breast-feeding could contribute to the decrease in the risk for cancer by eliminating cells with potentially unfavorable initial DNA damage. Breast-feeding promotes child spacing. The lactational amenorrhea method is up to 98% effective when used properly; women attempting to use this method should be exclusively breast-feeding infants who are under six months of age.42 Women who frequently supplement with formula should be advised to use other contraceptive methods. Hormonal changes induced by breast-feeding may be beneficial to the mother. Oxytocin secretion during the milk ejection reflex assists in uterine involution. Oxytocin secretion is also felt to play a role in maternal–infant bonding.43 Breast-feeding appears to reduce the maternal response to stress,44 perhaps due to modulation of the sympathetic nervous system. The long-term effect of lactation on osteoporosis is unclear. A study on women aged 20–25 who had breastfed their infants during pregnancies as adolescents demonstrated increased DEXA scores compared to women who had infants during their adolescent years but who had not breast-fed.45 Whether this difference persists and has any measurable effect on the development of osteoporosis or decrease in hip fracture rates is still uncertain, with some studies proving an effect,46 and others not.47

55.3.2 Infant Benefits Human breast milk is specifically made for human infants. Similar to other mammals, the composition of milk has the appropriate nutrients to supply a growing infant’s

needs. Many of the beneficial effects of breast-feeding are presumed to be due to the unique factors inherent to human breast milk; formula is an expensive albeit improving imitation. Significant short- and long-term infant benefits to breast-feeding have been identified through extensive epidemiological research. These infant benefits include decreasing rates of chronic diseases and infectious diseases, improving neurodevelopment, and decreasing rates of childhood autoimmune diseases. The breadth and depth of the literature in this topic continue to expand; while areas of controversy certainly remain, the benefits of breast-feeding are numerous. The particular effects of breast-feeding in developing countries should not be overlooked. Morbidity and mortality are lower in breast-fed compared with formula-fed infants. They have a lower incidence of gastroenteritis and respiratory infections.48,49 In developed countries, breastfed infants are hospitalized less and require fewer outpatient visits for acute illness than formula-fed infants. 50 While data extolling the benefits of breast-feeding are vast, breast-feeding research is still incomplete. Some studies are limited by recall bias, as mothers may over- or underreport the time they actually breast-fed their infants. Older studies may be limited by presenting breast-feeding as “ever-breast-fed” versus “never-breast-fed” without taking into account the length of time or role of supplementation. Few are prospective and even fewer are randomized—indeed, it would be unethical to randomize to breast-feeding versus not-breast-feeding. In the review that follows, we have attempted to discuss only points that have stood up to multiple investigations. As in most contentious areas of research, further investigation into the benefits of breast-feeding is crucial, in particular regarding the long-term effects of breast-feeding.

55.3.2.1 Gastrointestinal Effects The fetus has a sterile GI tract; upon delivery and exposure to the outside world, a newborn’s gut is colonized. The colonization of the infant gut begins with delivery. This can take up to one week to become stable.51 Differences in infant gut flora are seen at one month of age based on mode of delivery and on breast or formula feeding.52 Breast-fed infants have a preponderance of Lactobacillus bifidus and Bifidobacterium, up to 95% of organisms in culture. Infants fed formula have a predominantly gram-negative-based flora, including Enterobacter, Bacteroides, Clostridium, and Escherichia coli.53 Infants born through cesarean section may also have a lower number of bifidobacteria and Lactobacillus. Breast milk and colostrum appear to facilitate the preponderance of bifidobacteria; oligosaccharides found in human milk appear to specifically facilitate their growth.54 The actions of lactoferrin and lysozyme in human milk also seem to control growth of pathogenic bacteria.55 Free amino acids such as taurine and glutamine may assist in intestinal growth.56 Compared to formula, human milk increases the rate of gastric emptying,57 increases the lactase activity in premature infants,58 and decreases the intestinal permeability in early life in premature infants.59 There is a great deal of literature from premature infants demonstrating a reduced risk of necrotizing

55.3  Benefits of Breast-Feeding  677

enterocolitis in infants fed breast milk.60 This may be related to a number of anti-inflammatory agents (interleukin 10) and mediators (polyunsaturated fatty acids, PUFAs) present in breast milk.61,62 This may also be due to the large differences in flora seen in these infants compared with infants who are fed only formula.

55.3.2.2 Infectious Processes The immunological factors present in breast milk protect breast-fed babies and infants against infections in the first year of life. The concept of the enteromammary and bronchomammary immune systems may play a role. 29,63 Plasma cells from both of these locations migrate to the mammary epithelium, where they then produce IgA antibodies and provide specific protection against local pathogens. Formula-fed infants are more likely to develop a GI infection within the first year of life than breast-fed babies.64,65 Oligosaccharides also prevent attachment of respiratory pathogens such as Haemophilus influenzae and Streptococcus pneumoniae to respiratory epithelium.66 Breast milk may also transfer an innate immunity against respiratory syncytial virus (RSV). Compared to infants breast-fed for over four months, non-breast-fed infants were shown to be 3.6 times more likely to be hospitalized in their first year of life with lower respiratory tract infections.67 Most hospitalizations for respiratory issues are related to RSV infections. RSV-specific IgA has been shown to be expressed in breast milk,63 and milk lipids have antiviral activity as well. Episodes of acute and recurrent otitis media are also decreased in breast-fed infants. Infants breast-fed for at least four months had half the number of episodes of acute OM compared to infants who were not breast-fed.68 In this same study, infants breast-fed for over six months had a 10% reduction of recurrent OM compared to infants that were breastfed for less than four months.

55.3.2.3 Atopic Disease and Asthma In families with a history of allergic disease, breast-feeding may confer a protective effect on high-risk infants. Infants are at high risk of developing allergic disease when they have one or more affected first-degree relatives. In a metaanalysis of 18 studies, a protective effect against atopic disease (e.g., eczema) was shown with breast-feeding for over three months in infants with an affected first-degree relative.69 The prospective PROBIT trial (Promotion of Breast-feeding Intervention Trial), where breast-feeding was promoted at specific “intervention” hospitals, demonstrated a decreased risk in the first year of developing eczema among infants born at these intervention hospitals.70 Development of asthma also appears to be decreased in infants who have been breast-fed. A meta-analysis of 12 studies demonstrated that less than three months of exclusive breast-feeding increased the risk of developing asthma 1.9 times that of infants who were breast-fed for over three months.71 However, further research is needed, as not all studies support this conclusion. In particular, a large population-based cohort from Tasmania found no protective effect of breast-feeding on the development of

asthma after age seven; in fact, breast-feeding was instead a risk factor for current asthma at age 14 and older.72 Development of food allergies in relationship to breastfeeding is also another issue under scrutiny. Breast-feeding for 4 months or longer may be protective in the development of cow’s milk allergy.73 Once a food allergy has developed, intact allergens may be passed directly into breast milk.74 Regarding peanut allergy, an association between increased consumption by the mother during pregnancy and lactation has been shown to be associated with increased risk of peanut allergy in infants.75,76

55.3.2.4 Other Diseases Available studies point to an increased risk of developing type I diabetes mellitus later in life in infants exposed early to cow’s milk protein or breast-fed for shorter intervals. A meta-analysis from 1994 of available case-control studies showed that patients who had type I DM were less likely to have been breast-fed for >3 months and were more likely to have been exposed to cow’s milk protein under four months old.77 This is theorized to be due to a higher prevalence of islet cell autoantibodies in infants exposed to cow’s milk.78 The risk of developing type 2 DM in breast-fed infants has been studied in several observational trials, but the data are mixed and do not clearly indicate a protective effect. In theory, adipokines, such as ghrelin and leptin, that are present in breast milk79,80 may influence energy intake as well as the risk of future obesity and the metabolic syndrome. The data on childhood obesity and breast-feeding are also mixed. An American study of over 15,000 children showed a decreased risk of obesity from ages 9 to 14 in children who were breast-fed for seven months or longer after adjusting for a number of variables such as energy intake, physical activity, or maternal BMI.81 However, at the 6.5-year follow-up point for the PROBIT trial, children who had been part of the intervention group (increased breast-feeding promotion in the postpartum period, with a three-month continuation rate of 43.3% at three months) did not have any differences in adiposity or blood pressure than children who were part of the control group.82 Clearly, further investigation of this subject is necessary. Breast-feeding may be protective against future development of childhood leukemia, perhaps related to increased immunity to viral infections that may predispose children to the development of leukemia. Breast-feeding over six months is protective against acute lymphoblastic leukemia and acute myeloblastic leukemia.83

55.3.2.5 Neurodevelopment Establishing a clear benefit of breast-feeding on infant cognitive development is challenging. There are numerous variables that may confound studies, including maternal social class, maternal cognitive ability, or intrauterine events. Additionally, breast-feeding may have effects that are limited to the time of active breast-feeding or it may induce a “programming” effect on infants, with effects that carry over into later periods of development.

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We do know that the human brain nearly triples in size in the first year of life.12 Fifty to sixty percent of this growth is lipid. Fatty acid composition appears to be dependent on dietary intake, and breast-fed infants have been shown to have a higher cortical DHA content than formula-fed infants when necropsy specimens were examined after sudden death.84 Brain growth is also associated with increased uptake of PUFAs into cerebral cortex phospholipids. The PROBIT study was able to demonstrate a longterm effect of their breast-feeding intervention on verbal IQ scores—children in the intervention group had scores that were 7.5 points higher at 6.5 years compared to the control group. A study in Honduras randomized children to early introduction of complementary foods at four months versus exclusive breast-feeding for six months. Infants who were in the complementary food group crawled later and were less likely to be walking at 12 months.85 It is postulated that these effects may be related to intake of PUFAs found normally in breast milk. Increased dietary intake of these compounds has been linked to protection against heart disease and inflammatory diseases.86 Visual acuity has been studied in very low birth weight infants who had diets supplemented with omedg-3 fatty acids versus linoleic acid linolenic acid and demonstrated improved parameters compared to the omega 3 only supplemented infants.87 Arachidonic and docosahexaenoic acids have been associated with improved cognition, growth, and vision.88 There is evidence that these two PUFAs regulate a gene called FADS2, which encodes an enzyme involved in their metabolism; in a study investigating this gene, breast-feeding, and IQ, a certain variant was found in over 90% of the study cohort.89 Infants with this variant who were also breast-fed were found to have significantly higher IQs (6.4–7.0 points higher) than infants without this variant; breast-fed infants with other variants did not have the same IQ advantage.

55.4 PRACTICAL MANAGEMENT OF BREAST-FEEDING To establish an optimal cycle of milk production and release, mothers who plan to breast-feed their infants should begin to do so immediately after birth. The WHO

and UNICEF published the guideline, “Ten Steps to Successful Breastfeeding,” in their Baby Friendly Hospital Initiative.90 These provisions are listed in Table 55.1. The ten steps include initiation of breast-feeding within the first hour after delivery. Direct skin-to-skin contact between mother and infant immediately after delivery may assist with latching and future breast-feeding success. Most infants can latch on to the breast within an hour after birth. All infant care may be provided with the infant on the mother during the immediate postpartum recovery period. But most importantly, the memory of her baby successfully nursing immediately postpartum can sometimes help sustain a mother’s confidence that her baby can and will latch through the next ≥24 h, when many newborns are reluctant and uncoordinated feeders. The breast-feeding mother should be supported and educated during her postpartum care in the hospital. Rooming-in allows parents to learn the infant’s feeding cues in order to feed on demand. Direct assistance with and feedback regarding positioning and latching should be provided by nursing and medical staff. Proper positioning is crucial to establishing a proper latch-on. The three common positions are the cradle, football, and side-by-side positions. The infant’s head should be opposite the nipple, with the neck slightly extended. The infant’s head, shoulders, and hips should then be in alignment. Latching involves forming a tight seal between the infant’s lips around the nipple, drawing the nipple into the back of the mouth. The breast may be supported by the mother or her support person’s hand in the shape of a “C,” with four fingers below the breast and the thumb above the areola, pointing toward the midline. The infant’s head and neck are supported with the mother’s other hand, and the infant’s lips can then be rubbed with the nipple to elicit a rooting reflex. As the infant opens his or her mouth wide, the infant’s head is quickly brought to the breast with the mouth over the nipple. A proper latch includes the whole nipple and as much of the areola as possible. The pressure of the infant’s hard palate during suckling compresses lactiferous sinuses beyond the base of the nipple to increase the amount of milk transferred. Specific features of an adequate latch can be assessed. Audible sucking and swallowing can be heard. Both the chin and nose are close to the breast, and the lower lip should be turned out toward the breast. The tongue may extend over the lower dental ridge and should be in contact with the breast when the lower lip is moved away.

TABLE 55.1  Ten steps to successful breast-feeding

1. Have a written breast-feeding policy that is routinely communicated to all health care staff. 2. Train all health care staff in skills necessary to implement this policy. 3. Inform all pregnant women about the benefits and management of breast-feeding. 4. Help mothers initiate breast-feeding within one h of birth. 5. Show mothers how to breast-feed and how to maintain lactation, even if they are separated from their infants. 6. Give newborn infants no food or drink other than breast milk, unless medically indicated. (A hospital must pay fair market price for all formula and infant feeding supplies that it uses and cannot accept free or heavily discounted formula and supplies.) 7. Practice rooming-in—allow mothers and infants to remain together—24 h a day. 8. Encourage breast-feeding on demand. 9. Give no artificial teats or pacifiers to breast-feeding infants. 10. Foster the establishment of breast-feeding support groups and refer mothers to them on discharge from the hospital or clinic. Source:  Adapted from the World Health Organization, Division of Child Health and Development, Evidence for the Ten Steps to Successful Breastfeeding (Revised), World Health Organization, Geneva, Switzerland, 1998

55.4  Practical Management of Breast-Feeding  679

Length of feeding on each breast varies with infant age. In a typical feeding session, the infant should first be offered one breast. Feeding from this breast should continue until the infant demonstrates a loss of interest. The infant should then be offered the second breast and may need to be awakened by undressing, changing the diaper, or repeatedly changing the infant’s position in order to encourage latching. The infant signals satiety by voluntary release of the nipple and relaxation of the facial muscles and hands, and young infants may fall asleep. Breast-feeding for some infants may be soporific, leading to sleep almost immediately after latching on to the breast. In these cases, stimulation of the infant to maintain an awake state in order for milk transfer to occur requires careful attention by the parents. Normal satiety signals may not apply to these infants, and their nutritional adequacy may have to be monitored by weight gain and assessment of hydration. The initial frequency of breast-feeding in the first two weeks postpartum may be as often as every hour, with an average of 8–12 times/day. Breast-feeding mothers should be encouraged to wake their infants at least every four h for feeding during the first two weeks postpartum. This will promote the infant receiving adequate nutrition. The overall frequency of breast-feeding diminishes by four weeks, with an average of seven to nine feedings per day. This is a result of improved nursing skills and increased milk volume. Cluster feeding, or periods where the infant feeds with greater frequency during growth spurts, is also common intermittently. Sore nipples are a frequent challenge for the new nursing mother. The sensation of suckling should be perceived by the mother as a painless undulation. Nipples are increasingly sensitive in the immediate postpartum period, peaking around four days postpartum. Nipple soreness or pain should be differentiated from sensitivity when assessing a woman with this complaint. Normal sensitivity typically goes away after the first minute of suckling and should overall disappear after one week. Nipple pain is typically persistent throughout the cycle of breast-feeding and may be a result of trauma to the nipple. This is frequently the result of poor latch or positioning. Skin breakdown is manifest by blistered, cracking skin with bruising of the nipples and areola. Infant thrush and candidiasis of the breast are a common cause of nipple pain, and both the mother and infant should be treated if this is suspected. In women with sore nipples, the infant should also be assessed for ankyloglossia, or “tongue tie,” which is caused by a tight frenulum limiting tongue extension and possibly impairing latch. Sometimes this requires that the frenulum be clipped—a simple procedure for those familiar with the technique. Additionally, the mother’s choice of breast cleansing agents may play a role in skin breakdown, and the use of harsh agents or abrasive cleansing should be discouraged. Relief of soreness can be provided in several ways. Nipples should be air-dried after nursing to promote healing; in addition, breast milk or colostrum can be expressed and spread on the affected surface and to assist with healing. The use of soap to clean the breast should be avoided as it removes the natural lubrication produced by the glands of Montgomery. Lanolin cream application can

also provide moisture to promote healing. “All Purpose Nipple Ointment,” a combination of mupirocin, steroid cream such as betamethasone, and an antifungal powder, can be prescribed for women with refractory breakdown and pain. Although no formal evaluations of its efficacy have been performed, it is widely used as an apparent helpful adjunct for women in this situation. The formulation is mupirocin 2% ointment (15 g), betamethasone 0.1% ointment (15 g), and miconazole powder mixed to a final concentration of 2%; the ointment is available only through compounding pharmacies. This may be applied sparingly after each feeding and does not need to be washed off between feedings. Most importantly, the mother should be supported and encouraged to continue breast-feeding during the time of nipple soreness. Flat or inverted nipples can be another challenge encountered by the breast-feeding mother. It has been estimated that 10% of women have inverted or non-protractile nipples, which may contribute to breast-feeding problems.91 To diagnose a truly inverted nipple, one may press the areola between the thumb and index finger; an inverted nipple will retract while a normal or flat nipple will protrude. Multiple treatments have been suggested for inverted nipples, such as Hoffman exercises, which involve stretching or pulling on the nipple, or wearing breast shells, which are plastic disks with holes in the center. However, evidence suggests that these do not improve breast-feeding rates in these women.91 When flat or inverted nipples are identified prenatally, mothers should be instructed to seek consultation from a lactation consultant in the postpartum period to address any problems with latching. The use of a pulsatile electric pump may facilitate latch-on in these patients. Sometimes a nipple shield will be required (a nipple-shaped flexible device placed over the areola to help the baby latch), but these should be used only with instruction.

55.4.1 Assessment of Intake Adequacy Infants typically lose 5–7% of body weight in the first five days of life. This weight is usually regained within two weeks. Infants receiving appropriate nutrition should gain between 15 and 40 g/day. The AAP recommends a postdischarge hospital visit within three to five days of age for all breast-feeding infants.92 At this time, the infant should be weighed, breast-feeding practices can be assessed, and the mother can be instructed and encouraged. In our hospital, we give new mothers a checklist to help them track the number of feeds, voids, and bowel movements their infant has on a daily basis. A well-hydrated infant should have three to five voids and three to four stools daily by days three to five, and then four to eight voids and three or more stools daily by days five to seven of age.3 Weight loss greater than 7% from birth weight indicates possible feeding problems and should initiate investigation into practices and improvement of milk transfer. Clinicians caring for the nursing dyad are often faced with the dilemma of when to supplement. Health care workers sometimes offer formula to support tired mothers while not taking into account the adverse effect this may have on the initiation and maintenance of milk supply.

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The American Academy of Breastfeeding Medicine recommends that hospitals have a policy that supplementation of a breast-fed baby requires a physician’s order. Their thorough protocol is available at https://abm.memberclicks.net/assets/DOCUMENTS/PROTOCOLS/3supplementation-protocol-english.pdf.93

Areolar engorgement may be solved by manual expression or warm soaks of the nipple prior to feeding. Women may need to manually express breast milk. However, the most important step is to ensure continued drainage of the breasts, however possible, to prevent increased intraductal pressure, which may ultimately decrease milk supply.16,98

55.4.2 Contraindications to Breast-Feeding

55.5.2 Mastitis

In the United States, there are a few contraindications to exclusive breast-feeding. These are as follows3:

Mastitis is a bacterial infection within breast tissue that may be seen at any time during lactation. This can occur in 2–10% of breast-feeding women, and it is most common within the first six weeks postpartum. The symptoms include redness, tenderness, and warmth of the overlying skin, with systemic symptoms of fever of 101°F or higher, myalgias, and malaise. The most common organisms are staphylococcus species and E.coli; streptococci are less commonly implicated. Risk factors include incomplete emptying of the breasts or missed feedings, plugged ducts, broken skin on the nipples, or breast constriction. Treatment includes oral antibiotic therapy for 10–14 days. Dicloxacillin is first-line in women who are not allergic to penicillins. Sulfa drugs should be avoided for women with infants less than one month. In addition to antibiotics, it is equally important that women with mastitis use local measures to promote recovery. They can continue feeding on both sides and should use heat and massage prior to feedings to increase emptying of the breasts. Many centers are noticing an increase in mastitis caused by methicillin-resistant Staphylococcus aureus (MRSA).99 Trimethoprim-sulfamethoxazole, clindamycin, and linezolid are all appropriate outpatient therapies for women suspected of having MRSA mastitis. If a patient is unresponsive to first-line treatment, milk cultures and sensitivities should be obtained. Imaging is useful if supportive care and antibiotics do not begin to give a response after 48 to 72 hours. Breast abscess formation is an infrequent complication of mastitis, with a reported incidence of 0.1%, and may be related to delayed or inadequate treatment. Ultrasonography is useful for diagnosis. An abscess may be more common when MRSA is the offending organism. The primary treatment is drainage, and fluid collected should be sent for culture and sensitivities. Drainage may be accomplished with needle aspiration, with or without ultrasound guidance, for women without overlying skin changes, and should be repeated every two to three days until the fluid collection resolves.100,101 For women with more advanced cases, incision and drainage should be considered. Both of these approaches require adjunct use of antibiotics with anti-staphylococcal coverage or coverage based on culture results. Breast-feeding should be continued if the site of drainage does not interfere with latching. If interference occurs, pumping or hand expression should continue until feeding can be resumed.

Infant with classic galactosemia Maternal active untreated tuberculosis Maternal positivity for human T-cell lymphotropic virus type I or II Mothers receiving diagnostic or therapeutic radioactive isotopes or with exposure to radioactive materials (at least until the materials are no longer present in the milk) Maternal antimetabolite or chemotherapeutic agent use Maternal drug abuse Active herpes simplex outbreak on the breast Maternal HIV infection is also considered a contraindication to breast-feeding in the United States,94 while in developing countries many experts think that the risks to infants of infectious diseases and nutritional deficiencies outweigh the risks of HIV transmission in breast milk. Maternal infection with hepatitis B or C is not a contraindication to breast-feeding, as the risk of transmission of either of these viruses via breast milk is low.12 Infants born to hepatitis B-positive mothers should receive the hepatitis B immunoglobulin at birth and the full vaccine series; if a breast-feeding mother has acute peripartum hepatitis, it is reasonable to abstain from breast-feeding until its etiology can be determined. Maternal cytomegalovirus (CMV) seropositivity does not seem to be related to significant clinical illness in healthy full-term infants; however, premature infants should not be given milk that is known to be CMVpositive.95 Freeze-thaw cycles may reduce CMV transmission, but further prospective studies are needed. Recent alcohol use is a relative contraindication to breast-feeding, and mothers should be encouraged to abstain from feeding for 2 h after a single alcoholic beverage in general.96,97

55.5 PROBLEMS RELATED TO BREAST-FEEDING 55.5.1 Engorgement Engorgement involves congestion and increased vascularity of the breast, a physiological response following delivery of the placenta, milk accumulation, and edema from swelling and obstruction of lymphatic system drainage by alveolar fullness. When skin edema is noted on the breast, intervention is needed.

55.5.3 Prior Breast Surgery Breast augmentation surgery has become a more accepted and common procedure. Many young women who undergo this surgery do so prior to childbearing and lactation.

55.6  Breast-Feeding Support 

Most implants used are inserted between the chest wall and breast and do not interfere with breast tissue. The incision used to place the implant may be on the axilla or near the areola; for women who desire future breastfeeding, an axillary incision is preferable. Saline implants have replaced silicone implants, and women with intact silicone implants do not have any contraindications for breast-feeding. Because of its destructive nature, breast reduction surgery may pose a different picture for the woman who desires to breast-feed. In 2009, 78,427 women had breast reduction surgery.102 This surgery often interferes with ductal anatomy and the innervation of the remaining tissue. Breast-feeding may be successful in up to 65% of women after reduction,103,104 depending somewhat on the location of tissue removed. Importantly, breast-feeding should not be discouraged in these patients. They should instead be offered anticipatory guidance and support, and the baby’s weight should be carefully monitored. Women who have undergone breast surgery may find the website www.BFAR.org105 a helpful resource—this site compiles information and supports resources for women who have undergone breast or nipple surgery.

55.5.4 Medications and Lactation The risks and benefits of medications in lactating women must be considered by all prescribers. Many factors influence the passage of a medication into the milk supply as well as its effect on infants. These include consideration of each drug’s route of administration, absorption, size, solubility, and protein binding. Passive diffusion is the main way most drugs enter into milk. The effects of drugs on the infant itself is often less well studied but is important to consider, as nearly any drug a breast-feeding mother consumes will be found in her milk. Length of time of administration may be a factor. In certain cases, a woman may need to pump and discard milk until she has completed her course of therapy. As women breast-feed for longer periods of time, physicians from all medical specialties will care for them and will need to be familiar with the principles of medication use. Many resources exist both online and in print form. LactMed106 is a searchable online reference developed by an expert panel through the National Library of Medicine. The web address is http:​//tox​net.n​lm.ni​h.gov​/ cgi-​bin/s​is/ht​mlgen​?LACT​.

55.6 BREAST-FEEDING SUPPORT Support for breast-feeding is best begun with the provider in routine medical encounters but does not end there. Physicians and other providers should educate themselves about the resources in their own community to better serve their breast-feeding mothers. International Board Certified Lactation Consultants (IBCLCs) are specialists in the clinical management of breast-feeding. They may work in a variety of settings, including hospitals, pediatric practices, private clinics, and public health settings. They provide support and

681

management of many common breast-feeding concerns. In the United States, the International Lactation Consultant Association is the professional association for IBCLCs, and their website, www.ilca.org, provides information about practitioners throughout the country. As of 2016, the United States had over 15,000 IBCLCs, with practitioners in every state.107 Many community resources also exist. La Leche League, International (LLLI), is an international organization initially formed in the 1950s to combat low breastfeeding rates. Today, they have a global mission to help women breast-feed. Their Internet resources are available to practitioners and patients at www.llli.org, and there are LLL chapters in every U.S. state.108 Many states offer additional breast-feeding resources and support. The U.S. Breast-feeding Committee is an independent nonprofit coalition with organizations in all 50 states. Their website, http://www.usbreastfeeding.org/, provides links to the coalition sites for each state, which in turn provides resources for patients and practitioners in their areas.109 Often hospitals or sometimes organizations that do childbirth education have breast-feeding support programs. Identifying such local options is important for those who work in clinical settings that frequently deal with the breast-feeding dyad.110

55.6.1 Pumping Breast Milk (Working and Nursing) With so many women in the workforce, it is impossible to meet national breast-feeding goals without the expression of breast milk, often referred to as pumping. The commercial market for breast pumps has expanded greatly from the initial manual pumping devices. These devices are all FDA-regulated and are available to mothers for purchase or rent. Many insurance companies cover these for various indications, in particular for mothers who must be separated from their infant. In most states, Women, Infants, and Children (WIC) also provides breast pumps at no cost. Pumping supplies are now considered a deductible medical expense by the IRS.111 For women who plan to pump only occasionally, manual pumps or battery-operated pumps may be adequate. For women who intend to return to work, need to pump large volumes of milk for their infant for any reason, or need to stimulate their milk supply, an electric pump is ideal. The federal Fair Labor Standards Act states that employers are required to provide “reasonable break time for an employee to express breast milk for her nursing child for 1 year after the child’s birth each time such employee has need to express the milk.”112 Employers are also required to provide “a place, other than a bathroom, that is shielded from view and free from intrusion from coworkers and the public, which may be used by an employee to express breast milk.” While there are exceptions to these rules, an increasing number of workplaces are making breast-feeding facilities available to their workers. Legislation protecting a woman’s right to breastfeed in public and at work is an important component to reaching national breast-feeding goals.

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Ideally, women should empty their breasts at the same frequency they would as if they were doing in-person feeding. This helps maintain the supply necessary for adequate nutrition. Mothers who pump should also be encouraged to breast-feed while at home, not only for the purpose of feeding but also to promote bonding and maintain supply. Massage of the breast while pumping increases delivery of hindmilk as well. The Human Milk Banking Association of North America recommends storage of breast milk at room temperature (101°F (>38.3°C) • abnormal cervical mucopurulent discharge or cervical friability • presence of abundant numbers of WBC on saline microscopy of vaginal fluid • elevated erythrocyte sedimentation rate • elevated C-reactive protein • laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis The most specific criteria for diagnosing PID include: • endometrial biopsy with histopathologic evidence of endometritis • transvaginal sonography or magnetic resonance imaging techniques showing thickened, fluid-filled tubes, with or without free pelvic fluid, or a tuboovarian complex, or Doppler studies suggesting pelvic infection (e.g. tubal hyperemia) • laparoscopic findings consistent with PID Most cases of PID are considered polymicrobial. 22 As an inpatient, Cefoxitin 2 grams IV every six hours with doxycycline 100 mg orally, twice daily for 14 days is recommended. Cefotetan plus doxycycline or clindamycin plus gentamicin may also be used. There are alternative regimens available if a patient has known allergies. As an outpatient, a single dose of ceftriaxone 250 mg intramuscularly, as well as doxycycline 100 mg orally, twice daily for 14 days, plus or minus Metronidazole 500 mg orally, twice daily for 14 days is recommended.

57.3.3 Chlamydia Chlamydial infection is caused by the bacteria C. trachomatis. It is the most commonly reported STI in the United

57.3  Diagnosis and Treatment of Sexually Transmitted Infections  701

States, with almost 1.6 million cases reported in 2016. 27 The rate of reported cases of chlamydia among African Americans is 5.9 times the rate among Caucasians. 28 Because nearly 50% of infected women are asymptomatic, the number of reported cases is likely underrepresented. Transmission of genital chlamydia from men to women and vice versa is efficient, at approximately 70%. 28 Adolescents and young adults, ages 15–24, are at increased risk due to a combination of biological, behavioral, and cultural reasons. Cervical ectopy in young women, with columnar epithelium extending onto the external surface of the cervix, may be more susceptible to infection and friable during intercourse. 28 Rectal and oropharyngeal infection can occur, but the clinical significance of these infections is unclear. Routine screening of these areas of possible infection is not recommended by the CDC. Less commonly, invasive serovars, L1, L2, and L3, of C. trachomatis can cause lymphogranuloma venereum, an inflammation of the lymphatics and inguinal lymph nodes. This infection is more common in men who have sex with men and patients with HIV infection. Symptoms include genital ulceration, urethritis, or proctitis, followed by secondary inguinal lymphadenopathy and tertiary genital elephantiasis, lymph node scarring, and fissures. 29 There are several methods used for laboratory detection of chlamydial infection. The patient may provide a “dirty” or first-catch urine specimen, or the provider may collect a cervical or vaginal swab. Nucleic Acid Amplification Testing (NAATs) is the preferred testing method. 27 Treatment of chlamydia can help prevent adverse reproductive health outcomes and continued sexual transmission. There are two recommended treatment regimens. A single one-gram dose of azithromycin may be administered, which has increased compliance. Alternatively, 100 mg of doxycycline twice daily for seven days may be given. Both of these regimens have excellent efficacy. For pregnant women or women with allergies, there are a number of other acceptable alternative regimens. Untreated chlamydia leads to PID in approximately 30% of cases. Sexual contacts should be treated if possible, because most post-treatment infections do not result from treatment failure but from reinfection. Cure rates with recommended treatment regimens approach 100%. However, because of high reinfection rates, men and women who are treated for chlamydia should be retested in three months. They should abstain from sexual intercourse for seven days from single dose treatment or until a seven day course of treatment is completed. The use of chlamydial NAATs at 5 mm, but consideration for biopsy should be given for any symptomatic woman.120 Another study found that in 82 women with an incidentally found, suspected endometrial polyp on imaging, who subsequently underwent evaluation with operative hysteroscopy, no malignancy was found. Sixty-eight polyps were found, of which one contained simple endometrial hyperplasia. No premalignant conditions, such as complex atypical hyperplasia, were found. The overall complication rate reported was 3.6%.121 A larger study examined 1,152 women who underwent hysteroscopic removal of polyps found during sonohysterography. The women were all asymptomatic and postmenopausal. There was one endometrial cancer in a polyp (5 years) was associated with an increased risk of CIN 2 or 3, but this finding disappeared after adjustment for age, smoking, and HPV infection. In the adjusted analysis, a history of pregnancy was associated with increased risk. A dose–dependent significantly increased risk with smoking was reported, which was found to be present even after adjustment for HPV exposure.146 Tobacco smoking has been implicated as a significant risk factor in the development of high-grade cervical dysplasia and cervical cancer. This may be mediated either by direct carcinogenic activity on cervical cells or through

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suppression of the immune system’s ability to clear HPV infection. A 10-year prospective study in Oregon enrolled 1,812 women identified to have infection with high-risk HPV at enrollment and completed a survey regarding smoking, oral contraceptive use, and reproductive history. Oral contraceptive use and parity were not associated with the development of high-grade dysplasia (CIN 3) or cervical cancer. Final analysis demonstrated an increased risk of CIN 3 or cervical cancer for current or former smokers, with odds ratios 2.9–4.3, with the highest risk in those smoking more than one pack per day.147 Several cohort studies have examined alcohol use and risk of cervical cancer and found increased risk; however, many did not adjust for confounding factors such as HPV infection, number of sexual partners, smoking, or access to Pap screening. Several of those studies were also performed in select populations (waitresses, alcohol abusers). In the Million Women Study, which was conducted in the general population and controlled for the aforementioned confounding factors, no association between alcohol consumption and risk of cervical cancer was reported. Case– control study results have been mixed, with no overall, clear association but a positive trend toward increased risk with increased alcohol consumption.148 In prior studies, higher intake of fruits and vegetables and certain micronutrients has been associated with a decreased risk of cervical dysplasia, but the evidence is largely from observation and is not overwhelming. A recent case–control study compared 231 women diagnosed with CIN 3 to 453 controls. Significantly reduced fruit and vegetable intake was noted when those with CIN 3 were surveyed, compared with controls. Smokers in both groups reported lower overall fruit and vegetable consumption. Sexual history and reproductive factors were similar among both smokers and nonsmokers in the CIN 3 group. Lower fruit and vegetable intake was associated with an increased risk of high-grade cervical dysplasia, with an odds ratio of 1.14. However, smokers with a higher intake of fruits and vegetables had a higher risk, with an odds ratio of 1.83. The study suggests a

weak association with dietary intake, but a stronger effect of smoking on the development of cervical dysplasia.149 There have been some studies showing benefit from vitamins C and E, carotene, and lycopene in ameliorating HPV persistence. Additionally, folate, retinol, vitamin B12 , lutein, and cryptoxanthin have been discussed as protective against cervical neoplasia. However, most analyses do not demonstrate strong evidence for dietary protection when HPV is taken into account.150

59.5.4 Intervention/Prevention A recent development in the prevention of cervical cancer has been the introduction of the vaccines Gardasil and Cervarix. Both are protective against the high-risk HPV strains 16 and 18, which have been implicated as being the most frequent strains associated with cervical cancer in the United States. Gardasil adds additional protection against HPV strains 6 and 11, which are low risk for the development of cervical cancer but cause genital warts. In the approximate three-year follow-up of the vaccines, the efficacy of Gardasil has been reported to be near 100% for HPV 16 and 18 CIN 2/3, adenocarcinoma in situ, vulvar intraepithelial neoplasia 2/3, and vaginal intraepithelial neoplasia 2/3 (high-risk dysplasia or carcinoma in situ). Similarly, 99–100% efficacy for genital warts was reported. Cervarix was found to have a rate of 93% protection for HPV-16 and -18-associated lesions. Both have also demonstrated cross-protection for several other strains of HPV. Even if sexual activity has been initiated, it should not preclude administration of the vaccine, as women may not have been exposed to any or all strains of HPV covered by the vaccines. The vaccines are currently approved for routine vaccination of girls aged 11–12 years, at the physician’s discretion at ages nine to 10, and for catch-up vaccination at ages 13–26. Gardasil has also been approved for males aged nine to 26 for the prevention of genital warts but could potentially also reduce the burden of HPV transmission.151

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52. Darbre PD. Metalloestrogens: An emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. J Appl Toxicol. 2006; 2693): 191–7. 53. Sappino AP, et al. Aluminum promotes anchorage-independent growth in human mammary epithelial cells. J Appl Toxicol 2012; 32(3): 233–43. 54. Manello F, et al. Analysis of aluminium content and iron homeostasis in nipple aspirate fluids from healthy women and breast cancer-affected patients. J Appl Toxicol 2011; 31(3): 262–9. 55. Pineau, et al. If exposure to aluminum in antiperspirants presents health risks, its content should be reduced. J Trace Elem Med Biol 2014; 28(2): 157–50. 56. Guillard O, et al. Hyperaluminemia in a woman using an aluminum-containing antiperspirant for 4 years. Am J Med 2004; 117(12): 956–9. 57. Flynn-Evans EE, et al. Total visual blindness is protective against breast cancer. Cancer Causes Control 2009; 29(9): 1753–6. 58. He C, et al. Circadian disrupting exposures and breast cancer risk: A metaanalysis. Int Arch Occup Environ Health 2015; 88(5): 533–47. 59. Hurley S, et al. Light at night and breast cancer risk among California teachers. Epidemiology 2014; 25(5): 697–706. 60. Bauer SE, et al. A case-referent study: Light at night and breast cancer risk in Georgia. Int J Health Geogr 2013; 12: 23. 61. Loog I, et al. Light at night co-distributes with incident breast but not lung cancer in the female population in Israel. Chronobiol Int 2008; 25(1): 65–81. 62. Li Q, et al. Light at night and breast cancer risk: Results from a population-based case-control study in Connecticut, USA. Cancer Causes Control 2010; 21912): 2281–5. 63. Collaborative Group on Hormonal Factors in Breast Cancer. Alcohol, tobacco, and breast cancer— Collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 2002; 87: 1234–1245. 64. Rice LW. Hormone prevention strategies for breast, endometrial, and ovarian cancers. Gynecol Oncol 2010; 118(2): 202–207. 65. Hastert TA, et al. Adherence to WCRF/ AICR cancer prevention recommendations and risk of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 2013; 22(9): 1498–508. 66. Peters TM, et al. Intensity and timing of physical activity in relation to postmenopausal breast cancer risk: The prospective NIH-AARP diet and health study. BMC Cancer 2009; 9: 349. 67. Schorge SO, et al. SGO White Paper on ovarian cancer: Etiology, screening and surveillance. Gynecol Oncol 2010; 119(1): 7–17. 68. Titus-Ernstoff L, Perez K, Cramer DW, Harlow BL, Baron JA, Greenberg ER. Menstrual and reproductive factors in relation to ovarian cancer risk. Br J Cancer 2001; 84: 714–721. 69. Yen ML, Yen BL, Bai CH, Lin RS. Risk factors for ovarian cancer in Taiwan: A case-control study in a low-incidence

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87. Riman T, et al. Some life-style factors and the risk of invasive epithelial ovarian cancer in Swedish women. Eur J Epidemiol 2004; 19: 1011–1019. 88. Jordan SJ, Whiteman DC, Purdie DM, Green AC, Webb PM. Does smoking increase ovarian cancer risk? A systematic review. Gynecol Oncol 2006; 103(3): 1122–1129. 89. Modugno F, Ness RB, Allen GO. Alcohol consumption and the risk of mucinous and nonmucinous epithelial ovarian cancer. Obstet Gynecol 2003; 102: 1336–1343. 90. Chang ET, et al. Wine and other alcohol consumption and risk of ovarian cancer in the California Teachers Study cohort. Cancer Causes Control 2007; 18: 91–103. 91. Schulz M, et al. No association of consumption of animal foods with risk of ovarian cancer. Cancer Epidemiol Biomarkers 2007; 16(4): 852–855. 92. Thomson CA, et al. The role of antioxidants and vitamin A in ovarian cancer: Results from the Women’s Health Initiative. Nutr Cancer 2008; 60(6): 710–719. 93. Silvera S, Jain M, Howe G, Miller A, Rohan T. Dietary fiber intake and ovarian cancer risk: A prospective cohort study. Cancer Causes Control 2007; 18: 335–341. 94. Rossing MA, Cushing-Haugen KL, Wicklund KG, Doherty JA, Weiss NS. Recreational physical activity and risk of epithelial ovarian cancer. Cancer Causes Control 2010; 21: 485–491. 95. Hannan LM, et al. Physical activity and risk of ovarian cancer: A prospective cohort study in the United States. Cancer Epidemiol Biomarkers Prev 2004; 13(5): 765–770. 96. Myung SK, Ju W, Choi HF, Kim SC. Soy intake and risk of endocrine-related gynaecological cancer: A meta-analysis. BJOG 2009; 116: 1697–1705. 97. Larsson SC, Wolk A. Tea consumption and ovarian cancer risk in a populationbased cohort. Arch Intern Med 2005; 165: 2683–2686. 98. Ness RB, et al. Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives. SHARE Study Group. Steroid Hormones and Reproductions. Am J Epidemiol 2000; 152: 233–241. 99. Beral V, et al. Mortality associated with oral contraceptive use: 25 Year follow up of cohort of 46,000 women from Royal College of General Practitioners’ oral contraception study. BMJ 1999; 318: 96–100. 100. Tworoger SS, Faireld KM, Colditz GA, Rosner BA, Hankinson SE. Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. Am J Epidemiol 2007; 166: 894–901. 101. Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: Collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol 1992; 136: 1184–1203. 102. Hankinson SE, et al. Tubal ligation, hysterectomy, and risk of ovarian cancer. JAMA 1993; 270: 2813–2818.

103. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingooophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 2009; 101: 80–87. 104. Finch A, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA 2006; 296: 185–192. 105. Lu KH, et al. Occult ovarian tumors in women with BRCA1 or BRCA2 mutations undergoing prophylactic oophorectomy. J Clin Oncol 2000; 18: 2728–2732. 106. Kauff ND, et al. Risk-reducing salpingooophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002; 346: 1609–1615. 107. Society of Gynecologic Oncologists Clinical Practice Committee statement on prophylactic salpingo-oophorectomy. Gynecol Oncol 2005; 98: 179–181. 108. King MC, Marks JH, Mandell JB, Group New York Breast Cancer Study. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003; 302: 643–646. 109. Schmeler KM, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the lynch syndrome. N Engl J Med 2006; 354: 261–269. 110. ACOG Practice Bulletin 65. Obstet Gynecol 2005; 106(2): 413–425. 111. Fearnley E, et al. Australian Ovarian Cancer Study Group and Australian National Endometrial Cancer Study Group. Polycystic ovarian syndrome increases the risk of endometrial cancer in women aged less than 50 years: An Australian case-control study. Cancer Causes Control 2010; 21(12): 2303– 2308. E-pub ahead of print). 112. Smith R, et al. American Cancer Society guidelines for the early detection of cancer: Update of early detection guidelines for prostate, colorectal, and endometrial cancers. CA Cancer J Clin 2001; 51: 38–75. 113. Fader A, Arriba L, Frasure H, Von Gruenigen V. Endometrial cancer and obesity: Epidemiology, biomarkers, prevention, and survivorship. Gynecol Oncol 2009; 114: 121–127. 114. Soliman P, et al. Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol 2005; 105: 575–580. 115. Emons G, Fleckenstein G, Hinney B, Huschmand A, Heyl W. Hormonal interactions in endometrial cancer. Endocr Relat Cancer 2000; 7: 227–242. 116. Lu KH. Hereditary gynecologic cancers: Differential diagnosis, surveillance, management and surgical prophylaxis. Fam Cancer 2008; 7: 53–58. 117. Resnick K, Hampel H, Fishel R, Cohn D. Current and emerging trends in Lynch syndrome identification in women with endometrial cancer. Gynecol Oncol 2009; 114(1): 128–134. 118. Lancaster JM, et al. Society of gynecologic oncologists education committee statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol 2007; 107: 159–162. 119. Goldstein S. Modern evaluation of the endometrium. Obstet Gynecol 2010; 116: 168–176.

References  731 120. Smith-Bindman R, Weiss E, Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol 2004; 24(5): 558–565. 121. Lev-Sagie A, Hamani Y, Imbar T, Hurwitz A, Lavy Y. The significance of intrauterine lesions detected by ultrasound in asymptomatic postmenopausal patients. BJOG 2005; 112: 379–381. 122. Ferrazzi E, et al. How often are endometrial polyps malignant in asymptomatic postmenopausal women? A multicenter study. Am J Obstet Gynecol 2009; 200: 235.e1–235.e6. 123. Renehan A, Tyson M, Egger M, Heller R, Zwahlen M. Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371: 569–578. 124. Moore SC, Gierach GL, Schatzkin A, Matthews CE. Physical activity, sedentary behaviours, and the prevention of endometrial cancer. BJ Cancer 2010; 103: 933–938. 125. John EM, Koo J, Horn-Ross PL. Lifetime physical activity and risk of endometrial cancer. Cancer Epidemiol Biomarkers Prev 2010; 19(5): 1276–1283. 126. Terry P, Baron JA, Weiderpass E, Yuen J, Lichtenstein P, Nyren O. Lifestyle and endometrial cancer risk: A cohort study from the Swedish Twin Registry. Int J Cancer 1999; 82: 38–42. 127. Bandera EV, et al. Fruits and vegetables and endometrial cancer risk: A systematic literature review and meta-analysis. Nutr Cancer 2007; 58: 6–21. 128. Bravi F, et al. Food groups and endometrial cancer risk: A case-control study from Italy. Am J Obstet Gynecol 2009; 200: 293.e1–293.e7. 129. McCullough ML, et al. A prospective study of fruits, vegetables, and risk of endometrial cancer. Am J Epidemiol 2007; 166: 902–911. 130. Bertone-Johnson E. Vitamin D and breast cancer. Ann Epidemiol 2009; 19: 462–467.

131. Kakuta Y, et al. Case-control study of green tea consumption and the risk of endometrial endometrioid adenocarcinoma. Cancer Causes Control 2009; 20: 617–624. 132. Mueck A, Seeger H, Rabe T. Hormonal contraception and risk of endometrial cancer: A systematic review. Endocr Relat Cancer 2010; 17: R263–R271. 133. Hubacher D, Grimes DA. Noncontraceptive health benefits of intrauterine devices: A systematic review. Obstet Gynecol Surv 2002; 57(2): 120–128. 134. Scarselli G, et al. Levonorgestrel-releasing intrauterine system. LNG-IUS) as an effective treatment option for endometrial hyperplasia: A 15-year follow-up study. Fertil Steril 2010; 95(1): 420–422. 135. Cade TJ, Quinn MA, Rome RM, Neesham D. Progestogen treatment options for early endometrial cancer. BJOG 2010; 117: 879–884. 136. Moore D. Cervical cancer. Obstet Gynecol 2006; 107: 1152–1161. 137. ACOG Practice Bulletin 61. Obstet Gynecol 2005; 105(4): 905–918. 138. Melkert PW, et al. Prevalence of HPV in cytomorphologically normal cervical smears, as determined by the polymerase chain reaction, is age-dependent. Int J Cancer 1993; 53: 919–923. 139. Kjaer SK, et al. Determinants for genital human papillomavirus. HPV) infection in 1000 randomly chosen young Danish women with normal Pap smear: Are there different risk profiles for oncogenic and nononcogenic HPV types? Cancer Epidemiol Biomarkers Prev 1997; 6: 799–805. 140. Duong TH, Flowers LC. Vulvo-vaginal cancers: Risks, evaluation, prevention, and early detection. Obstet Gynecol Clin North Am 2007; 34(4): 783–802. 141. ACOG Practice Bulletin 109. Obstet Gynecol 2009; 114: 1409–1420. 142. Sonnex C, Strauss S, Gray JJ. Detection of human papillomavirus DNA on the fingers of patients with genital warts. Sex Transm Infect 1999; 75: 317–319.

143. Van Doornum GJ, et al. Prevalence of human papillomavirus infections among heterosexual men and women with multiple sexual partners. J Med Virol 1992; 37: 13–21. 144. Munoz N, et al. Role of parity and human papillomavirus in cervical cancer: The IARC multicentric case control study. Lancet 2002; 359: 1093–1101. 145. International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical cancer and hormonal contraceptives: Collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet 2007; 370: 1609–1621. 146. Kjellberg L, et al. Smoking, diet, pregnancy, and oral contraceptive use as risk factors for cervical intraepithelial neoplasia in relation to human papillomavirus infection. Br J Cancer 2000; 82(7): 1332–1338. 147. Castle PE, et al. A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. J Natl Cancer Inst 2002; 94(18): 1406–1414. 148. Hjartaker A, Meo M, Weiderpass E. Alcohol and gynecological cancers: An overview. Eur J Cancer Prev 2010; 19: 1–10. 149. Tomita L, Roteli-Martins C, Villa L, Franco E, Cardoso M. Associations of dietary deep-green and dark-yellow vegetables and fruits with cervical intraepithelial neoplasia: Modification by smoking. Br J Nutr 2010; 24: 1–9. 150. Garcia-Closas R, Castellsague X, Bosch X, Gonzalez CA. The role of diet and nutrition in cervical carcinogenesis: A review of recent evidence. Int J Cancer 2005; 117: 629–637. 151. Garland SM, Smith JS. Human papillomavirus vaccines, current status and future prospects. Drugs 2010; 70(9): 1079–1098.

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XII PA RT

Cardiovascular Rehabilitation and Secondary Prevention Kathy Berra, MSN, NP-BC, FAANP, FPCNA, FAHA, FAAN and Barry A. Franklin, PhD

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Medication Dosing and Adherence in Secondary Prevention Ozlem Bilen, MD and Nanette K. Wenger, MD, MACC, MACP, FAHA

Key Points.................................................................................. 735 60.1  Optimal Medical Management in Secondary Prevention...... 735 60.2  Potential Explanations....................................................... 736 60.3  Medication Nonadherence: Scope of the Problem............. 736 60.4  Factors Contributing to Medication Nonadherence............ 737

KEY POINTS • Pharmacotherapies shown to reduce risk of death, stroke, recurrent coronary ischemia following Acute Myocardial Infarction are often not titrated to the recommended dose following discharge. • Medication nonadherence following hospital discharge is associated with adverse clinical outcomes. • Medication nonadherence can be a result of poorquality provider–patient interactions, polypharmacy, low health literacy, and cost, among others. • Mobile Health Technologies with two-way communications can improve adherence.

60.1 OPTIMAL MEDICAL MANAGEMENT IN SECONDARY PREVENTION The cornerstones of secondary prevention of myocardial infarction (MI) are drug therapy, cardiac rehabilitation, and lifestyle measures. The latter are discussed elsewhere while this chapter addresses solely pharmacotherapy. Several clinical trials have shown that certain pharmacotherapies are efficacious in reducing the risk of MI, death, stroke, or recurrent coronary ischemia in patients surviving initial therapy for MI. Trials comparing low vs. high doses of these medications have demonstrated that optimal dosing is necessary to achieve the full clinical benefit of these therapies.1–3 For statins, two large clinical trials have shown that higher statin doses are superior in reducing the risk of rehospitalization and death after an AMI.4,5 A trial comparing low vs. high doses of lisinopril and a second comparative effectiveness study of different

60.5  Strategies to Improve Adherence...................................... 738 60.6 Conclusion........................................................................ 738 60.7  Future Directions.............................................................. 738 Clinical Implications................................................................... 738 References................................................................................ 738

doses of both losartan and candesartan demonstrated that higher doses of these classes of medications reduced the risk of heart failure hospitalizations and death. 2,3 Finally, for beta-blockers, two trials of heart failure patients showed that target doses of bucindilol and carvedilol were associated with greater improvement in ejection fraction, fewer hospitalizations, and lower mortality compared with low or moderate doses.1,6 In an effort to standardize and improve the quality of care provided to patients with MI, the American College of Cardiology and American Heart Association developed performance measures to quantify the use of evidence-based treatments.7 The goal of these measures is to promote the widespread and uniform application of best practices in MI care and, in turn, improve patients’ survival and quality of life.8 Current performance measures assess whether patients are prescribed selected medications but not the dose of treatment. Often, lower doses of secondary prevention medications are initiated at hospital discharge and doing so may be reasonable, particularly in patients with marginal hemodynamics (e.g. low blood pressure or heart rate) or left ventricular (LV) systolic dysfunction. However, these therapies should be quickly up-titrated after discharge to the levels with established benefit in clinical trials. Also, unfortunately, some patients initiated on and tolerating appropriate high-dose statins at admission for an MI are discharged on a lower dose of the statin medication. Although several studies have reported rates of medication treatment among patients hospitalized with MI at discharge and follow-up, these studies have not examined treatment doses or intensification of therapy over time.9–11 Arnold et al. assessed treatment doses of beta-blockers, statins, and angiotensin converting enzyme inhibitor [ACE] or angiotensin II receptor blocker [ARB] at discharge and 12 months after AMI among 6,748 patients from 31 hospitals enrolled in

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two U.S. registries (2003–08). Prescribed doses were categorized as none, low (87%) were prescribed some dose of each medication at discharge; however, only one in three patients were prescribed these medications at goal doses. Of patients not discharged on goal doses, up-titration during follow-up occurred infrequently (~25% of patients for each medication). At 12 months, goal doses of beta-blockers, statins, and ACE/ARBs were achieved in only 12%, 26%, and 32% of eligible patients, respectively. After multivariable adjustment, prescription of goal dose at discharge was strongly associated with being at the goal dose at follow-up: beta-blockers, adjusted odds ratio (OR): 6.08 (95% CI: 3.70–10.01); statins, adjusted OR: 8.22 (95% CI: 6.20–10.90); ACE/ARBs, adjusted OR: 5.80 (95% CI: 2.56–13.16); p 50% of the target doses.13 Another study of 382 patients with AMI from 41 hospitals found that 76% of patients discharged on a statin were on the same dose one year later, with intensification of therapy occurring in only 12%.14 Therefore, although it is important that trialproven effective doses of medications be used, this is not routinely done.

60.2 POTENTIAL EXPLANATIONS There are several potential reasons as to why patients might have been treated at doses far lower than those with the most established efficacy. First, some patients who are on lower doses of medications are truly receiving their maximally tolerated dose (e.g. low blood pressure for beta-blockers and ACE/ARBs) Furthermore, there may be some patients who were not up-titrated due to side effects, such as light-headedness or myalgias, or due to patient preference. Second, as hospitalization stays for MI have continued to decrease over the past decade,15 clinicians today have less time to optimize medical therapy during the index hospitalization and, thus, defer intensification of medication therapy until outpatient follow-up. However, there is significant clinical inertia in intensifying treatment during the outpatient period. Some clinicians may not view up-titration of these medications as an important therapeutic goal, are unaware of the target medication doses (i.e. the doses with proven, best clinical efficacy), or have other competing medical issues that they need to address during follow-up visits.16 Interestingly, compared to primary care physicians, cardiologists may be more aggressive in up-titrating these medications.12 As current

performance measures evaluate only whether patients are on a medication, clinicians also may mistakenly equate being on a treatment as being on the most effective treatment. Strategies such as improved care coordination at discharge17 or outpatient tools that assist providers with automating medication titrations (e.g. pharmacist-assisted monitoring, clinical reminders, education, and feedback) may lead to greater success in treatment intensification during follow-up.18

60.3 MEDICATION NONADHERENCE: SCOPE OF THE PROBLEM Medication success requires both compliance of the prescribing physician and adherence of the patient. It is a particularly important modifiable, behavioral risk factor and is a cornerstone of cardiovascular disease (CVD) management. Nonadherence in CVD is associated with adverse outcomes and increased healthcare costs.19,20 Nonadherence costs the United States healthcare system over $100 billion in avoidable costs annually. Because of the importance of nonadherence as a global health issue, the World Health Organization (WHO) released a report, “Adherence to Long-Term Therapies: Evidence for Action” in 2003. The WHO proposed a five-dimensional model of adherence that incorporates social and economic factors, therapy-related factors, patient factors, conditionrelated factors, and health system or healthcare team factors as contributors to adherence. 21 Particularly for chronic diseases such as CVD and hypertension, improving adherence would have a far greater impact on health than developing additional therapies. Several studies have demonstrated an association between suboptimal medication adherence and adverse clinical outcomes among patients with CVD. 22However, as with other chronic diseases, many patients with CVD have suboptimal adherence to medications. Among patients with a previous MI, adherence rates range from 13% to 61%. 23,24 Ho et al. retrospectively analyzed a cohort of 15,767 patients with coronary artery disease (CAD). Medication adherence was calculated as the proportion of days covered for filled prescriptions of beta-blocker, ACE inhibitor, and statin medications. Median follow-up was 4.1 years. Rates of medication nonadherence were 28.8% for beta-blockers, 21.6% for ACE inhibitors, and 26.0% for statins. In unadjusted analysis, nonadherence to each class of medication was associated with higher all-cause and cardiovascular mortality. In multivariable analysis, nonadherence remained significantly associated with increased all-cause mortality risk for beta-blockers (hazard ratio [HR] 1.50, 95% CI: 1.33–1.71), ACE inhibitors (HR 1.74, 95% CI: 1.52–1.98), and statins (HR 1.85, 95% CI: 1.63–2.09). In addition, nonadherence remained significantly associated with higher risk of cardiovascular mortality for beta-blockers (HR 1.53, 95% CI: 1.16– 2.01), ACE inhibitors (HR 1.66, 95% CI: 1.26–2.20), and statins (HR 1.62, 95% CI: 1.124–2.13). The findings of increased risk associated with nonadherence were consistent for cardiovascular hospitalizations and revascularization procedures. 25

60.4  Factors Contributing to Medication Nonadherence  737

It is important that patients remain adherent to medications in the months and years following admission for MI to derive the long-term benefit demonstrated in clinical trials. In a multicenter study of 13,830 patients, for patients prescribed medications at discharge, 8–20% no longer reported taking the medication at the six-month follow-up. Adherence to aspirin (92%), statins (87%), and beta-blockers (88%) was slightly higher than for ACE inhibitors (80%). Multivariate analysis showed that adherence to aspirin and beta-blocker therapy was related to age, with younger patients more likely to have better adherence than older patients. Care by a cardiologist, as opposed to a nonspecialist, correlated with greater adherence to aspirin therapy, while adherence to beta-blocker therapy was greater among patients with ST segment elevation AMI. 26 One study conducted in Germany reported that aspirin use in post myocardial infarction patients was 80% in patients contacted a few months to several years after discharge. 27 Roe et al. showed that compliance with ACE inhibitor therapy in heart failure patients six months following discharge was 65%. 28 The United Kingdom MediPlus Study reported six-month compliance rates of 40% to 50% for beta-blockers and ACE inhibitors in patients with hypertension. 29 Krumholz et al. reported a six-month compliance of 53% for ACE inhibitors used for left ventricular dysfunction after myocardial infarction.30 Newby et al., using the Duke Databank for Cardiovascular Disease for the years 1995–2002, determined the annual prevalence and consistency of selfreported use of aspirin, beta blockers, lipid-lowering agents, and their combinations in all CAD patients and of ACE inhibitors in those with and without heart failure. Use of all agents and combinations thereof increased yearly. In 2002, 83% reported aspirin use; 61%, beta blocker use; 63%, lipid-lowering therapy use; 54%, aspirin and betablocker use; and 39%, use of all three. Consistent use was as follows: for aspirin, 71%; beta blockers, 46%; lipidlowering therapy, 44%; aspirin and beta blockers, 36%; and all three, 21%. Among patients without heart failure, 39% reported ACEI use in 2002; consistent use was 20%. Among heart failure patients, ACEI use was 51% in 2002 and consistent use was 39%. Except for ACEIs among patients without heart failure, consistent use was associated with lower adjusted mortality: HR, 0.58 and 95% CI: 0.54–0.62; beta-blockers, HR, 0.63 and 95% CI: 0.59–0.67; lipid-lowering therapy, HR, 0.52 and 95% CI: 0.42–0.65; all three, HR, 0.67 and 95% CI: 0.59– 0.77; aspirin and beta-blockers, HR, 0.61 and 95% CI: 0.57–0.65; and ACEIs among heart failure patients, HR, 0.75 and 95% CI: 0.67 to 0.84.11 Of important concern is that consistent use of evidence-based medications was paradoxically lower among groups with the highest risk of poor outcomes including elderly patients and those with diabetes and heart failure, and therefore those who could potentially benefit the most from sustained therapy. These findings suggest that it may be possible to design educational and compliance intervention programs targeted to groups of patients at high risk for both underuse of medications in secondary prevention and adverse clinical outcomes. These could include direct, patient-focused interventions as well as those implemented through pharmacists and medical care providers.

60.4 FACTORS CONTRIBUTING TO MEDICATION NONADHERENCE Adherence is a complex series of behaviors composed of three phases: beginning a new medication;31 continuing to take a medication as prescribed over time; and stopping a medication for any reason (either when not recommended or at the end of a specific course of treatment). 21 The rates of adherence may differ across phases. For example, at the beginning phase, one in five Medicare patients fail to fill their prescriptions within seven days after a percutaneous intervention with a drug-eluting stent. 32 Regarding implementation, fewer than 50% of patients are persistent with their statins one year after initiation despite statins being associated with a 45% reduction in risk of mortality.32,33 For patients with diabetes, hypertension, and dyslipidemia, up to 50% of patients stop their medications in the first year of prescription.10,34,35 Across the phases, common barriers for medication adherence include poor quality of provider–patient relationship, poor communication, polypharmacy, low disease-related knowledge, low health literacy, barriers to obtaining medication, forgetfulness, and cost, among others. 36–38 Patient–physician interactions may be an important modifier of patient nonadherence. A survey of paired patient–physician respondents found that 61% of patients rarely or never discussed adherence with their physicians, and two-thirds of the patients had moderate or poor adherence. Although the physicians agreed that adherence was important, 67% were unaware of how often their patients missed medication. 39 Factors that have been more consistently associated with nonadherence include female gender, Hispanic or non-white race, increased medication cost, increased dosing frequency, and using multiple different providers or pharmacies. Medication class has been a predictor as well, with some pharmacologic categories in a therapeutic class having less adherence due to side effects or other difficulties with administrations (for example, diuretics compared to other antihypertensive drugs).40 The medical condition is also contributory, with asymptomatic chronic disease and lack of physical clues associated with nonadherence, as well as mental health disorders such as depression. The patient categories relate to physical impairments such as vision problems or impaired dexterity or dysphasia, cognitive impairment, and psychological/behavioral issues. While increasing age is not a risk factor for nonadherence, older patients have age-related issues that may pose unique barriers to adherence. For example, sensory losses, dysphagia, loss of cognitive function, and physical decline are all more common at elderly age and likely provide unique barriers to optimal medication adherence.41 The therapy characteristics also contribute to nonadherence, particularly the complexity of the regimen and side effects. Factors to increase adherence include reduction of medication cost, i.e. the use of generic medications and lower copays, and facilitating access to therapy such as better access to pharmacy, mail order, or assistance.42 The simplification of the dosing regimen, such as once daily dosing, as well as convenient administration time and association with a clue such as meals, etc. are valuable

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strategies.43 Adherence aids, both low-tech and high-tech, include family help, pill boxes, calendars, alarms, and mobile applications. Of note, low-cost reminder aids such as digital timer caps have been shown to be less helpful than expected in improving adherence.44 It is important to involve and educate the family and caregivers. Patients stop their medications for a number of reasons.45 Patient-related factors that are likely to influence adherence include the severity of the illness, perceived susceptibility to disease, perceived efficacy of the treatment, fear of dependence on medications, and a sense of loss of control. Nonadherence is more likely in patients who are isolated, perceive or experience drug-related side effects, lack knowledge about the disease, or suffer from psychiatric disorders. Depression, in particular, has been suggested as a potential cause for nonadherence.46 Dementia, residing in a nursing home, medication availability (with respect to the healthcare provider), and being a racial/ethnic minority are also associated with poorer adherence. Effective communication is also thought to be an important determinant of adherence to treatment. Physician–patient interactions that are effective, collegial, explicit, and appropriate promote adherence, as do strategies that change patients’ misconceptions about the disorder being treated or the medication used.47–49 If patients clearly understand why a drug is being used, its correct dose and duration of treatment, and the potential consequences of not taking it, they are more likely to continue the treatment, assuming too that the prescribing physicians are aware of the clear and sustained benefits of evidence-based therapies.

60.5 STRATEGIES TO IMPROVE ADHERENCE Prior studies suggest that nonadherence is modifiable. Systematic review of recently published randomized controlled trials targeting medication adherence revealed effective intervention strategies including the following: (1) facilitating patient–provider communication, (2) using mobile health technologies with emphasis on two-way communication, (3) providing patient education in tandem with lifestyle and behavioral counseling, and (4) providing psychosocial support.50 The Fractional Flow Reserve vs. Angiography for Multivessel Evaluation

(FAME) investigators used a multicomponent intervention composed of standardized medical education, regular follow-up with pharmacists, and medications dispensed in specific packs and demonstrated improvements in medication adherence and blood pressure levels among those randomized to the intervention. 51

60.6 CONCLUSION The composite of the literature to date suggests that medication nonadherence is important and should be routinely assessed in clinical practice; once identified, clinicians should engage patients in a discussion of the barriers and suggest strategies to improve medication adherence.

60.7 FUTURE DIRECTIONS Quality measures include not only medication prescription but also appropriate dosing and titration by the physician. Moreover, quality improvement efforts should be expanded to include medication adherence as a key component of secondary prevention care in addition to prescription of indicated medications. Importantly, quality improvement interventions need to be focused on the patient, not just hospitals and clinicians, to achieve better outcomes that are consistent with the need for a more “patient-centered” health care system. Cardiac rehabilitation can serve as an aid to medication adherence and, unfortunately, the referral to cardiac rehabilitation tends also to be suboptimal among the patient populations characterized as more likely to be medication non-adherent.

CLINICAL IMPLICATIONS • Improved patient–provider communications can result in improved medication adherence and clinical outcomes. • Clinicians should provide patient-specific lifestyle and behavioral counseling to support medication adherence. • Medication nonadherence should be routinely assessed in clinical practice. • Barriers and strategies to improve adherence should be provided at most clinical encounters.

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ATLAS Study Group. Circulation. 1999;100(23):2312–8. 3. Svanstrom H, Pasternak B, Hviid A. Association of treatment with losartan vs candesartan and mortality among patients with heart failure. JAMA. 2012;307(14):1506–12. . Murphy SA, Cannon CP, Wiviott SD, de 4 Lemos JA, Blazing MA, McCabe CH, et al. Effect of intensive lipid-lowering therapy on mortality after acute coronary syndrome (a patient-level analysis of the Aggrastat to Zocor and Pravastatin or

Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trials). Am J Cardiol. 2007;100(7):1047–51. 5. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495–504. . Bristow MR, O’Connell JB, Gilbert 6 EM, French WJ, Leatherman G, Kantrowitz NE, et al. Dose-response

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740  Chapter 60  Medication Dosing and Adherence in Secondary Prevention 46. Ziegelstein RC, Bush DE, Fauerbach JA. Depression, adherence behavior, and coronary disease outcomes. Arch Intern Med. 1998;158(7):808–9. 47. Wang PS, Bohn RL, Knight E, Glynn RJ, Mogun H, Avorn J. Noncompliance with antihypertensive medications: The impact of depressive symptoms and psychosocial factors. J Gen Intern Med. 2002;17(7):504–11.

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50. Zullig LL, Ramos K, Bosworth HB. Improving medication adherence in coronary heart disease. Curr Cardiol Rep. 2017;19(11):113. 51. Lee JK, Grace KA, Taylor AJ. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: A randomized controlled trial. JAMA. 2006;296(21):2563–71.

61 CHAPTER

Using Digital Health Technology to Promote Cardiovascular Disease Risk Reduction in Secondary Prevention Neil F. Gordon, MD, PhD, MPH, FACC, Richard D. Salmon, DDS, MBA, Mandy K. Salmon, ChBE, and Prabakar Ponnusamy, MS

Key Points...................................................................................741 61.1 Introduction.......................................................................741 61.2 Effectiveness and Role of Home-based Alternative Cardiac Rehabilitation and Secondary Prevention Delivery Models................................................................ 743 61.3 Effectiveness of Digital Health Technologies for Lifestyle Intervention and CVD Secondary Prevention........ 744

Disclosures: Neil Gordon, Richard Salmon, and Prabakar Ponnusamy are members and/or employees of a population health management company (INTERVENT International, LLC).

KEY POINTS • A broad spectrum of alternative, secondary prevention delivery models that incorporate novel digital health technologies have been proposed for rectifying barriers to low rates of utilization of traditional cardiac rehabilitation programs and for the provision of ongoing, evidence-based, secondary prevention interventions. • Despite the numerous flaws and limitations of existing research, the preponderance of evidence to date is highly supportive of the great potential of digital health technologies to facilitate lifestyle modification and cardiovascular disease (CVD) risk reduction. • Digital health interventions appear to be most effective when integrated with evidence-based behavioral change strategies and direct interaction between participants and healthcare providers. • Additional research and healthcare policy change are needed to move the promise of new digital health technologies for CVD risk reduction towards reality.

61.4  Healthcare Transformation in the Era of Digital Health....... 746 61.5 Case Study of an Evidence-based, Digital Health Technology-enabled, CVD Risk Reduction Program........... 746 Clinical Implications................................................................... 749 References................................................................................ 749

61.1 INTRODUCTION Although sound clinical reasons exist for emphasizing secondary prevention in day-to-day medical practice, studies indicate that physicians often fail to provide recommended CVD risk reduction interventions and, even when provided, patients often fail to comply with the prescribed lifestyle and pharmacologic interventions.1,2 Clearly, to achieve the American Heart Association’s (AHA) 2020 Impact Goals of reducing deaths attributable to CVD and stroke by 20%, increased emphasis is needed on secondary prevention through evidence-based management and control of health behaviors and risk factors.3 Traditional hospital- and clinic-based outpatient cardiac rehabilitation reduces morbidity, hospital readmissions, and mortality vs. usual care.4–7 Every recent secondary prevention guideline from the AHA and American College of Cardiology (ACC) provides a Class I-level recommendation (i.e. there is evidence for and/or general agreement that the intervention is beneficial, useful, and effective; the intervention should be performed) for cardiac rehabilitation referral.4–6 However, despite the proven benefits, the use of cardiac rehabilitation remains dismally low.4–9 Multiple strategies have been proposed for rectifying barriers to low rates of participation in and completion of traditional onsite cardiac rehabilitation programs. These include a broad spectrum of home- and communitybased alternative secondary prevention delivery models

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742  Chapter 61  Using Digital Health Technology to Promote Cardiovascular Disease Risk Reduction

that incorporate novel technologies to facilitate CVD risk reduction.4,5,10–12 Modern-day cardiovascular medicine is a “high tech” industry.13 According to a 2017 report of the ACC Task Force on Health Policy Statements and Systems of Care,14 key recent technologic innovations of paramount importance for the future transformation of cardiovascular care include: (1) digital health, with smartphone, wearable, sensor-based, and other electronic technologies; (2) big data, comprising the aggregation of large quantities of structured and unstructured health information and sophisticated analyses with artificial intelligence, machine learning, and natural language processing techniques; and (3) precision health, using approaches aimed at the identification of individual-level risks and the determinants of wellness and pathogenicity. The intra- and inter-connections among emerging innovations and developments in digital health, big data, and precision health, as summarized by the ACC, are shown in Figure 61.1. In this chapter, we focus primarily on the use of digital health to promote CVD risk reduction. A 2015 scientific statement from the AHA on consumer use of mobile health for CVD prevention defines

eHealth (also referred to as digital health) as the use of emerging communication and information technologies, especially the Internet, to improve health and health care and mHealth as a subsegment of eHealth that involves the use of mobile computing and communication technologies for health services and information (see glossary of commonly used terms in Table 61.1).15 While digital technologies have revolutionized broad sectors of our society and economy, ranging from entertainment to dating, travel, news, and finance, the healthcare industry generally has been slower to respond.13,14 However, given the ubiquity of mobile devices and Internet access, digital health interventions that incorporate technologies such as telemedicine, videoconferencing, text messaging, social networking, mobile phone applications (apps), and data from electronic medical records, blood pressure monitors, digital scales, glucometers, heart rate monitors, activity trackers, and other wearable devices are now rapidly emerging as an integral component of traditional cardiac rehabilitation programs and, especially, home-based alternative cardiac rehabilitation/secondary prevention delivery models.

Figure 61.1  New innovations in cardiovascular healthcare: infographic of emerging innovations and developments in digital health, big data, and precision health and their intraconnections and interconnections. Abbreviations: 3d = 3-dimensional; CRISPR = clustered regularly interspaced short palindromic repeats; DNA = deoxyrybonucleic acid; iPSC = induced pluripotent stem cells; RNA = ribonucleic acid; SNP = single nucleotide polymorphism; WGS = whole genome sequencing. (From Bhavnani SP, Parakh K, Atreja A, et al., J Am Coll Cardiol 2017;70:2696-2718. With permission.)

61.2  Effectiveness and Role of Home-based Alternative Cardiac Rehabilitation and Secondary Prevention Delivery Models  743 TABLE 61.1  Glossary of commonly used digital health terms

61

Term

Explanation

eHealth

eHealth, or digital health, is the use of emerging communication and information technologies, especially the use of the Internet, to improve health and health care.

mHealth

A subsegment of eHealth, mHealth is the use of mobile computing and communication technologies (e.g. mobile phones, wearable sensors) for health services and information.

Smartphone

A handheld personal computer with a mobile operating system and an integrated mobile broadband cellular network connection for voice, SMS, and Internet data communication; most, if not all, smartphones also support Wi-Fi.

SMS

A text messaging service component of mobile devices. It uses standardized communications protocols to allow mobile phone devices to exchange short text messages. The terms “text messaging” and “texting” are used interchangeably to refer to both the medium and messages, and the term “text message” refers to the individual message sent.

MMS

The next evolutionary step from SMS. MMS allows mobile phone users to exchange pictures with sound clips on their handsets or digital cameras.

App

App is short for application, which is the same thing as a software program. Although an app may refer to a program for any hardware platform, it is most often used to describe programs for mobile devices such as smartphones and tablets.

Wireless

Being wireless means not using wires to send and receive electronic signals (i.e. sending and receiving electronic signals by using radio waves).

Wi-Fi

A wireless networking technology that allows computers and other devices to communicate over a wireless signal.

Bluetooth

This wireless technology enables communication between Bluetooth-compatible devices. It is used for short-range connections between desktop and laptop computers, a mouse, digital cameras, scanners, cellular phones, earphones, headsets, and printers.

Operating system

An operating system, or OS, is software that communicates with the hardware and allows other programs to run. Common mobile OSs include Android, iOS, and Windows Phone.

iOS

A mobile OS developed by Apple. It was originally called the iPhone OS, but was renamed to the iOS in June 2009. The iOS currently runs on the iPhone, iPod Touch, and iPad.

Android OS

A Linux-based open-source platform for mobile cellular handsets developed by Google and the Open Handset Alliance. Android 1.0 was released in September 2008.

Bandwidth

In computer networks, bandwidth is used as a synonym for data transfer rate, the amount of data that can be transmitted from one point to another in a given time period (usually a second). Network bandwidth is usually expressed in bits per second (bps); modern networks typically have speeds measured in the millions of bits per second (megabits per second or Mbps) or billions of bits per second (gigabits per second or Gbps).

MMS indicates multimedia messaging service; OS, operating system; and SMS, short messaging service. (From Burke LE, et al., Circulation 2015;32:1157–213. Adapted with permission.)

61.2 EFFECTIVENESS AND ROLE OF HOME-BASED ALTERNATIVE CARDIAC REHABILITATION AND SECONDARY PREVENTION DELIVERY MODELS A 2017 Cochrane systematic review of data from 23 randomized controlled trials involving 2,890 participants compared the effect of home-based and supervised center-based cardiac rehabilitation in adult patients who were post myocardial infarction or had angina, heart failure, or underwent coronary revascularization.16 For the review, home-based cardiac rehabilitation was defined as a structured program (including exercise training) with clear objectives for the participants, including monitoring,

follow-up visits, letters or telephone calls from staff, or, at least, self-monitoring diaries. The review found no evidence of a significant difference between home- and center-based cardiac rehabilitation either in the short-term (three to 12 months) or longer-term (up to 24 months) for total mortality, cardiac events, exercise capacity, multiple modifiable CVD risk factors, or health-related quality of life. The authors concluded that while additional research is warranted, their data support previous conclusions that home- and center-based forms of cardiac rehabilitation seem to be similarly effective. In a 2011 presidential advisory,4 the AHA identified the testing of novel, technology-based, alternative approaches to cardiac rehabilitation, such as home-based secondary prevention programs with telephonic and Internet-based interventions, as a future priority. In accordance with this recommendation, the National Heart, Lung, and Blood Institute released a funding opportunity announcement in

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2017 focusing on increasing cardiac rehabilitation utilization with the use of newer, technology-based, alternative delivery models.17 In a recent multi-center study involving 12,984 patients who completed a traditional onsite cardiac rehabilitation program, very few patients had all CVD risk factors at levels currently recommended for ideal cardiovascular health at program completion.18 These data emphasize the need for ongoing surveillance and intensive intervention aimed at residual CVD risk reduction in most patients who complete traditional onsite cardiac rehabilitation programs. In addition to their use as an alternative to onsite programs, home-based programs that incorporate novel digital health technologies can be leveraged to provide ongoing secondary prevention intervention after the completion of onsite cardiac rehabilitation.18

61.3 EFFECTIVENESS OF DIGITAL HEALTH TECHNOLOGIES FOR LIFESTYLE INTERVENTION AND CVD SECONDARY PREVENTION It has been estimated that about 90% of the world’s population will own a smartphone by 2020.19,20 From the perspective of addressing existing disparities in the provision of cardiac rehabilitation and secondary prevention services, it is especially important to note that according to 2014 statistics from the Pew Research Center, almost half of individuals with an annual household income below $30,000 owned a smartphone.15 Moreover, the highest smartphone ownership was among Hispanics (61%) and African Americans (59%), and Hispanics and African Americans were more likely to rely heavily on smartphones for information about a health condition than were whites.15 Thus, unlike the initial digital divide that placed Internet access and computer use beyond the reach of many disadvantaged populations, smartphones have been widely adopted across demographic groups, including ethnic minorities, and older, lower socioeconomic status and/or other currently underserved populations who may be most in need of secondary prevention interventions.15 The 2015 AHA scientific statement on consumer use of mobile health reviewed the scientific literature on mHealth tools related to CVD prevention.15 For the review, the authors conducted a literature search that included a variety of mHealth-related terms. The search included studies conducted in the U.S. and other developed countries but was limited to 2004–2014 studies reported in the English language and studies enrolling adults (except for smoking cessation, which included adolescents). Key findings pertaining to the use of mHealth to improve weight management, physical activity participation, smoking cessation, self-management of diabetes mellitus, hypertension care, and management of dyslipidemia were evaluated together with gaps in knowledge and suggestions were made for future research. The literature searches identified a wide variety of mHealth products (for example, a search of the

Google and iTunes App Stores conducted in April 2015 identified over 4,000 weight loss-related apps and over 6,000 exercise-related apps) together with a glaring paucity of published outcomes data on their effectiveness. Several common themes and concerns were noted, including: (1) study design concerns, such as use of pre-post designs without concurrent control groups or randomized comparison groups, reliance on self-reported data, failure to use intention-to-treat analyses, evaluation in motivated participants and selected settings, and short duration of the studies; (2) evaluation of a single digital health technology compared with usual care rather than head-tohead studies comparing various digital health technologies with each other; (3) unanswered questions about product safety; (4) inability to demonstrate which components in an intervention are pivotal to success or whether the impact of a specific digital health product varies depending on the mode of use or delivery; and (5)  absence of meaningful data on how best to incorporate the digital health technologies into a broader collaborative model of health care. Even with the abovementioned flaws, limitations, and unanswered questions, the authors concluded that their review of the evidence clearly demonstrates the great potential that mobile technologies can have to aid in lifestyle modification and that the current absence of sufficient evidence should not be interpreted as evidence of an absence of effectiveness. Regarding the latter, the authors emphasized that healthcare professionals instead should rise to the challenge of producing the needed evidence on the effectiveness of digital health technologies and how best to adopt them in daily clinical practice to optimize health.15 In a 2016 publication, Afshin et al. systematically reviewed, synthesized, and graded the scientific evidence on the effectiveness of novel information and communication technologies to reduce noncommunicable disease risk. 21 The authors systematically searched PubMed for studies evaluating the effect of Internet, mobile phone, personal sensors, or stand-alone computer software on diet, physical activity, adiposity, tobacco, or alcohol use. They included all interventional and prospective observational studies conducted among generally healthy adults published between January 1990 and November 2013. AHA criteria were used to grade the strength of evidence. From 8,654 abstracts, 224 relevant reports were identified. Internet and mobile interventions were most common. Internet interventions improved diet (n = 20 studies; AHA Class IIa A, namely: weight of evidence/opinion is in favor of usefulness/efficacy; it is reasonable to perform the intervention; and data derived from multiple randomized clinical trials), physical activity (n = 33), adiposity (n = 35), tobacco (n = 22), and excess alcohol (n = 47) (AHA Class I A each, namely: there is evidence for and/or general agreement that the intervention is beneficial, useful, and effective; the intervention should be performed; and data derived from multiple randomized clinical trials). Mobile interventions improved physical activity (n = 6) and adiposity (n = 3) (AHA Class I A each). Evidence limitations included relatively brief durations (generally less than six months, nearly always less than one year), heterogeneity in intervention content/intensity, and limited

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representation from middle/low-income countries. The authors concluded that Internet and mobile interventions improve important lifestyle behaviors for up to one year and that their review supports the need for long-term interventions to evaluate sustainability. Interestingly, the authors also observed that: (1) using evidence-based behavioral change strategies could increase the effectiveness of Internet and mobile interventions (for example, in studies of diet/adiposity, interventions were more effective if adopting multiple modes of communication, using tailored messages, and integrating goal-setting and selfmonitoring, and in studies of physical activity, developing the Internet intervention content based on psychological theories of behavioral change increased both effectiveness and participant retention); and (2) interaction with healthcare providers could increase the success rate of the interventions (for example, in studies of smoking cessation, the interventions tended to be more effective if they incorporated a direct interaction between smokers and their healthcare providers). In 2017, Khan et al. reviewed what they considered to be the most important and relevant recent studies addressing digital health technologies to promote lifestyle change and medication adherence, including text messaging, smartphone apps, and wearable devices. 20 They concluded that: (1) the current literature indicates that digital health technologies will likely play a prominent role in future CVD management, risk reduction, and delivery of health care in both resource-rich and resource-limited settings; (2) digital health technology research remains in an early stage both in terms of the available data and the methodology for how it is conducted; (3) there is limited large-scale evidence to support adoption of existing interventions; (4) additional clinical research and healthcare policy change are needed to move the promise of new digital health technologies towards reality; and (5) with many new digital health interventions bypassing clearance from the Food and Drug Administration, academic medical centers and professional medical organizations should provide broader guidance to consumers/patients. The authors also expressed concern that, because the development of digital health technologies is often driven by non-clinicians, unique challenges exist related to integration into daily clinical workflows. Moreover, because clinicians are increasingly burdened by time-consuming use of electronic medical records and data overload, there may be limited capacity for them to take on additional responsibilities by processing and reacting to digital healthrelated data. 20 Through a comprehensive search of databases from 2002–2016, Park et al. conducted a quantitative systematic review of mobile phone interventions for the secondary prevention of CVD. 22 The identified studies were critically evaluated to extract and summarize pertinent characteristics and outcomes. A large majority of studies (22 of 28, or 79%) demonstrated that text messaging, mobile applications, and telemonitoring via mobile phones were effective in improving outcomes. Key factors associated with successful interventions included personalized messages with tailored advice, greater engagement (e.g. two-way text messaging and higher frequency of

messages), and use of multiple digital health modalities. Overall, text messaging appeared more effective than smartphone-based interventions. Based on their observations and experiences, the authors speculated that future mHealth interventions will likely use a combination of different technologies (e.g. basic cellular phones, smartphones, computers, and tablets) and that with the widespread proliferation of smartphones, mHealth apps will likely expand on their connectivity with social media to maximize consumer engagement. However, in doing so, concerns of privacy and security issues will need to be adequately addressed. 22 From a wearable technology perspective, the utility of wrist-worn heart rate monitors is of particular relevance to home-based cardiac rehabilitation programming and exercise prescription. Wang et al. recently compared the accuracy of four popular wrist-worn heart rate monitors (namely, Fitbit Charge HR, Apple Watch, Mio Alpha, and Basis Peak) to that of standard electrocardiographic limb leads and a Polar H7 chest strap monitor in 50 healthy adults. 23 Heart rate was assessed at rest and at treadmill speeds of two, three, four, five, and six miles per hour. Participants exercised at each speed for three minutes to achieve a steady state and heart rate was recorded instantaneously at the three-minute point. After completion of the treadmill protocol, heart rate was recorded at 30, 60, and 90 seconds of recovery. When compared with electrocardiographically measured heart rates, the heart rate monitors had variable accuracy as assessed by the concordance correlation coefficient. Of the four wrist-worn devices, the Apple Watch and Mio Fuse both had the best accuracy with concordance correlation coefficients of 0.91 whereas the Fitbit Charge HR and Basis Peak had concordance correlation coefficients of 0.84 and 0.83, respectively. None of the wrist-worn devices were as accurate as the Polar H7 chest strap monitor, which had a concordance correlation coefficient of 0.99. In general, the accuracy of the wrist-worn monitors was best at rest and diminished during exercise. While the Basis Peak overestimated heart rate during moderate exercise, with median differences of –8.9 and –7.3 beats/minute at 2 (p < .001) and three miles/hour (p = .001), respectively, the Fitbit Charge HR underestimated heart rate during more vigorous exercise, with median differences of 7.2 and 6.4 beats/minute at four (p < .001) and six miles/hour (p < .001), respectively (comparing each device with electrocardiogram). Analyses further showed that variability occurred across the spectrum of midrange heart rates during exercise, with less variability at the tail ends. The Apple Watch and Mio Fuse had 95% of differences fall within –27 and +29 beats/minute of the electrocardiogram, while Fitbit Charge HR had 95% of values within –34 and +39 beats/minute, and the corresponding values for the Basis Peak were within –39 and +33 beats/minute. The investigators concluded that electrode-containing chest monitors should be used when accurate heart rate measurement is imperative. They further recommended that, because cardiac patients increasingly rely on heart rate monitors to stay within prescribed target heart rate ranges, appropriate validation of these devices in such patients is imperative.

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61.4 HEALTHCARE TRANSFORMATION IN THE ERA OF DIGITAL HEALTH Newly developed and rapidly evolving technological innovations have the potential to play a pivotal role in the shift from volume- to value-based health care. However, as emphasized in the 2017 report of the ACC Task Force on Health Policy Statements and Systems of Care,14 technological transformation often occurs too rapidly for existing healthcare practice to keep pace, thus creating a mismatch between the rate of development of novel technologies and preparedness of the healthcare system for effective integration and utilization of novel technologies. Thus, despite billions of dollars of investment in digital health technologies, there are numerous reasons why the digital transformation of health care still lags behind the rate of transformation that has occurred in other industries.13,14 Simultaneous with the publication of the 2017 ACC Task Force report, Walsh and Rumsfeld13 proposed the following among key reasons for health care lagging behind other industries in the adoption of potentially transformative new technologies: (1) health care is not entertainment; the healthcare system is extremely complex and simply not set up to rapidly absorb innovation; (2) the stakes in health care are very high, involving life-or-death decisions and, thus, rightfully requiring convincing evidence for technology solutions before widespread clinical adoption; (3) many technology companies lack the necessary clinical insights; (4) while electronic medical records were a first step in the digital transformation of health care, dissatisfaction and criticism abound, with many physicians considering the introduction of electronic medical records a significant misstep; (5) digital health companies have often been fearful of entering the healthcare regulatory process and many have chosen not to aim innovation at the clinician–patient interface, instead solely developing consumer products; and (6) for the most part, there are nonaligned incentives or payment models in place to support digital health transformation of care delivery. To help accelerate new innovations for positive care transformation, the ACC has launched the initial phase of an innovation strategy that advocates that digital health technologies must be effective and safe, improve efficiency of care, improve patient–clinician interaction, and be supported by appropriate payment models.13,14 When deploying digital health technologies as a component of alternative secondary prevention models, the following key policy recommendations from the AHA should be considered: (1) cardiac rehabilitation and secondary prevention programs should be reengineered to include a wide array of service options that meet the needs of individual patients and provide more flexible programs within and beyond the traditional clinical center to enhance access, adherence, and effectiveness; (2) such alternative approaches should not replace traditional programs but should be used to engage the many patients who currently do not participate and to provide ongoing monitoring and treatment after completion of traditional onsite cardiac rehabilitation programs; (3) alternative

approaches to traditional programs should meet reputable quality standards and existing standards may need to be customized for each model accordingly; (4) any new approach should not be widely implemented until it has been shown to be effective as evidenced by results of clinical studies published in peer-reviewed journals; and (5) third-party payers should cover the costs of evidencebased alternative models of delivery that have been shown to be effective in peer-reviewed published clinical trials such as hybrid programs, home-based models, and telephone/Internet-based models.4

61.5 CASE STUDY OF AN EVIDENCEBASED, DIGITAL HEALTH TECHNOLOGY-ENABLED, CVD RISK REDUCTION PROGRAM In 2007, the ACC launched its CardioSmart patient-centered care initiative to improve patient communication, education, and engagement. 24 CardioSmart serves as an extension of the cardiologist’s office or hospital, continuing the partnership between the healthcare team and the patient between clinical office visits. Several recent CardioSmart initiatives included access to an evidencebased telehealth coaching intervention that is provided by a commercial vendor (INTERVENT International), utilizes a variety of digital health technologies, and has been shown to be effective in individuals with or at heightened risk for CVD. 24–26 The primary objectives of the digital technologyenabled telehealth coaching program are to help participants: (1) make and adhere to meaningful, evidence-based lifestyle changes (especially, regular exercise/physical activity, healthy nutrition, weight management, stress management, and tobacco cessation); (2) learn about CVD/risk factors and acquire appropriate self-management skills (including understanding untoward symptoms/ signs, when to contact their physicians/providers, medication compliance, and avoidance of re-hospitalization); (3) address gaps in preventive care (e.g. compliance with recommended preventive screenings/tests/immunizations); and (5) comply with prescribed medications and other aspects of their regular medical care. To accomplish these objectives and help ensure the attainment of clinically meaningful/reproducible outcomes, telehealth coaching is delivered using a formal, structured, systematic approach together with rigorous quality assurance protocols. The core components of the program and key steps involved in their delivery are summarized in Figure 61.2. There is no single innovation that makes the telehealth coaching intervention novel; rather, it is due to the synergistic manner in which multiple novel approaches and digital health technologies have been incorporated into a single program to facilitate the provision of comprehensive CVD risk reduction services and the achievement of reproducible outcomes. A few of the many innovative aspects of the telehealth coaching intervention include the use of:

61.5  Case Study of an Evidence-based, Digital Health Technology-enabled, CVD Risk Reduction Program  747 Step 1: Participant identification and enrollment - Physicians can refer patients using a variety of methods, including via a smartphone app and electronic medical records - Potential participants are also identified using multiple data sources, such as health risk assessments, laboratory data, medical/pharmacy claims data, and data from wearables/other devices Step 2: Intake assessment and risk stratification - Self-reported data (including medical history, risk factors, lifestyle habits, and readiness to change) can be entered directly by participants into the program’s HIPAA-compliant, secure, mobile-friendly (iOS and Android phones, tablets, etc.), participant-facing, online portal - Data are integrated into participants’ records from multiple sources, including electronic medical records, laboratory data, medical/pharmacy claims data, and wearables/other devices - Automated risk stratification algorithms determine the most appropriate nature and intensity of the telehealth coaching intervention Step 3: Goal setting and action plan formulation Based on the intake assessment and with the use of artificial intelligence: - Computer-generated, individualized, short- and long-term goals are set for multiple CVD risk factors and health behaviors - Computer-generated, individualized, action plans are formulated to help participants achieve their short/long-term goals - In addition to behavior modification, action plans identify the need for specific preventive screenings, immunizations, other self-care activities, and physician referrals (e.g. for medication changes to optimize CVD risk reduction, including statins, antihypertensive agents, antidiabetic medications, and platelet inhibitors) Step 4: Review/revision of goals and action plans - Based on their interaction with participants and/or input from the participants’ physicians/healthcare providers, health coaches can revise the computer-generated goals/action plans - Participants can access their goals/action plan reports via the online participant portal -If the action plan includes referral to a physician/other healthcare provider, the health coach emphasizes the importance, facilitates the referral, and documents the outcome of the referral in the program’s HIPAA-compliant, secure, mobile-friendly, online coaching portal Step 5: Action plan implementation - With guidance from the program’s online coaching portal and using behavioral interventions derived from multiple well-established behavior change models (e.g. adult learning theory, social learning theory, motivational interviewing, single concept learning, and the stages of change model), coaches assist participants in implementing their individualized action plans - Coaching occurs during proactive, formally structured, 1-on-1, brief (usually ~15-30 minutes in duration) prescheduled telephone appointments and, if the participant prefers, via secure videoconferencing, online chat, or e-mail - Participants can access numerous resources/features via the online participant portal, including: personalized reports; interactive (store participant responses to activities), behaviorally-oriented, educational modules with audios on over 100 comprehensive topics, including quizzes to check/document mastery of content; interactive self-monitoring diaries/logs (e.g. exercise, nutrition, stress, tobacco, symptoms/signs, medications); recipes; health-related challenges and accompanying rewards/incentives; ability to synchronize numerous wearable/other devices to the portal, including heart rate monitors, activity trackers, scales, blood pressure monitors, and glucometers; game-based learning activities that consider health literacy; and the CardioSmart.org education website Step 6: Follow-up assessment, with provision of progress reports and revision of goals/action plans - After ~12 weeks and 1 year of program participation, and at least annually thereafter, participants typically complete formal followup assessments and receive online reports documenting their progress and updating their goals/action plans -If the revised action plan includes referral to a physician/other healthcare provider, the health coach emphasizes the importance, facilitates the referral, and documents the outcome of the referral in the online coaching portal Step 7: Maintenance - Compliance with scheduled coaching sessions and interventions is tracked using the online coaching portal’s participant manage ment and tracking features (participants typically enroll in the program for 1 year at a time and may re-enroll on an annual/ongoing basis) - Ongoing mining/analysis of multiple data sources is performed to identify participants requiring special intervention (e.g. for untoward symptoms/signs, out -of-range values, and non-compliance with recommended interventions) Step 8: Outcomes assessment - Detailed aggregate outcomes reports are generated on a regular basis for specific groups of program participants - Benchmarking may be included using book -of-business analyses

Figure 61.2  Summary of core components and key steps involved in an evidence-based, technology-enabled, lifestyle management and cardiovascular disease risk reduction program. Abbreviations: CVD = cardiovascular disease; HIPAA = Health Insurance Portability and Accountability Act of 1996.



1. A home-based program that originally was based on the protocols/procedures deployed in the Stanford Coronary Risk Intervention Project, 27 subsequently enhanced over a period of more than 20 years, and addresses not only prescribed physical activity/exercise training but many other important components of comprehensive cardiac rehabilitation/secondary prevention programs as part of a single, integrated

intervention. These other components include modification of multiple CVD risk factors via education and behaviorally-oriented health coaching, stress/emotional health interventions, symptom management, and compliance with prescribed evidence-based CVD risk reduction medications, recommended preventive tests/immunizations, and other aspects of regular medical care. The program

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748  Chapter 61  Using Digital Health Technology to Promote Cardiovascular Disease Risk Reduction TABLE 61.2  Case study of an evidence-based, digital health technology-enabled, CVD risk reduction program: key published randomized clinical trials Reference, year; title; objectives; study design/duration

Results, conclusions, and implications

Gordon et al, Am J Cardiol 2002; “Effectiveness of Three Models for Comprehensive Cardiovascular Disease Risk Reduction”33 This randomized clinical trial compared the clinical effectiveness of two, less costly and potentially more accessible, approaches to CVD risk reduction with that of a contemporary phase 2 onsite cardiac rehabilitation program. Low- or moderate-risk coronary artery disease patients (n = 155) were randomly assigned to 12 weeks of participation in a contemporary phase 2 cardiac rehabilitation program (n = 52), a physician supervised, nurse-case-managed CVD risk reduction program (n = 54), or a comprehensive health coaching program administered by exercise physiologists guided by a computerized participant management system based on reputable national clinical guidelines (n = 49). 142 patients (91.6%) completed testing at baseline and after 12 weeks of intervention.

• For patients with abnormal baseline values, statistically significant (p < 0.05) improvements were observed with all 3 interventions for multiple CVD risk factors. With the exception of maximal oxygen uptake, no statistically significant risk factor differences were observed among the 3 programs. For patients with a baseline maximal oxygen uptake < 7 METs, maximal oxygen uptake increased to a greater degree in patients in the contemporary phase 2 cardiac rehabilitation program and the health coaching program versus the physician supervised, nurse-case-managed program. • These data demonstrate that an evidence-based, technologyenabled health coaching program can be at least as effective as other more costly and potentially less accessible interventions (including traditional onsite cardiac rehabilitation) in low- and moderate-risk coronary artery disease patients. The data have important potential implications for cost-containment and for increasing accessibility to clinically effective comprehensive CVD risk reduction services.

Maron et al, J Cardiovasc Nursing 2008; “Health Risk Appraisal With or Without Disease Management for Worksite Cardiovascular Risk Reduction”34 This randomized clinical trial evaluated how the intensity of intervention after the provision of a health risk assessment affects CVD risk. 133 employees with CVD risk factors were randomly assigned for 1 year to a health risk assessment plus comprehensive health coaching group (higher intensity intervention; HC group) or a health risk assessment plus information about worksite health promotion programs group (lower intensity intervention; HRA group). The HC group participated in a 1-year technology-enabled, health coaching program, whereas the HRA group received one feedback session about their CVD risk factors and information about free worksite health promotion programs. The primary outcome measure was the change in Framingham 10-year coronary heart disease risk scores.

• In the HC group, the mean Framingham 10-year coronary heart disease risk score decreased by 22.6% (relative risk reduction); in the HRA group, the mean score rose by 4.3% (p = 0.017 for the difference between groups). • The data demonstrate that a health risk assessment followed by participation in an evidence-based, technology-enabled, health coaching program can be more effective than a health risk assessment followed by one feedback session and the provision of information about free worksite health promotion programs. The data also serve to highlight that not just any kind of lifestyle management program done in any way will produce high levels of clinical benefit. It is evident from this study that lifestyle management programs must be appropriately designed and executed in an effective manner in order to significantly impact multiple clinical variables and facilitate CVD risk reduction.

Derdeyn et al, Lancet 2014; “Aggressive Medical Treatment With or Without Stenting in High-risk Patients With Intracranial Artery Stenosis (SAMMPRIS): the Final Results of a Randomised Trial”30 and Turan et al, Neurology 2017; “Relationship Between Risk Factor Control and Vascular Events in the SAMMPRIS Trial” 31 This study, conducted at 50 medical centers in the U.S., randomly assigned 451 patients with recent transient ischemic attack or stroke related to 70–99% stenosis of a major intracranial artery to aggressive medical management (including antiplatelet therapy, intensive management of vascular risk factors, and participation in an evidence-based, technology-enabled, telehealth coaching program) or aggressive medical management plus intracranial stenting with the Wingspan stent. The primary endpoint was any of the following: stroke or death within 30 days after enrolment, ischemic stroke in the territory of the qualifying artery beyond 30 days of enrolment, or stroke or death within 30 days after a revascularization procedure of the qualifying lesion during follow-up. Patients were followed for a median of 32.4 months.

• 15% of patients in the medical management-only group and 23% of patients in the stenting group had a primary endpoint event. The primary endpoint rate in the medical management-only group (14.1% at 2 years) was much lower than was projected based on the results of the WASID trial (24.7% at 2 years), an observation that was attributed to differences in medical treatment in these trials, including the use of telehealth coaching in SAMMPRIS but not WASID. Throughout the duration of the study, there were continued improvements in CVD risk factor control. Multivariate analyses demonstrated that, of the various CVD risk factors, physical inactivity was by far the most important predictor of poor outcomes—greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death by 40% (odds ratio 0.6, confidence interval 0.4–0.8). The investigators attributed increases in physical activity to compliance with the telehealth coaching program, which also contributed to the high percentage of patients achieving other risk factor targets. • The study highlights the potential benefits of physical activity for the prevention of recurrent stroke and the role that evidence-based, digital technology-enabled, telehealth coaching can play in helping patients achieve CVD risk factor goals. The study also helps allay concerns regarding the long-term sustainability of CVD risk factor control.

Abbreviations: CVD = cardiovascular disease; SAMMPRIS = Stenting and Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis; WASID = Warfarin Aspirin Symptomatic Intracranial Disease. (Adapted, in part, from Gordon NF, et al., Am J Lifestyle Med 2017;11:153–166.)

References  749

is in daily use throughout the U.S. in a variety of real-world settings, both in English and Spanish. 2. Multiple, novel digital health technologies including telemedicine, videoconferencing, text messaging, social networking, online smartphone apps, gamebased learning, and integration of data from electronic medical records, blood pressure monitors, digital scales, glucometers, heart rate monitors, activity trackers, and other wearable devices/sensors. While the telehealth coaching program incorporates multiple digital technologies, individuals who are unable to use such technologies are still able to participate and achieve meaningful clinical benefits, making the intervention suitable for use with a broad spectrum of underserved populations. In fact, the minimum needed for participation is telephone access. All core participant educational materials are available in hard copy format, interactive online format (including health coaches having access to online activities completed by participants), and audio formats (for verbal learners and individuals who, for example, are illiterate or visually impaired). No special resources (e.g. exercise equipment or fitness center membership) are required, but participants can elect to use and synchronize a variety of wearable/monitoring devices to the program’s online participant and coaching portals. 3. A sophisticated online coaching portal that provides health coaches access to the resources, data, and automated guidance they need to provide evidencebased, behaviorally-oriented coaching aimed at helping participants acquire the skills, motivation, and support needed to implement and adhere to their individualized action plans. 4. Multiple features to facilitate provider engagement and interaction with participants to improve adherence to evidence-based secondary prevention interventions. For example, using artificial intelligence programmed into the online coaching portal, evidence-based, individualized goals and action plan reports and progress reports are automatically generated for program participants. Healthcare providers are able to access these reports, recommend changes, and provide electronic input to their patients’ health coaches. Where indicated on the basis of reputable clinical guidelines, including to optimize CVD risk reduction medication



management, coaches facilitate the referral of participants to their healthcare providers. 5. Big data mining to provide the business intelligence to enhance participant engagement and optimize the nature and intensity of CVD risk reduction interventions. Data sources include health risk assessments, electronic medical records, laboratory data, medical/pharmacy claims data, and data from wearables/ other devices.

The program’s effectiveness has been evaluated as part of numerous formal research initiatives. Most recently, the telehealth coaching program was successfully deployed as part of the aggressive medical management component of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) multi-center clinical trial, 28–31 and it is currently being used as part of the aggressive medical management component of the multi-center Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Study (CREST-2).32 Results of several of the key randomized clinical trials are summarized in Table 61.2. 28–31,33,34

CLINICAL IMPLICATIONS • Newly developed and rapidly evolving technological innovations, including digital health, have the potential to play a pivotal role in the shift from volume- to value-based health care. • Evidence-based, digital health technology-enabled, lifestyle management and CVD risk reduction programs are a viable alternative to traditional onsite cardiac rehabilitation programs. • Such alternative approaches should not replace onsite cardiac rehabilitation but rather be used to engage the many patients who currently do not participate and to provide ongoing, evidence-based, secondary prevention interventions post-cardiac rehabilitation. • Healthcare professionals should rise to the challenge of producing the needed evidence on the long-term effectiveness of digital technologies and determining how best to adopt them in daily practice to help optimize patient health.

REFERENCES 1. Tomaselli GF, Harty M-B, Horton K, and Schoeberl M. The American Heart Association and the Million Hearts Initiative: A presidential advisory from the American Heart Association. Circulation 2011;124:1795–1799. 2. Spring B, Ockene JK, Gidding SS, et al., on behalf of the American Heart Association Behavior Change Committee of the Council on Epidemiology and Prevention, Council on Lifestyle and Cardiometabolic Health, Council for High Blood Pressure Research, and Council on Cardiovascular and Stroke Nursing. Better population

health through behavior change in adults: A call to action. Circulation 2013;128:2169–2176. 3. Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics – 2017 update. A report from the American Heart Association. Circulation 2017;135:e1–e458. . Balady GJ, Ades PA, Bittner VA, et al. 4 Referral, enrollment and delivery of cardiac rehabilitation/secondary prevention programs at clinical centers and beyond: A presidential advisory from the American Heart Association. Circulation 2011;124:2951–2960.

5. Sandesara PB, Lambert CT, Gordon NF, et al. Cardiac rehabilitation and risk reduction: Time to “rebrand and reinvigorate.” J. Am. Coll. Cardiol. 2015;65:389–395. 6. Ades PA, Keteyian SJ, Wright JS, et al. Increasing cardiac rehabilitation participation from 20% to 70%: A road map from the Million Hearts Cardiac Rehabilitation Collaborative. Mayo Clin. Proc. 2017;92:234–242. 7. Fang J, Ayala C, Luncheon C, Ritchey M, and Loustalot F. Use of outpatient cardiac rehabilitation among heart attack survivors—20 states and the District of

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Columbia, 2013 and four states, 2015. MMWR Morb. Mortal. Wkly. Rep. 2017;66:869–873. Arena R, Williams M, Forman DE, et al. Increasing referral and participation rates to outpatient cardiac rehabilitation: The valuable role of healthcare professionals in the inpatient and home health settings: A science advisory from the American Heart Association. Circulation 2012;125:1321–1329. Doll JA, Hellkamp A, Ho PM, et al. Participation in cardiac rehabilitation programs among older patients after acute myocardial infarction. JAMA Intern. Med. 2015;175:1700–1702. Gordon NF and Haskell WL. Comprehensive cardiovascular disease risk reduction in a cardiac rehabilitation setting. Am. J. Cardiol. 1997;80(8B):69H–73H. Gordon NF. Comprehensive cardiovascular disease risk reduction in the clinical setting. Coronary Artery Dis. 1998;9:731–735. Gordon NF, Salmon RD, Mitchell BS, et al. Innovative approaches to comprehensive cardiovascular disease risk reduction in clinical and community-based settings. Curr. Atheroscler. Rep. 2001;3:498–506. Walsh MN and Rumsfeld JS. Leading the digital transformation of healthcare. The ACC innovation strategy. J. Am. Coll. Cardiol. 2017;70:2719–2722. Bhavnani SP, Parakh K, Atreja A, et al. 2017  roadmap for innovation—ACC health policy statement on healthcare transformation in the era of digital health, big data, and precision health. J. Am. Coll. Cardiol. 2017;70:2696–2718. Burke LE, Ma J, Azar KMJ, et al. Current science on consumer use of mobile health for cardiovascular disease prevention: A scientific statement from the American Heart Association. Circulation 2015;32:1157–1213. Anderson L, Sharp GA, Norton RJ, et al. Home-based versus centre-based cardiac rehabilitation. Cochrane Database Syst. Rev. 2017;(6). Art. No.: CD007130. doi: 10.1002/14651858.CD007130.pub4. National Heart, Lung, and Blood Institute. Increasing use of cardiovascular and pulmonary rehabilitation in

18.

19.

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23. 24. 25.

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traditional and community settings (R61/ R33). https​: //gr​ants.​n ih.g​ov/gr​ants/​g uide​ /rfa-​fi les​/ RFA-​H L-18​- 019.​html. Accessed October 3, 2017. Gordon NF, Salmon RD, Sperling LS, et al. Temporal trends in the achievement of atherosclerotic cardiovascular disease risk factor goals during cardiac rehabilitation. J. Cardiopulm. Rehabil. Prev. 2017;37:11–31. Wood B. By 2020, 90% of World’s population aged over 6 will have a mobile phone: Report [Internet]. Next Web 2014. Available from: http:​//the​nextw​eb.co​m / ins​ider/​2014/​11/18​/ 2020​-90-w​orlds​-popu​ latio​n-age​d-6-w​ill-m​obile​-phon​e -rep​ort/. Accessed November 27, 2017. Khan N, Marvel FA, Wang J, and Martin SS. Digital health technologies to promote lifestyle change and adherence. Curr. Treat. Options Cardio. Med. 2017;19: Published Online June 24, 2017. DOI 10.1007/s11936-017-0560-4. Afshin A, Babalola D, Mclean M, et al. Information technology and lifestyle: A systematic evaluation of internet and mobile interventions for improving diet, physical activity, obesity, tobacco, and alcohol use. J. Am. Heart Assoc. 2016;5:e003058. DOI: 10.1161/ JAHA.115.003058. Park LG, Beatty A, Stafford Z, and Whooley MA. Mobile phone interventions for the secondary prevention of cardiovascular disease. Prog. Cardiovasc. Dis. 2016;58:639–650. Wang R, Blackburn G, Desai M, et al. Accuracy of wrist-worn heart rate monitors. JAMA Cardiol. 2017;2:104–106. Gulati M. Patient-centered care. Treating the patient, not the disease. J. Am. Coll. Cardiol. 2017;69:2871–2874. Gordon NF, Salmon RD, Wright BS, Faircloth GC, Reid KS, and Gordon TL. Clinical effectiveness of lifestyle health coaching: Case study of an evidencebased program. Am. J. Lifestyle Med. 2017;11:153–166. Gordon NF, Salmon RD, Wright BS, et al. Evaluation of the CardioSmart population health management initiative: Changes in health risks and participant satisfaction. J. Am. Coll. Cardiol. 2017;69:1836.

27. Haskell WL, Alderman EL, Fair JM, et al. Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. The Stanford Coronary Risk Intervention Project (SCRIP). Circulation 1994;89:975–990. 28. Chimowitz MI, Lynn MJ, Derdeyn CP, et al., for the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N. Engl. J. Med. 2011;365:993–1003. 29. Turan TN, Lynn MJ, Nizam A, et al., for the SAMMPRIS Trial Investigators. Rationale, design, and implementation of aggressive risk factor management in the Stenting and Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. Circ. Cardiovasc. Qual. Outcomes 2012;5:e51–e60. 30. Derdeyn CP, Chimowitz MI, Lynn MJ, et al., the SAMMPRIS Trial Investigators. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): The final results of a randomised trial. Lancet 2014;383:333–341. 31. Turan TN, Nizam A, Lynn MJ, et al. Relationship between risk factor control and vascular events in the SAMMPRIS trial. Neurology 2017;88:379–385. 32. Howard VJ, Meschia JF, Lal BK, et al. Carotid revascularization and medical management for asymptomatic carotid stenosis: Protocol of the CREST-2 clinical trials. Int. J. Stroke 2017;12:770–778. 33. Gordon NF, English CD, Contractor AS, et al. Effectiveness of 3 models for comprehensive cardiovascular disease risk reduction. Am. J. Cardiol. 2002;89:1263–1268. 34. Maron DJ, Forbes BL, Groves JR, Dietrich MS, Sells P, and DiGenio. Health-risk appraisal with or without disease management for worksite cardiovascular risk reduction. J. Cardiovasc. Nurs. 2008;23:513–518.

62 CHAPTER

Psychosocial Risk Factors as Modulators of Cardiovascular Outcomes in Secondary Prevention Joel W. Hughes, PhD, FAACVPR and David Ede, Jr., BS

CONTENTS Key Points��������������������������������������������������������������������������������� 751 62.1  Meet Secondary Prevention Patient Patricia��������������������� 751 62.2  Secondary Prevention and Psychosocial Factors�������������� 752 62.3  Psychosocial Factors in Heart Disease����������������������������� 752 62.4 What Are the Psychosocial Factors that Moderate Outcomes in Secondary Prevention?�������������������������������� 753 62.4.1  Social Support����������������������������������������������������� 753 62.4.2 Anger/Hostility����������������������������������������������������� 753 62.4.3 Anxiety����������������������������������������������������������������� 753 62.4.4 Depression���������������������������������������������������������� 753 62.5  Addressing Depression in Secondary Prevention�������������� 753 62.5.1  Screening for Depression������������������������������������� 753 62.5.2  Treating Depression in Secondary Prevention������� 754

Conflict of Interest: The authors declare no conflict of interest.

KEY POINTS • Many patients with heart disease experience psychosocial comorbidities, such as depression, anxiety, social isolation, and anger/hostility. • These comorbidities moderate risk in secondary prevention, and, for example, patients with depression have a greater risk of a poor outcome. • Treatments for psychosocial comorbidities have generally not been shown to reduce the associated risk. • Outpatient cardiac rehabilitation improves psychosocial comorbidities and quality of life, as well as reduces risk factors and the risk of mortality.

62.1 MEET SECONDARY PREVENTION PATIENT PATRICIA Patricia’s heart attack was not that surprising. A lifetime of fast food and a history of smoking combined with rheumatoid arthritis and a sedentary tech job precipitated a

62.5.3  Antidepressant Medication����������������������������������� 754 62.5.4 Psychotherapy����������������������������������������������������� 754 62.5.5  Cardiac Rehabilitation������������������������������������������ 755 62.5.6  Depression in Heart Failure���������������������������������� 755 62.6  Future Directions������������������������������������������������������������� 756 62.6.1 Better Understanding of the Independent and Joint Effects of Psychosocial Moderators of Risk������756 62.6.2  Easier Treatments for Psychosocial Factors���������� 756 62.6.3 Complementary and Alternative Medicine Approaches��������������������������������������������������������� 757 62.6.4 More Clarity on Effects of Antidepressants in Heart Disease������������������������������������������������������ 757 62.7 Conclusion����������������������������������������������������������������������� 757 Clinical Applications������������������������������������������������������������������ 757 References������������������������������������������������������������������������������� 757

myocardial infarction (MI) before her 63rd birthday. She called the paramedics, right from her cubicle, when she felt pain radiating down her left arm and tightness in her chest punctuated with sharp pains every time she drew a breath. The cardiologist said that her left-anterior descending coronary artery was almost fully blocked, so they performed a percutaneous coronary intervention (PCI). Apparently, this meant that they inserted a medicated stent that smashed the blockage flat against that artery wall to try to keep the artery open and the blood flowing. The procedure was not as dramatic as Patricia thought it would be because she stayed awake (but sedated) the entire time and was discharged after only one night in the hospital. She felt incredible relief that she did not die right there at work, but she was also really worried about how close she had come to dropping dead, widowing her husband, and orphaning her kids. She felt too young to die. She did not even have grandchildren yet! Patricia knew that things were going to have to change. She had stopped smoking over 30 years ago when she became pregnant with her first child but started another ten years of smoking in her 40s before she finally quit for good. She knew that her diet, extra pounds, and poor fitness were also a big part of the problem. Although she had plenty of arthritis medication, 751

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the pain made it uncomfortable to exercise. In college, she played a lot of volleyball, but now she was ashamed of how she had let herself go. Meeting with the cardiologist a week later, she was hoping to hear that everything was fixed. However, her physician made it clear that Patricia was now on the path of secondary prevention of cardiovascular disease. As a woman with known heart disease, who had already experienced an acute coronary syndrome (ACS), Patricia needed to understand that the stent just opened the artery and that the artery could become blocked again in just a year. The doctor said, “Maybe a 10% chance in one year and perhaps 50-50 in 10 years.” Furthermore, as a woman (i.e. with smaller arteries), Patricia was at greater risk of the artery re-occluding without aggressive treatment. So, there were new pills to take every day, the seemingly futile advice to eat better and lose weight, and an automatic referral to cardiac rehabilitation. Patricia started to feel hopeless and discouraged. “Is this my fate?” she wondered. “No retirement, and dead before I meet any grandkids?”

62.2 SECONDARY PREVENTION AND PSYCHOSOCIAL FACTORS There are millions of men and women like Patricia in the United States. Cardiovascular disease (CVD) causes nearly one out of every three deaths in the United States, and every year, over 1.1 million Americans have a first or recurrent coronary event.1,2 Advances in cardiology have resulted in many more patients surviving their first encounter with heart disease, leading to an increase in the population of patients requiring secondary prevention, as well as a growing number of patients living with heart failure (HF). Secondary prevention is attempting to reduce the risk of ACS and cardiac mortality in people with established CVD. The cornerstone of secondary prevention is risk reduction in multiple areas including smoking, BP control, lipid management, physical activity, weight management, type 2 diabetes management, antiplatelet and anticoagulant agents, renin-angiotensin-aldosterone system blockers (e.g. ACE inhibitors), beta-blockers, influenza vaccination, depression screening, and cardiac rehabilitation.3 In 2011, the most recent American Heart Association/American College of Cardiology (AHA/ACC) guidelines for secondary prevention listed cardiac rehabilitation as a class 1-A recommendation.3 Furthermore, screening patients who are potentially at risk for depression is now recommended. These are changes from the earlier 2006 guidelines.4 The role of psychosocial factors, such as depression, in moderating risk in secondary prevention is increasingly recognized, and the importance of cardiac rehabilitation as part of secondary prevention is now well established. For example, would Patricia become depressed? Does this have any effect on her risk of future cardiac events? What are the appropriate treatments for depression and would they influence her cardiac risk? Will she enroll in and complete cardiac rehabilitation? Would depression influence how she engages in cardiac rehabilitation?

62.3 PSYCHOSOCIAL FACTORS IN HEART DISEASE Psychosocial factors have been recognized as moderators of outcomes in secondary prevention for decades, meaning that patients with known heart disease who have certain psychosocial characteristics may have better or worse outcomes. For example, the Type-A behavior pattern was first recognized in the 1950s, 5 prompting decades of research into coronary-prone personality types and the role of anger and hostility in primary and secondary prevention. Currently, the most prominent example of a moderating role of psychosocial factors is that patients with comorbid heart disease and depression have worse outcomes than those without depression.6–11 In the early 2000s, excellent reviews of the broader topic of psychosocial factors in heart disease were published. For example, Smith et al.6 described how psychosocial influences could influence the pathophysiology of coronary heart disease and identified a number of psychosocial risk factors. Those relevant to secondary prevention included hostility, depression, anxiety, social isolation, interpersonal conflict, and occupational stress. Psychological interventions attempting to mitigate these risks were conducted, such as the landmark Enhancing Recovery In Coronary Heart Disease (ENRICHD)12 and Sertraline and Depression Heart Attack Randomized Trial (SADHART)13 trials for post-MI patients with depression (or social isolation in the case of ENRICHD). The mixed results of these trials were widely discussed, and this only underscored the need for physicians to be aware of the role of psychosocial factors in secondary prevention.11 The call to screen for and intervene with psychosocial risk factors increased. In fact, what some called the field of “behavioral cardiology”10,11 emerged to examine the application of behavioral, pharmacological, and rehabilitative interventions on cardiac outcomes. In this chapter, we focus on the more recent literature and important developments in our understanding of psychopathology, pharmacological interventions, and behavioral interventions. Although behavioral cardiology is broader than the topic of this chapter, as it includes health behaviors and psychosocial factors and is concerned with both primary and secondary prevention,10 in an updated review Rozanski10 reiterated that depression14 and anger/ hostility15 are associated with poorer prognosis in secondary prevention. Furthermore, it was noted that the contribution of behavioral and psychosocial factors to risk is commensurate with that conferred by more traditional risk factors (e.g. cholesterol). No clinical consensus has emerged for how cardiology practitioners should approach behavioral and psychosocial factors in the clinical management of coronary heart disease. However, this review repeated the recommendation for “stepped” behavioral healthcare in which physicians are the front-line clinicians, followed by behavioral health interventions (e.g. cardiac rehabilitation) and behavioral health specialists (e.g. psychologists) in the second and third tiers, respectively.10 Affirming the thesis that psychosocial factors are important but neglected in secondary prevention, a recent review of the impact of cardiac rehabilitation on

62.5  Addressing Depression in Secondary Prevention  753

psychosocial risk factors in secondary prevention reported that cardiac rehabilitation or structured exercise programs reduce anger/hostility, anxiety, depression, and stress.7 In our view, and that of the authors of the review, cardiac rehabilitation is a particularly appropriate context for addressing psychosocial factors in secondary prevention. For example, including stress management training (SMT) in cardiac rehabilitation programs can be beneficial, as the combination of SMT with cardiac rehabilitation may be especially effective compared to psychosocial interventions not involving exercise.

62.4 WHAT ARE THE PSYCHOSOCIAL FACTORS THAT MODERATE OUTCOMES IN SECONDARY PREVENTION? 62.4.1 Social Support A classic study reported that patients who were socially isolated or who lacked a close confidant were at greater risk for mortality after a myocardial infarction (MI) than those with better social support.16 Recently, a systematic review reported that loneliness and social isolation predict incident cardiac disease and stroke,17 and it is generally recognized that adequate social support is necessary for recovery from ACS. For example, heart transplant candidates are typically required to identify a support person during the eligibility evaluation before transplantation. Medicare guidelines for cardiac rehabilitation also require an evaluation of social support (i.e. “aspects of family/home situation”) that affect treatment, although screening procedures were not specified. However, treatment of loneliness is not merely structural, as shown in a broader population meta-analysis, which demonstrated that interventions targeting social cognition were more effective than those that merely increased opportunities for interaction.18

62.4.2 Anger/Hostility Reviews confirm that anger and hostility remain important psychosocial factors for prognosis in primary and secondary prevention of cardiovascular disease.6,10,11 In one meta-analysis, the association between anger/hostility and outcomes was stronger for men than for women.15 However, psychosocial interventions for hostility have been rare,19 and it has been suggested that the widespread adoption of pharmacological interventions acting on the putative biological mechanism (i.e., beta-blockers) has resulted in a less prominent role for hostility in secondary prevention in recent decades.

62.4.3 Anxiety Anxiety also worsens prognosis in secondary prevention of cardiovascular disease.7,20 Screening for anxiety is less common than screening for depression, possibly because

of the heterogeneity of anxiety disorders, the overlap with depression, and the much larger literature on the risk associated with depression. Anxiety predicts mortality in stable heart disease, but the risk may be shared with depression20 or potentiate the risk associated with depression.21

62.4.4 Depression The fact that depression worsens prognosis in secondary prevention is now well established,7 and screening for depression has been incorporated into the most recent AHA/ACC statements.9 The relationship between depression and heart disease is complex, as depression is also a risk factor for the development of cardiovascular disease. In primary prevention, depression has been associated with approximately a 65% increase in the risk of developing cardiovascular disease among persons initially free from heart disease.22 In secondary prevention, depression contributes a two- to five-fold increase in the risk of mortality.8,9 Depression is also very common in cardiac patients, with perhaps 15–20% of patients qualifying for a diagnosis of major depressive disorder and an additional 15–20% exhibiting clinically significant symptoms of depression without meeting diagnostic criteria. Depression can be exacerbated by the stress of ACS, but can also predate the cardiac event or emerge later. For example, half of the patients enrolled in SADHART were depressed prior to their ACS.13 Therefore, depression has become an important consideration in secondary prevention for patients with cardiovascular disease, but efforts to reduce the risk of mortality by alleviating depression have not been very successful.

62.5 ADDRESSING DEPRESSION IN SECONDARY PREVENTION 62.5.1 Screening for Depression Although screening for depression in secondary prevention is recommended9,23 and has become common, there has not been an evaluation of the impact of depression screening on patient outcomes in cardiovascular care. 24 Some have argued that we need not bother, 25 and this may be due in part to the unfortunate reality that treatments for depression in heart disease are not particularly effective, as well as the fact that although they reduce depression and improve quality of life, they have yet to convincingly reduce the risks attributable to depression. A 25-year review of interventions for depression in heart disease concluded that many cases of depression remit “spontaneously” and that there is no strong evidence that either antidepressants or psychotherapy influence prognosis. 26 However, two recent developments in psychiatry, discussed below, may help to explain why efforts to address depression in heart disease have been so challenging. (Note: these two developments are the realization that the mechanisms of action for antidepressants are largely psychological and the recognition that most mental disorders are not “natural kinds,” or discrete categories.)

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62.5.2 Treating Depression in Secondary Prevention The conclusion of this literature is that the first-line treatments for depression in heart disease are newer antidepressants (e.g. SSRIs) or psychotherapy (e.g. cognitive behavioral therapy), that the effectiveness of these approaches is moderate at best, that these treatments do not improve cardiac prognosis much, if at all, and that patients whose depression persists continue to have elevated risk of poorer outcomes. The often-overlooked option is exercise, a key component of cardiac rehabilitation, which, as we will see, both reduces depression and improves prognosis.

62.5.3 Antidepressant Medication Concerning antidepressants, they are often the first treatment option, and SSRIs, in particular, appear to be safe for use in patients with cardiovascular disease.27 However, in the SADHART trial, sertraline was only effective for patients with a history of depression.13 In the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial, citalopram had a small-to-medium effect relative to placebo in reducing depression.28 Again, most of this benefit was limited to those patients with recurrent depression.29 In the Myocardial Infarction and Depression-Intervention (MIND-IT) Trial, antidepressants improved neither depression nor prognosis.30,31 Antidepressants have also been administered prophylactically, and escitalopram was reported to prevent depression episodes following ACS relative to placebo.32 Thus, evidence for the effectiveness of antidepressants in secondary prevention is mixed, and may not match patient preference. Specifically, among the general population of patients experiencing their first episode of major depression, 41% prefer psychotherapy and 31% prefer antidepressants.33 However, the disappointing effectiveness of antidepressants for patients with heart disease may be better understood by appreciating recent revelations on the shortcomings of antidepressants more broadly. Fairly recently, it has become clear that much of the effect of modern antidepressants on depression is due to psychological factors like hope, a sense of efficacy in doing something about the depression, and the expectation of getting better (this may not be as true for the effects of antidepressants on anxiety or other conditions).34,35 In fact, antidepressants appear to have a greater effect on depression if the patient experiences more side effects, as the side effects apparently remind the user that they are taking the medication and imply that the medication must be working. 36 It has been argued that fluoxetine would not have received approval from the Federal Drug Administration (FDA) had the studies with negative results been reported.37 A less charitable way of saying this is that a substantial part of the effectiveness of antidepressants is a placebo effect.35,38,39 Between the years 2002 and 2010, this erupted into a public controversy. Some associates within the field of Psychiatry were not amused.40 Of course, there are caveats and vigorous debate,41 and it must be acknowledged that antidepressants do

“work,” whatever the mechanism may be. For example, the response curve for both placebo and active drug appear robust, and drug trials rarely include a study arm of patients receiving no treatment at all. The small effect of antidepressants may only be relative to placebo, and untreated patients may not improve at all. Furthermore, in clinical practice, it is strongly recommended that patients not abruptly discontinue antidepressants without medical supervision because some patients have discontinuation symptoms and the chance of relapse into another depressive episode is high.42 Even for antidepressants-asplacebo, the therapy infrastructure is often so poor that, for many patients, the only option may be antidepressants. However, lifestyle cognitive and behavioral habits, rather than taking medication, will be a more enduring solution for most cases of depression and anxiety. Why is there so little effect of antidepressants that can be attributed to the medication itself? It is not known for certain. It is suspected that the chemical imbalance theory of depression (really a metaphor) is overly simplistic.43,44 First, treatment cannot inform etiology. For example, a headache is not caused by an aspirin deficiency. The fact that aspirin works (anti-inflammatory medications reduce prostaglandins) does not suggest an “aspirin imbalance” in a patient’s brain. This is not to suggest that the serotonergic systems of the central nervous system are not at all involved in depression, but the chemical imbalance metaphor appears to be dramatically oversimplified. Whatever the mechanism of action for antidepressant medication, they appear more effective in patients with recurrent depression and do not appear to influence prognosis in secondary prevention.

62.5.4 Psychotherapy With respect to psychotherapy, cognitive behavioral therapy (CBT) used in the ENRICHD trial modestly reduced depression relative to control and did not reduce mortality rates.12 Patients whose depression persisted continued to have a worse prognosis.45 One alternative to CBT, interpersonal psychotherapy for depression, was evaluated by the CREATE trial but was not more effective than clinical management for depression in patients with coronary artery disease.28 In the more recent Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS) trial, stepped care (as suggested by Rozanski10,11) was compared to treatment-as-usual (e.g. locally determined care by the patient’s healthcare provider).46 Those allocated to stepped care initially received problem-solving therapy via telephone followed by the option to receive antidepressants. Reductions in depression were greater for stepped care than for treatment-as-usual, potentially suggesting that patient preference (e.g. choice, agency) is important for the effectiveness of treatment. However, improvement in depression was not associated with better secondary prevention in the areas of aspirin adherence, diet, exercise, use of tobacco, or blood pressure control.47 A fairly recent Cochrane review of psychological interventions for patients with heart disease concluded that reductions in depression are small to moderate and that they are not accompanied by improved prognosis.48 Given the disappointing

62.5  Addressing Depression in Secondary Prevention  755

effectiveness of both antidepressants and psychotherapy for addressing psychosocial factors that moderate risk in secondary prevention, alternative approaches are needed. The most promising resource for addressing depression is existing secondary prevention as provided by participation in cardiac rehabilitation.

62.5.5 Cardiac Rehabilitation Outpatient (Phase II) cardiac rehabilitation is a multifaceted secondary prevention program for patients that includes up to 36 sessions (e.g. 12 weeks) of exercise and education on lifestyle risk factor management, and is reimbursed by Medicare and other insurance carriers.49 Because cardiac rehabilitation lowers rates of reinfarction and mortality, 50 it is an evidence-based treatment recommendation for eligible patients with cardiovascular disease following cardiac events such as myocardial infarction, Percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and cardiac valve surgery. 51,52 The goals of cardiac rehabilitation are to improve fitness, biomarkers such as lipids, and quality of life, and engage in and maintain secondary prevention behaviors including exercise, diet, smoking cessation, and medication management. There is no question that cardiac rehabilitation is effective for secondary prevention. However, less than 20% of eligible patients enroll in outpatient cardiac rehabilitation, 52–54 and only 49–70% of these complete the program. 52–55 Furthermore, health disparities persist in cardiac rehabilitation participation, with lower participation rates observed among the elderly, sicker patients, women, minorities, and persons of lower socioeconomic status (SES). 56–58 Interestingly, psychosocial factors are not always barriers to participation in cardiac rehabilitation. Although depression is consistently associated with poorer adherence to CR, 59 among older (>65) Medicare patients experiencing a myocardial infarction, depression actually increased the odds of enrolling in cardiac rehabilitation.60 Furthermore, cardiac rehabilitation has a beneficial effect on psychosocial factors, as it reliably reduces depression.7 For example, although women starting cardiac rehabilitation have higher depression scores, they also experience a greater reduction in depression.61 Exercise is at least as effective as antidepressant medication for depression,62 and combined exercise and antidepressants appeared to have greater benefits on a biomarker of risk (heart rate variability) than either intervention alone.63 Finally, integrating 12 weeks of stress management training with cardiac rehabilitation reduced

mortality relative to cardiac rehabilitation alone, suggesting that combining psychosocial interventions with cardiac rehabilitation may provide even better secondary prevention.64 Given that cardiac rehabilitation is effective for reducing both mortality and depression, combined with the disappointing results of two decades of attempts to ameliorate the poorer prognosis of cardiac patients with comorbid depression, it is our view that future efforts should focus on increasing utilization of cardiac rehabilitation and integrating psychosocial interventions with cardiac rehabilitation or other structured exercise programs (see Table 62.1).

62.5.6 Depression in Heart Failure Most secondary prevention efforts used to target coronary heart disease and patients experiencing ACS. The success of modern cardiology has led to an increased prevalence of patients with heart failure (HF), as they survive the initial MI and live longer with heart disease. Now that stable systolic HF is an approved indication for cardiac rehabilitation, this population will receive increased secondary prevention efforts. Currently, over 5 million Americans have heart failure (HF), and nearly 1 million new cases are diagnosed each year.65,66 The prevalence of HF is expected to increase 46% by 2030, and more than 8 million U.S. adults will have HF.67 Mortality in HF remains high, as one out of two HF patients die within five years of diagnosis.68–70 As with other forms of heart disease, many individuals with HF experience depressive symptoms or clinical depression. At least 20–40% of patients with HF experience depression symptoms during their illness,71 which doubles the risk of all-cause mortality.71,72 Depression in HF patients is also associated with other negative health outcomes and increased healthcare utilization. For example, depressed HF patients have a two-fold risk of emergency room visits,73 and higher hospital readmission rates.71,74 Annual healthcare costs are 29% higher for HF patients with depression and/or prescribed antidepressants as compared to non-depressed HF patients.75 Inpatient and outpatient medical visits account for the majority of this increase in cost. Depression undermines disease management programs for HF 76 and is a barrier to effective patient self-management. For example, medication nonadherence increases the risk of mortality in depressed patients with HF.77 Some of the lessons from other heart disease conditions about psychosocial factors in secondary prevention are being repeated in patients with HF. For example, neither

TABLE 62.1  Treatments for Depression in Cardiovascular Disease Antidepressants

Antidepressants are not very effective, except for patients with a history of recurrent depression. Antidepressants do not reduce risk associated with depression.

Psychotherapy

Cognitive behavioral therapy is somewhat effective but does not reduce risk associated with depression. Newer psychotherapies such as acceptance and commitment and mindfulness-based cognitive therapy have not yet been evaluated.

Cardiac rehabilitation

Cardiac rehabilitation, which includes exercise, is effective for depression and reduces risk of mortality. Enhancing cardiac rehabilitation with stress management or other psychosocial interventions has promise.

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sertraline78 nor escitalopram79 is efficacious for depression in patients with HF; and although both were safe, they did not improve clinical status.78,79 Furthermore, as with the broader population of depressed individuals,80,81 HF patients tend to prefer behavioral treatments to antidepressants.82 Patients are also more willing to participate in clinical trials of psychotherapy than trials of antidepressants for depression.83 Freedland et al.84 recently conducted the most comprehensive clinical trial to date evaluating CBT for depression and self-care in HF. Patients (n = 158; 54% men) with HF (most with LVEF < 45%) and comorbid depression were randomized to CBT or enhanced usual care (e.g. educational materials including three 30-min phone calls). CBT as compared to control resulted in greater reductions in depression symptoms at six months and superior remission of depression (46% vs. 19%), but the trial was not powered to detect improved prognosis. As with cardiac patients more broadly, exercise also reduces depression in systolic HF.85 The HF-ACTION trial randomized 2,322 patients with HF to exercise or education and usual care. Depression scores were reduced at three months and 12 months, but the clinical significance of the improvement could not be demonstrated. The effect of exercise training on depression was a 40% reduction in symptoms, and those who remained depressed continued to have an elevated risk of mortality.86 Intriguingly, depressed patients who completed exercise training had almost a 60% reduction in mortality.86

62.6 FUTURE DIRECTIONS The public health burden of cardiovascular disease is likely to increase as the population ages and advances in cardiology result in more patients being appropriate for secondary prevention. Psychosocial factors are known to moderate cardiovascular outcomes, but efforts to ameliorate this risk have been difficult. Here we argued that addressing psychosocial factors in the context of cardiac rehabilitation is a promising approach.87 There are a number of other directions for future research that merit comment.

62.6.1 Better Understanding of the Independent and Joint Effects of Psychosocial Moderators of Risk Several psychosocial risk factors have been identified, including social isolation, anger/hostility, depression, and anxiety. These are known to overlap, and future research may be able to delineate the independent and joint effects of these factors. For example, Watkins et al. in 2013 found that the risk conferred by anxiety was independent of depression 21 but that patients with comorbid anxiety and depression had even greater risk than those with anxiety or depression alone. One advance in psychiatry may bear directly on these questions. It has become clear that, for a number of reasons, most mental disorders are not natural kinds.88,89 This means that most mental disorders are continuous

dimensions, with no abrupt discontinuity that suggests the existence of a category in nature. In the case of depression, for example, depression symptoms exhibit a negatively skewed exponential distribution. Many people exhibit low symptoms levels, and a minority have a high level of symptoms. It is possible that some subtypes, such as “endogenous” (i.e. biological) depression, are a category in nature (like sickle cell disease), but the majority of cases of depression are continuous (like high blood pressure). There is not a “cutoff” that maximizes identification of a category in nature, because no such category exists. Thus, major depressive disorder is a label we apply when people hit a practical threshold for sufficient symptoms on the underlying dimensions (e.g. mood, behavior). The diagnosis is needed for practical reasons such as treatment, but depression is not a discrete entity any more than elevated blood pressure would be. The implications of this contemporary understanding of psychopathology have not been explored in cardiovascular behavioral medicine. For example, perhaps antidepressants work better for patients with recurrent depression because they are more likely to have endogenous depression, a suggestion that can only be a hypothesis at this point. Furthermore, the “essential features” of depression vs. anxiety or social isolation are not rooted in differences between categories in nature but rather merely reflect the degree to which the underlying dimensions are correlated. Finally, we need not debate whether cases of depression in heart disease are “merely” due to the stress or pathophysiological sequelae of ACS (e.g. inflammatory cytokines), because any circumstances that alter a person’s position on the number line of depression are contributing factors. It is our hope that further implications of this understanding of psychosocial factors can be further elaborated and yield new insights and novel hypotheses for addressing risk in secondary prevention.

62.6.2 Easier Treatments for Psychosocial Factors Another promising direction for further research is the development of behavioral interventions that are easier to implement, particularly in the context of other secondary prevention efforts such as primary care and cardiac rehabilitation. The front-line treatments at this point are antidepressant medications, which are not particularly effective, and psychotherapy, which is time and labor intensive. The mental health infrastructure is poor in many communities, and it would be valuable to have interventions that can be provided to more patients. Along this line, there has been an evolution of psychotherapy to include more acceptance of distress and more mindbody interventions such as meditation. The so-called “third wave” of psychotherapy departs from cognitive behavioral therapy90–92 by de-emphasizing the focus on dysfunctional or depressogenic cognition, instead asking patients to accept and tolerate some distress. The major therapies in this tradition are acceptance and commitment therapy93 and those which incorporate mindfulness meditation.94 Two clinical trials of acceptance and commitment therapy for patients with heart disease are currently underway.95,96 A meta-analysis and systematic review of mindfulness-based interventions

References  757

for patients with vascular diseases included nine clinical trials (three in heart disease) and reported effects for psychological but not medical outcomes.97 If newer therapies continue to grow in popularity and availability, it will be important to evaluate their suitability for secondary prevention. There is great enthusiasm for incorporating some of the techniques (e.g. meditation) into cardiac rehabilitation, but the research is currently lacking.

62.6.3 Complementary and Alternative Medicine Approaches98 As approaches historically considered “alternative,” such as meditation and yoga, are incorporated into mental health interventions, there will be increasing interest in complementary and alternative approaches to addressing psychosocial comorbidities in heart disease. For example, one systematic review examined randomized controlled trials comparing Chinese herbal medicines with either placebos or antidepressants for depression outcomes in coronary heart disease patients.99 Herbal medicines were not superior to placebo at four weeks but were superior at eight weeks. A combination treatment of herbal medicines and antidepressants was shown to be efficacious at both four and eight weeks. Some trials also suggested that herbal medicines were associated with fewer adverse effects than a control intervention. However, due to small sample sizes and potential for biases, these results should be interpreted with caution.

62.6.4 More Clarity on Effects of Antidepressants in Heart Disease Finally, as our understanding of the nature of depression in heart disease improves, it will be important to develop a clearer understanding of the effects of antidepressants. For example, the cardiovascular risk profile of SSRIs appears moderated by whether or not the patient has heart disease. A meta-analysis found that antidepressants increase cardiovascular risk for a general population sample, while not affecting the risk for the sample of cardiovascular disease patients. This may be due to the anticlotting properties of antidepressants that may be adaptive for cardiovascular patients.100 Whether or not they reduce cardiac risk, antidepressants have had disappointing efficacy relative to placebo for patients with heart disease, particularly those with HF.

62.7 CONCLUSION Secondary prevention patient Patricia, whom we met at the beginning of this chapter, is at a relatively high risk of developing clinically significant depression following her ACS. She expressed hopelessness and discouragement, and should, at minimum, be screened for depression. Whether her symptoms meet the admittedly arbitrary threshold for major depressive disorder is not as important as whether they cause clinically significant distress and impairment, as most psychiatric diagnoses are practical categories and not discrete entities in nature. First-line treatment options include newer antidepressants and psychotherapy. Antidepressants are not much more effective than placebo, and her risk of relapse when they are discontinued is very high. Psychotherapy is likely to reduce symptoms of depression but would be unlikely to improve her cardiac prognosis. Therefore, cardiac rehabilitation is the preferred approach to secondary prevention and is likely to benefit her psychosocial concerns as well as improve her chances of long-term survival. If necessary and feasible, behavioral interventions can be integrated with or added to cardiac rehabilitation. As Rozanski10,11 recommended, stepped care can be employed, in which cardiac rehabilitation is tried first, and a referral for increased assessment and treatment can be provided if determined to be necessary upon repeated screening for depression.

CLINICAL APPLICATIONS Psychosocial Considerations in Secondary Prevention Social support/ social isolation

Isolated patients or those with low social support are at greater risk of mortality.

Anger/hostility

Patients high in anger or hostility have poorer outcomes, but interventions are rare and beta-blockers may directly target the physiological mechanism responsible.

Anxiety

High anxiety increases risk of mortality independent of depression, and comorbid anxiety and depression may have a greater effect than either alone.

Depression

Depression is common in heart disease and confers a 2- to 5-fold increased risk of mortality. All patients should be screened for depression.

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63 CHAPTER

A Patient’s Perspective on the Keys to Longevity 40 Years after Undergoing Coronary Artery Bypass Surgery Joseph C. Piscatella, BA

Key Points.................................................................................. 761 63.1  A Teachable Moment........................................................ 761 63.2  If I Were a Doctor.............................................................. 763 63.3  Stop Smoking................................................................... 763 63.4  Exercise Regularly............................................................ 763

KEY POINTS • Helping patients manage heart disease is more than imparting the science of cardiac health—monitoring cholesterol numbers, BMI, and blood pressure, for example—and it is more than medication compliance. • The key to patient progress is the adoption of positive lifestyle habits—eating healthy, not smoking, exercising regularly, managing stress, and developing a positive mental attitude. • Providers are key to delivering the healthy lifestyle message, but it must go beyond basic information, i.e. “don’t smoke.” Cognitive understanding alone does not result in long-term behavior change. • Providers must motivate and encourage positive behavior change with helpful tips on how to accomplish such changes. They must help the patient develop focused repetition of positive behaviors until a habit is formed. I am a believer in the efficacy of healthy lifestyle choices for the primary and secondary prevention of coronary heart disease. As a result, I make a serious effort to engage in powerful health-promoting actions such as eating a healthy diet, exercising regularly, managing stress effectively, having a positive mind-set, and avoiding cigarette smoke. These actions help me to manage my weight, control glucose, c-reactive protein, cholesterol and other lipids, reduce inflammation, and keep in good physical shape. Looking back on my life, I would love to tell you that my commitment to heart-healthy living was the result of native intelligence, but it was not. Instead, it was born

63.5  Eat Healthy Food, but Not Too Much of It........................... 764 63.6  Manage Stress................................................................. 764 63.7  Develop a Positive Mind-Set............................................. 765 63.8  A Last Word...................................................................... 765 Clinical Applications................................................................... 765

purely out of need. For the first 32 years of my life, healthy living took a backseat to other, seemingly more important things that took my time and interest: my family, work, and community. Besides, I had always been healthy. Serious diseases such as heart disease and cancer happened to other people. Sure, there were things that could have been improved. My cholesterol was too high, I could stand to lose a few pounds, and my exercise regimen was sporadic. There would be time, I thought, to improve my numbers and my health while I was rocking in retirement. But I was wrong. In 1977, I underwent coronary bypass surgery. I was 32 years old. My wife and I had not yet celebrated our 10th wedding anniversary. My daughter was six years old; my son was just four. And my new business had been in operation for three years. That experience became the motivating force for us to understand the health impact of lifestyle habits and to take action to improve those choices. In retrospect, it was a hard way to learn important lessons. What I had to be taught for rehabilitation I should have learned for prevention.

63.1 A TEACHABLE MOMENT It was a hot afternoon in July 1977, and for the second time in a week, I was seated in the office of a prominent cardiologist in Tacoma, Washington. I was bewildered as to why I was there. Five days earlier, I had been to see my family doctor about what I thought was a bronchial problem. For about a month, I had experienced shortness of breath and a lowgrade but nagging chest pain as I warmed up to play tennis. 761

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The pain was dull, more like a feeling of fullness or pressure. By the end of the warm-up, it would usually disappear. I ignored the pain, hoping it would just go away. But one day, it remained with me through two hours of play. It was then that I decided to call him. “I’ve got a problem in my lungs, probably a touch of bronchitis,” I told him. He asked me to come in right away. I had seen him just four months earlier for an annual physical and the results then were excellent, so I was not expecting anything more than a short visit and perhaps a prescription. The examination indicated that my lungs were fine. The results of an electrocardiogram, however, were not. The previous test from my annual physical showed normal results. The results now, however, were drastically different. “Joe, the test indicates possible obstructions of the coronary arteries,” my doctor said. “I want you to see a cardiologist immediately, today. In fact, I’m closing my practice for the rest of the day and driving you to his office. I don’t want you behind the wheel of a car.” So, three hours after my “routine” examination, I found myself undergoing a thorough cardiac examination and exercise stress test. I did not take seeing a cardiologist lightly. But I did not believe there was anything seriously wrong, either; I was certain it was a mistake. Like the electrocardiogram, the results of the stress test indicated a problem. I subsequently had coronary angiography that indicated three arterial blockages ranging from 50% to 95%. “You have coronary heart disease,” the doctor said. “I recommend coronary artery bypass surgery be done immediately… I mean within the next few days. At this moment, you are a heart attack statistic just waiting to happen.” The shock of his words hit me like a slap in the face. This couldn’t happen to me. I was not prepared to hear what he had to say; I had difficulty understanding. He was speaking about a heart problem—my heart problem!—that, psychologically, I could not accept. Thoughts of escape filled my mind. “Just get up and leave,” I told myself. “It’s all a mistake. You’re not supposed to be here.” Once safely back in my world, I reasoned, I would surely awaken from this horrible nightmare. As I continued to listen numbly to the doctor, I was confused. Like most people, I knew something about the workings of the heart and the coronary arteries, but the information was chiefly of the Biology 101 variety. It was not that information was not available. The American Heart Association, among others, had produced and disseminated a tremendous amount of it. But, quite frankly, it had been of remote interest to me. Such information, indeed the subject itself, was simply not relevant to my life. What did arterial blockages or heart attacks have to do with me, a young guy in the prime of life? Unknowingly, I had succumbed to the “what I don’t know won’t hurt me” syndrome. In reality, what I didn’t know could not only hurt me, it could kill me. • What I didn’t know was that coronary heart disease usually develops silently, insidiously, over a long period of time, generally 20 to 40 years. Once it surfaces, however, the primary result, a heart attack, is often immediately devastating.

• What I didn’t know was that more than 13 million Americans have coronary heart disease and that every year, some 1.5 million people suffer a heart attack, causing 600,000 to 800,000 fatalities— equal to the casualties from 10 Vietnam wars! • What I didn’t know was that heart disease causes about 45% of all deaths in the United States each year, more than cancer, AIDS, auto accidents, floods, and airplane disasters combined. • What I didn’t know was that for about one-third of heart attack victims, the first heart attack was the only one, resulting in sudden cardiac death. • What I didn’t know was that while genetic history is important, most Americans with heart disease have it because of poor lifestyle habits involving diet, exercise, stress, and smoking. As Dr. William Roberts, Editor in-Chief of the American Journal of Cardiology, stated, “For every one person with heart disease primarily because of bad genes, 499 have it because of poor lifestyle habits.” But, conversely, improving those habits could contribute to better cardiac health. Such information was simply outside the realm of my everyday life. But it all changed for me on that July afternoon. As the diagnosis sank in, the age of innocence and ignorance ended for me. I was gripped by pure stomach-churning fear. At 32 years old, I had felt a kind of immortality that only the young experience. The concept of death had been a remote one. I pictured it at the end of a long life, after years of accomplishment, fulfillment, and joy. Old age was something that I looked forward to sharing with my wife. I had never contemplated the idea of death taking me in my prime. On that July day, the alarm clock of reality rang. I realized that not only could death happen now, but also it probably would happen now, the result of a time bomb located inside my chest. A decision was made to undergo the surgery. A week after surgery, I went home to recover, elated simply to be alive and with my family again. But I was very concerned about my future. Surgery had circumvented the immediate problem—having a heart attack—but had not stopped the disease. Bypass did not “cure” me. As my doctor counseled, “You had heart disease the day before surgery, you had heart disease the day after surgery, and you have it today as well. The surgery took away the pain but it did not remove the disease. Only a change in your lifestyle habits can reduce your future heart attack risk.” This knowledge was complicated by the prediction of another doctor, a nationally known lipid specialist. I saw him after the surgery for advice on how to manage my cholesterol. “Should I change my diet?” I asked. “Don’t bother,” was his reply. “You have an aggressive form of coronary heart disease at a very early age. Frankly, I’d be surprised if you live to be 40. The chances of seeing your children graduate from high school are slim.” While his bedside manner was harsh, I had to acknowledge that he might be right. For a week or two, I was depressed, unable to see a clear path or take decisive action. Then my wife put it all into perspective: “His

63.4  Exercise Regularly  763

prediction is not pre-destination,” she said. “It’s true, you can’t change the cards you were dealt. You do have aggressive heart disease at age 32. But you can change the way that you play those cards. And we are going to do everything possible to eat healthier and exercise more effectively to even up the odds.” And that is what we have done. How has it worked? I recently celebrated the 40th anniversary of my bypass surgery by hiking on Mount Rainier with my wife. My current biometric measurements—cholesterol, weight, and blood pressure—show that I’m in better health now than in 1977. As a result, I have experienced the joy of seeing my daughter and son graduate from high school, college, law school, and graduate school; of walking my daughter down the aisle and making a toast at my son’s wedding; of celebrating 50 years of marriage; of gathering with family at my 73rd birthday; and of holding our four grandchildren. None of this would have happened without practicing healthier lifestyle habits.

63.2 IF I WERE A DOCTOR Let’s face it: most patients come to the doctor’s office looking for a pill or a prescription that will make everything right. This is complicated by the fact that many physicians are enamored with emerging cardiac science. But if I were a doctor, I would spend less time discussing the science and more time instructing the patient on healthy lifestyle habits. This is critical as no one has the ability to influence patient behavior more than physicians do. How many anecdotes have we heard about the heart patient who continues to smoke because “my doctor never told me to stop?” So, while it is easy to become enthralled with the science of cardiac health, helping the patient create a healthier lifestyle is the core issue. If I were a doctor, counseling patients on primary or secondary prevention of coronary heart disease, here is what I would advise based on my 40 years of managing my own heart disease successfully.

63.3 STOP SMOKING Responsible for more than 500,000 deaths annually, smoking has historically been the single most preventable cause of death in the United States. According to the American Lung Association, if a person starts smoking before age 20, each cigarette costs about 20 seconds of life. For a two-packs-a-day smoker, this means throwing away more than eight years of life span. Most people assume that the greatest health risk from smoking is cancer. And while it is true that smoking leads to more than 150,000 cancer deaths each year, the impact of smoking on the risk of heart disease is much greater. By increasing risk factors such as elevating blood pressure, decreasing exercise tolerance, and increasing the tendency for blood to clot, smoking contributes to about 40% of all cardiac deaths. Smokers are twice as likely as nonsmokers to have a heart attack and are five times more likely to die from sudden cardiac death. But I would stress to my patients that there is hope for those who give it up. Research shows that within two to

three years of quitting, former smokers reduce their risk of heart attack and stroke to levels similar to those of people who never smoked. And within five years of quitting, former smokers have a 50% to 70% lower risk of heart attack than current smokers. The bottom line is that if the patient is not a smoker, encourage him not to start. If the patient is a smoker, provide advice and information such as • Joining a stop smoking clinic or group • Using nicotine replacement products, and • Taking medication to help the patient to stop smoking

63.4 EXERCISE REGULARLY “If exercise could be packaged into a pill,” says Dr. Robert Butler, former director of the National Institutes on Aging, “it would be the single most widely prescribed and beneficial medicine in the nation.” With physical activity ranking so high on the list of smart things to do for your heart and health, you would think most Americans would have gotten the message to exercise regularly. If you judged us by our appearance—jogging shoes, yoga pants, and warm-up suits—you would think the country was in the middle of a fitness boom. Think again. Americans generally do not exercise. As one doctor told me, “We just buy exercise stuff!” According to government data, about half the adult population admits to being sedentary, and of those who claim to exercise, fewer than 15% do it often enough or hard enough to produce cardiovascular benefits. Says Dr. Jeffrey Koplan, former director of the Centers for Disease Control and Prevention, “Physical inactivity, along with overweight, accounts for more than 300,000 premature deaths each year in the United States.” This is a tragedy for heart health as regular physical activity confers so many benefits. It strengthens the heart, boosts high-density lipoprotein cholesterol, reduces blood clotting, lowers blood pressure, aids in weight loss, maintains muscle strength, and helps to manage stress. A balanced exercise program should include daily physical activity (such as walking the dog), weight training for building strength, flexibility exercises (such as stretching or yoga) to prevent injury, and, most important, aerobic exercise to promote cardiovascular endurance and fat burning. If I were a doctor, I would encourage patients to find a form of aerobic exercise that they like and will do. Brisk walking, jogging, aerobic dance, swimming, stair stepping—it does not matter what the exercise is as long as it conforms to the F.I.T. criterion: F stands for frequency. The American College of Sports Medicine counsels an aerobic workout three times a week or, better still, every other day. Fewer than three days a week may not be as effective. I stands for intensity. Aerobic walking, for example, is not a casual stroll. Instead, you have your arms pumping, your stride is long, and you have sweat on your upper lip. You should feel like you are late for a doctor’s appointment.

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T stands for time. The historic recommendation is 20 minutes of nonstop activity as a minimum. But many people use the 20-minute mark as a maximum. It takes more time than that to produce cardiovascular benefit. I would also counsel patients on getting an exercise partner. It is a key to making a commitment to exercise regularly.

63.5 EAT HEALTHY FOOD, BUT NOT TOO MUCH OF IT Perhaps nothing is more important for cardiac health than eating a healthy, balanced diet. But the American diet is the antithesis of healthy eating. About 34% of calories consumed comes as fat, much of it saturated and trans fats; 24% comes as refined sugar (or about 150 pounds per year for adults); and 5% comes as alcohol. There are also problems with what we do not eat: some 40% of adults eat no fruit, 80% eat no whole grains, and 40% eat no vegetables. (Actually, the vegetable number is worse as it seems that half of those claiming to eat vegetables list french fries as the only vegetable eaten!) The Surgeon General’s Report on Nutrition and Health characterizes Americans as “gobbling their way to the grave.” The report identifies a causal link between the typical American diet and five of the ten leading causes of death: CHD, cancer, high blood pressure, stroke, cirrhosis of the liver, and the nation’s leading ailment, obesity. There are many reasons behind such an unhealthy dietary pattern. Our fast-paced, out-of-time lifestyle has moved people away from shopping and cooking. Instead, they often eat on the run and settle for what is available, quickly, from restaurants, take-out places, and food stores. Many people have simply traded nutrition for convenience. “And when you add in what choices are available,” according to Dr. Kelly Brownell, an obesity expert at Yale University, “the problem is compounded. We live in a toxic environment for making healthy food choices.” If I were a doctor, I would keep the nutrition message simple by recommending the Mediterranean diet: eat healthy fats such as olive oil; avoid refined carbohydrates such as commercially baked goods, sugary desserts and soft drinks; minimize saturated fat and avoid trans fats; center your diet on fruits, whole grains, and vegetables; eat cardio-protective foods such as oatmeal, orange juice, fish, and nuts; when you eat meat, make it lean; stay away from high-sodium foods; drink water; have an occasional glass of wine; choose low-fat and fat-free dairy products; choose whole foods over processed foods; and, of great importance, cook more at home. From a practical standpoint, this can be accomplished with three actions. First, don’t crash diet. It is a game for fools. Fad diets might help you lose a few pounds in the short run, but they are ineffective for a life-time. Consider this: we have had more than 60 years of quick weight-loss diet books. If a single one had worked—if the “cabbage soup” diet had worked!—we would be a nation of skinny folks.

Secondly, eat real foods. We struggled in our house to eat healthy foods after my surgery, as these foods were often bland and tasteless. Then I came upon a piece of information that changed our thinking. Data show that most American families prepare 12 recipes 80% of the time. So, if you can identify your 12 favorites and modify them to make them healthier—but only to the point that taste remains—you get the best of both worlds: familiar recipes that are tasty and healthier. And finally, talk to the patient about portion size. As compared with the 1970s, the average person today consumes over 500 extra calories a day. Restaurant meals and processed foods have become “super-sized.” Dinner plates now look like hubcaps. Most people have little understanding of portion size and that has an impact on our obesity epidemic. Eating for heart health is not just about specific foods, it is also about how much is eaten. A simple way to estimate healthy portions is to use your palm, fist, and thumb as a guide: • 1 palm = 3 ounces. The size of your palm is about the size of a 3-oz serving of cooked meat, fish, or poultry. • 1 fist = 1 cup. One cup of cereal, spaghetti, potatoes, vegetables, or cut fruit is about the size of a woman’s closed fist. A man’s closed fist is about 1.5 cups. • Thumb tip = 1 teaspoon. One teaspoon of butter, peanut butter, mayonnaise, or sugar is about the size of the top joint of your thumb. Three such portions make up about 1 tablespoon. • 1 or 2 handfuls = 1 ounce of snack food. For nuts or small candies, 1 handful equals about 1 ounce. For chips or pretzels, two handfuls is about 1 ounce.

63.6 MANAGE STRESS There is growing evidence that chronic stress can directly penalize cardiovascular health by raising cholesterol and/ or blood pressure, promoting coronary inflammation and triggering sudden cardiac death. While much more study needs to take place, there is great consensus about the indirect impact of daily stress: it can destroy healthy lifestyle habits. People under stress tend to smoke, eat a poor diet, and lead sedentary lives. More and more experts are now concluding that chronic stress may be the chief barrier to non-adherence to healthy habits, particularly diet and exercise. Most people today are not overly stressed by “bigticket” items such as a poor diagnosis from their doctor or a dip in their 401K. Instead, most chronic stress comes from the fact that we are out of time. We simply do not have the time to do all the things we need or want to do. One female executive recently told me, “I’m answering e-mails at 9 p.m., doing my laundry at midnight, in a grocery store at 6 a.m., then drive my kids to school and go to work. I do a lot of different things during the day, but because I’m always short of time, I don’t feel that I do any of them well.” When people are stressed like this, it makes no difference how much they know about healthy living—and we know a lot!—a candy bar still becomes lunch, exercise

Clinical Applications  765

is skipped, and cigarettes are smoked. If we have learned anything in the past 20 years of health messaging, it is this: cognitive understanding does not automatically lead to positive behavior change. If it did, we would be a nation of nonsmokers. If I were a doctor, I would drive home the point that while stress cannot be reduced, it can be managed successfully with physical and mental techniques such as: • • • •

Deep breathing Regular exercise Meditation, and Taking time out daily to relax your mind.

63.7 DEVELOP A POSITIVE MIND-SET Many cardiac patients feel discouraged, some to the point of depression, about their health condition. I know that was my experience. Luckily, I had a doctor that not only explained what needed to be done to institute a hearthealthy lifestyle, but he encouraged me to develop a positive mind-set. His acting as a cheerleader gave me the support I needed to make sustained progress. He encouraged me to establish a goal and set a specific time frame. Just to declare “more exercise” as a goal didn’t cut it with him. “Walking three miles in 45 minutes by month’s end” was more his style (and mine). He encouraged me to do one small thing today better than I did yesterday. If I had walked for 30 minutes yesterday, I’d do 35 minutes today.

He encouraged me to be resilient and persistent. “Failure is not falling down,” he would say. “That’s part of the human condition. Real failure is not getting back up.” And finally, he would encourage me with motivational quotes. One of my favorites was “There are no gold medals for the 95-yard dash.”

63.8 A LAST WORD Making healthy changes to benefit cardiovascular health is simple—not easy, but simple. Many patients can become discouraged, particularly if they have a lot to change or feel pressure to do it all at once. Advise them to make changes just for today. Don’t fret about yesterday; it’s over and you can’t call it back. Don’t be concerned with tomorrow as it is not yet here. Instead, live healthy today. Pretty soon, the days will add up to months and years, and changes will become habits. That’s what I’ve done for 40 years…one day at a time.

CLINICAL APPLICATIONS • Take advantage of teachable moments at each clinical visit. • For patients, time spent by clinicians supporting healthy lifestyle habits is as valuable as time spent explaining the science. • Motivating patients to change lifestyle habits should be incorporated into each clinical visit. • Keep healthy lifestyle messages simple and positive.

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64 CHAPTER

Lipid Management in Secondary Prevention Paul D. Thompson, MD and Antonio B. Fernandez, MD

Key Points.................................................................................. 767 64.1 Introduction...................................................................... 767 64.2  Treatment Goals................................................................ 767 64.3  Dietary Therapy................................................................ 767 64.4  Statin Treatment............................................................... 768

KEY POINTS • The benefit of LDL-C reduction appears to have no lower boundary. • Our treatment goal in managing patients with ASCVD is to lower the LDL-C as much as possible without producing side effects. • Most patients cannot achieve sufficiently low levels with dietary intervention alone. • High-intensity statin treatment is the cornerstone of secondary prevention and LDL-C management in patients with ASCVD. • Non-statin lipid lowering drugs should be considered in patients intolerant of statins or in whom the LDL-C levels are not sufficiently low.

64.1 INTRODUCTION The initiation and progression of atherosclerotic cardiovascular disease (ASCVD) is driven by low-density lipoprotein (LDL) cholesterol (C), and reducing LDL-C reduces the incidence of both primary and secondary cardiovascular events. The benefit of LDL-C reduction appears to have no lower boundary. GLAGOV (the Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound) trial randomized 968 statin-treated patients with angiographic coronary artery disease to the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor, evolocumab, or to placebo. LDL-C at 78 weeks was 93 and 37 mg/dL in the placebo and evolocumab subjects, respectively.1 The percent atheromata volume measured by intracoronary ultrasound increased 0.05% with placebo but decreased 0.95% with evolocumab (p < 0.001). Analysis of the regression curve demonstrated increasing reductions in atheromata volume with decreasing LDL-C all the way down to LDL-C levels of 20 mg/dL.1 Similarly, FOURIER or the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk demonstrated

64.5  Managing Statin-associated Muscle Complaints............... 768 64.6  PCSK9 Inhibitors............................................................... 769 Clinical Implications................................................................... 770 References................................................................................ 770

that evolocumab added to statin reduced cardiovascular events at 48 weeks when compared to placebo. LDL-C levels decreased from 92 mg/dL to 30 mg/dL with evolocumab treatment. 2 Both GLAVOV and FOURIER suggest that greater LDL-C reduction produce greater reductions in cardiovascular events, and both trials support the hypothesis that lower LDL-C is better in patients with established ASCVD. This chapter will describe our rationale and approach for treating LDL-C in ASCVD patients.

64.2 TREATMENT GOALS Our treatment goal in managing patients with ASCVD is to lower the LDL-C as much as possible without producing side effects. This goal varies from present guidelines for LDL-C reduction in ASCVD patients, and there is also variation among the available guidelines. The American College of Cardiology/American Heart Association 2013 guidelines recommend high-intensity statin treatment for all patients with ASCVD and moderate intensity statin treatment for those not suitable for high-intensity treatment.3 High-intensity statin treatment limits the medication choices to rosuvastatin ≥ 20 mg or atorvastatin ≥ 40 mg daily. The National Lipid Association 2014 guidelines recommend an LDL-C < 70 for high-risk patients.4 In contrast, the American Association of Clinical Endocrinologists (ACCE) 2017 guidelines recommend an LDL < 70 for very high-risk patients and < 55 mg/dl for those considered at extreme risk. 5 These ACCE guidelines suggest that writing groups are also appreciating the benefit of even lower LDL-C levels.

64.3 DIETARY THERAPY Such LDL values can rarely be obtained by dietary therapy alone. Strict vegans and vegetarians can achieve low LDL-C levels, but most patients cannot achieve sufficiently 767

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low levels with dietary intervention alone. We strongly recommend that patients follow low saturated fat diets, exercise, and practice calorie control, but do not depend on these interventions to achieve our LDL-C goals. Many clinicians cite the Lifestyle Heart Trial as evidence that diet alone can reduce atherosclerotic cardiovascular disease.6 This study assigned 53 patients to an intervention and 43 patients to a control group and followed their coronary progression using pre- and post-intervention angiograms. Only 28 intervention and 20 control patients agreed to participate. One control patient and six intervention patients did not have usable repeat angiograms. One of the intervention patients did not have a repeat angiogram because he died while exercising. Consequently, results of the study depend on only 22 treatment and 19 control patients. Furthermore, the intervention patients spent seven weeks practicing stress management, eight hours attending support groups, and three hours exercising. Such a design makes it impossible to attribute any improvement in symptoms or coronary caliber to the lowfat diet alone, and we strongly recommend that patients embark on pharmacologic LDL-C reduction.

64.4 STATIN TREATMENT High-intensity statin treatment is the cornerstone of secondary prevention and LDL-C management in patients with ASCVD. Statins reduce secondary events by both LDL-C reduction and decreasing inflammation.7 Patients with acute coronary syndromes (ACS) or recent interventions should be started on high dose statins such as atorvastatin 80 or rosuvastatin 40 mg daily. Such treatment should be continued as long as possible, but we consider decreasing the dose to atorvastatin 40 or rosuvastatin 20 after two years of higher dose therapy. We specify two years, because approximately two years of aggressive therapy is the duration frequently observed in trials demonstrating atherosclerotic regression.8 Also, aggressive lipid treatment produces maximum atherosclerotic plaque reduction with two years of treatment (Figures 64.1 and 64.2).9 We routinely add ezetimibe to high-intensity statin treatment since the IMPROVE-IT or Improved Reduction of Outcomes: Vytorin Efficacy International Trial demonstrated a 2% absolute reduction in cardiovascular events in patients with acute coronary syndromes (ACS) treated with the combination of statin and ezetimibe vs. statin alone (p = 0.016).10

64.5 MANAGING STATIN-ASSOCIATED MUSCLE COMPLAINTS Approximately 10% of patients treated with moderateto-high dose statins report muscle complaints that they attribute to the statin.11 Our double-blind, placebo-controlled study demonstrated that 9.4% of subjects treated for six months with atorvastatin 80 mg daily developed muscle complaints compared to only 4.6% of placebotreated subjects.12 This suggests that approximately 5% of patients have true statin-associated muscle symptoms (SAMS). These patients do not generally demonstrate

Figure 64.1 Carotid Plaque Lipid Depletion and Time Course During Three-Year Lipid Therapy—After three years of intensive lipid therapy, lipid-rich necrotic core volume (LRNC-V) (green squares) significantly decreased from 60.4 mm3 to 37.4 mm3. Percent LRNC (%LRNC) (pink circles) also significantly decreased from 14.2% to 7.4%. The plaque lipid depletion time course over three years showed that %LRNC for pooled slices containing lipid at any time point significantly decreased by 3.2% in the first year, significantly decreased by 3.0% in the second year, and decreased by 0.9% in the third year (the change from year two to three was not statistically significant). Bars around the estimates are standard error bars. Taken with permission from Zhao et al. JACC Cardiovasc Imaging 2011.

objective evidence of muscle injury such as elevated CK levels or documented muscle weakness. Some experts maintain that statins do not produce muscle complaints without marked CK elevations and that such patient complaints are due to the nocebo effect or the expectation that the drug will cause harm.13 Whether or not SAMS are real, and we believe they are,14 is really a moot point for clinicians because clinicians cannot ignore a patient’s complaints and expect to maintain a good relationship. We have described our approach to managing SAMS.15,16 We determine whether the patient can tolerate the symptoms and measures CK to make sure that it is not elevated to >10 times the upper limits of normal. We reassure the patient that SAMS are almost always reversible and not progressive. We stress the importance of statin treatment in secondary prevention and the lifesaving role of statin therapy. Nevertheless, we stop the statin until the patient has no symptoms if the patient remains concerned or intolerably symptomatic. Reversal of the symptoms within several weeks of statin discontinuation supports the diagnosis of SAMS.17 We next try the same or another statin at a comparable or lower dose. If re-challenge with a statin also produces symptoms, we try ezetimibe alone. Ezetimibe produces approximately a 20% average reduction in LDL-C levels. We then retry the statin at very low doses such as rosuvastatin 2.5 or 5 mg, atorvastatin 5 or 10 mg, or pitavastatin 1 mg, Monday and Friday. These

64.6  PCSK9 Inhibitors 

769

ASCVD risk >7.5%, DM, clinical CVD or FH

Myalgias with normal CK levels

CK 10X ULN rule out Rhabdomyolysis

Low dose, high potency stan or stan disconnuaon based on symptom severity

Disconnue stan Check UA, creanine

Reassess patient within 6 weeks of restarting or changing statin, clarify LDL goal based on ASCVD risk

Statin rechallenge?

Tolerang stan but not at goal

Statin-associated muscle symptoms

Statin-associated muscle symptoms

Consider alternative therapies: Ezetamibe, bile acid sequestrants, PCSK9 inhibitors

Figure 64.2  Clinical Applications Flow Chart—Our approach to lipid management in statin-intolerant patients.

agents are not approved for intermittent dosing, but the long half-lives of these statins produce an ≈20% reduction in LDL-C with such intermittent dosing.18 Clinicians often forget that the largest percent reduction in LDL-C per mg of statin occurs with the lowest doses. The combination of ezetimibe and low-dose statin is often able to normalize LDL-C levels in many patients. Co-Q10 supplementation is often recommended for patients with SAMS for several plausible reasons,19 but our studies20 and a systematic review21 did not demonstrate that Co-Q10 supplementation is effective in SAMS. Nevertheless, we occasionally use it in selected patients. We discuss the absence of effect in controlled studies, but also emphasized that some patients have had remarkable responses to Co-Q10 supplementation. We will occasionally try Co-Q10 supplementation even though its effectiveness may be only a placebo effect. Finally, we try other agents. Bile sequestrant resins can be used to lower LDL-C. Our preference is to use colesevelam in packet form with the evening meal. One packet of colesevelam produces a similar result, approximately 20% reduction in LDL-C levels, as six packets of other sequestrants, such as cholestyramine. Niacin is in disfavor because of the results of both the AIM HIGH 22 and HPS-2 THRIVE 22,23 trials. Patients in these trials were on statin therapy when the niacin was initiated and had LDL-C levels at baseline of 72 and 74 and 63 and 62 mg/dl in the placebo and niacin treated arms, respectively, before initiating niacin therapy. Consequently, it is not surprising that niacin was ineffective in producing further

reduction of ASCVD events over the five-year duration of the trials. In contrast, niacin in the Coronary Drug Project before statins were available reduced recurrent myocardial infarction (a secondary endpoint) by 29% ( p < 0.05) at 6.2 years and total deaths by 11% (p = 0.0004) at 15 years. 24 Fenofibrate is also in disfavor because it was not effective in reducing cardiovascular events among diabetic patients in the ACCORD Trial Lipid Lowering Arm. 25 Patients in ACCORD, however, had baseline triglyceride levels of only 164 and 162 mg/dL, in the fenofibrate and placebo groups, respectively, so were unlikely to be treated with fenofibrate in most clinical practices. Fenofibrate did appear to reduce ASCVD events among those diabetic patients with triglyceride levels ≥ 204 mg/dl and an HDL < 34 mg/dl, and these results approached statistical significance (p = 0.06). 25 Consequently, we often perform therapeutic trials of niacin or fenofibrate in combination with low doses of other agents to see if these are effective in selective individuals, especially if they cannot procure PCSK9 inhibitors because of insurance issues.

64.6 PCSK9 INHIBITORS The PCSK9 inhibitors are our go-to drugs in patients intolerant of statins or in whom other lipid-lowering agents cannot reduce their LDL-C levels to a sufficiently low level. PCSK9 inhibitors are approved for use in patients with familial hypercholesterolemia and in patients with documented ASCVD who do not achieve sufficient LDL-C

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reductions by dietary and statin therapy. FDA approval of the PCSK9 inhibitors was provided before IMPROVE-IT documented that ezetimibe, when added to a statin, reduces ASCVD events more than statins alone.10 Present best practice, therefore, would require that ezetimibe be included in the treatment before progressing to the much more expensive PCSK9 inhibitors. What level of LDL-C warrants PCSK9 therapy is the clinician’s decision but as mentioned earlier, we aim for an LDL-C at least < 70 mg/dL in patients with established ASCVD. PCSK9 inhibitors will likely be more widely used to achieve low LDL-C levels in patients with ASCVD. We do not use them prematurely, however, because these drugs are expensive. We restrict the use to those individuals who cannot achieve a sufficiently low LDL-C level using statins, ezetimibe, niacin, fibric acid derivatives, or bile acid sequestrant resins. We do not necessarily try all these agents in patients with ASCVD before proceeding to a PCSK9 inhibitor but do consider these other drugs as part of our therapeutic regimen. We do proceed directly to PCSK9 inhibition in patients with very high LDL levels so that it is unlikely that other agents will be effective. The combination of statin, ezetimibe, and PCSK9inhibitor therapy has the potential to markedly reduce

recurrent rates of ASCVD events in patients with documented disease by reducing LDL-C so low that recurrent events become extremely unlikely. Such aggressive therapy has the potential to further enhance the already excellent survival of ASCVD patients.

CLINICAL IMPLICATIONS • ASCVD is primarily driven by LDL-C. Reducing LDL-C reduces the incidence of both primary and secondary cardiovascular events. • The benefit of LDL-C reduction appears to have no lower boundary. Some of the different professional society prevention guidelines follow a trend targeting lower LDL-C levels for secondary ASCVD prevention. This opens the window for an aggressive lipid-lowering therapy in high-risk individuals to decrease the LDL-C as low as possible. • It is also important to understand the cost of newer drugs, such as PCSK9 inhibitors, to maintain a cost-effective care. These emerging lipid-lowering agents will continue to reduce recurrent ASCVD events.

REFERENCES 1. Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, et al. (2016) Effect of evolocumab on progression of coronary disease in statin-treated patients: The GLAGOV randomized clinical trial. JAMA 316: 2373–2384. 2. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, et al. (2017) Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. 376: 1713–1722. 3. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, et al. (2013) 2013  ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129: S1–S45. 4. Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, et al. (2014) National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 – Executive summary. J. Clin. Lipidol. 8: 473–488. 5. Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, et al. (2017) American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr. Pract. 23: 1–87. 6. Thompson PD (1998) More on low-fat diets. N. Engl. J. Med. 338: 1623–1624. 7. McLean DS, Ravid S, Blazing M, Gersh B, Shui A, et al. (2008) Effect of statin dose on incidence of atrial fibrillation: Data from the Pravastatin or Atorvastatin Evaluation and Infection TherapyThrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Aggrastat to Zocor (A to Z) trials. Am. Heart J. 155: 298–302.

8. Noyes AM and Thompson PD (2014) A systematic review of the time course of atherosclerotic plaque regression. Atherosclerosis 234: 75–84. 9. Zhao XQ, Dong L, Hatsukami T, Phan BA, Chu B, et al. (2011) MR imaging of carotid plaque composition during lipidlowering therapy a prospective assessment of effect and time course. JACC Cardiovasc. Imaging 4: 977–986. 10. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, et al. (2015) Ezetimibe added to statin therapy after acute coronary syndromes. N. Engl. J. Med. 372: 2387–2397. 11. Bruckert E, Hayem G, Dejager S, Yau C, and Begaud B (2005) Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients – The PRIMO study. Cardiovasc. Drugs Ther. 19: 403–414. 12. Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, et al. (2012) Effect of statins on skeletal muscle function. Circulation 127: 96–103. 13. Collins R, Reith C, Emberson J, Armitage J, Baigent C, et al. (2016) Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 388: 2532–2561. 14. Thompson PD and Taylor B (2017) Safety and efficacy of statins. Lancet 389: 1098–1099. 15. Thompson PD, Panza G, Zaleski A, and Taylor B (2016) Statin-associated side effects. J. Am. Coll. Cardiol. 67: 2395–2410. 16. Thompson PD (2016) What to believe and do about statin-associated adverse effects. JAMA 316: 1969–1970. 17. Rosenson RS, Gandra SR, McKendrick J, Dent R, Wieffer H, et al. (2017) Identification and management of statinassociated symptoms in clinical practice:

18.

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Extension of a clinician survey to 12 further countries. Cardiovasc. Drugs Ther. 31: 187–195. Gadarla M, Kearns AK, and Thompson PD (2008) Efficacy of rosuvastatin (5 mg and 10 mg) twice a week in patients intolerant to daily statins. Am. J. Cardiol. 101: 1747–1748. Zaleski AL, Taylor BA, and Thompson PD (Invited; in press) The role of coenzyme Q10 in statin-associated muscle symptoms. Adv. Nutr. Taylor BA, Lorson L, White CM, and Thompson PD (2015) A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. Atherosclerosis 238: 329–335. Banach M, Serban C, Sahebkar A, Ursoniu S, Rysz J, et al. (2015) Effects of coenzyme Q10 on statin-induced myopathy: A meta-analysis of randomized controlled trials. Mayo Clin. Proc. 90: 24–34. Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, et al. (2011) Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N. Engl. J. Med. 365: 2255–2267. Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, et al. (2014) Effects of extended-release niacin with laropiprant in high-risk patients. N. Engl. J. Med. 371: 203–212. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, et al. (1986) Fifteen year mortality in Coronary Drug Project patients: Long-term benefit with niacin. J. Am. Coll. Cardiol. 8: 1245–1255. Ginsberg HN, Elam MB, Lovato LC, Crouse JR, 3rd, Leiter LA, et al. (2010) Effects of combination lipid therapy in type 2 diabetes mellitus. N. Engl. J. Med. 362: 1563–1574.

65 CHAPTER

Complementary Effects of Lifestyle Modification on Cardioprotective Medications in Primary/Secondary Prevention Xisui Shirley Chen, MD and Philip Greenland, MD

Key Points.................................................................................. 771 65.1 Introduction...................................................................... 771 65.2 Nutrition........................................................................... 772 65.3  Physical Activity................................................................ 773 65.4  Smoking Cessation........................................................... 775

KEY POINTS • Risk factor control in CVD populations remains inadequate despite increasing use of cardioprotective medications. • Lifestyle modifications are effective for primary and secondary CVD prevention and provide additive and often synergistic benefits when added to pharmacotherapy. • Healthy dietary patterns such as the Mediterranean and DASH diet, regular physical activity, and smoking cessation can be as effective as pharmacotherapy in the reduction of CV risk and mortality. • Psychosocial interventions that address comorbid psychiatric conditions, stress, and social isolation have also been associated with lower CV risk. • RCTs on the efficacy of lifestyle interventions compared to pharmacotherapy remain limited with significant heterogeneity in study design and quality. • Further studies are needed to directly compare lifestyle interventions and pharmacotherapy and evaluate potential interactions.

65.1 INTRODUCTION Advances in pharmacotherapy have re-shaped the modern era of evidence-based management of cardiovascular disease (CVD). The demonstrated efficacy of cardioprotective medications in large randomized controlled trials has driven changes in clinical guidelines and treatment goals. However, declines in CVD-related deaths have been reported to have stagnated in the United States.1 According to the World Health Organization (WHO), CVD remains

65.5  Psychosocial Health.......................................................... 775 65.6  Summary and Take-home Messages................................ 777 Clinical Applications................................................................... 777 References................................................................................ 777

the leading cause of mortality worldwide, accounting for 31% of all deaths. 2 Unhealthy lifestyles and behaviors are widely acknowledged as modifiable risk factors that lead to CVD. In the INTERHEART case-control study of first myocardial infarction in a large, multi-national population, the nine risk factors of dyslipidemia, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, diet, alcohol, and physical activity accounted for 90% of the population attributable risk. 3 While the use of cardioprotective medications has increased over time, trends in behavioral risk factor modification have been less favorable. Several recent observational studies have shown that the majority of CAD patients do not achieve recommended targets for risk factor control and secondary prevention, especially with regard to lifestyle measures. Analyses from the OASIS trial population of acute coronary syndrome (ACS) patients from 41 countries showed that less than 50% of patients were adherent to diet, exercise, or smoking cessation at the six-month follow-up. Reported medication use was higher: 96% for anti-platelets, 79% for statins and 72% for drugs that act on the renin-angiotensin-aldosterone system (RAAS).4 These findings were supported by EUROASPIRE IV, a large multicenter study of patients hospitalized for ACS symptoms or requiring revascularization in 24 European countries during the years 2012– 2013. Cardioprotective medication use was relatively high with 93.8% of patients on anti-platelets, 82.6% on betablockers, 75% on RAAS drugs, and 85.7% on statins. In contrast, at six-months, just over half of smokers at the time of the event had quit smoking, only 40% of patients reported at least 20 minutes of vigorous physical activity once a week, and less than half of obese patients reported following dietary recommendations. 5 Compared to data from EUROASPIRE II (1999–2000) and EUROASPIRE 771

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III (2006–2007), the most recent study findings (2012– 2013) paint a picture of worsening attention to lifestyle habits over time. Across three iterations of the study, there was no improvement in smoking prevalence while rates of obesity and of self-reported diabetes increased.6 These findings suggest that CVD prevention programs must be multi-pronged with greater emphasis on promoting healthy and sustainable lifestyle changes in addition to prescribing beneficial medications. Current guidelines on CVD prevention and management from the American Heart Association (AHA) and the American College of Cardiology (ACC) and the European Society for Cardiology (ESC) advocate for a multifaceted approach with class 1 recommendations for lifestyle interventions in addition to pharmacotherapy to achieve blood pressure and lipid goals.7,8 Lifestyle modification encompasses a broad spectrum of behavioral change that should be addressed at both the individual and population level. Smoking cessation, physical activity, dietary patterns, and psychosocial risk factors have been identified as important lifestyle considerations in the primary and secondary prevention of CVD and are areas of emphasis in current guidelines. For lower-risk individuals, lifestyle changes are often the initial intervention in a medication-sparing prevention scheme. For high-risk individuals and in secondary prevention, pharmacotherapy is added to lifestyle changes for greater and often synergistic effects. In the current landscape of cardiovascular medicine and research, this combination of guideline-driven, non-invasive measures has been referred to as “optimal medical therapy” (OMT). In two recent landmark trials, OMT alone has proven to be an effective and non-inferior management strategy compared to OMT with revascularization in patients with chronic angina and stable coronary artery disease (CAD) (COURAGE), including those with comorbid diabetes (BARI 2D).9,10 During five years of follow-up, there was no significant mortality benefit to percutaneous coronary intervention (PCI) in either trial, though in BARI 2D, there was an 8% reduction in major cardiovascular events in the coronary artery bypass graft (CABG) cohort compared to OMT alone. Overall, these results provide strong evidence that OMT including lifestyle intervention is an effective initial option for the management of many patients with chronic and stable CAD. In addition, costeffectiveness analyses of both COURAGE and BARI 2D favored OMT over revascularization. In COURAGE, the added cost of PCI translated to $168,000–$300,000 per quality-adjusted life-year gained whereas, in BARI 2D, lifetime projections of cost-effectiveness found that OMT was cost effective at $600 per life-year added.11,12 Thus, the efficacy and benefits of a comprehensive and intensive regimen of pharmacotherapy and lifestyle intervention have been demonstrated. Understanding the complementary effects of lifestyle modifications on cardioprotective medication is essential to facilitating and improving patient adherence to healthy behaviors.

65.2 NUTRITION Optimizing nutrition and dietary intake is recognized as an important component of the primary and secondary

prevention of CVD. The current literature emphasizes dietary patterns rather than focusing on specific nutrients, vitamins/supplements, or food groups. Given the complex factors that lead to CVD, dietary patterns promote realistic and sustainable dietary guidelines that avoid a reductionist approach and account for the interactions between dietary components. The best-studied dietary patterns for CVD prevention are the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet.13 These dietary approaches have been shown to positively mitigate CVD risk factors such as dyslipidemia, hypertension, glycemic control, and obesity. In addition, they may also have additional beneficial anti-oxidant and antiinflammatory effects that have been associated with lower risks of CVD in addition to some types of cancers and other chronic diseases. The Mediterranean diet is characterized by high intake of fruits, vegetables, and whole grains, olive oil as the primary fat source, decreased red meat intake, and increased fish intake, mild-to-moderate red wine consumption, and limited intake of sweets and processed foods. In general, the composition of the Mediterranean diet is moderate in healthy fats (32–35% of total calories), such as polyunsaturated fatty acids, while relatively low in saturated fat (70% of VO2max was necessary if cardiorespiratory fitness (CRF) is to be improved in children. The usual guidelines for training of CRF have been continuous or intermittent training of a duration of at least 15 minutes at a high relative intensity. However, this concept has been challenged, as studies have shown that habitual physical activity is important both to preserve CRF and to improve the CVD risk factor profile. Habitual physical activity is usually sporadic and with lower intensity. One type of habitual physical activity which has been studied in recent years is active travel, walking, and cycling. Observational studies have shown higher CRF and better MetS scores in children who cycle to school.34 –36 The longitudinal development of CVD risk factors and CRF is also diminished in children cycling to school.36,37 Many of the children cycled not much more than one km to school, but the mean fitness of all the children cycling to school was still around 9% better than children walking or using passive transport. A plausible explanation for the quite marked effect of cycling to school is that the activity is frequent. The trip is twice a day five days a week. These observational studies have later been supported by a randomized trial of cycling to school.38 In this trial, non-cycling children living >1 km from school were randomized to control or cycling groups. In the intervention group, a composite MetS score improved 0.6 SD after just eight weeks of commuting compared to the control group. The study was not powered to show improvements in CRF. However, it is very interesting that even a quite low but frequent dose of physical activity which can be integrated into everyday living has measurable effects on cardiovascular risk factors. There is some health effect of walking, but it is less than for cycling in both adults and children.39,40 For example, Østergaard et al. found in a cross-sectional study that walking to school was associated with 0.65 lower odds of being overweight.39 The reason why cycling is more effective is probably because self-chosen intensity is higher in cycling than in walking.41 Oja et al. found that self-chosen intensity corresponded to 50% of VO2max in walking and 60% in cycling.41 Another type of habitual physical activity in children is play. We are not aware of studies looking at the association

between play and CMRF, but some studies have quantified the importance of playground facilities on physical activity level. For example, Nielsen et al.42 found the number of play facilities on the school grounds was positively associated with all measures of children’s activity assessed by accelerometry. In preschool, every ten additional play facilities the children had access to was associated with an increase in the average accelerometer counts of 14% in school time and 6.9% overall. In conclusion, contrary to what was earlier believed, structured training is not the only way to improve CRF. Interventions do work as long as they are continued, and habitual physical activity such as commuter cycling can improve CRF even in healthy children with a relatively high CRF level. In addition, cycling improves MetS composite score substantially. Intensity may still be important because cycling is more effective than walking, but even walking may impact the risk of obesity.

75.3 SEDENTARY BEHAVIORS AND CMRF MVPA has long been associated with the risk of developing the MetS and CMRF in both adults and children. Within the past decade, researchers have started to examine sedentary behavior, or physical inactivity, as an independent risk factor, particularly with regard to obesity.43– 45 Specifically, screen time, either television viewing, computer, or gaming, appears to be associated with obesity.46,47 The general assumption was that physical inactivity time is the reverse of time spent in MVPA;48 therefore, the relationship should be reciprocal, and more physical inactivity should correspond to less MVPA. However, this may not be the case. Studies by Zakarian et al.49 and Feldman et al., 50 using television viewing as a surrogate for sedentary behavior, found no significant association between hours of television watched and levels of vigorous exercise in a study of 9th- and 11th-grade adolescents. The lack of association could be related to the fact that most television viewing occurs in the evening, while most physical activity occurs during the day. Feldman et al. also examined the data differentiating productive sedentary behaviors (computer, reading, homework) and unproductive sedentary behaviors (video games, television/videos) and found that youth who spent more time in productive sedentary behaviors appeared more physically active. 50 Carson et al. in their review suggested that physical inactivity be divided into screen time and non-screen time.44 Their review noted that higher levels of screen time were associated with MetS, while higher levels of reading and homework were not associated with MetS. Thus, not all sedentary behavior should be considered similar. The importance of sedentary behaviors as a CMRF or MetS risk is controversial. Robinson et al., using 264 7- to 10-year-olds, examined the relationship between screenbased time (TV, computers electronic games) and obesity or CMRF using accelerometry and a parental proxy questionnaire.51 They found that total screen-based time was associated with obesity (BMI), but there were differential

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effects when the screen time was broken down to the three categories. Television viewing was directly associated with obesity and systolic blood pressure, while electronic gaming was associated with higher levels of low-density lipoproteins. However, it appeared that general computer use was not significantly associated with obesity and CMRF. Once again, the results suggest that there is a need to differentiate between types of screen-based behaviors when evaluating the association between CMRF and screen behaviors in children. It seems that it may not be the physical inactivity per se but rather other health behaviors such as snacking that may drive the association. Other studies have also questioned the relationship between sedentary behavior and CMRF. Ekelund and coworkers, using pooled data from the International Children’s Accelerometry Database that included 14 studies of 20,871 youth, found that sedentary time was not associated with any outcome independent of time in MVPA.52 Furthermore, higher levels of MVPA were associated with better CMRF profiles regardless of levels of sedentary time. They further noted that systolic blood pressure, serum insulin, and triglyceride levels were inversely related to MVPA, but serum insulin was the only risk factor associated with sedentary behaviors. However, increased sedentary behaviors did predict increased waist circumference. Quite interestingly, neither changes in MVPA nor sedentary time were related to any change in CMRF two years later. Carson et al. found that sedentary behaviors of 4,169 6–17-year-olds were directly related to risk of developing obesity but not high blood pressure, blood lipids, insulin, or C-reactive protein. Conversely, levels of MVPA were associated with many of the CMRFs as well as obesity. 53 DeMoraes and associates used the IDEFICS cohort of 16,228 6-year-old children and found that those children who maintained >2 hours of TV/DVD/video and computer/ games-console use had a 28% greater risk of developing high blood pressure two years later.54 Another IDEFICS finding was that low levels of television/video/DVD viewing were associated with a lower composite MetS score45 (lower scores are better). The relationships did not appear in children less than six years of age and were only marginally significant in youth six to nine years of age. These data suggest the progression of the influence of sedentary behavior takes time to develop. Furthermore, the progressions do not occur simultaneously, with blood pressure and HOMA influences occurring before lipids. Also, sedentariness and PA are two independent risk factors. The relationship between sedentary behaviors and vascular intima-media thickness (IMT) has also been investigated. Horta et al., using pulse wave velocity as an estimate of arterial stiffness, found that those youth in the highest quartile for sedentary behaviors (measured via accelerometry) had more arterial stiffness and higher diastolic blood pressure than those in the lowest quartile for sedentary behaviors. 55 Pahkala et al. studied vascular IMT in adolescents at ages 13, 15, and 17 years and found that sedentary youth at age 13 who increased their PA to greater than 30 min per day had decreased the progression of IMT thickness compared to those who remained sedentary ( 0.14). Conversely, the relationship between BMI and the IMT measures was positive and significant (p 0.54 is predictive of insulin resistance (HOMA-IR),120 a known CMRF, while Buchan et al. uses a ratio of 0.50.68 Although height without shoes is easy to measure, the waist measure is, again, the concern. WHtR is promising, but the overall utility cannot be determined until accepted methodology is agreed on. Since CMRF and MetS are highly associated with obesity, one would think that a measure of body fat would be the best non-invasive method to assess CMRF. Precise measurement of body fat is not simple, requiring a DEXA machine122,123 or an underwater weighing apparatus. The method also requires that the child remains still for considerable time (DEXA) or is comfortable blowing out all their air while underwater. To avoid these problems, some researchers and non-clinicians have used skinfold measures,69,106,124,125 which are highly correlated with percentage of body fat (r ~ 0.85).124 McMurray et al. have shown that simple measures of triceps and subscapular skinfolds are highly and more consistently related to insulin resistance than BMI or waist circumference, but separate cutpoint values are needed for each sex.69 Freedman et al. noted that skinfold can be as accurate as BMI in estimating CMRF.106 In addition, Freedman et al. have validated the use of the two-site Slaughter equations as a good estimate of body fat in over 7,900 youth, although it does tend to overestimate body fat at very thin skinfolds and underestimate in those with very large skinfolds.124 This

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suggests that only two sites for skinfold measurement are needed, a methodology used by McMurray.69 The problem with skinfolds is that they are difficult to consistently measure, requiring much training. Because of these issues, skinfold measures to estimate CMRF or MetS are not recommended.69,106,125 In general, anthropometry appears to be adequate to assess the risk of MetS and CMRF. Body mass index is most used and is highly regarded, particularly from an epidemiologic perspective. On an individual basis, waistto-height ratio may be more appropriate because it does not require tables to interpret. The caveat is that a consistent methodology for waist measurement needs to be developed so that researchers, non-clinicians, and clinicians can compare results.

75.5.2 Ultrasound Ultrasound has become a useful tool for the early detection of cardiovascular/atherosclerosis disease before any overt symptoms are present.126 Ultrasound is typically used to determine thickness of the inner two layers of either the carotid artery or the aorta, the intima and media layers (IMT). An IMT greater than 0.9–1 mm is highly likely to be indicative of atherosclerosis and increased risk of cardiovascular disease.127 The carotid artery measurement is typically made in one of three locations: (1) the common carotid proximal to the divide, (2) at the bifurcation, or (3) in the internal carotid artery.128 The test is not new,129 but the application of the test as a screening measure in children is recent. The IMT has been recently applied to children as an assessment of cardiovascular disease and atherosclerosis. It typically serves as the dependent variable for which other markers are compared. Melo et al. determined the relationships between carotid IMT and measures of adiposity, muscular strength, and CRF in 366 11- to 12-year-old children.61,130 They found that low muscle strength was associated with increased IMT independently of CRF and adiposity. Furthermore, children with low strength had the highest values of IMT, waist circumference, and systolic blood pressure, and the lowest CRF. They concluded that along with low CRF and high adiposity, low muscular strength should be included in a CMRF risk assessment. Ried-Larsen et al. used IMT as the indicator of atherosclerosis to determine the influence of physical activity and CRF on the disease. 3,4 They found inverse relationships between levels of moderateto-vigorous physical activity and CRF and IMT thickness. These associations were independent of adiposity. 3 They also noted that high levels of moderate-to-vigorous physical activity from childhood through early adulthood were associated with better IMT and arterial compliance.4 From these studies it appears that ultrasound has an important role in assessing CVD during childhood. However, the use of ultrasound for determining the relationship between CMRF or MetS and aortic thickness and left ventricular size is in need of further research. The main concern is that the cost of the equipment and time involved make this methodology less than ideal for population screening.

75.5.3 Cardiorespiratory Fitness In a recent article, Pianosi and associates pointed out the significance of measuring cardiorespiratory fitness (CRF) in children.131 They say that “cardiorespiratory exercise testing provides clinicians with biomarkers and clinical outcomes, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response hidden at rest” for multiple disease states. Other studies have also shown the importance of measuring CRF and its relationship to CMRF or MetS.63,69,117,132,133 For example, Andersen et al., using 484 6- and 9-year-old children, found no association between CRF and CMRF at age six, but by nine years of age there was a strong and significant relationship,134 thus suggesting the development of both CMRF and CRF as children age. Lerum et al., using 911 youth, also found the CRF and fatness provided similar accuracy for identifying children that might be at risk for developing CVD later in life.133 Ogunleye et al. found that low CRF is an independent predictor of elevated blood pressure, even in obese children.63 Thus, CFR is an important non-invasive tool for estimating the risk of having CMRF and MetS. The questions have always been which is the best method for assessing CRF, what units should be used, and how can this time-consuming test be used as a screening tool in large group settings. Although CMRF can be estimated from some form of submaximal testing (cycle ergometer, step-test, 12-min walk/run, 6-min run for distance, even treadmill time), the accuracy of the results has been questioned, since the results correlate only about 0.55 to 0.85 compared to measured VO2max.135 The best methodologies appear to be those that maximally challenge the aerobic system of the child.131 Using maximal tests to estimate CRF usually gives results which are closer associated with MetS than fatness measures (skinfold, waist, and BMI).136 However, having children sufficiently motivated to provide a maximal effort is sometimes difficult. This is one of the main reasons for submaximal estimate methods. The most precise method is to directly measure oxygen uptake during the maximal exercise test. However, this requires expensive equipment and personnel, and the test usually has to be individually administered. Thus, other tests have been devised that maximally tax the metabolic system and then estimate the oxygen uptake using a validated formula. One method that has gained popularity is the 20-meter shuttle run (20-MST), in which the child completes segments of 20-meter runs at increasing prescribed speeds.137,138 The test ends when the subject can no longer keep up for two segments, and CRF is computed as maximal oxygen uptake (VO2max) based on a formula. The test can be completed in a gym, hallway, or outdoors, with multiple youth participating at one time. The correlations between measured and predicted VO2max from the 20-MST is ~ 0.51–0.66.139 The correlations were improved when using the Matsuzaka formula for calculating VO2max.140 Since there remains some controversy regarding the calculation of VO2max from the 20-MST, and whether the unit of ml/kg/min is the most appropriate unit to express VO2max, the suggestion is to use the numbers of segments completed as the final outcome.73

75.6  Key Mechanisms Linking Physical Activity to the Clustering of CVD Risk Factors  881

Another option is the Andersen test, where no equipment is needed.141 This test also uses a 20-m court where children run from one line to the other and touch the floor at each turn. They run for 15 seconds and rest for 15 seconds. The total distance covered after 10 minutes is the result and can be used to estimate VO2max. The validity is the same as for the 20 m shuttle run, but it has the advantage that it is intermittent and all children exercise in all 10 minutes. In the shuttle run, children leave the court when they cannot keep up with the progressive speed, and it is obvious for all other children who are least fit. Since low CRF is related to CMRF and MetS, at what critical cut-point should we be concerned? Recently, Ruiz et al. completed a systematic review and meta-analysis of studies (1980–2015) that determined a CRF cut-point that predicted cardiovascular disease risk in youth.82 Boys with CRF 25 times increased risk of having clustered CVD risk than the lower quartile, even in a normal healthy, young population.146 It is, therefore, important to understand the relationship between physical activity and insulin sensitivity, and how insulin affects CVD levels, but it is also important to understand that physical activity has beneficial effects through different independent physiological mechanisms, which all change risk factor levels in a positive direction. Acute physical activity causes different physiological changes, which influence CVD risk factors. Some of these mechanisms are shared with adiposity, while others are unique for physical activity but may affect fat accumulation. The most important physiological changes are probably insulin and catecholamine (adrenalin) sensitivity, and both of these hormones can double their action after a few weeks (days for insulin) or months of exercise training. Training improves insulin sensitivity specifically in the trained muscle. One study, utilizing a single-leg training protocol, found increased glucose clearance limited to the trained

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leg, with the same amount of insulin causing the glucose clearance to double in the trained leg.78 Training increases adrenaline sensitivity and decreases its release, leading to increased glucose clearance, since adrenaline blocks insulin-mediated glucose uptake at a given exercise intensity and at rest.147 Besides this effect of training, glucose uptake occurs independently of insulin.147 Moderate-to-vigorous exercise appears to activate a second “pool” of transporters independent of insulin.148 Thus, the same glucose uptake requires less insulin after exercise. This adaptation may affect lipid storage in the fat cells and indirectly appetite regulation. The contraction-mediated glucose uptake in the muscle cell is increased when the stored glycogen is used during prolonged exercise. Further, the contraction-mediated glucose uptake is not blocked by adrenaline.149 Even during periods of stress, physical activity may help to maintain low levels of insulin. Other acute effects are a lowering of triglyceride level and increased HDL.150 In contrast to these mechanisms located in the muscle cells, fat tissue releases cytokines such as TNF-α into the circulation, which can decrease insulin sensitivity systemically.151 Most of the common CVD risk factors are exacerbated by the action of insulin, which affects both metabolic pathways (blood lipids) and sympathetic nervous system (blood pressure). The insulin sensitivity of the muscle cells is, therefore, extremely important because 80%–90% of the ingested glucose will enter the muscle cell mainly mediated by insulin under normal resting conditions. Other mechanisms related to prolonged training are increased lipoprotein lipase (LPL) activity and increased oxidative enzymes in the trained muscles. LPL is situated on the inner wall of the capillaries, and the number of capillaries increases in proportion to the training state of the muscle.152 LPL catalyzes triglyceride transported from LDL or VLDL cholesterol into the muscle cell, where it is metabolized, thereby improving the ratio of total cholesterol/ HDL. Changes in oxidative enzymes related to training are substantial. In untrained young subjects, eight weeks of exercise training caused key oxidative enzymes such as succinate dehydrogenase and hydroxyacyl dehydrogenase to increase by 30%–40%.90 This change improves the metabolism of triglycerides, which in turn improves glucose uptake. Exercise training also increases superoxide dismutase, catalase, and glutathione peroxidase, which reduces damage from free radicals. Thus, increases in these oxidative enzymes have the potential to reduce free radical formation, which has been associated with atherosclerotic plaque formation. However, the effect of training on oxidative enzyme levels disappears as fast as it develops after the cessation of training. More recent research has shown that muscle, similar to fat tissue, functions as a secretory organ.153 Cytokines and other peptides are produced, expressed, and released

by muscle fibers and exert either autocrine, paracrine, or endocrine effects. The muscle secretes several hundred peptides. This finding provides a new understanding of how muscles communicate with other organs such as adipose tissue, liver, pancreas, bones, and brain. Also, several myokines exert their effects within the muscle itself. Many proteins produced by skeletal muscle are dependent upon contraction and it is likely that myokines may contribute to the mediation of the health benefits of exercise.

75.7 CONCLUSION A sedentary lifestyle in children is associated with increased levels in disease risk factors, which are known to increase risk of premature death later in life, and the prevalence of clustered cardiovascular risk is more common in sedentary children. Further, a large percentage of European and American children have a lifestyle sedentary to a degree that it may increase the risk of developing premature atherosclerosis and lifestyle diseases such as CVD and type 2 diabetes. It has also been verified that both risk factors and sedentary behavior track during childhood and into adulthood. In addition, a recent study has shown that lifestyle prevention may be more important than treatment.154 Therefore, there is a strong rationale for early prevention, starting in childhood. Interventions aiming at increasing physical activity in children are efficient in changing behavior to a more physically active lifestyle and have resulted in decreased CVD risk factor levels. However, the intervention must be sustained. An important setting for this may be the school. Physical education lessons, activities in breaks, active commuting to the school, as well as after-school sports have the possibility to reach all children and also children at risk through specific activity programs. However, physical education programs have been more successful when educated teachers have run the lessons,155 and there may be a major job to do before expert teachers are available in many countries.

CLINICAL APPLICATIONS • Cardiovascular risk factors cluster in children, and low physical fitness is as strong a predictor of clustering as obesity • a simple measure combining waist/height and cardiorespiratory fitness can be used as clustering of CVD risk factors and can be used as a screening tool in a school setting. • Physical activity interventions in school have proven effective to increase physical activity but must be sustained.

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for adiposity in youth. Int. J. Child Adolesc. Health 2010; 3: 93–8. 121. Taylor RW, Williams SM, Grant AM, Taylor BJ, and Goulding A. Predictive ability of waist-to-height in relation to adiposity in children is not improved with age and sex-specific values. Obesity (Silver Spring) 2011; 19(5): 1062–8. 122. Dencker M, Wollmer P, Karlsson MK, Linden C, Andersen LB, and Thorsson O. Body fat, abdominal fat and body fat distribution related to cardiovascular risk factors in prepubertal children. Acta Paediatr. 2012; 101(8): 852–7. 123. Hetherington-Rauth M, Bea JW, Lee VR, et al. Comparison of direct measures of adiposity with indirect measures for assessing cardiometabolic risk factors in preadolescent girls. Nutr. J. 2017; 16(1): 15. 124. Freedman DS, Ogden CL, and Kit BK. Interrelationships between BMI, skinfold thicknesses, percent body fat, and cardiovascular disease risk factors among U.S. children and adolescents. BMC Pediatr. 2015; 15: 188. 125. Liddle K, O'Callaghan M, Mamun A, Najman J, and Williams G. Comparison of body mass index and triceps skinfold at 5 years and young adult body mass index, waist circumference and blood pressure. J. Paediatr. Child Health 2012; 48(5): 424–9. 126. de Groot E, van Leuven SI, Duivenvoorden R, et al. Measurement of carotid intima-media thickness to assess progression and regression of atherosclerosis. Nat. Clin. Pract. Cardiovasc. Med. 2008; 5(5): 280–8. 127. Molinari F, Suri J, and Kathuria C. Atherosclerosis Disease Management. Berlin: Springer; 2010. 128. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, Najjar SS, Rembold CM, and Post WS. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: A consensus statement from the American Society of Echocardiography Carotid IntimaMedia Thickness Task Force. J. Am. Soc. Echocardiogr. 2008; 21: 93–111. 129. Pignoli P. Ultrasound B-mode imaging for arterial wall thickness measurement. Atherosclerosis Rev. 1984; 12: 177–84. 130. Melo X, Santa-Clara H, Santos DA, et al. Independent association of muscular strength and carotid intima-media thickness in children. Int. J. Sports Med. 2015; 36(8): 624–30. 131. Pianosi PT, Liem RI, McMurray RG, Cerny FJ, Falk B, and Kemper HC. Pediatric exercise testing: Value and implications of peak oxygen uptake. Children (Basel) 2017; 4(1). 132. Adegboye AR, Anderssen SA, Froberg K, et al. Recommended aerobic fitness level for metabolic health in children and adolescents: A study of diagnostic accuracy. Br. J. Sports Med. 2011; 45(9): 722–8. 133. Lerum O, Aadland E, Andersen LB, Anderssen SA, and Resaland GK. Validity of noninvasive composite scores to assess cardiovascular risk in 10-year-old children. Scand. J. Med. Sci. Sports 2017; 27(8): 865–72. 134. Andersen LB, Bugge A, Dencker M, Eiberg S, and El-Naaman B. The association between physical activity, physical fitness and development of metabolic

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886  Chapter 75  Cardiovascular Risk and Physical Activity in Children disorders. Int. J. Pediatr. Obes. 2011; 6 Suppl 1: 29–34. 135. McMurray RG, Ainsworth BE, Harrell JS, Griggs TR, and Williams OD. Is physical activity or aerobic power more influential on reducing cardiovascular disease risk factors. Med. Sci. Sports Exerc. 1998; 30: 1521–9. 136. Andersen LB, Sardinha LB, Froberg K, Riddoch CJ, Page AS, and Anderssen SA. Fitness, fatness and clustering of cardiovascular risk factors in children from Denmark, Estonia and Portugal: The European Youth Heart Study. Int. J. Pediatr. Obes. 2008; 3 Suppl 1: 58–66. 137. Léger LA and Lambert J. A maximal multistage 20-m shuttle-run test to predict VO2max. Eur. J. Appl. Physiol. 1982; 49: 1–12. 138. Leger LA, Mercier D, Gadoury C, and Lambert J. The multistage 20 metre shuttle run test for aerobic fitness. J. Sports Sci. 1988; 6(2): 93–101. 139. van Mechelen W, Hlobil H, and Kemper HC. Validation of two running tests as estimates of maximal aerobic power in children. Eur. J. Appl. Physiol. Occup. Physiol. 1986; 55(5): 503–6. 140. Matsuzaka A, Takahashi Y, Yamazoe M, Kumakura N, Ikeda A, Wilk B, and Bar-Or O. Validity of the multistage 20-m shuttle-run test for japanese children, adolescents, and adults. Pediatr. Exerc. Sci. 2004; 16: 113–25. 141. Andersen LB, Andersen TE, Andersen E, and Anderssen SA. An intermittent running test to estimate maximal oxygen uptake: The Andersen test. J. Sports Med. Phys. Fitness 2008; 48: 434–7.

142. Silva G, Aires L, Mota J, Oliveira J, and Ribeiro JC. Normative and criterionrelated standards for shuttle run performance in youth. Pediatr. Exerc. Sci. 2012; 24(2): 157–69. 143. Farah BQ, Christofaro DG, Balagopal PB, Cavalcante BR, de Barros MV, and Ritti-Dias RM. Association between resting heart rate and cardiovascular risk factors in adolescents. Eur. J. Pediatr. 2015; 174(12): 1621–8. 144. Yamano Y, Miyakawa S, and Nakadate T. Association of arteriosclerosis index and oxidative stress markers in school children. Pediatr. Int. 2015; 57(3): 449–54. 145. Andersen LB, Wedderkopp N, Hansen HS, Cooper AR, and Froberg K. Biological cardiovascular risk factors cluster in Danish children and adolescents. Danish part of the European Heart Study. Prev. Med. 2003; 37: 363–7. 146. Andersen LB, Boreham CA, Young IS, et al. Insulin sensitivity and clustering of coronary heart disease risk factors in young adults. The Northern Ireland Young Hearts Study. Prev. Med. 2006; 42(1): 73–7. 147. Franck J, Aslesen R, and Jensen J. Regulation of glycogen synthesis in rat skeletal muscle after glycogen-depleting contractile activity: Effects of adrenaline on glycogen synthesis and activation of glycogen synthase and glycogen phosphorylase. Biochemical J. 1999; 344: 231–5. 148. Houmard JA, Hickey MS, Tyndall GL, Gavigan KE, and Dohm GL. Seven days of exercise increase GLUT-4 protein

content in human skeletal muscle. J. Appl. Physiol. 1995; 79(6): 1936–8. 149. Franch J, Aslesen R, and Jensen J. Regulation of glycogen synthesis in different types of rat skeletal muscles after intense in vitro stimulation. J. Sports Sci. 2004; 16, nr. 5: 462–3. 150. Hicks AL, MacDougall JD, and Muckle TJ. Acute changes in high-density lipoprotein cholesterol with exercise of different intensities. J. Appl. Physiol. 1987; 63: 1956–60. 151. McMurray RG and Hackney AC. Endocrine responses to exercise and training. In: Garrett WG, Kirkendall DT, eds. Sports Medicine, vol 1. Baltimore: Williams & Wilkins; 2000: 135–62. 152. Shono N, Mizuno M, Nishida H, et al. Decreased skeletal muscle capillary density is related to higher serum levels of low-density lipoprotein cholesterol and apolipoprotein B in men. Metabolism 1999; 48(10): 1267–71. 153. Pedersen BK. Muscle as a secretory organ. Compr. Physiol. 2013; 3(3): 1337–62. 154. Ondrak KS, McMurray RG, Hackney AC, and Harrell JS. Interrelationships among chances in leptin, cortisol, growth hormone and weight status in youth J. Clin. Res. Pediatr. Endocr. 2011; in press. 155. Dobbins M, De CK, Robeson P, Husson H, and Tirilis D. School-based physical activity programs for promoting physical activity and fitness in children and adolescents aged 6–18. Cochrane Database Syst. Rev. 2009; 21(1): CD007651.

76 CHAPTER

Cardiovascular Risk and Diet in Children Jessica L. Hildebrandt, MS, RD and Sarah C. Couch, PhD, RD

Key Concepts............................................................................. 887 76.1 Introduction...................................................................... 887 76.2 Obesity............................................................................. 888 76.2.1  Etiology and Pathophysiology................................ 888 76.2.2  Diet and Lifestyle Approaches to Management...... 888 76.2.2.1 Diet........................................................ 889 76.2.2.2  Physical Activity and Sleep Time............. 889 76.2.2.3  Screen Time........................................... 889 76.2.2.4  Family Climate....................................... 889 76.2.3  Clinical Applications.............................................. 889 76.2.3.1  USDA Dietary Guidelines........................ 890 76.2.3.2  USDA MyPlate........................................ 890 76.3 Dyslipidemia..................................................................... 890 76.3.1  Definitions and Targets for Lifestyle Therapy......... 890

KEY CONCEPTS • More than one-third of U.S. children between the ages of 2 and 19 years are overweight, and 17% are obese. • Pediatric obesity is associated with a broad range of health problems, including dyslipidemia and hypertension, which are established cardiovascular disease (CVD) risk factors. • Pediatric CVD risk factors track into adulthood in line with eating behaviors, creating an urgent need for early intervention to remediate unhealthy lifestyle practices. • A CVD-protective diet emphasizes unprocessed fruits, vegetables, and whole grains with energy from fat, carbohydrates, and protein in proportions appropriate for age and as recommended by the 2015–2020 Dietary Guidelines for Americans (DGA).1

76.1 INTRODUCTION Compelling evidence shows that the atherosclerotic process begins in childhood and progresses slowly into adulthood.2–5 Later in life, this often leads to coronary heart disease, the leading cause of death in the United States.6 Several risk factors are important for the development of cardiovascular disease (CVD), including family history of CVD, obesity, elevated blood pressure, dyslipidemia, diabetes, and cigarette smoking. Diets high in saturated and trans fat, excessive energy intake, and physical inactivity

76.3.2 Dietary and Other Lifestyle Approaches to Management of Dyslipidemia������������������������������� 891 76.3.3 Strategies to Improve Compliance to a CHILD-2 Diet�������������������������������������������������������� 893 76.4 Hypertension.................................................................... 894 76.4.1  Definitions and Targets for Lifestyle Therapy......... 894 76.4.2 Dietary Approaches and Blood Pressure Management������������������������������������������������������� 894 76.4.2.1  Weight Management.............................. 894 76.4.2.2  Dietary Patterns..................................... 895 76.4.2.3 Sodium.................................................. 895 76.5 Conclusion........................................................................ 896 Clinical Applications................................................................... 896 References................................................................................ 896

are lifestyle-related behaviors that can increase risk of CVD.7 Childhood obesity remains a major public health crisis both nationally and internationally. Today, about one in three children in the United States is overweight or obese.6 Overweight and obese children and adolescents are at greater risk for serious health problems compared to their normal-weight peers. What have previously been considered adult metabolic disorders related to obesity such as hypertension, dyslipidemias, type 2 diabetes, metabolic syndrome, and non-alcoholic fatty liver disease are now increasingly prevalent among children.8–10 This continues to make prevention and treatment of childhood overweight and obesity an important public health focus. Based on data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014, approximately one in five youths had high total cholesterol, low high-density lipoprotein cholesterol (HDL-C), or high non-HDL-cholesterol.11 Youth with obesity had greater prevalence of high total cholesterol, low HDL-C, and high non-HDL-cholesterol than their normal-weight counterparts. Additionally, more than one in ten children and adolescents had borderline high or high blood pressure.12 While genetics play a role in the development of disorders of lipid metabolism and blood pressure regulation in children, these CV risk factors are largely influenced by lifestyle-related factors, primarily overnutrition, poor diet quality, and inadequate physical activity. A diet pattern that exceeds recommendations for calories, fat, and added sugars should be considered suboptimal. Dietary patterns that encourage increased intake of fruits and vegetables, whole grains, low-fat dairy, and fish should be recommended as 887

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dietary approaches to reduce CVD risk. In this chapter, we will discuss the consequences of suboptimal diet quality in regard to CV risk factors, and approaches to achieve optimum nutrition in children and adolescents.

76.2 OBESITY Childhood and adolescent overweight and obesity in the United States remains a major health problem. It is estimated that approximately 17% (or 12.7 million) of U.S. children between the ages of two and nineteen years are obese, and 31.8% are overweight or obese.7 Non-Hispanic black and Hispanic children have higher prevalence rates than non-Hispanic white and non-Hispanic Asian children.13 Lower-income children and adolescents are more likely to be obese than their higher-income counterparts, but the relationship is not consistent across race and ethnicity groups.14 There is an increased risk of obesity for children with one or two obese parents.15 Additionally, children with obesity are more likely to be obese as an adult.16 Weight status in children is defined using body mass index (BMI). BMI is an anthropometric measurement of body weight in kilograms (kg) divided by the square of the height in meters. Percentile distributions relative to gender and age in the 2000 Centers for Disease Control and Prevention (CDC) growth charts are used as reference points.17 BMI has been accepted as a useful tool to assess body fat as increasing BMI levels correlate with excess body fat.18 Children over the age of two years and less than 20 years with a BMI greater than the 85th percentile and less than the 95th percentile for age and sex are diagnosed as overweight. Children at or above the 95th percentile are diagnosed as obese. A child with a BMI greater than or equal to the 120th percentile of the 95th percentile is classified as extremely obese. For children under the age of two years, the World Health Organization (WHO) sexspecific weight-for-recumbent-length charts are used.19 Weight-for-lengths at or above the 97.7th percentile are diagnosed as obese.

hypertension, 20,21 elevated serum lipid levels, 22 low HDLC,11 elevated hepatic enzyme levels or fatty liver disease, 23 type 2 diabetes, 24 respiratory problems (including sleep apnea, and asthma), 25,26 and joint and musculoskeletal problems. 25,27 Overweight and obesity in childhood are strongly associated with increased cardiovascular mortality in adulthood. 28–30 Psychological stress such as depression, behavioral problems, and issues in school are associated with childhood obesity.31–33 Children with obesity are also more likely to be bullied and teased more than their normal-weight peers and are more likely to suffer from social isolation and lower self-esteem. 34,35

76.2.2 Diet and Lifestyle Approaches to Management Weight loss in children is associated with significant changes in cardiometabolic outcomes, including HDL-C, triglycerides (TG), and systolic blood pressure. A  1  kg weight loss can help reduce serum TG by 5 mg/dL and increase HDL-C by approximately 1.5 mg/dL. Decreasing BMI by one unit in adolescents is expected to reduce systolic blood pressure by 6 mm/Hg. 36 Several lifestyle-related behaviors are considered risk factors for the development of childhood overweight and obesity, as seen in Table 76.1. Therefore, behavior changes in these key areas should be considered as targets for intervention when working with overweight or obese children and their families. TABLE 76.1  Behaviors associated with childhood weight status Impact on child obesity Positively Associated

• Regular intakes of SSB • Greater intakes of fast food • Increased intakes of dietary fats • Increased intakes of added sugars • Eating larger portions of food • Breakfast skipping • Low dairy and calcium-rich food intake • Parental dietary dis-inhibition and restraint • Lack of physical activity and sedentary lifestyle • Screen time exceeding two hours per day • Shorter sleep duration and poor-quality sleep • Negative aspects of family functioning • Lack of parental support or over-possessiveness • Parental concern about child’s weight status

Negatively Associated

• Increased intakes of fruits and vegetables • Family meals • Eating daily breakfast • Positive family - level interpersonal dynamics at meals • Positive parent-level food-related dynamics at meals • Regular physical activity and participation in sports

76.2.1 Etiology and Pathophysiology Fat accumulates in excess during childhood and adolescence, when total energy intake exceeds total energy expenditure. This creates an energy imbalance caused by a complex interplay of various genetic, hormonal, behavioral, and environmental factors. Excessive energy intake from poor food choices and/or a low energy expenditure from a mostly sedentary lifestyle can result in being overfat. There are some genetic and hormonal disorders associated with childhood obesity, including Prader-Willi syndrome, Laurence-Moon-Biedl (Bardet-Biedl) syndrome, growth hormone deficiency, hypothyroidism, and leptin deficiency. While genes may increase a person’s susceptibility to weight gain, many environmental factors, such as lack of physical activity and an overabundant food supply, are required to develop overweight or obesity. Pediatric obesity is associated with an increased risk of a broad range of health problems, including

Behavior

76.2  Obesity  889

76.2.2.1 Diet

76.2.2.4 Family Climate

Dietary factors that increase the risk of excessive energy intake relative to energy expenditure include regular intakes of sugar-sweetened beverages (SSB), greater intakes of fast food, increased intakes of dietary fats and added sugars, and eating larger portions of food. These factors are positively associated with childhood overweight. 37 Increased intake of fruits and vegetables may be associated with a decreased risk of obesity in children.37 Additionally, some observational research indicates that low dairy and calcium-rich food intake may increase obesity risk. 37 Breakfast skipping has been indicated as a dietary behavior that is associated with obesity. Consequently, eating breakfast daily is associated with weight loss and weight maintenance in addition to improving nutrient intake.38 Family meals, especially those with positive family-andparent-level interpersonal dynamics (i.e., warmth, group enjoyment, parental positive reinforcement) and with positive parent-level-food-related dynamics (i.e., positive food communication, parental food positive reinforcement) are associated with a reduced risk of childhood overweight and obesity.39

Parental dietary dis-inhibition and restraint, negative aspects of family functioning (such as lack of parental support or over-possessiveness), and parental concern about the child’s weight status are positively associated with childhood overweight or obesity. Conversely, positive aspects of family functioning (such as family cohesion, expressiveness, democratic style, parental support, and cognitive stimulation at home) are negatively associated with childhood overweight or obesity. Household food insecurity may or may not be related to pediatric overweight or obesity, as the relationship remains unclear. 37

76.2.2.2 Physical Activity and Sleep Time Lack of physical activity and sedentary lifestyle play key roles in the development of pediatric obesity. Regular physical activity and participation in sports may decrease the risk of development of obesity in children.37 Shorter sleep duration and poor sleep quality can increase the risk of obesity. 37

76.2.2.3 Screen Time Television viewing, playing video games, and recreational use of computers and cell phones are sedentary behaviors. Screen time exceeding two hours per day increases childhood obesity risk. 37 Additionally, foods low in nutrients and high in total calories, sugars, salt, and fat are highly advertised and marketed through media targeted to children and adolescents.40 This can influence food intake and increase overall caloric intake.

76.2.3 Clinical Applications The Expert Committee Recommendations Regarding the Prevention, Assessment, and Treatment of Child and Adolescent Overweight and Obesity provide recommendations for practitioners working with pediatric patients and their families in all areas of obesity care.15 Interventions are categorized into different stages according to severity of obesity. The appropriate stage of treatment is based on age, BMI-for-age percentile, and the presence of other health risks. The Academy of Nutrition and Dietetics EAL Evidence-Based Pediatric Weight Management Nutrition Practice Guidelines, 2007, provide complementary guidelines.37 The stages of obesity treatment presented in the Academy of Nutrition and Dietetics guidelines are outlined below. Stage 1: Prevention Plus A family approach focusing on healthful eating and activity behaviors aimed at improving BMI status. The involvement of the child’s parent or caregiver is recommended, especially for children ages 6–12 years. Targeted behaviors for Stage 1 obesity treatment are summarized in Table 76.2. Stage 2: Structured Weight Management This stage includes the support of a Registered Dietitian Nutritionist (RDN). A nutrition prescription,

TABLE 76.2  Targeted behaviors for Stage 1 obesity treatment Targeted behaviors • Limiting consumption of sugar-sweetened beverages and juice. • Encouraging diets with adequate fruit and vegetable consumption. • Limiting television and other screen time to ≤2 hours per day. • Eating a healthy breakfast daily. • Limiting eating out at restaurants especially fast food restaurants. • Encouraging family meals in which parents and children eat together. • Limiting portion sizes. • Consumption of diets rich in calcium. • Consumption of diets high in fiber. • Limiting consumption of energy-dense foods. • Eating a diet with balanced macronutrients (energy from fat, carbohydrates and protein in proportions for age as recommended by USDA Dietary Guidelines for Americans) • Encouraging exclusive breastfeeding for six months of age. • Maintenance of breastfeeding after introduction of solid food to 12 months of age and beyond, consistent with American Academy of Pediatrics recommendations41,42 • Promoting moderate to vigorous physical activity for at least 60 minutes each day.

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890  Chapter 76  Cardiovascular Risk and Diet in Children

including a mild energy deficit, is included in this stage. Balanced hypo-caloric diets are prescribed to achieve a healthier weight or promote weight stabilization. Nutrition prescriptions are used to help guide the clinician and are not always disclosed to the parent or the patient. They can be translated into an eating plan. A meal and snack schedule as well as one hour of supervised and planned daily physical activity are also included. Self-monitoring is implemented by the family, with staff support, using motivational interviewing techniques to help set goals and identify barriers. Stage 3: Comprehensive Multidisciplinary Intervention The intensity of behavior changes and frequency of visits is increased in this intervention. An interdisciplinary team of specialists with experience working with overweight or obese children is also included. During this phase, medical nutrition therapy should be provided for a minimum of three months or until baseline weight management goals are reached. More successful weight loss and weight maintenance may be achieved by increasing the frequency of contacts between the patient and practitioner. Stage 4: Tertiary Care Intervention This stage may be appropriate for severely obese children (BMI-for-age greater than the 99th percentile) who have attempted the Stage 3 intervention. Interventions are more aggressive and include medications, very-low-energy diets, and weight-control surgery with standard clinical protocols. Nutrition plays a vital role in the healthy growth and development of children. A healthy diet and regular physical activity are important to prevent obesity in children. Eating patterns established in childhood often track into adulthood so it is important to set healthy habits early in life. Information and links to established recommendations for healthy eating and obesity prevention are summarized below.

76.2.3.1 USDA Dietary Guidelines Link: https​://he​alth.​gov/d​ietar​yguid​eline​s/201​5/gui​delin​es/ The 2015–2020 DGA, developed by the U.S. Department of Agriculture (USDA) and the U.S. Department of Health and Human Services (USDHHS), provide recommendations for healthy eating and maintenance of a healthy weight based on current scientific and medical knowledge. The current DGA are designed for professionals to help all Americans ages two years and older and their families consume a healthy, nutritionally adequate diet.1

76.2.3.2 USDA MyPlate Link: https://www.choosemyplate.gov/ MyPlate serves as an example of the implementation of the DGA to help individuals, families, and communities achieve healthy eating patterns.43 The Endocrine Society Clinical Practice Guideline for Pediatric Obesity Link: https://doi.org/10.1210/jc.2016-2573

The Endocrine Society recently published clinical practice guidelines for the assessment, treatment, and prevention of pediatric obesity.44 Academy of Nutrition and Dietetics (AND) Nutrition Guidance for Healthy Children Link: https​: //do​i.org​/10.1​016/j​.jand​. 2014​.06.0​01 The AND provides dietary recommendations and guidelines for physical activity. The science-based nutrition messages are designed to improve the nutritional wellbeing of children and are provided for food and nutrition practitioners.45 American Heart Association Dietary Recommendations for Healthy Children Link: http:​//www​.hear​t.org ​/ HEAR​TORG/ ​Healt​hyLiv​ ing/D​ietar ​y-Rec​ommen​datio​ns-fo​r-Hea​lthy- ​Child ​ren_U​ CM_30​3886_​A rtic​le.js​p#.Wo​3rP3x​G2Uk The AHA dietary recommendations start in infancy. Eating patterns for families are also recommended.46

76.3 DYSLIPIDEMIA (See also Chapter 79 on Identification and Management of Children with Dyslipidemia) Lipoproteins are complex particles that transport cholesterol, triglyceride, phospholipid, and protein in the blood. Defects in the production, transport, and/or clearance pathways for lipoproteins can result in abnormally high or low blood lipid concentrations (dyslipidemia). An elevated level of cholesterol carried by circulating lipoproteins containing apolipoprotein (apo) B is the predominant underlying cause of atherosclerotic cardiovascular disease (ASCVD).47,48 ASCVD may present as coronary heart disease, stroke, and peripheral arterial disease. Although these events rarely occur in children, depending on the type, severity, and duration of the dyslipidemia, adverse cardiovascular consequences can occur, sometimes early in life.49

76.3.1 Definitions and Targets for Lifestyle Therapy Several forms of dyslipidemias have strong genetic components. Observational data from youth with genetic mutations that alter apoB-containing lipoproteins (low-density lipoprotein cholesterol [LDL-C] and non-high-density lipoprotein cholesterol [non-HDL-C]) show an increased age-adjusted rate of ASCVD-related events.50 Therefore, early identification and treatment of dyslipidemia are considered the cornerstone of primary prevention for ASCVD.49 Notably, non-HDL-C, which includes both cholesterol-rich and triglyceride-rich atherogenic lipoproteins is now considered to be a better marker for ASCVD risk than LDL-C. 51 Measures of body adiposity and blood triglycerides are more highly correlated with non-HDL-C compared to LDL-C, and there is less ethnic variation in non-HDL-C compared to LDL-C. 52 Lipid and lipoprotein targets, as reported in the National Lipid Association recommendations for patient-centered management of dyslipidemia51 for primary prevention of ASCVD in children and adolescents, are shown in Table 76.3.

76.3  Dyslipidemia 

891

TABLE 76.3  Acceptable, borderline, and high plasma lipoproteins and lipid concentrations for children and adolescents Lipid/lipoprotein

Low, mg/dl

Acceptable, mg/dl

Borderline, mg/dl

High, mg/dl

TC

–

85th percentile, at which point blood pressure quadrupled. This finding held true independent of race or sex. For overweight African American females, each 5% increase in BMI percentile increased the risk of elevated blood pressure or hypertension by 33%; the risk was nearly doubled that for other race or gender groups. Lifestyle interventions that achieve weight loss have consistently been found to favorably impact pediatric blood pressure and other cardiometabolic risk factors.88 For example, Reinehr et al.89 prospectively analyzed results from a one-year weight loss intervention in overweight and obese children between the ages of five and seventeen years. Participants who were able to reduce their BMI standard deviation score (SDS) by >0.25 in one year (equivalent to a BMI reduction of 0.5 kg/m 2 in a seven-year-old child and 1.0 kg/m 2 in a 13-year-old) achieved an average reduction in systolic blood pressure of −3.2 mm Hg and diastolic blood pressure of −2.2 mm Hg, respectively. Furthermore, in this same study, a BMI-SDS reduction of >0.5 was associated with a twofold greater blood pressure lowering, with −6.0 mm Hg and −5.1 mm Hg reduction in systolic and diastolic blood pressure, respectively. Given the benefits of weight loss on cardiovascular risk factors in youth, weight reduction is recommended as a primary

TABLE 76.7  Definitions of blood pressure categories and stages in children and adolescents Blood pressure category

For children ages 1- 13 years of age

Normal

500 mg/dL refer to Lipid specialist

changes. As shown in Figure 79.5, if the TGs are 130, < 500 mg/dL, 10-19 yrs • Start CHILD-1 + lifestyle changes • Weight loss if BMI > 85th% 3 months FLP

TG < 100 mg/dL, < 10 yrs < 130 mg/dL, 10-19 yrs • Continue CHILD-1 • Repeat FLP every 12 mo

TG > 100, < 500 mg/dL, < 10 yrs > 130, < 500 mg/dL, 10-19 yrs • Start CHILD-2-TG • Refer to Dietitian • Continue lifestyle change s, weight loss 3 months FLP

TG < 100 mg/dL, < 10 yrs < 130 mg/dL, 10-19 yrs • Continue CHILD-2-TG • Continue lifestyle changes • Continue weight loss if BMI remains > 85th% • Repeat FLP every 6-12 mo

TG > 100, < 200 mg/dL, < 10 yrs > 130, < 200 mg/dL, 10-19 yrs • Intensify CHILD-2-TG • Repeat visit with dietitian • Continue attempts at weight loss • Increase dietary intake of low mercury fish • Repeat FLP in 6 months

TG > 200, < 500 mg/dL • Consider omega-3 fish oil therapy • Consider refer to lipid specialist • If non-HDL-c > 145 mg/dL after LDL-c target attained, refer to lipid specialist

Figure 79.5  Dietary Therapy Targets for High Triglycerides (Adapted from Kavey et al. 20117 Figure 9.2). FLP=fasting lipid profile; mo=months; TG=triglyceride; wks=weeks.

Clinical Applications  933

medication may be considered if the TG levels remain greater than the target. The target TG and non-HDL-C levels are shown in Figure 79.5. Please note that if the average of two fasting TG levels is at least 500 mg/dL or a single fasting TG level is 1000 mg/dL or higher, this is likely due to some form of genetic hypertriglyceridemia and the patient should be referred to a lipid specialist.

79.9.3 Long-Chain Omega-3 Fatty Acids Omega-3 fatty acids (or fish oil) decrease the synthesis of hepatic fatty acid and TG and increase the degradation of fatty acids, leading to decreased VLDL-C release and lower TG levels. The use of omega-3 fish oil capsules at doses of 2 to 4 g/day is safe and effective in adults and can lower TG by 30–45% and increase HDL-C levels by 6–17%, but it may increase LDL-C levels up to 31%. 50 There have been mixed results in the adult literature regarding primary CVD reduction with TG lowering from omega-3 fatty acids, 51,52 but those with elevated TGs and low HDL-C levels appear to be a subgroup in which CVD risk reduction may be seen. 53 In children, one small randomized trial of 25 patients with hypertriglyceridemia (average TG 227 mg/dL) using four grams of prescription fish oil (Lovaza) did not show a significant difference in the treatment versus the placebo groups. 54 There have been no reports of adverse effects on muscle, liver, or glucose levels. 50 There are a few FDA approved fish oil capsule preparations as well as several over-the-counter omega-3 fish oil capsules sold as nutritional supplements. Dosing for TG-lowering effect should be 2000 to 4000 mg daily of the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) components of the fish oil capsule.

79.9.4 Fibric Acid Derivatives Fibric acid derivatives, or fibrates, work in a complex way to break down VLDL-C and TGs and decrease hepatic synthesis of TG. Fibrates have been shown to lower TGs and increase HDL-C levels without an increase in LDL-C levels. Although not currently FDA approved for children, a small study in children demonstrated efficacy in lowering TG levels.55 Prescribing fibrates in the pediatric population should occur only under the guidance of a lipid specialist.

79.9.5 Therapy Goals Goals for dietary and medication management therapy are TG levels 90th percentile

Re-measure BP twice and average

If BP > 90th percentile and oscillometric, then repeat manually x2 and average

Normal BP

Classify BP and determine appropriate next steps

Figure 80.1  The 2017 Modified BP Measurement Algorithm.

TABLE 80.1  Definition of hypertension For children 1 to 4 drinks, average

0.4(0.0) *

0.1(0.0)

0.1(0.0)

3.3(0.0) *

3.8(0.1) *

3.5(0.0)

Characteristic Cigarette smoking

Alcohol drinking

Other   Fruit and vegetable score, average   Block dietary fat score, average

27.3(0.3) *

21.6(0.9)

24.1(0.3)

  Always or nearly always (%)

85.5(0.3) *

95.1(0.8)

96.3(0.4)

  Sometimes or seldom (%)

11.3(0.3) *

Seatbelt wearing

  Never (%)

3.2(0.2) *

4.5(0.8) *

3.3(0.4)

0.4(0.2)

0.4(0.1)

* p ≤ 0.0001 for the difference between this Behavioral Risk Factor Surveillance System of the Centers for Disease Control and Prevention (BRFSS) category and the Women Physicians’ Health Study [15]. Source: Data from Erica Frank, “The Women Physicians’ Health Study: Background, Objectives, and Methods,” Journal of the American Medical Women’s Association 50 (1995): 64–6.

tobacco account for substantial mortality rates—approximately 40% of U.S. mortality23—but, even so, physicians do not perform prevention counseling at very high rates.24–28

88.4 PHYSICIAN EXERCISE AND HEALTHY PATIENTS As previously established, those physicians with the healthiest habits are most likely to advise their patients about related preventive habits. This is particularly true for exercise. 29 North American physicians (and medical students) generally report significantly better exercise habits when compared to their same-age peer groups, which in turn highly correlates with positive mental and physical health outcomes not only for the physicians but also for their patients. As with other healthy habits, findings on exercise highlight the importance of medical school and physician “health interventions” in order to increase present and future rates of physician-delivered exercise prescriptions.11,14,17,24,27,28,30–46

88.5 WHICH DETERMINANTS MATTER MOST WHEN IT COMES TO PHYSICIANS COUNSELING PATIENTS? Determinants surrounding physicians’ personal habits— exercise represents but one example—are worth knowing because intervention on malleable variables can then occur, producing physicians with stronger preventionrelated skills. To explore the effect of potential counseling- and screening-related variables in 4,501 respondents to the Women Physicians' Health Study, a questionnaire-based study of a representative sample of U.S. women doctors was performed.3 Table 88.3 delineates the study’s central findings. Being a primary care practitioner and having related healthy habits oneself were the most significant correlates of U.S. women physicians' self-reported, preventionrelated counseling and screening practices. Table 88.4 exhibits these specifics.

88

1036  Chapter 88  Physician Health Practices and Lifestyle Medicine TABLE 88.3  U.S. women physicians’ personal health practices vs. their counseling or screening patients at least once per year Characteristic

Percentage of physicians performing counseling at least once per year

Physicians’ fat consumption:   Below median fat score

30.2% (on cholesterol)*

  Median fat score

22.6% (on cholesterol)*

Physicians’ exercise:   Complies with CDC/ ACSM recommendations

46.1% (on exercise)*

  Does not comply with CDC/ACSM recommendations

39.6% (on exercise)*

Physicians’ alcohol consumption:   ≤ 2 drinks per week

41.7% (on alcohol use)*

  > 2 drinks per week

31.9% (on alcohol use)*

Physicians’ cigarette smoking:  Non-smoker

63.4% (on tobacco use)

  Current smoker

47.8% (on tobacco use)

Physicians receiving flu shot in the last year:  Yes

51.2% (recommending flu shot)**

 No

32.9% (recommending flu shot)**

Physicians performing breast self-exam:   ≥ 12 times/year

61.6% (on breast self-exam)

  < 12 times/year

51.0% (on breast self-exam)

Physicians’ sunscreen use:   Always or almost always

30.6% (on skin cancer risks)**

  Seldom or rarely or never

19.3% (on skin cancer risks)**

Post-menopausal physicians’ hormone replacement therapy (HRT) use:  Yes

45.5% (on HRT)**

 No

28.8% (on HRT)**

88.5.1 Individual Case Study #1: For One Physician, Healthy Meets Multi-tasking Before laptop computers emerged on the scene, I (Dr. Erica Frank, chapter co-author) read journals and books that were not too heavy to hold while I pedaled an exercise bike. But once I had ridden a few miles with a laptop secured to the front of my bike, I knew I had found my preferred regular exercise modality. Here was a healthpromotion activity that satisfied so many criteria simultaneously! I no longer experienced remorse over wasting time getting a special outfit for exercise, getting to and from my place of exercise, or even performing the exercise itself (no longer feeling that my brain and hands and quadriceps should all have higher purposes). Additionally, I no longer stewed in boredom while exercising, a serious impediment to any previously regular exercise. In the thousands of miles ridden since that day, I have not only learned to bike and simultaneously read and write but even to chair conference calls—although the latter usually with the video function turned off. And now, when I leave home, I also strive for fun, multitasking exercise. As an assistant professor, I would usually commute to and from work on my bicycle, about 20 minutes to Emory University or to Grady Memorial Hospital each way; this was a wonderful way to begin and end each day. Likewise, I’ve found it’s often an educational and cardiovascular treat to walk around a new urban or biologically rich environment en route to a task. Walking while talking with friends can be fruitful too, whether with a buddy in person or on the phone, a child in a stroller, or as a stroll with a significant other that pays attention to the light, weather, and one’s shared ecosystem. And how do I judge the efficacy of my activities? At age 55, I retain a normal BMI, blood pressure, and lipids without medication, can accomplish without pain any physical feats needed or desired, and sporadically participate in triathlons without special preparation before or any pain after, although always (and contentedly) at the very back of the pack.

Physicians’ cholesterol tested:  Yes

33.8% (screening for/counseling on cholesterol)**

 No

21.9% (screening for/counseling on cholesterol)**

Physicians’ blood stool tested:  Yes

35.9% (screening for/counseling on colorectal cancer)

 No

31.6% (screening for/counseling on colorectal cancer)

Physicians’ skin examined:  Yes

36.2% (screening for/counseling on skin cancer, sunscreen)

 No

22.3% (screening for/counseling on skin cancer, sunscreen)

*p≤0.01; **p≤0.001 Source: Erica Frank, Richard Rothenberg, Charles Lewis, et al., “Correlates of Physicians’ Prevention-Related Practices: Findings from the Women’s Physicians Health Study,” Archives of Family Medicine 9 (2000): 359–67.

88.5.2 Individual Case Study #2: Exercise Vanquishes Stress When she had completed the first half of her medical internship in the oncology department of a large community hospital, Verena R. had a very hard time leaving behind the suffering and strokes of fate that her patients endured when she stepped through the hospital’s exit door each night. In addition, she lived in staff housing in very close proximity to the hospital—her living room faced the windows of the ward in which she worked. She just couldn’t seem to get away. That’s when Verena took up running. Every day after work, she exchanged her scrubs for running tights and a t-shirt and took off into the nearby forest. Sometimes she listened to music, podcasts, or audiobooks; sometimes her brain needed the peace and quiet, and she would simply run and become one with the beautiful natural settings surrounding her.

–

–

–

Cholesterol

***

****

–

*

Practices related personal habit

Has screened self in past year

Personal history of related disease

Changing related habits

–

****

–

–

–

Practice site

More work control

More career satisfaction

Performs more continuing medical education

–

–

–

–

–

–

–

–

****

–

*

–

–

–

Colorectal Cancer

–

–

–

–

–

****

–

–

–

****

****

–

–

–

–

–

****

–

–

–

–

–

HIV Risks, Testing

**

–

–

*

–

****

–

–

–

–

****

Flu Vaccine

–

–

–

–

*

****

***

–

–

–

–

Diet

**

–

–

–

–

****

***

–

–

–

–

Weight

*

–

–

–

–

****

–

**

–

–

*

Exercise

–

–

–

–

–

****

–

*

–

–

**

Smoking Cessation

**

–

–

–

*

****

*

–

–

–

****

Alcohol Use

–

–

–

–

–

****

–

–

–

–

**

Breast Exam

–

–

–

–

–

****

–

–

–

**

–

Mammo-gram

Source: Erica Frank, Richard Rothenberg, Charles Lewis, et al., “Correlates of Physicians’ Prevention-Related Practices: Findings from the Women’s Physicians Health Study,” Archives of Family Medicine 9 (2000): 359–67.

*p≤0.05; **p≤0.01; ***p≤0.001; ****p≤0.0001

–

–

Region of country

****

****

Primary care/ Ob/Gyn

–

****

Ethnicity

–

Blood Pressure

Physician Characteristic

Skin Cancer, Sunscreen Use

TABLE 88.4  Models for significant correlates of women physicians’ counseling on prevention at least once a year, by prevention type

–

–

**

*

*

****

–

–

–

–

***

HRT

88.5  Which Determinants Matter Most When It Comes to Physicians Counseling Patients?  1037

88

1038  Chapter 88  Physician Health Practices and Lifestyle Medicine

After an hour or so, Verena would return home drenched in sweat but with a peaceful mind. She was able to create the much-needed distance and larger perspective that allowed her to continue working in the medical profession without sacrificing her own well-being. Six years later, she still runs, having completed several halfmarathons, a marathon, and a half-ironman distance triathlon. The sport has given her joy, a healthy body, and best of all, her most important outlet for stress. Thanks to running, she falls asleep happy and content every night.

88.6 A NEW, OBJECTIVE VIEW FROM ISRAEL’S LARGEST HMO Instead of merely relying on physicians’ self-reported counseling and preventive practices, the Healthy Doctor = Healthy Patient8 relationship was recently assessed through objectively measured clinical experiences. Frank et al.7 accessed complete vaccination and screening records from Clalit Health Services (CHS), Israel’s largest health maintenance organization, the electronic medical records of (a) primary care physicians who worked in and were also patients in CHS (n = 1,488), and (b) these CHS physicians’ adult patients (n = 1,886,791), Eight prevention-related (screening and immunization practices) quality health indicators were chosen: 1. Mammography in women 50–74 years of age 2. Colorectal cancer screening in patients 50–74 years of age 3. Low-density lipoprotein (LDL) measurement every five years for patients aged 35–54 and yearly among patients aged 55–74 years 4. Blood pressure measurement every five years for patients aged < 40 years 5. Blood pressure measurement every two years for patients 41–54 years 60

%



6. Blood pressure measurement annually for patients > 55 years 7. Pneumococcal vaccination among patients with a chronic illness and those > 65 years 8. Annual influenza vaccine among patients with chronic illness and those > 65 years

For all eight indicators, patients whose physicians were compliant with the preventive practices were more likely (p < 0.05) to also have undergone these preventive measures than patients with noncompliant physicians. The investigators also found that more closely related preventive practices showed an even more robust relationship.7

88.7 HEALTHIER PHYSICIAN HABITS: PATIENTS RESPOND As touched upon earlier, providers who disclose their healthy personal health practices are perceived as more credible and motivating; rates of prevention counseling increase and patients become more receptive to health promotion counseling from physicians who demonstrate healthy behaviors themselves. 21,47 Frank, Breyan, and Elon 21 conducted a small study (n = 130) in an Emory University general medical clinic waiting room. They randomized individuals to watch either a standard two-minute video from me (co-author Frank) on healthy diet and exercise habits or the standard video plus an extra 30 seconds divulging my personal health habits regarding diet and exercise. Patients found me in the “physician-disclosure” video to be significantly healthier (p = 0.004), also finding me more believable and more motivating overall. Specifically, regarding both diet and exercise, patients found the extra 30 seconds made me more believable on both diet and exercise (p = 0.006 and p = 0.002, respectively) and also more motivating on diet and exercise (p = 0.006 and p = 0.004, respectively). 21 Figures 88.1 and 88.2 exhibit these results in graph form.

DOCTOR’S HEALTH

50

• Control • Treatment

P=.0004

40 30

7.0

20 10 0

60

%

5.7 1.5

3.5

7.5

9.5

OVERALL BELIEVABILITY

%

OVERALL MOTIVATION

60

50

50

P=.107

40

7.4

30 20

1.5

3.5

5.5

7.5

40

P=.0002 7.3

30 20

6.8

10 0

5.5

10 9.5

0

6.3 1.5

3.5

5.5

7.5

9.5

Figure 88.1  Emory University waiting room study: doctor’s health, overall believability, and overall motivation.

88.9  The Healthy Doctor = Healthy Patient Project  1039 60

BELIEVABILITY / DIET

%

50

60 50

P=.006

40

7.4

30 20

40

1.5 %

3.5

5.5

7.5

9.5

MOTIVATION / DIET

7.6

30 6.6

0

60 50

P=.0060 7.2

30 20

1.5

3.5

5.5

7.5

9.5

MOTIVATION / EXERCISE

%

P=.0004

40

7.2

30 20

10 0

P=.002

40

10

6.4

0

50

BELIEVABILITY / EXERCISE

20

10

60

%

10

6.9 1.5

3.5

5.5

7.5

9.5

0

6.4 1.5

3.5

5.5

7.5

9.5

Figure 88.2  Emory University waiting room study: doctor’s believability with respect to (a) diet and (b) exercise, and doctor’s motivation with respect to (a) diet and (b) exercise.

88.8 DOES COUNSELING ACTUALLY MAKE A DIFFERENCE IN PATIENT OUTCOMES? Is counseling worth the time? Yes, since tobacco, diet, exercise, and alcohol account for about 40% of U.S. mortality, and counseling from one’s physician on these topics increases the likelihood that patients will act healthily. 23 Surely, then, physicians must be counseling their patients increasingly...and, if not, why not, and what can we do about it?

88.9 THE HEALTHY DOCTOR = HEALTHY PATIENT PROJECT The Healthy Doctor = Healthy Patient project was a five-year-long action research intervention, performed at Emory University School of Medicine and led by coauthor Frank, to improve medical student health, with the hypothesis that this could improve patient health. The scientific foundation of the Healthy Doctor = Healthy Patient principle is as follows: • North American physicians tend to live longer than their peers. • Physicians live longer because they have healthier habits (including as medical students) than their contemporaries. • Four behavioral choices (exercise, diet, alcohol, and tobacco) account for about 40% of U.S. mortality. 23 • Physicians and medical students with the healthiest habits are more likely to advise their patients about related preventive habits. • Appropriate physician revelation about healthy personal habits can make physicians more believable and motivating to patients.

• When medical schools encourage students to be healthy, it positively and significantly influences the students’ patient counseling frequency (p = 0.002) and their perceived relevance (p = 0.0007) of such counseling. • Counseling patients makes a difference in patients’ habits and in their health. • Despite all this, many physicians have areas of potential personal health improvement and do not perform prevention counseling at very high rates. To determine basic health practices and status, a survey was conducted of medical students (n = 2,316 individuals responding to ≥1 survey) in the Class of 2003 at freshman orientation, entrance to wards, and senior year in a nationally representative sample of 16 medical schools (response rate = 80.3%). Most medical students (84%) reported never having smoked cigarettes, and both genders typically drank two drinks per drinking episode (with bingeing more common among men). Students exercised a median of at least four hours per week and preferred strenuous exercise. Medical students across all years and both genders reported a median of seven hours of sleep per night. Nearly all (97%) reported their health to be at least good, typically with one or fewer days of poor physical or mental health in the past month. Both genders (particularly women) were unlikely to be overweight or obese. Reported rates of any chronic condition were ≤2% except for hypertension among men, and obesity, dyslipidemia, and depression in both genders. Unlike their other relatively positive behaviors compared with their peers, medical students had variable rates of preventive screening.8,48 Overall, medical students in the United States were healthy and reported many good health behaviors when compared with other young U.S. adults. However, for some, there was room for improvement, as health behaviors and personal health practices either did not meet national goals or placed students at risk.48 For example,

88

1040  Chapter 88  Physician Health Practices and Lifestyle Medicine

• Average daily fruit/vegetable consumption (2.5 servings) was as poor as that of their peers. • Binge drinking rates (25% females and 43% males) for the previous month were also poor, with no change over medical school (p = 0.5). • Unlike their other relatively positive behaviors as compared with their peers, medical students had low rates of preventive screening.

88.9.1 More on Medical Students and Personal–Clinical Relationships The Healthy Doctor = Healthy Patient relationship ideally begins with freshman medical student interventions: medical schools must concentrate on maximizing the growth of these ideals—and individuals—early on. For example, to determine personal and clinical exerciserelated attitudes and behaviors of freshmen U.S. medical students, Frank et al.49 looked at the 1,906 entering

freshman medical students (response rate = 87%; average age = 24 years) in the 17 U.S. medical schools surveyed. Students reported a median of 45 minutes per day of exercise, 80 minutes per week each of mild and moderate exercise, and 100 minutes per week of strenuous exercise. Nearly all freshman medical students (97.6%) engaged in some moderate or vigorous exercise in a typical week, with 64% complying with U.S. Department of Health and Human Services exercise recommendations. Most (79%) freshmen believed it would be highly relevant to their future practices to counsel patients about exercise; professional predictors included the intention to be a primary care provider, and personal predictors included excellent general health, a prevention emphasis by their personal physicians, and performing more strenuous exercise.49 The follow-up study by Frank et al. 2 reported predictors of multiple prevention counseling practices among U.S. medical students. These results are summarized in Table 88.5 and in Figure 88.3.

TABLE 88.5  Medical students: personal health behaviors vs. counseling frequency and perceived relevance Characteristic

Relevance (percent highly)

N

Alcohol consumption:

P-value

Frequency (percent usually/always)

N

0.003

0.2

  Heavy/Binge drinker

1,561

46

493

24

  Light to moderate

2,008

55

589

30

 None

1,015

62

291

32

Tobacco use in past month:  None

0.009

0.001

3,663

69

1,116

58

 Light/Infrequent

808

63

213

50

  > 10 cigarettes/day or   > 19 days any tobacco

156

58

57

47

Priority of practicing safe sex when sexually involved (sexually active singles):   < High  High

0.0006

0.004

512

46

190

10

1,552

59

369

21

Fruit and vegetable consumption, servings/day

0.0006

0.03

  ≥ 0 to ≤ 1.9

1,075

49

381

13

  > 1.9 to ≤ 2.7

1,062

61

307

15

  > 2.7 to ≤ 4.0

1,098

62

285

20

  > 4.0

1,055

70

266

24

Exercise score based upon Godin score quartiles

P-value

0.3

0.08

  ≥ 0 to ≤ 26

1,104

66

329

26

  > 26 to ≤ 41

1,085

69

294

33

  > 41 to ≤ 57

1,114

70

327

29

  > 57

1,053

71

323

36

Source: Erica Frank, Lisa K. Elon, Jennifer S. Carrera, et al., “Predictors of U.S. Medical Students’ Prevention Counseling Practices,” Preventive Medicine 44 (2007): 76–81.

88.9  The Healthy Doctor = Healthy Patient Project  1041

88

Figure 88.3  Medical students’ health habits (fruit/vegetable intake, physical activity, cigarette smoking, and drinking) and related counseling attitudes.

88.9.2 Study: Colombian Medical Students’ Healthy Personal Habits and Attitudes toward Preventive Counseling Physician-delivered preventive counseling is important for the prevention and management of chronic diseases. Data from the United States indicate that medical students with healthy personal habits have better attitudes toward preventive counseling. The following study, the first relating to this association in medical students in developing regions, examined the association between personal health practices and attitudes towards preventive counseling among first- and fifth-year students from 8 medical schools in Bogotá, Colombia.1,33. During 2006, a total of 661 first- and fifth-year medical students completed a culturally adapted Spanish version of the Healthy Doctor = Healthy Patient survey (response rate  = 78%). Logistic regression analyses were used to assess the association between overall personal practices on physical activity, nutrition, weight control, smoking, alcohol use (main exposure variable), and student attitudes towards preventive counseling on these issues (main outcome variable), stratified by year of training and adjusting by gender and medical training-related factors (basic knowledge, perceived adequacy of training, and perception of the school's promotion on each healthy habit). The median age and percentage of females for the firstand fifth-year students were 21 years and 59.5% and 25 years and 65%, respectively. After controlling for gender and medical training-related factors, the investigators found that the consumption of five or more daily servings of fruits and/or vegetables and not being a smoker or binge drinker were associated with a positive attitude toward counseling on nutrition (OR = 4.71; CI: 1.6–14.1; p = 0.006) smoking (OR = 2.62; CI: 1.1–5.9; p = 0.022), and counseling on alcohol (OR = 2.61; CI: 1.3–5.4; p = 0.009). Data for senior medical students (independent of gender and medical-related training factors) are seen in Table 88.6 below.1 As with the U.S. physician and medical students, a positive association was found between the personal health

TABLE 88.6  Personal health and perceived counseling relevance, senior medical students (n = 254), Bogotá, Colombia, 2007 Characteristic

Odds ratio

P-value

Consumption of ≥ 5 fruits/vegetables per day

4.7

0.006

Physical activity ≥ 150 minutes/week (moderate-to-vigorous physical activity)

1.7

0.3

Non-smoker status

2.6

0.02

Abstinence from alcohol

2.6

0.009

Source: John Duperly, Felipe Lobelo, Carolina Segura, et al., “The Association between Colombian Medical Students’ Healthy Personal Habits and a Positive Attitude toward Preventive Counseling: Cross-sectional Analyses,” BMC Public Health 9 (2009): 218.

habits of Colombian medical students and their corresponding attitudes toward preventive counseling, independent of gender and medical training-related factors. Importantly, these findings also suggest that within the medical school context, interventions focused on promoting healthy student lifestyles can potentially improve these future physicians’ attitudes toward preventive counseling.

88.9.3 Intervention for Medical Students: A Large-Scale Case Study Our analysis and quantitative assessment of our four-yearlong intervention did, in fact, indicate that the intervention had promoted healthy physical habits among medical students.8,9 The class of 2003 (using the class of 2002 as a control) at Emory University School of Medicine was extensively studied after various interventions were performed throughout their schooling; several specifics are provided in this section to provide potentially useful ideas for other institutions. Curricular and extracurricular interventions for firstyear medical students included the following8: • Orientation lecture on Healthy Doctor = Healthy Patient principles.

1042  Chapter 88  Physician Health Practices and Lifestyle Medicine

• Anatomy manual on muscles and related exercises. • Use of students’ own data in biostatistics class and for homework. • Student presentations on physician health in small group sessions. • Lunchtime panels (with free, healthy lunch) on wellbalanced, integrated lifestyles • A “healthy quick cooking” class. • Personal health prescriptions provided to students subsequent to lifestyle review. • Hike and healthy dinner at energy-independent mountain lodge. Curricular and extracurricular activities for secondyear medical students included the following8: • Working with Problem-based Learning mentors on Healthy Doctor = Healthy Patient concept. • Pathophysiology of hepatic disease, lecture on personal practices. • Behavioral science, one-hour talk on medical student alcohol/tobacco use. • Behavioral science, physician panel of former substance users. • Nutrition course, plant-based diet lecture. • Exercise elective and seminar. • Monthly walks/runs. • Sponsored entrance fees for races. • Wine-tasting seminars to teach about more appropriate use surrounding alcohol. • “Health Heads Up,” a monthly emailed summary of a half-dozen prevention-related studies written by classmates. • Weekly yoga classes. • Healthy breakfasts before exams. • Healthy Asian cooking class. • Massage with free lunch (talk and demo), with data on physiological effects of massage. • Principal investigator presented Healthy Doctor = Healthy Patient at Student National Medical Association meeting in Atlanta. • Lunchtime yoga/meditation seminar by visiting doctor on the health and psychological effects of yoga and meditation (free healthy lunch provided). • Personal health prescriptions provided to students subsequent to lifestyle review. • Lunchtime talk (free healthy lunch provided) on pathophysiology of stress and what can be done about it. Curricular interventions offered for third- and fourthyear medical students included8: • All clerkships: Dr. Frank (principal investigator) met with clerkship directors, encouraging healthy food on occasions (e.g. morning Grand Rounds, lunchtime didactics) where food would typically be offered to the students, and at least one additional clerkship-based personal health promotion activity for the medical students.

• Dermatology: letter on the importance of skin cancer prevention for themselves and their patients, a review article on skin cancer-prevention strategies, and a container of sunscreen for their own use. • Ethics/Medicine: completed advanced directives and living wills for themselves. • Ethics/Psychiatry: completed a Beck Depression Inventory and an alcohol (CAGE) screening questionnaire on themselves. • Family/internal medicine: tobacco lecture, instruction, and practice with health-risk appraisals (HRAs), model counseling. • Family medicine: students (and occasionally preceptors) kept one-week logs of daily number of fruits/ vegetables and exercise amount/type; students wrote descriptions of their ideal lifestyle a decade hence. • Gynecology/Obstetrics: articles assigned on women physicians’ characteristics during pregnancy, sexual abuse/domestic violence rates, and depression/suicide rates; students given American Cancer Society breast self-exam shower card; students given condoms and emergency contraception offered (as requested). • Pediatrics: presentation on personal health practices on rotation and in life. • Psychiatry: suicide and depression article. • Surgery: presentation on personal health practices of director. • Validation project: validation study for food-frequency screener, including five in-person, 24-hour recalls; two food-frequency questionnaires; personal analysis of fat and fruit–vegetable intake. In this four-year controlled trial addressing lifestyle behaviors over the course of medical school, the final analysis found that medical students had made improvements in their personal health practices. For instance, control group males increased their use of tobacco products between ward orientation and their senior year, while intervention group males decreased their use—the control males reported twice the tobacco use reported by males in the intervention (43% vs. 22%, p = 0.02) even though the two groups had previously reported very similar levels (31% vs. 29%, p=0.8). 5,9 Importantly, students’ diet counseling and exercise counseling (as reported by standardized patients) were also strongly positively related to the intervention.9 Observational Healthy Doctor = Healthy Patient study hypotheses were confirmed: • Medical students were healthy and reported many good health habits when compared with other young U.S. adults. • Medical schools’ encouragement of students to be healthy significantly influences students’ patient counseling frequency (p = 0.002) and perceived relevance (p = 0.0007) of such counseling.8 • Medical students’ personal health practices are correlated with their counseling frequency (p < 0.0001) and perceived relevance (p = 0.008). 2

Clinical Applications  1043 TABLE 88.7  Effect of student interventions upon the frequency of counseling patients during their examinations: extensive vs. minimal/no counseling (adjusted for gender, intended specialty, and agreement, at baseline, with the statement “Physicians have a responsibility to promote prevention”) Crude odds ratio (95% confidence interval)

Adjusted odds ratio (95% confidence interval)

P value from adjusted odds ratio

Diet

1.49 (1.04–2.12)

1.49 (1.01–2.19)

0.04

Exercise

1.65 (1.16–2.35)

1.56 (1.04–2.34)

0.03

Topic

A medical student-focused health promotion intervention can improve students’ self-reported personal health behaviors, their perceptions of the healthfulness of their medical school environment, and their (objectively measured) standardized patient prevention counseling practices.9 Likewise, the comprehensive study by Frank et al. 2 found that students reporting a healthier medical school environment also reported highly significantly better patient counseling practices. The remarkable effect of student interventions upon the frequency of their patient counseling is exhibited in Table 88.7. These findings suggest that further refinements and broader implementation of interventions such as those discussed in this chapter could be efficient and valuable methods to improve the health of healthcare professionals and the vast populations of patients they serve.

88.10 INTERVENTION FOR PHYSICIANS Although physicians’ and medical students’ personal health practices are better than those of the general population (at least in Canada and the United States), multiple studies suggest the need to further foster physicians’ personal preventive practices, both to promote the personal health of physicians themselves and to improve outcomes for their patients. In addition, such programs need to be studied in order to determine how best to actively encourage physician health and, correspondingly, the Healthy Doctor = Healthy Patient association.7,8 To date, this chapter’s authors know of no such published studies, although we are now collaborating with Bar-Ilan University’s (in Safed, Israel) medical school and with www.NextGenU.org’s (in >200 countries) free, accredited Lifestyle Medicine course on such a study. We look forward to encouraging and enabling other such interventions—particularly with readers of this chapter interested in such (Erica.Frank@ ubc.ca, [email protected], and EFrank@NextGenU. org being enduring emails for such purposes).

88.11 BOTTOM LINE The health of North American health among both physicians and medical students. Especially when looking through the lens that shows a healthy doctor is more likely

to produce a healthy patient, physicians’ health status takes on paramount importance. The medical and healthcare communities, along with North American universities, must implement new approaches to achieve these goals. As physicians, we must (a) discuss ways to simultaneously improve our health and that of our patients, and (b) consider the most important new questions to ask regarding physician health. We must take care of ourselves as well as our patients: when we do, we will witness more positive personal health outcomes for all concerned. Physician health is rarely systematically promoted anywhere in the world, suggesting that policy-makers believe that physicians are already adequately supported. In the few places where support programs for physicians exist, they concentrate heavily on suitability and competence to practice, on mental health and illness (especially around substance abuse), and on practice-related psychological motivation and physical stamina. The medical profession needs to do more than this; however—a failure to miss these opportunities is also a failure to efficiently improve the health of everyone in the system.7

CLINICAL APPLICATIONS These findings should encourage leaders to test various ways to address and promote the following: • Physician health, including and especially as a way to encourage patient health. • Recognition that a physician’s patient counseling is strongly related to the physician’s own health practices. • Medical student health, through efforts to ensure medical schools, produce healthy doctors and avid preventionists. 50 • Healthcare systems that promote and support physician health around the globe. • Recognition that physicians can positively influence patient health by counseling patients on prevention and health-promoting behaviors. • The health of entire patient populations, which profit from more efficient and effective health promotion counseling. 5 • Further exploration of the correlations between physicians’ healthy personal habits and preventionrelated counseling and screening, which should encourage new directions for physician training.

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REFERENCES 1. Duperly J, Lobelo F, Segura C, et al. The association between Colombian medical students’ healthy personal habits and a positive attitude toward preventive counseling: Cross-sectional analyses. BMC Public Health 2009;9:218. Available from: https://doi. org/10.1186/1471-2458-9-218 2. Frank E, Elon LK, Carrera JS, et al. Predictors of U.S. medical students’ prevention counseling practices. Prev. Med. 2007;44:76–81. 3. Frank E, Rothenberg R, Lewis C, et al. Correlates of physicians’ preventionrelation practices. Findings from the Women’s Physicians Health Study. Arch. Fam. Med. 2000;9:359–367. 4. Frank E, Segura C, Shen H, et al. Predictors of Canadian physicians’ prevention counseling practices. Can. J. Public Health 2010;101:390–395. 5. Oberg EB and Frank E. Physicians’ health practices strongly influence patient health practices. J. R. Coll. Physicians Edinb. 2009;39(4):290–291. Available from: https​: //ww​w.ncb​i.nlm​.nih.​gov/p​mc/ar​ ticle​s /PMC​30585​99 6. Wells KB, Lewis CE, Leake B, et al. Do physicians preach what they practice? A study of physicians’ health habits and counseling practices. JAMA 1984;252:2846–2848. 7. Frank E, Dresner Y, Shani M, et al. The association between physicians’ and patients’ preventive health practices. CMAJ 2013. Available from: https://doi. org/10.1503/cmaj.121028 8. Frank E, Smith D, and Fitzmaurice D. A description and qualitative assessment of a 4-year intervention to improve patient counseling by improving medical student health. Med. Gen. Med. 2005;7(2):4. Available from: https​: //ww​w.ncb​i.nlm​ .nih.​gov/p​mc/ar ​ticle​s /PMC​16815​78 9. Frank E, Elon L, and Hertzberg V. Quantitative assessment of a 4-year intervention that improved patient counseling through improving medical student health. Med. Gen. Med. 2007;9(2):58. Available from: http:​//www​.meds​cape.​ com/v​iewar​ticle ​/5570​88 10. Frank E, Biola H, and Burnett CA. Mortality rates and causes among U.S. physicians. Am. J. Prev. Med. 2000;19(3):155–159. 11. Williford HN, Barfield BR, Lazenby RB, et al. A survey of physicians’ attitudes and practices related to exercise promotion. Prev. Med. 1992;21:630–636. 12. Frank E, Brogan DJ, Mokdad AH, et al. Health-related behaviors of women physicians vs. other women in the United States. Arch. Intern. Med. 1998;158(4):342–348. 13. Centers for Disease Control and Prevention. Physician advice and individual behaviors about cardiovascular disease risk reduction—Seven states and Puerto Rico, 1997. MMWR Morb. Mortal. Wkly. Rep. 1997;48(4):74–77. Available from: https​: //bi​otech​.law.​lsu.e​ du/bl​aw/bt ​/mm48​0 4.pd​f 14. Abramson S, Stein J, Schaufele M, et al. Personal exercise habits and counseling practices of primary care physicians: A national survey. Clin. J. Sport Med. 2000;10:40–48.

15. Frank E. The Women Physicians’ Health Study: Background, objectives, and methods. J. Am. Med. Wom. Assoc. 1995;50:64–66. 16. Frank E, Wright EH, Serdula MK, et al. Personal and professional nutrition-related practices of U.S. female physicians. Am. J. Clin. Nutr. 2002;75:326–332. 17. Frank E, Bhat-Schelbert K, and Elon LK. Exercise counseling and personal exercise habits of U.S. women physicians. J. Am. Med. Wom. Assoc. 2003;58:178–184. 18. Frank E and Segura C. Health practices of Canadian physicians. Can. Fam. Physician 2009;55(8):810–811. Available from: http://www.cfp.ca/cgi/ reprint/55/8/810 19. Frank E. Physician health and patient care. JAMA 2004;291:637. 20. Vickers KS, Kircher KJ, Smith MD, et al. Health behavior counseling in primary care: Provider-reported rate and confidence. Fam. Med. 2007;39:730–735. 21. Frank E, Breyan J, and Elon LK. Physician disclosure of healthy personal behaviors improves credibility and ability to motivate. Arch. Fam. Med. 2000;9(3):287–290. 22. Lewis CE, Wells KB, and Ware J. A model for predicting the counseling practices of physicians. J. Gen. Intern. Med. 1986;1:14–19. 23. Mokdad AH, Marks JS, Stroup DF, et al. Actual causes of death in the United States, 2000. JAMA 2004;291(10):1238–1245. 24. Walsh JM, Swangard DM, Davis T, et al. Exercise counseling by primary care physicians in the era of managed care. Am. J. Prev. Med. 1999;16:307–313. 25. Lewis CE, Clancy C, Leake B, et al. The counseling practices of internists. Ann. Intern. Med. 1991;114:54–58. 26. Epel OB and Ziva RM. Quality and correlates of physical activity counseling by health care providers in Israel. Prev. Med. 2000;31:618–626. 27. Glasgow RE, Eakin EG, Fisher EB, et al. Physician advice and support for physical activity: Results from a national survey. Am. J. Prev. Med. 2001;21:189–196. 28. van der Ploeg HP, Smith BJ, Stubbs T, et al. Physical activity promotion: Are GPs getting the message? Aust. Fam. Physician 2007;36:871–874. 29. Frank E and Holmes D. Exercise, physician health, and healthy patients. In: Weiss Roberts L, editor. The Handbook of Personal Health and Wellbeing for Physicians and Trainees. New York (NY): Springer. 2018. 30. Buffart LM, van der Ploeg HP, Smith BJ, et al. General practitioners’ perceptions and practices of physical activity counselling: Changes over the past 10 years. Br. J. Sports Med. 2008. 31. Chevan J and Haskvitz EM. Do as I do: Exercise habits of physical therapists, physical therapist assistants, and student physical therapists. Phys. Ther. 2010;90(5):726–734. Available from: https://doi.org/10.2522/ptj.20090112 32. Clair JH, Wilson DB, and Clore JN. Assessing the health of future physicians: An opportunity for preventive education. J. Contin. Educ. Health Prof. 2004;24:82–89.

33. Duperly J, Lobelo F, Segura C, et al. Personal habits are independently associated with a positive attitude towards healthy lifestyle counseling among Colombian medical students. Circulation 2008;117:198–291. 34. Duperly J, Segura C, Herrera DM, et al. Medical students’ knowledge on physical activity counseling is associated with their physical activity levels. Med. Sci. Sports Exerc. 2008;40(5):S251. 35. Frank E, Tong E, Lobelo F, et al. Physical activity levels and counseling practices of U.S. medical students. Med. Sci. Sports Exerc. 2008;40(3):413–421. 36. Garry JP, Diamond JJ, and Whitley TW. Physical activity curricula in medical schools. Acad. Med. 2002;77:818–820. 37. Lobelo F, Duperly J, and Frank E. Physical activity habits of doctors and medical students influence their counseling practices. Br. J. Sports Med. 2008. 38. Najem GR, Passannante MR, and Foster JD. Health risk factors and health promoting behavior of medical, dental and nursing students. J. Clin. Epidemiol. 1995;48:841–849. 39. Orleans CT, George LK, Houpt JL, et al. Health promotion in primary care: A survey of U.S. family practitioners. Prev. Med. 1985;14:636–647. 40. Peterson DF, Degenhardt BF, and Smith CM. Correlation between prior exercise and present health and fitness status of entering medical students. J. Am. Osteopath. Assoc. 2003;103:361–366. 41. Podl TR, Goodwin MA, Kikano GE, et al. Direct observation of exercise counseling in community family practice. Am. J. Prev. Med. 1999;17:207–210. 42. Reed BD, Jensen JD, and Gorenflo DW. Physicians and exercise promotion. Am. J. Prev. Med. 1991;7:410–415. 43. Rogers LQ, Gutin B, Humphries MC, et al. A physician fitness program: Enhancing the physician as an “exercise” role model for patients. Teach. Learn. Med. 2005;17:27–35. 44. Sherman SE and Hershman WY. Exercise counseling: How do general internists do? J. Gen. Intern. Med. 1993;8:243–248. 45. Wee CC, McCarthy EP, Davis RB, et al. Physician counseling about exercise. JAMA 1999;282:1583–1588. 46. Wells KB, Lewis CE, Leake B, et al. The practices of general and subspecialty internists in counseling about smoking and exercise. Am. J. Public Health 1986;76:1009–1013. 47. Rogers LQ, Gutin B, Humphries MC, et al. Evaluation of internal medicine residents as exercise role models and associations with self-reported counseling behavior, confidence, and perceived success. Teach. Learn. Med. 2006;18:215–221. 48. Frank E, Carrera JS, Elon L, et al. Basic demographics, health practices, and health status of U.S. medical students. Am. J. Prev. Med. 2006;31(6):499–505. 49. Frank E, Galuska DA, Elon LK, et al. Personal and clinical exercise-related attitudes and behaviors of freshmen U.S. medical students. Res. Q. Exerc. Sport. 2004;75:112–121. 50. Frank E. Osler was wrong: You are a preventionist. Am. J. Prev. Med. 1991;7:128.

XV PA RT

Substance Abuse and Addiction Elizabeth Pegg Frates, MD and Joji Suzuki, MD

1045

89 CHAPTER

Introduction to Addiction Section Joji Suzuki, MD, Elizabeth Pegg Frates, MD, and Irena Matanovic

Key Points................................................................................ 1047 Clinical Applications................................................................. 1049

KEY POINTS • People suffering from addiction or substance use disorders are not getting the help they require to tackle their medical problem. • People with addiction problems are similar to people with hypertension and diabetes in that they need specialized care and diagnosis as the first step. • All clinicians, including Lifestyle Medicine practitioners, need to become familiar with the signs, symptoms, and diagnosis and treatment options for those people suffering from substance use disorders. Given that smoking is a major cause of disease leading to heart disease and cancer, two of our major killers, it is important for Lifestyle Medicine practitioners to be comfortable with the identification, diagnosis, treatment, and counseling strategies that are most effective for people suffering from addictions. Mokdad and colleagues pointed out that smoking was the number one “actual cause of death” in the United States in his landmark article published in JAMA in 2004.1 On that same list of actual causes of death is alcohol and illegal drugs. Lifestyle Medicine practitioners are going to treat patients who are smoking, who are drinking, who are using cannabis, and who are using opioids. Knowing the treatment options, identifying people in need of assistance, and recommending appropriate follow up are all important aspects of Lifestyle Medicine practice. There are assessment tools that can be used prior to the clinic visit. In addition, there is a methodology of counseling patients that will open up the conversation for discussions about these habits, which are often hidden from physicians. Patients and family members are in denial themselves, in many cases. Thus, the role of the Lifestyle Medicine practitioner is to be a non-judgmental source of information, inspiration, and support for those individuals who are struggling to stay drug- or alcohol-free. There are addiction specialists who have for trained years in order to effectively help people who are using tobacco, alcohol, and drugs to excess or in a way that is causing themselves harm physically or emotionally. Many psychiatrists, psychologists, social workers, nurses, and

References.............................................................................. 1049

other health care professionals are focusing on this population of patients every day. Knowing about the clinicians who specialize in addictions and the resources available through the hospital and community centers, becoming familiar with medications that may help people stay drug free, identifying technologies that can assist patients, and understanding the value of rehabilitation centers is essential for Lifestyle Medicine practitioners in order to help their patients embrace healthy living. People might be eating a healthy diet and exercising, but they may also be drinking too much. Because substance use disorders can be missed and purposefully hidden, Lifestyle Medicine practitioners will be one step ahead after reading this section. This is a new section in this third edition of the textbook. It is evidence that the editors are staying current with the times and feeding practitioners cutting-edge information. The naming of this field of medicine has been a source of controversy and even the definition of addiction is something that is not agreed upon by all providers and patients. The history of addictions is reviewed in the chapter entitled, “History of Alcohol and Opioid Use and Treatment in the United States.” The current favored term and the one used in the DSM is “Substance Use Disorders.” Substance Use Disorders (SUD) refers to a group of disorders that involve the compulsive and repeated use of substances that are associated with negative physical and psychological health consequences. 2 Historically, Lifestyle Medicine practitioners have not been routinely involved with the assessment and management of SUDs. However, in the context of the growing opioid crisis and the continued contribution of SUD to adverse health outcomes, every clinician should be aware of the epidemiology, approach to diagnosis, and the basics of SUD treatment. While not every clinician can provide the full spectrum of SUD treatments, it is imperative that clinicians have the basic knowledge and skills necessary to identify and diagnose SUD, provide basic treatment where appropriate, and refer to local community resources. Today, a variety of effective evidence-based pharmacologic and psychosocial services are available that healthcare providers can utilize in their day-to-day practice. Considering the degree to which SUDs are common in clinical populations, as well as the negative impact 1047

1048  Chapter 89  Introduction to Addiction Section 

to patients, families, employers, and communities, clinicians can no longer opt out of providing these basic services to patients. There is a long history of humans using a variety of substances for both therapeutic and recreational purposes, which is outlined in the chapter entitled “History of Alcohol and Opioid Use and Treatment in the United States.” The World Health Organization has recognized that substance use remains one of the most common contributing factors to premature death (in the year 2000, alcohol, tobacco, and illicit drug use contributed together to 12.4% of all deaths worldwide) as well as other medical, psychiatric complications that reduce quality of life and contribute to a heavy economic burden through lost productivity, criminal justice costs, and health care costs.3 Today, SUD continues to be a major public health problem in the United States, with over 19 million Americans ages 18 and older (7.8%) suffering from some form of SUD in 2016.4 A national epidemiologic survey of alcohol and related conditions estimated that lifetime prevalence of alcohol-related disorders is 20.3% and drug use-related disorders is 10.3%. 5 When separated out by gender, males experience SUD at much higher rates (10.7% of U.S. males) compared to females (5.7% of U.S. females).6 The typical age at which individuals begin to meet criteria for a SUD is during young adulthood, ages 18-25. At this age, due to the insufficient development of their frontal lobes, individuals are less able to inhibit risk behaviors and are at heightened risk from developing a SUD. Tobacco remains the most commonly used substance that is associated with considerable morbidity and mortality. While the rate of tobacco use has declined over the past several decades, 28.5% of Americans continue to engage in the regular use of tobacco products.4 More than 480,000 deaths annually are attributable to tobacco use, far overshadowing deaths from all other substance use combined.7 Behavioral approaches to tobacco use disorder is addressed in the chapter, “Behavioral Approaches to Enhancing Smoking Cessation.” Alcohol is also frequently consumed in the U.S., with 86.4% of the population consuming alcohol at least occasionally at some point in their lifetime.8 Among those who do consumed alcohol regularly in 2014, about 60.9 million (26.9% of the U.S. population) reported binge drinking (defined as drinking more than five [for men] or four [for women] or more drinks in one occasion) and 16.3 million (7%) reported heavy drinking (defined as binge drinking on five or more days in the past month).8 Binge drinking is an important contributing factor to injuries, such as falls and motor vehicle accidents. In that same year, 6.2% of individuals 18 years and older meet criteria for an alcohol use disorder,6 which causes additional harm to the individual by damaging all organ systems in the body but with a particular focus on the neurologic and cardiovascular systems. The approach to the diagnosis and treatment of alcohol use disorders is presented in the chapter entitled, “Alcohol Use Disorders: Diagnosis and Treatments.” Illicit drugs such as cocaine, prescribed medications such as oxycodone and benzodiazepines, and cannabis (now legal in some states) are also used frequently in the U.S., with approximately 10.2% of individuals in 2014 engaging in the regular use of such substances.6 While the

use of heroin and cocaine have existed in the U.S. for the better part of the 20th century, there has been an alarming rise in the non-medical use of prescription medications in the last two decades.9 This has led to an unprecedented rise in the number of overdose deaths due to misuse of prescription opioids and benzodiazepines. More recently, the misuse of illicitly produced synthetic opioids such as fentanyl has further contributed to the growing number of individuals unintentionally overdosing. The approach to the diagnosis and treatment of opioid use disorders is covered in the chapter entitled, “Diagnosis and Treatment of Opioid Use Disorder.” Cannabis Use Disorder and Treatment is also reviewed in the chapter by Dr. Hasin. Unfortunately, despite the high prevalence of SUDs in the U.S., addiction treatment has been largely fragmented from general medical treatment. A typical patient with SUD seeking help would not receive any substantial assistance from their healthcare provider. A typical primary care physician is well equipped to handle most of the common illnesses that patients suffer from, including diabetes, obesity, and hypertension. In the context of the growing opioid crisis, this discrepancy in the ability of the health care system to help those suffering from SUDs has been exposed. A major contributing factor for this failing stems from considering SUD as a moral failing and criminal behavior per se, which has led to a disproportionate use of law enforcement approaches to reduce substance use. Instead of offering treatment, individuals with SUD were punished for their substance use. Fortunately, as the scientific understanding of SUD increased, there has been a shift from the law enforcement approach to the public health approach. Instead of criminalizing the behavior, the growing evidence base points to SUD as a chronic disease, not unlike diabetes or hypertension. Treatment for SUD has a considerable impact on the individual, but it requires ongoing treatment and management of the underlying illness. As in diabetes treatment, there is no cure for SUD even if there is a cessation of substance use. Once SUD develops, the individuals remain at heightened risk of relapse, and ongoing attempts at preventing relapse are necessary. As such, a critical component of treatment involves ensuring that patients are engaged with their own treatment. One possible strategy for this is to incorporate mobile applications and smartphones to increase patient self-efficacy in managing their SUD. The chapter “Smartphone-Based Technologies in Addiction Treatment” presents an overview of using smartphone apps to help support individuals with SUD. In addition, the chapter on “Psychosocial Interventions for Treatment of Substance Use Disorders” reviews a variety of psychosocial services and peer supports that patients can utilize to support their recovery in the long-term. Healthcare providers of all disciplines have historically been provided with sub-optimal education on SUDs. This meant medical schools devoted minimal time to teaching the diagnosis and treatment of SUDs and employed few faculty members who were experts on SUD. In graduate medical education, only psychiatry residents are required to complete any rotation in addiction. To this day, internal medicine residents are not required to complete any dedicated rotation in addiction medicine. The limited exposure to addiction education as well as the limited number

References  1049

of preceptors and mentors experienced in the treatment of SUD has meant that entire generations of physicians are ill-equipped to diagnose and treat SUD once they begin practicing. As such, the chapters in the Addiction section are meant to provide a succinct overview of the common SUD encountered by clinicians in their practice and cover the basics of assessment and treatment of these conditions.

CLINICAL APPLICATIONS • This addiction section is new to the lifestyle medicine textbook, and it is an important one as people with addictions are often hiding or masking their

problems when speaking with primary care physicians or other clinicians. • Knowing how to recognize different substance use disorders will save the Lifestyle Medicine clinician time because patients trying to manage an addiction can be pre-occupied with that substance (like nicotine for smokers) and thus have difficulty adopting other healthy habits. • It is possible that Lifestyle Medicine clinicians might be the clinicians that patients choose to share their addiction history with after rapport has been created and trust developed. For this reason, these clinicians need to be well versed in substance use disorder diagnosis and treatment.

REFERENCES 1. Mokdad AH, James S, Marks M, Stroup DF, and Gerberding JL. Actual causes of death in the United States, 2000. JAMA 2004;291(10):1238–1245. 2. American Psychiatric Association. Substance Use Disoders. Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Washington, DC. 2013. 3. World Health Organization. The global burden. Substance abuse. 2018. Available at: http: ​//www​.who.​i nt/s​ubsta​nce_a​buse/​ facts ​/glob​al_bu ​rden/​en/. 4. Park-Lee E, Lipari RN, Hedden SL, and Kroutil LA. Receipt of Services for Substance Use and Mental Health Issues Among Adults: Results from the

2016 National Survey on Drug Use and Health. NSDUH Data Review. 2017. 5. Merikangas KR and McClair VL. Epidemiology of substance use disorders. Hum. Genet. 2012;131:779–789. . Center for Behavioral Health Statistics 6 and Quality. Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health. HHS Publication No. SMA 15-4927, NSDUH Series H-50. 2015. 7. U.S. Department of Health and Human Services. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Atlanta, GA. 2014.

8. National Institute of Alcohol Abuse and Alcoholism. Alcohol Use in the United States. Alcohol Facts and Statistics. June 2017. Available at: https​: //pu​bs.ni​aaa.n​ ih.go​v/pub​licat​ions/​A lcoh​olFac​ts&St​ats/ A ​lcoho​l Fact​s&Sta​ts.ht​m. 9. Volkow ND. America’s Addiction to Opioids: Heroin and Prescription Drug Abuse (Testemony to Congress). National Institute on Drug Abuse, 2014. https​: //ww ​w.dru​gabus​e.gov​/abou​t-nid​a / leg​islat​ive-a​c tivi​ties/​testi​mony-​to-co​ngres​ s/201​6/ame​ricas​-addi​c tion​-to-o​pioid​s-her​ oin-p​rescr​iptio​n-dru​g-abuse.

89

90 CHAPTER

History of Alcohol and Opioid Use and Treatment in the United States Sanchit Maruti, MD, MS and Steven A. Adelman, MD

Key Points................................................................................ 1051 90.1 Alcohol........................................................................... 1051 90.2 Opioids........................................................................... 1052 90.3 Adverse Effects of Legal and Societal Changes on Addiction Treatment ....................................................... 1053

KEY POINTS

90.4  A Revival of Addiction Treatment in America.................... 1053 90.5 Summary........................................................................ 1054 Clinical Applications................................................................. 1055 References.............................................................................. 1055

90.1 ALCOHOL

• Perceptions of substance use have evolved over time from widespread use and social acceptance, then to restriction and stigmatization, and now to recognition as a neurobiological phenomenon. • Social, legal, and medical responses to addiction have had a significant impact on individuals and society. • Understanding the historical basis of addiction and treatment can assist us in integrating traditional medical management with the growing knowledge of lifestyle therapeutic approaches for the wellbeing of the individual. “Whereof what’s past is prologue” - William Shakespeare, Scene 1, The Tempest Human history is replete with the use of intoxicating and potentially addictive substances in various cultures in different epochs of time. Archeologic evidence suggests that alcohol has been consumed by humans over the past 9,000 years and opium over the past 8,000 years. These substances have been used in religious practices, for recreation, and for their medicinal properties. Over the past several centuries technological innovations, such as distillation, chemical synthetic processes, and the invention of the hypodermic syringe have increased the potency and availability of these substances and streamlined delivery into the body. Today, alcohol and opioid use disorders are responsible for significant morbidity and mortality throughout the world. With improved understanding of the neurobiological basis of addiction, Lifestyle Medicine approaches can potentially contribute to prevention and recovery.

The earliest record of excessive use of alcohol as an illness was described during the 5th century by Heroditus. At the beginning of the colonization of America, alcohol was consumed by men, women, and children throughout the day as the fresh water supply was not often safe for consumption. Colonists adhered to the traditional belief that distilled spirits were aqua vitae or water of life. Over the next 200 years, alcohol was routinely consumed in general society. Between 1780 and 1830, there was a proliferation of distilleries resulting in a tripling of per-capita consumption of alcohol. Even the first president of the United States, George Washington, was actively involved in making alcohol. In fact, in 1799, the year of George Washington’s death, his distillery produced nearly 11,000 gallons of spirits, making it the largest whiskey distillery in America at the time. Despite this widespread acceptance, excessive consumption of alcohol was causing increasing concern. Early Native American tribes used plant-based medicinals to decrease cravings and induce aversion to alcohol. In 1774, the abolitionist and educator Antoine Bénézet warned of alcohol as a “poison” and in 1784, Dr. Benjamin Rush wrote the “Inquiry into the effects of ardent spirits on the human mind and body.” In this work, he described the symptoms and progression of excessive alcohol use. Additionally, Dr. Rush was one of the first physicians to recognize that excessive alcohol use was an illness that required medical treatment. He believed that the properties of alcohol, rather than the choice of the individual are responsible for the illness. He was an advocate for humane treatment and argued that individuals with this condition can be restored to full health with a return to society through proper medical treatment. These concerns and recommendations from important societal

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figures led to the beginning of the American Temperance movement. During the 19th century there emerged increasing medical evidence of the harms caused by excessive drinking, including the recognition of delirium tremens in 1813 by Dr. Thomas Sutton, the identification of the triad of ophthalmoplegia, ataxia, and confusion by Dr. Carl Wernicke, and the description by Dr. Sergei Korsakoff of memory defects and confabulation associated with chronic, excessive alcohol use. By mid-century, there was increasing recognition of excessive alcohol use as a medical condition. In 1849, Dr. Magnus Huss compiled the chronic effects of intoxication and formulated the term “Alcoholism.” Concurrently there was growing social support for the establishment of physician-directed inebriate asylums to provide specialized residential care. In 1864, the New York State Inebriate Asylum opened, and by the late 1870s, large hospitals such as Bellevue created inebriate wards to provide care for patients in urban settings. It is noteworthy that during this time many patented medications for treating addiction contained alcohol, cocaine, morphine, or opium. The diagnostic term that emerged from the medical field in the 19th century was “inebriety” with further specifications based on the substance of interest. One of the earliest addiction organizations, the American Association for the Cure of Inebriety (AACI) was created in 1870. This organization held regular meetings and published the first specialized medical journal, Journal of Addiction. The founding principles of the AACI appear now to have been remarkably forward thinking and recognized “inebriety” as a curable disease that was either inherited or acquired. They advocated for the civil authorities to support the establishment of specialized treatment facilities for the scientific treatment of inebriety in place of penal methods.1 The growing evidence of the medical etiology of addiction encouraged the American Medical Association (AMA), which was founded in 1847, to support the creation of the American Medical Temperance Association (AMTA) in 1891. As the historian William White summarizes, “The field of addiction medicine experienced professionalism and specialization between 1830 and 1900.” Thus, the approach to addiction in America in the 18th and 19th centuries was formed by the combined influences of medicine, morality, and social activism. 2 Despite the medical progress, during the same time in 19th century America, momentum was building for connecting excessive alcohol use to a moral failing. In 1826, the American Temperance Society was formed with the premise of reducing alcohol use rather than complete abstinence. In 1827, Reverend Lyman Beecher published, “Six sermons on the nature, occasion, signs, and remedy of intemperance.” He described the individual who excessively used alcohol as “addicted to sin.” He championed the concept of abstinence on an individual and societal level. The 1830s saw the emergence of the Teetotalism which promoted complete abstinence from all alcoholic beverages. Mutual Aid Groups first started in the 18th Century with early Native American recovery circles. In 1840, the Washingtonian Movement was founded by six individuals who had achieved sobriety from former

alcohol use. The premise was that a fellowship of individuals could support each other’s sobriety by conducting outreach to individuals who were struggling with excessive alcohol use, relying on each other, sharing their experiences with alcohol and nurturing an environment of comradery. These principles were eventually incorporated in the Alcoholics Anonymous organization.

90.2 OPIOIDS Opium is derived from the poppy Papaver somniferum and contains the opiates morphine and codeine. The first references to opium cultivation are from 6000 BC in lower Mesopotamia. Opium’s use spread to different parts of the world with evidence from an Egyptian papyrus of cultivation in Egypt in 1500 BC. In 460 BC, Hippocrates noted the usefulness of opium for treating internal diseases, epidemics, and diseases of women. In the 16th century, Paracelsus created laudanum, which was a tincture of opium for the treatment of pain. In the 17th century, Dr. Thomas Syndenham, renowned as the “English Hippocrates,” compounded a proprietary form of laudanum and promoted it for a variety of medical conditions. The use of opium and laudanum soon became widespread in Europe and America for the treatment of cardiac ailments, infectious diseases, mental conditions, and pain by patients of all ages, including children. In 1804, Friedrich Sertürner isolated morphine (after the Greek god of dreams, Morpheus) from opium, and by 1827 the Merck pharmaceutical company began the manufacturing and marketing of morphine. In the 1850s the work of Drs. Francis Rynd, CharlesGabriel Pravaz, Louis-Jules Béhier, and Alexander Wood led to the creation and clinical use of the hypodermic needle. The combination of the increased potency of morphine over opium and the ability to inject the solution directly into the bloodstream catalyzed increasing use of morphine. The discovery of the hypodermic syringe occurred just before the start of the United States Civil War, and the use of injected morphine during treatment of war injuries is reported to have resulted in addiction in thousands of veterans after the war. 3 In 1874, C.R. Wright synthesized diacetylmorphine from morphine.4 Chemists at Bayer pharmaceuticals optimized the synthetic process and Bayer marketed diacetylmorphine under the brand name “Heroin” (from the Greek word heros), as a “safe, nonaddictive” alternative to morphine from 1895–1910 for pain and coughs. It is noteworthy that during this time consumption of medications with opioids was considered normal and with minimal risk. Women were widely prescribed opioids after childbirth, or to treat “female problems” (menstrual cramps). In the 1800s, opioids and cocaine were mostly unregulated. The anthropologist Dr. Marcus Aurin writes that until the latter part of the 19th century, “It was viewed perfectly normal for individuals to take regular daily doses of opium as a ‘constitutional’ for vague conditions….”5 This acceptance and lack of regulation led to the development and commercialization of hundreds of patented medicines containing opioids during this time period.

90.4  A Revival of Addiction Treatment in America  1053

90.3 ADVERSE EFFECTS OF LEGAL AND SOCIETAL CHANGES ON ADDICTION TREATMENT The period of 1900–1935 saw a decrease in medical influence on addiction treatment in America as increasingly pejorative characterizations of individuals with substance use disorders led to a shift from viewing substance use as a medical condition or socially normative behavior and instead to judging it as a weakness in character and a willful, selfish choosing of sin over virtue. In the 1890s, the Anti-Saloon League was the leading organization lobbying for prohibition in the United States. It allied with the Women’s Christian Temperance Union and the Prohibition Party to support the passage of the Eighteenth Amendment to the United States Constitution in 1919. This law made the production, transport, and sale of alcohol (though not the consumption or private possession) illegal. In parallel, there was soaring public sentiment against the availability and use of opioids. The combination of the availability of morphine and the hypodermic needle had resulted in growing opioid addiction rates in individuals. In addition, social sentiment started shifting when there were increasing cases of addiction amongst the immigrant population, such as railroad workers who emigrated from China. The first drug control ordinances in U.S. history were issued in San Francisco in 1875 in an attempt to stop the spread of “opium dens.” The U.S. government began taxing opium in 1890, and the passage of the Pure Food and Drug Act of 1906 forced manufacturers to disclose the ingredients of their products, so consumers would know the content of their medications. Shortly after, in 1909, the Smoking Opium Exclusion Act banned the importation, possession, and use of “smoking opium.” Although the Act did not regulate opium-based medications, it became the first federal law to ban the use of non-medical substances. On a global level, Charles Henry Brent, an American Episcopal bishop convened the Brent Commission, which recommended that narcotics be subject to international control. In 1912, the United States and many other countries signed the International Opium Convention, which regulated the import, manufacture, and sale of morphine. Shortly afterward, the Harrison Narcotics Tax Act of 1914 was passed. This law regulated and taxed the production, importation, and distribution of opiates and cocoa products. It deemed that physicians could prescribe or dispense opioids to their patients, if they kept records. However, the moral sentiment affected medical opinion and the U.S. Public Health Service advocated that addiction was not a medical problem but a social one. In 1919, the AMA passed a resolution opposing outpatient treatment of opioid addiction. In 1919, the Webb amendment to the Harrison Act made offering maintenance treatment an “illegitimate medical practice” and one that was a Federal offense. During this time many physicians were indicted under the Harrison Act and several actually went to jail. The United States vs. Behrman Supreme Court decision in 1922 resulted in the closure of nearly all

clinics treating opioid addiction, as it made it illegal for doctors to prescribe opioids to addicts under any circumstances. Thus, over the course of fifty years, the pendulum had shifted from the medical and multi-factorial perspective of addictions espoused by the ACCI to one emphasizing moral responsibility, legal regulation, and punitive consequences.

90.4 A REVIVAL OF ADDICTION TREATMENT IN AMERICA The benefits to society of punitive legislative actions did not materialize as promised. After the passage of the Eighteenth Amendment, crime rates increased as the criminal element became wealthy from the profitable, violent, illicit market for alcohol. Prohibition started becoming unpopular across the country as the federal government and law enforcement agencies were not able to take adequate countermeasures. As a result, society became willing to reexamine and re-engage with the problem of addiction. With increased awareness and support, treatment approaches were reconsidered. Publication of medical research offered physicians a voice advocating for treatment. The pendulum swung back towards a clinical perspective through a series of legislative actions and court decisions. In 1925, the Linder vs. the United States Supreme Court decision ruled that the federal government overstepped its power to regulate medicine in the Behrman case. In 1929, the Narcotic Farms Act allocated funds for U.S. Public Health Service to construct and operate two residential treatment facilities. Ultimately, the Twenty-First Amendment, which repealed the Eighteenth Amendment, was ratified by a majority of states at the end of 1933. Another pivotal development in the treatment of addiction was the founding in 1935 of Alcoholics Anonymous (AA), a non-profit mutual aid society, by Bill Watson and Dr. Bob Smith. They posited that the primary purpose of the alcoholic was to “stay sober and help other alcoholics achieve sobriety.” Subsequently, they published the “Big Book” and developed AA’s 12-Step program of spiritual and character development. Although AA was not the first mutual aid group, it is the oldest and largest still operating with over 2 million members worldwide and 100,000 active groups. AA has served as inspiration for scores of mutual support groups that focus on specific substances and sub-populations. In 1949, the Minnesota Model (also known as the Abstinence Model) was created, which proposed the blending of professional and trained nonprofessional (recovering) staff who integrated the principles of AA. In addition, patients received individualized treatment plans with active family involvement in a 28-day inpatient setting. More recently, the Self-Management and Recovery Training (SMART) nonprofit organization was founded in 1994 as a mutual support organization based on evidence-based scientific knowledge. SMART Recovery emphasizes the 4-point program in the process of recovery including: (1) building and maintaining motivation, (2) coping with urges,

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(3) managing thoughts, feelings, and behaviors, and (4) living a balanced life using principles of Motivational Enhancement Therapy (MET) and techniques taken from Cognitive Behavior Therapy (CBT). In contrast to AA and other 12-step approaches, individual goals in SMART Recovery may include moderation of substance use rather than complete abstinence. Starting in the 1930s, pharmacologic developments started providing hope and medical credibility to conceptualizing addiction as a medical condition. Methadone was discovered in 1937 in Germany and ultimately gained Food and Drug Administration (FDA) approval in 1947 for treating pain. By 1965, Dr. Marie Nyswander and Dr. Vincent Dole published evidence hypothesizing that heroin addiction was a metabolic condition and that methadone could be used as a medication to treat this illness. In 1970, the FDA approved methadone for medically assisted withdrawal (“detoxification”) and in 1973 for maintenance therapy. Other medications for the treatment of opioid use disorder include naltrexone which was synthesized in 1963 and FDA approved in 1984, with its extended-release injectable version receiving FDA approval in 2010. Buprenorphine was discovered in 1966 and received FDA approval for treating opioid use disorder in 2002.6 Medications for the management of alcohol use disorder were discovered and developed over roughly the same time period, with disulfiram, a deterrent medication that increases adverse reactions to alcohol, receiving FDA approval in 1951, followed by oral naltrexone, which works to decrease craving and reinforcing effects of alcohol, being approved in 1994 and its extended-release injectable version in 2006. Acamprosate, another medication intended to decrease craving, received FDA approval in 2004.7 Support from state and federal governments allowed a foundation for enhancing treatment and conducting and disseminating research. The Addiction Research Center was founded in 1948 and served as a precursor for the formation of the National Institute on Drug Abuse (NIDA), which was formed by the Drug Abuse Office and Treatment Act in 1972. In 1992, NIDA became part of the National Institutes of Health (NIH). The Comprehensive Alcoholism Prevention and Treatment Act created the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in 1970. In addition, in 1992, the Substance Abuse and Mental Health Services Administration (SAMHSA) was established by Congress for improving the quality and availability of treatment and rehabilitative services for individuals with substance use disorders and mental illness. The Narcotic Addict Treatment Act was passed in 1974 and it recognized the use of an opioid medication to treat opioid addiction as critical and, for the first time in federal law, defined “maintenance treatment.” The Drug Addiction Treatment Act (DATA), which passed in 2000, allows providers to dispense or prescribe schedule III, IV, or V controlled substances for opioid addiction in treatment settings other than traditional Opioid Treatment Program (OTP) settings. This has allowed patients with opioid use disorder to receive care in outpatient settings as they would for any health condition. Coverage for treatment was made easier by the Mental Health Parity and Addiction Equity Act (MHPAEA) of

2008, which required health insurers and group health plans to provide the same level of benefits for mental and/ or substance use treatment and services that they do for medical/surgical care. The passage of the Comprehensive Addiction and Recovery Act (CARA) of 2016 allowed for improved access to treatment by expanding prescribing privileges to nurse practitioners (NPs) and physician assistants (PAs) until 2021. There are several instances of government collaboration with professional organizations. The Provider’s Clinical Support System for Medication-Assisted Treatment (PCSSMAT) is an example of a national collaborative effort led by American Academy of Addiction Psychiatry (AAAP) in partnership with American Osteopathic Academy of Addiction Medicine (AOAAM), American Psychiatric Association (APA) and American Society of Addiction Medicine (ASAM). PCSS-MAT is a national training and mentoring project developed in response to the prescription opioid misuse epidemic and the availability of pharmacotherapies to address opioid use disorder. These initiatives have led to a better understanding of the neurobiological basis of addiction. Research has outlined the processes of neuroplasticity fundamental to learning and memory. The identification of various receptors such as α-ami​no-3-​hydro​x y-5-​methy​l-4-i​soxaz​olepr​ opion​ ic acid (AMPA), N-methyl-d-aspartate (NMDA), and gamma-Aminobutyric acid (GABA) and their neuroanatomic distribution has been coupled with greater knowledge of the effects of neurotransmitters such as dopamine, glutamate, and GABA. Synthesizing the findings of biochemical research with behavioral studies has shed greater light on functional significance.8 This has allowed concepts such as triggers, cravings, preoccupation, anticipation, and withdrawal to be viewed from a biological perspective. Despite these active initiatives, a large treatment gap exists in the United States for patients suffering from addiction. In 2016, only 10% of patients with substance use disorders (SUDs) who needed treatment received it in a specialty treatment facility in the past year.9 Addiction is a chronic condition with a significant public health impact. The incidence and prevalence of addiction can potentially be decreased by the use of evidence-based lifestyle therapeutic approaches that can help to guide and empower individuals to replace potentially harmful substances with healthy habits.10 For example, improved knowledge and skill building for stress management can have a significant effect on individuals having alternatives to alcohol and tobacco use. This can, in turn, have salient and systemic benefits for the individual and society.

90.5 SUMMARY Humans have used mind-altering substances for thousands of years for a variety of reasons. Substance use in America has undergone cycles of acceptance, widespread use and under-appreciation of risk, recognition of problematic use leading to the criminalization of substances and stigmatization of users, to the legalization of certain substances and medical treatment. Access to treatment has vacillated based on cultural perceptions, social norms,

References  1055

legal decisions, and legislative actions. Addiction continues to pose a significant challenge. In 2016, approximately 20.1 million individuals aged 12 or older were diagnosed with a SUD in the past year. This statistic was comprised of 15.1 million individuals with an alcohol use disorder and 7.4 million with an illicit drug use disorder.9 These data potentially underestimate the prevalence of negative consequences of addictive substances since they do not include individuals whose use causes harms or increases risks but does not meet full criteria for a substance use disorder. The current opioid epidemic highlights the significant morbidity, mortality, and devastating economic and societal costs of this condition. However, the scientific and medical advances coupled with economic benefits of treatment represent hope for individuals, their families, and society. SAMHSA summarizes this sentiment: “Behavioral health is essential to health; Prevention works; Treatment is effective; People recover.”

CLINICAL APPLICATIONS • Humans have utilized alcohol and opioids for thousands of years for a variety of reasons including for medical, recreational, and spiritual purposes. • Although the use of these substances was initially accepted in society, the increased potency, widespread availability, and improvement in methods of delivery resulted in significant pernicious consequences for the individual and society at large. • Societal perception and treatment availability have vacillated from viewing addiction through a lens of morality and deviance to the recognition of it as a treatable, chronic medical condition. • Our current medical knowledge of addiction presents an important opportunity to utilize evidencebased lifestyle medicine approaches to prevent addiction and enhance recovery.

REFERENCES 1. American Association for the Cure of Inebriety (AACI). The Disease of Inebriety from Alcohol, Opium, and Other Narcotic Drugs, its Etiology, Pathology, Treatment and Medico-Legal Relations. New York City: E.B. Treat, 1893. 2. White W. Slaying the Dragon: The History of Addiction Treatment and Recovery in America, 2nd ed. Chicago, IL: Chestnut Health Systems, 2014. 3. Lewy J. The army disease: Drug addiction and the civil war. War Hist. 2013;21:102–119. 4. Brook K, Bennett J, and Desai SP. The chemical history of morphine: An 8000year journey, from resin to de-novo synthesis. J. Anesth. Hist. 2017;3:50–55. 5. Aurin M. Chasing the dragon: The cultural metamorphosis of opium in

the United States, 1825-1935. Med. Anthropol. Q. 2000;14:414–441. 6. Center for Substance Abuse Treatment. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43. HHS Publication No. (SMA) 12-4214. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2005. . Center for Substance Abuse 7 Treatment. Incorporating Alcohol Pharmacotherapies into Medical Practice. Treatment Improvement Protocol (TIP) Series 49. HHS Publication No. (SMA) 09-4380. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2009.

8. Volkow ND, Koob GF, and McLellan AT. Neurobiologic advances from the brain disease model of addiction. N. Engl. J. Med. 2016;374:363–371. 9. Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results from the 2016 National Survey on Drug Use and Health (HHS Publication No. SMA 17-5044, NSDUH Series H-52). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, 2017. Retrieved from https://www. samhsa.gov/data/ 10. Bodai BI, Nakata TE, Wong WT, et al. Lifestyle medicine: A brief review of its dramatic impact on health and survival. Perm. J. 2018;22:17–25.

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91 CHAPTER

Behavioral Approaches to Enhancing Smoking Cessation Joseph T. Ciccolo, PhD, CSCS, Nicholas J. SantaBarbara, MS, and Andrew M. Busch, PhD

91.1  Health Consequences of Smoking................................... 1057 91.2  Smoking Prevalence and Epidemiology........................... 1058 91.3  RATES of Smoking Cessation.......................................... 1058 91.4  Pharmacological Aids for Smoking Cessation.................. 1058 91.5  Behavioral Smoking Cessation Strategies....................... 1058 91.6  Counseling and Therapy-Based Approaches................... 1059 91.6.1  Individual Counseling.......................................... 1059 91.6.2  Group Therapy.................................................... 1059 91.6.3  Telephone Counseling......................................... 1059 91.6.4  Motivational Interviewing.................................... 1059 91.7  Smoking Cessation in Medical Settings........................... 1060 91.7.1  Primary Care Visits.............................................. 1060 91.7.2  Inpatient Hospitalization...................................... 1061 91.8  Community-Based Approaches....................................... 1061 91.8.1  Mass Media Campaigns...................................... 1061

More than six million deaths worldwide can be attributed to cigarette smoking each year.1 In high-income countries like the United States, significant strides have been made to reduce the smoking prevalence among certain segments of the population, but there are some areas where gains have been minimal. One area of particular importance that will likely be helpful in reducing smoking rates is the recent change to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), 2 which added “Tobacco Use Disorder” as a diagnosis in 2013. This properly aligned cigarette smoking with other substance use disorders, given that those who regularly smoke cigarettes experience symptoms similar to those who regularly use other drugs of abuse. Moreover, the diagnosis should help to accurately identify those who are most at risk for negative consequences from use, identify those who need active intervention, and inform treatment recommendations, such as what type or dose of treatment is needed.3 Hence, the purpose of this chapter is to: • Provide a brief overview of the health consequences and prevalence of cigarette smoking in the United States. • Conduct a review of the literature on key behavioral approaches and strategies that have been used to enhance smoking cessation.

91.8.2  Worksite Programs........................................... 1061 91.9  Technology-Driven Approaches..................................... 1062 91.9.1  Internet-Based Interventions............................. 1062 91.9.2  Mobile Phone Interventions............................... 1062 91.10  Smoking Cessation in Special PopulationS.................... 1062 91.10.1  Young Adult and Adolescent Smokers............. 1062 91.10.2  Minority and Disadvantaged Smokers............. 1063 91.10.3  Pregnant Smokers.......................................... 1063 91.10.4  Mentally Ill Smokers....................................... 1063 91.11  Other Behavioral Approaches........................................ 1063 91.11.1 Exercise......................................................... 1063 91.11.2  Electronic Cigarettes....................................... 1064 91.11.3  Abrupt Quitting and Gradual Reduction........... 1064 91.12  Summary and Conclusions........................................... 1064 References.............................................................................. 1065

• Highlight the research done in various settings and across different populations of vulnerable and atrisk smokers. • Summarize some of the most effective treatments and promising new research initiatives that are currently underway.

91.1 HEALTH CONSEQUENCES OF SMOKING The negative health effects that result from cigarette smoking are very clear. Evidence shows that any exposure to tobacco smoke is harmful because it contains more than 7,000 chemical compounds.4 Indeed, smoking harms nearly every organ of the body and can cause cardiovascular disease, stroke, periodontitis, aneurysms, pneumonia, chronic obstructive pulmonary disease (COPD), asthma, erectile dysfunction, and low bone mineral density.5 Cigarette smoking can also cause cancer of the lung, bladder, cervix, esophagus, oral cavity, larynx, stomach, kidney, uterus, and pharynx.5 Lastly, smoking has additional adverse effects on early childhood and reproductive health, including infertility, preterm delivery, stillbirth, low birth weight, and sudden infant death syndrome (SIDS).5

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In the United States, smoking remains the leading cause of preventable disease, disability, and death.5 More than 16 million Americans are living with a disease caused by smoking. In total, cigarette smoking is responsible for more than 480,000 deaths per year (approximately 1,300 each day), including more than 41,000 deaths resulting from secondhand smoke.5 Overall, it is estimated that the total economic cost of smoking is more than $300 billion a year, including nearly $170 billion in direct medical care for adults.5

91.2 SMOKING PREVALENCE AND EPIDEMIOLOGY In the United States, about 15% of the adult population (aged 18 and over) and 4% of youths (aged 12–17 years) are current smokers.6 Smoking is higher in males (16.8%) than in females (13.8%) and differs by various other demographics.6 For example, smoking rates are higher among those who have not completed a high school education (25.6%), live at or below the federal poverty line (24.6%), identify as a sexual minority (20.6%), and those with a disability (21.5%).6,7

91.3 RATES OF SMOKING CESSATION Both the risk and the severity of many diseases caused by smoking are directly related to how long the smoker has smoked and the number of cigarettes smoked per day. As such, it is beneficial to quit smoking at any age.5 More specifically, after quitting, the risk for a heart attack drops sharply after just one year; stroke risk can fall to about the same as a nonsmoker’s after two to five years; risks for cancer of the mouth, throat, esophagus, and bladder are cut in half after five years; and the risk for dying of lung cancer drops by half after ten years.4 The most recent estimates indicate that 68.0% of current smokers would like to stop smoking, 55.4% made a past-year quit attempt, and 7.4% were able to quit for greater than six months over the past year.7 Interest in quitting is reported to be higher among certain demographic groups, such as females, those aged    75  mmol/L), particularly in older adults. There have been only a limited number of large controlled randomized trials that have studied the effects of vitamin D supplementation on muscle mass and function as well as on incidence of falls in healthy communitydwelling elderly individuals.97 , 98  These trials have yielded mixed results, which is understandable considering differences between studies in regard to entry criteria, dosage

of vitamin D supplements, and measurement criteria. It appears from meta-analyses of these trials that elderly individuals who are the most deficient in vitamin D levels and those with the poorest baseline strength and mobility are the most likely to exhibit significant improvement in study parameters with vitamin D supplementation. Stockton et al.98  in their meta-analysis, based on data primarily related to reduced incidence of falls and associated fractures, recommend the titration of the dosage of a vitamin D supplement required to attain a proposed optimal level of serum 25 (O-) D of 30  ng/ml or more. Furthermore, it is clearly evident that those with severe vitamin D deficiency (15– 20  ng/ml) stand to gain the most in terms of muscular benefits from vitamin D supplementation. Large randomized controlled clinical trial research is required to determine the role of vitamin D supplementation alone and in combination with exercise training for prevention and management of sarcopenia and frailty.

98.28 FOOD-DERIVED ANTIOXIDANTS Oxidative stress, contributing to loss of muscle mass with aging, is counterbalanced by both the body’ s endogenous antioxidant enzyme defense system and by endogenous dietary antioxidants. Antioxidants present in fruits and vegetables include ascorbic acid, β  carotene, and other carotenoids with or without pro-vitamin A activity (e.g., lutein and lycopenes), flavonoids, and other polyphenol phytochemicals (e.g., resveratrol in the skin of red grapes and berries), and the minerals selenium and zinc. In addition, another potent exogenous antioxidant is vitamin E/ tocopherols, derived in the diet primarily from vegetable oils. A low dietary intake of all of these antioxidants is common in elderly individuals. A positive association has been reported in longitudinal observational studies in older men and women between the blood biomarkers of these exogenous antioxidants and skeletal muscle function and the risk of sarcopenia.99 –  101  For example, in the Italian Chianti Aging Study,100  which involved 929 men and women older than 65  years, high plasma levels of total carotenoids (generally regarded as a biomarker for fruit and vegetable intake), and other dietary antioxidants, was associated with reduced risk of developing severe walking disability over a six-year observational period. This association persisted after adjustment for potential confounding variables, including physical activity habits, vitamin E and selenium intake, and comorbidities. This association persisted after adjustment for potential confounding variables, including physical activity habits and intake of vitamin E and selenium. Skeletal muscle strength and physical performance, and reduced comorbidities, were also absent in this cohort associated with high plasma carotenoid levels. However, there have been only a limited number of randomized controlled trials to determine the effects of antioxidant nutrients or phytochemical supplements on muscle strength and other functions in elderly individuals.101  Furthermore, existing studies have yielded mixed results and raised questions regarding the

References  1137

usefulness of antioxidant supplements in reducing the risk of sarcopenia. Also, there is concern that administration of antioxidant supplements may impede physiological adaptations to exercise training. In addition, there are safety concerns, including possible increased risk of malignancies, particularly in cigarette smokers, because immune defense system cells use blasts of ROS to destroy malignant cells. Thus, public health authorities and gerontologists recommend limiting antioxidant intake to dietary sources with supplements primarily reserved for prevention and management of age-related macular degeneration, a common cause of non-traumatic blindness in elderly individuals.

CONCLUSIONS Aging is associated with multiple molecular and biochemical skeletal muscle changes which contribute to the development of sarcopenia and ultimately frailty. A lifelong comprehensive exercise program and healthy eating habits are postulated to attenuate many of these biological processes, reducing the risk and/or improving these conditions, thereby improving the quality of life of elderly individuals. However, controlled clinical trials are required to prove these postulated beneficial lifestyle benefits. Nevertheless, the potential benefits of these lifestyle recommendations, as compared with risks, makes them worth pursuing in the interim.

CLINICAL TAKE HOME POINTS • Lean muscle mass should be assessed in all patients. • There is an important role for exercise in the prevention and management of sarcopenia, including resistance training 2– 3  days per week, moderate-tovigorous aerobic/cardiorespiratory endurance training at least 3– 5  days per week for 30– 60  minutes, and flexibility and balance training weekly. • Nutrition also plays a key role in limiting loss of lean muscle mass. Nutritional considerations include regular energy-balanced meals with an adequate intake of whole grains, fruits and vegetables, low fat, fatfree dairy products, and daily servings of proteinrich animal products or protein-rich beans, nuts, and legumes. • The amount of protein in the diet is an area of active research. There is growing support for raising the recommended daily allowance (RDA) of protein in older individuals from 0.8  grams/kilogram of body weight to 1.0  grams/kilogram or more. • The quality of protein is also important. Highquality protein can be obtained from reduced fat or fat-free dairy products, egg whites, meat, poultry, and seafood or the combination of plant sources such as soy products plus whole grains. • Adequate Vitamin D levels also play a role in maintenance of lean body mass and should be assessed in all patients.

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99 CHAPTER

Aging-Associated Cognitive Decline and its Attenuation by Lifestyle Arthur S. Leon, MS, MD, FACSM

Key Points.................................................................................1141 99.1  Aging Effects on the Brain................................................1142 99.2  Cognitive Changes...........................................................1142 99.3  Age-Associated Memory Impairment (AAMI)....................1142 99.4  Mild Cognitive Impairment (MCI)......................................1142 99.5 Dementia.........................................................................1142 99.6  Alzheimer Disease (AD)....................................................1142 99.6.1  Cerebral Vascular Changes with Aging.................1143 99.7  Reduced Cognitive Reserve.............................................1143 99.8  Psychological Disturbances.............................................1143

KEY POINTS • Natural/primary aging generally is associated with regional brain atrophic changes. • In most individuals, this is only accompanied by relatively minor short-term memory deficits. • More advanced brain shrinkage, involving the same regional areas, results in additional cognitive decline, referred to as “mild cognitive impairment” (MCI). • Comorbidities, such as diabetes and heart disease, accelerate cognitive decline. • Dementia results from neurodegenerative, inflammatory conditions and/or vascular changes, which reduce cerebral blood flow. • The most common types of dementia are Alzheimer’s disease and vascular-induced or mixed forms of dementia. And men ought to know that from nothing else but thence [from the brain] came joys, delights, laughter and sports, and sorrows, griefs, despondency, and lamentations. And by this, in an especial manner, we acquire wisdom and knowledge, and see and hear, and know what are foul and what are fair, what are bad and what are good, what are sweet, and what unsavory… And by the same organ we become mad and delirious, and fears and

99.9  Traumatic Brain Injury (TBI)............................................1143 99.10  Atrial Fibrillation (AF)......................................................1144 99.11  CVD Risk Factors...........................................................1144 99.12  Dietary Habits................................................................1144 99.13  B Vitamins.....................................................................1144 99.14  Vitamin D.......................................................................1144 99.15  Physical Activity.............................................................1145 99.16 Conclusions...................................................................1145 Key Clinical Points....................................................................1146 References...............................................................................1146

terrors assail us…All these things we endure from the brain, when it is not healthy…In these ways I am of the opinion that the brain exercises the greatest power in the man. This is the interpreter to us of those things which emanate from the air, when it [the brain] happens to be in a sound state.1 As eloquently expressed in the quotation from Hippocrates, the brain is the central control center for all mental functions. At physical maturity, while it makes up only about 2% of body weight, however, because of its high metabolic activity, it requires more than 20% of the body’s total daily resting energy expenditure, 25% of total glucose uptake, and 15% of the body’s resting cardiac output. 2 Histologically, the human brain composition includes about 100 billion neurons and about an equal number of glial support cells.2,3 All brain functions result from extensive synapses between neurons, which constitute a total of about 150 km of neural networks. Over 90% of these neurons are located in the gray matter, while myelinated axon nerve fibers constitute the brain’s white matter. Chemical neurotransmitter activity at the neuronal synaptic junctions either amplify or inhibit nerve neuroactivity. Our current knowledge of the functions of these neural networks is still in its infancy. The multicenter White House BRAIN Initiative (“Brain Research Through Advanced Neurotechniques”), first announced in 2013, has as its goal the development of technologies required for mapping brain neural network activity, initially in animal models, and eventually in humans.4 1141

1142  Chapter 99  Lifestyle effects on aging-associated cognitive decline

99.1 AGING EFFECTS ON THE BRAIN After achieving its physical maturity by age 30 years, the brain experiences a progressive decline in volume with increasing age. Both cross-sectional and longitudinal epidemiologic studies estimate the rate of decline in brain volume to be about 0.3% per year, resulting in about an average 15% reduction between age 30 and 80 years.5 In addition, the aging brain experiences a gradual reduction in its ability to replace lost neurons via neurogenesis. Further, there is an aging-related progressive reduction in neural synapses and networks, as well as neurotransmitter activity at synapses. Both oxidative free radical damage of macromolecules and vascular changes, which reduce cerebral blood flow, contribute to these adverse neurologic changes.6 Postmortem histologic examinations reveal that this reduction in brain volume in non-demented elderly individuals is primarily due to neuronal atrophy, rather than neuronal loss by apoptosis or necrosis.7 In addition, aging is accompanied by adverse neuronal morphologic changes. These include accumulation in neurons of lipofuscin, a brownish-yellow pigment. This so-called wear and tear pigment appears to be a product of peroxidation of unsaturated fatty acids in cell membranes. A similar pigment also is associated with aging in other body tissues.8 Major regions of the brain affected during aging include the hippocampus and the cerebral cortex regions, major sites involved with cognition.9 However, there is a great deal of inter-individual variability in severity of these brain aging morphologic and associated cognitive functional effects. This variability is postulated to be related to both genetic and lifestyle as well other environmental factors. The presence or absence of aging-associated secondary disease processes (comorbidities), such as diabetes mellitus, which accelerate adverse effects of aging, is also considered to be related to this variability.9

99.2 COGNITIVE CHANGES Cognition is defined as the “underlying operations of the brain for processing information.”9 Cognitive processes include memory, learning ability, information processing, problem-solving, and so-called executive control (i.e., the ability to plan and execute complex multitask behavior). The relative severity of aging-associated cognitive changes has been clinically classified into three major categories,9 i.e., primary age-associated memory impairment (AAMI), mild cognitive impairment (MCI), and dementia.

99.3 AGE-ASSOCIATED MEMORY IMPAIRMENT (AAMI) Cognitive changes in the majority of healthy older individuals fall into this category. This designation refers to persons older than 50 years, whose cognitive decline consists primarily of a mild reduction in short-term, working memory, often referred to as “benign forgetfulness.” This is postulated to be primarily related to the reduced

speed of mental processing, due to morphologic changes in the gray matter of the hippocampus and cerebral cortex.9 Psychometric testing scores for those with AAMI fall within the normal range for age but are at least one standard deviation (SD) below the mean for young adults. Generally, only a small percentage of those with AAMI subsequently progress to dementia by age 70 years.9

99.4 MILD COGNITIVE IMPAIRMENT (MCI) MCI is associated with greater regional brain atrophy, as AAMI, and involves the same areas, especially the hippocampus. The diagnosis of MCI is made clinically by demonstration of below average scores on a battery of psychometric tests, as compared to average healthy individuals of the same age.9 Cognitive dysfunction associated with MCI is more marked than with normal aging. In addition, there commonly is some difficulty in selecting the correct words during conversations and the presence of so-called visuospatial disturbances (i.e., disorientation in usually familiar surroundings). However, there generally is no significant disturbance in abstract thinking nor in the ability to perform routine activities of daily living, a diagnostic criterion for dementia. Longitudinal studies reveal that about 15% of individuals with MCI subsequently develop dementia within one year and 50% within three years of follow-up.9 Thus, at least for some individuals, MCI represents either a prodromal or an early stage of dementia.

99.5 DEMENTIA Dementia is defined clinically as a syndrome resulting from neurodegenerative inflammatory disease processes throughout the brain.9 This results in a progressive deterioration in most major cognitive functions, resulting in an inability to independently perform routine activities of daily living. In addition, dementia is commonly accompanied by adverse personality and behavioral changes. The prevalence of reported dementia in the United States is about 5.2 million, with an incidence of newly diagnosed cases of about 400,000 per year.10 These figures include about 25% of the population older than age 75 years and 40% of those over 80 years of age. Women account for about two-thirds of dementia cases. This is attributed to women generally living longer than men do. In addition, dementia is ranked as the sixth leading cause of death in the United States for both sexes. By far the two most common types of dementia in the United States are Alzheimer’s disease (AD) and vascular dementia (VaD).

99.6 ALZHEIMER DISEASE (AD) (AD) is responsible for about two-thirds of reported cases of dementia among Americans. Hallmark diagnostic morphological features of the AD, demonstrated at autopsy, are beta-amyloid plaques and neurofibrillatory tangles.9,11

99.9  Traumatic Brain Injury (TBI)  1143

The tangles are composed of unfolded, phosphorylated tau proteins derived from degeneration of axon nerve fibers. The plaques and tangles are postulated to result in inflammation and induce neuronal atrophy. This results in a disruption of synapses and loss of nerve network, which is associated with about a threefold greater shrinkage of brain volume than with normal aging.12

99.6.1 Cerebral Vascular Changes with Aging Reduced cerebral blood flow with aging is an important contributor to brain shrinkage and cognitive decline across the spectrum from primary aging to dementia of all types.14 Vascular aging involves both the large arteries and the microvasculature supplying the brain. The hallmark of vascular aging, loss of elasticity of major arteries, is primarily due to displacement of elastic tissue with stiffer collagen fiber.13 Reduced conduit artery elasticity results in an increased force of pulse wave velocity (PWV) during systole. Increased PWV in turn damages microvasculature in the brain. This damage, coupled with an associated reduction with aging in microvascular replacement by angiogenesis, results in reduced brain density of arterioles and capillaries. Aging also is commonly associated with endothelial dysfunction (ED) reducing blood flow-mediated vasodilatation. ED also is involved in the development of atherosclerosis in middle-sized and major arteries, further reducing cerebral blood flow, and hence delivery of oxygen, glucose, and other essential nutrients to the brain. Subsequent thrombotic occlusions of atherosclerotic arteries supplying the brain result in areas of ischemic necrotic damage. Vascular-induced dementia or VaD results from such multiple mini strokes. VaD is the second most common cause of dementia in elderly adults and is responsible for 15% to 20% of American cases.14 Mixed VaD and AD also is often present. Table 99.1 lists major risk factors for accelerated cognitive decline with aging and increased risk of dementia. Generally, there is an interaction among multiple risk factors involved in increasing the risk of AD and VaD, and all cause dementia. Biological non-modifiable risk factors for dementia include advanced age, particularly in women, and a positive family history. A positive family history of earlyonset AD (age 30 to 60 years) is generally due to a known TABLE 99.1  Major risk factor for accelerated cognitive decline and risk of AD, VaD, and All-Cause dementia

1. Advanced age 2. Positive family history and genetic markers 3. Limited formal education 4. Limited regular intellectual stimulation and social engagement 5. Psychological problems 6. Traumatic brain injuries 7. Major risk factors for atherothrombotic heart attacks and strokes 8. Chronic atrial fibrillation 9. Poor dietary habits and obesity 10. Physical inactivity and reduced physical fitness 11. Alcohol and drug abuse

specific single gene. However, heritability appears to be responsible for only about 5% of AD cases in the United States.15 The vast majority of cases of AD, as well as other forms of dementia, initially become symptomatic after a person passes their mid-60. While no specific autosomal dominant gene is involved in the etiology of AD, a known genetic factor does increase risk. This is a mutation of a gene located on chromosome 11 responsible for formation of apolipoprotein E (apo E). The presence of the apo E4 allele increases risk of AD.16 It also is associated with elevated blood cholesterol and atherosclerotic cardiovascular disease. However, not everyone who inherits this genotype develops AD or CVD.

99.7 REDUCED COGNITIVE RESERVE It appears from both cross-sectional and longitudinal observational studies that low intellectual stimulation during childhood and youth reduces “cognitive reserve” capacity, thus increasing vulnerability for development of MCI and risk of all types of dementia during aging.9 Reduced cognitive reserve is associated with below average IQ, limited formal education (independent of socioeconomic status), and low social interactions. Further, later in life, the decline of cognitive reserve is enhanced by limited intellectual stimulation at work and during leisure time, and by limited social engagement (“if you don’t use it, you lose it”).

99.8 PSYCHOLOGICAL DISTURBANCES Chronic anxiety, depression, and sleep disorders have been reported in observational studies to be associated with increased risk of cognitive impairment with aging and in some (but not all) studies with subsequent development of dementia.9 Brain damage due to associated chronic elevations of cortisol levels is postulated to be involved. It also should be noted that an overdose of psychosomatic drugs used to manage these psychological disorders may be responsible for potentially reversible cognitive impairments.

99.9 TRAUMATIC BRAIN INJURY (TBI) TBI, particularly if it is associated with prolonged loss of consciousness for 30 minutes or more, at any stage of life is probably the best established environmental risk factor for dementia. However, even repeated low-level head trauma, such as sustained by professional athletes, appears to contribute the severity of cognitive decline with aging and to increased risk of dementia.9 Current research has demonstrated pathophysiologic mechanisms for the relationship of TBI to AD. Brain damage due to TBI, can result in deposition of both beta-amyloid and phosphorylate tau proteins, the hallmarks of AD. Carriers of the apo E4 genotype appear to be particularly susceptible.9,16 The most common causes of TBI are head injuries due to falls, especially in individuals over 75 years of age.

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1144  Chapter 99  Lifestyle effects on aging-associated cognitive decline

99.10 ATRIAL FIBRILLATION (AF) Recent research has reported the association of chronic AF with both VaD, AD, and all-cause dementia.17 Risk of non-valvular heart-disease-induced AF increases with age and affects over two million Americans. Its presence also markedly increases risk of a major stroke via embolism to the brain from blood clots formed in the fibrillating left atria. Multiple small strokes induced by AF directly cause VaD. However, as mentioned, other forms of dementia are associated with AF even in the absence of brain infarctions.

99.11 CVD RISK FACTORS Observational studies have consistently shown the association of major cardiovascular disease (CVD) risk factors (e.g., obesity, elevated blood cholesterol, hypertension, diabetes mellitus, and cigarette smoking) not only with VaD but also with AD and mixed dementia.9 Multiple plausible biological mechanisms support the causative role of each of these comorbidities with AD and VaD.

99.12 DIETARY HABITS Observational studies have also demonstrated an association of eating patterns with cognitive changes with aging and risk of dementia.18–20 The most widely studied of these associations has been with Mediterranean-style diets (MSD). Adherence to such dietary patterns, based on 13 or 14 food items, has been demonstrated in the majority of studies and by meta-analyses to be associated with reduced cognitive decline with aging and reduced risk of dementia, as well as reduced risk of death from coronary heart disease and all-cause mortality. The Dietary Approach to Stop Hypertension (DASH) diet, and a combination of dietary components of the MSD and DASH diet (the so-called MIND diet), also have been observed to be associated with reduced risk of dementia with aging.18,19 These diets are plant-based (that is, their principal sources of energy are plants). The MSD is characterized by a high intake of grains and cereals, fruits and vegetables, and legumes, as well as nuts, olive oil, and fish as fat sources. The MSD also contains a moderate quantity of cheese, yogurt, and poultry; a low intake of red meat and other sources of saturated animal fat; and regular small servings of red wine, generally with meals. In addition, the DASH dietary pattern is characterized by a reduced sodium and alcohol intake. A synergistic interaction of multiple components of the MSD and other plant-based diets is postulated to contribute to prevention of dementia as well as CVD. A major contributor to their preventive effects is postulated to be their fatty acid composition. Reduced serum cholesterol associated with a low intake of saturated and trans fat is postulated to be a major health-promoting factor. In addition, Omega-6 polyunsaturated fatty acids (PUIA) from vegetable oils and nuts also contribute to blood cholesterol lowering. Monounsaturated fatty acids rich in olive oil, a major component of the MSD, also are postulated to

have anti-inflammatory and anti-atherosclerotic effects. Long-chain omega-3 PUFA docahexaenoic (DHA) is a major component of neuronal cell and mitochondrial membranes, and thereby is essential for brain health. Fish and fish oils are rich in sources of DHA as well as its precursor, eicosapentaenoic acid (EPA). Alpha linoleic acid (ALA), a shorter-chain essential omega-3 PUFA found in vegetable oils, also can be enzymatically converted to EPA and DHA to meet some of the brain’s requirements. Patients with AD are commonly deficient in DHA, and supplementation with EPA and DHA has been shown clinically to improve cognitive function in patients with MCI and very mild AD, but not with advanced AD.18 The antioxidant components of fruits and vegetables and vegetable oils are postulated to play major roles in reducing neurodegenerative brain processes causing dementia.18 These include vitamins C and E and beta-carotene, as well as other pro-vitamin A and non-vitamin A precursor carotenoids. In addition, fruits and vegetables contain potent antioxidant phytochemical polyphenols, such as resveratrol, rich in skin of red grapes and berries. Antioxidant flavanols also are present in dark chocolate and other cocoa products, coffee, and black and green tea. A recent randomized controlled intervention in elderly individuals demonstrated that consumption of cocoarelated products, like dark chocolate, reduced some measures of age-associated cognitive dysfunction. 21,22

99.13 B VITAMINS Observational studies have reported that reduced blood levels of the B vitamins—thiamin, folate, B6, and B12— are associated with increased risk of dementia.18 An associated elevation of blood levels of homocysteine is postulated to play a role. A deficient intake of B12 is particularly a problem for vegetarians of all ages, since this vitamin is only naturally present in animal food products. Further, absorption of B12 from the GI tract is reduced during aging due to gastric atrophy. A marginal B12 deficiency as evidenced by blood assay levels  30 ng/ ml for serum 25-OHD.

KEY CLINICAL POINTS Observational studies have demonstrated an association of eating patterns with cognitive changes with aging and risk of dementia. The most widely associated dietary framework to reduce the risk of dementia is the Mediterranean diet. The Dietary Approach to Stop Hypertension (DASH) and a combination of Mediterranean and DASH diets (the so-called MIND diet) have also been

observed to be associated with reduced risk of dementia with aging. These diets are plant-based, as their principal source of energy is plants, and they are characterized by high intake of grains and cereals, fruits and vegetables, legumes, and nuts, olive oil, and fish as fat sources. Evolving research evidence suggests that regular aerobic activities attenuate many of the effects of aging on the brain, thereby reducing risk of MCI and dementia. Pharmacologic interventions to reduce cardiovascular disease risk factors not controlled by diet and exercise may include dyslipidemia, hypertension may lower the risk of aging-associated cognitive decline. Management of elevated blood glucose levels and obesity, and cessation of cigarette smoking, may also further reduce the risk of cognitive decline.

REFERENCES 1. Adams F. The genuine works of Hippocrates. Vol. 2, 1886;844–345. 2. Jerison H. Evolution of the brain and intelligence. Academic Press. 1973;55–74. 3. Pelvig DP, Pakkenberg H, Stark AK, Pakkenberg B. Neocortical glial cell numbers in human brains. Neurobiol Aging. 2008;29:1754–1762. 4. Alivisatos AP, Chan M, Church G, Greenspan R, et al. The Brain Activity Project and the challenge of functional connections. Neuron. 2012;74:970–974. 5. Raz N, Rodrigue KM. Differential aging of the brain: Patterns, cognitive correlates, and modifiers. Neurosci Biobehav Rev. 2006;30:730–748. 6. Whalley LJ, Deary IJ, Appleton CL, Starr, JM. Cognitive reserve and the neurobiology of cognitive aging. Aging Res Rev. 2004;3:169–182. 7. Haug H. Aging of the brain. In: Ludwig FC (Editor). Life Span Extension. Consequence and Open Questions. 1991. New York, Springer Publishing Company, 55–67. 8. Gaugler C, Lipofuscin W, Stanislaus. J Biochem Rev. 1997. 9. Fillit HM, Butler R, O’Connell AW, Albert MS, et al. Achieving and maintaining cognitive vitality with aging. Mayo Clinic Proc. 2002;77:681–696. 10. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons. JAMA. 1989;262:2551–2556. 11. Sayre LM. Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature. 1999;399(6738, Suppl):A23–A31. 12. Tiraboschi P, Hansen LA, Thai LJ, Corey-Bloom J. The importance of intrinsic plaques and tangles to the development and evolution of AD. Neurology. 2004;62:1987–1999. 13. Leon AS. Interaction of aging and exercise on the cardiovascular system of healthy adults. Am J Lifestyle Med. 2012;6:368–375.

14. Wetterling T, Kanitz RD, Borgis KS. Comparison of different diagnostic criteria for vascular dementia. Stroke. 1996;27:30–36. 15. Waning SC, Rosenberg RN. Genomewide association studies in Alzheimer’s disease. Arch Neurol. 2008;65:329–334. 16. Katzman R, Galasko DR, Saitoh T, Chen X, Pay, MM, Booth A, Thomas RG. Apolypoprotein-epsilon4 and head trauma: Synergistic or additive risks? Neurology. 1996;46:889–891. 17. Bunch TJ, Weiss JP, Crandall BG, et al. Atrial fibrillation is independently associated with senile, vascular, and Alzheimer’s dementia. Heart Rhythm. 2010;7:433–437. 18. Hu N, Jin-Tai Y, Lin T, et al. Nutrition and risk of Alzheimer’s disease. Biomed Res Intern. 2013;2013:1–21. 19. Willett WC, Sacks F, Trichopoulou A, Drescher G, et al. Mediterranean diet pyramid: A cultural model for healthy living. Am J Clin Nutri. 1995;61:14025–14065. 20. Hardman RJ, Kennedy G, Macpherson H, Scholey AB, Pipingas AA. Adherence to a Mediterranean-Style Diet and effects on cognition in adults: A quantitative- evaluation and systematic review of longitudinal and prospective trials. Front Nutr. 2016;3:22. doi: 10.3389/ fnut.2016.00022. eCollection 2016. 21. Moreira A, Diogenes MJ, de Mendonca A, Lunet N, Barros H, et al. Chocolate consumption is associated with a lower risk of cognitive decline. J Alzheimers Disease. 2016;53:85–93. 22. Mehig A. The neuroprotective effects of cocoa flavanol and its influence on cognitive function. Br J Clin Pharmacol. 2012;75:716–722. 23. Allen LH. How common is vitamin B-2 deficiency? Am J Clin Nutr. 2008;89:693S–696S. 24. Hossen-Nezhab A, Holick MI. Vitamin D for health: A global prospective. Mayo Clin Proc. 2013;88:720–755.

25. Lee JH, O’Keefe JH, Bell D, Hensrud DD, Holick MF. Vitamin D deficiency. An important common and easily treatable cardiovascular risk factor. J Am Col Cardiol. 2008;52:1949–1956. 26. Littlejohns TG, Hensley W, Lang IA, Annwieler C, et al. Vitamin D and risk of dementia and Alzheimer’s disease. Neurology. 2014;83:1–9. 27. Gezen-Ak D, Yilmazer S, Dursun E. Why vitamin D in Alzheimer’s disease? The hypothesis. J Alzheimers Dis. 2014;40:257–269. 28. Fluza-Luces C, Garathachea N, Bergen NA, Lucia A. Exercise is the real polypill. Physiology. 2013;28:330–358. 29. Bherer L, Erickson KI, Liu-Ambrose T. A review of the effects of physical activity and exercise on cognitive and brain functions in older adults. J Aging Res. 2013;2013:657508. 30. Lautenschlager NT. The influence of exercise on brain aging and dementia. Biochem Biophys Acta 2012;1822:474–481. 31. Lista I, Sorrentine G. Biological mechanisms of physical activity in preventing cognitive decline. Cell Mol Neurolbiol. 2010;30:493–503. 32. Barnes JN. Exercise, cognitive function and aging. Adv Physiol Educ. 2015;39:55–62. 33. Ahlskog JE, Geda YE, Graff-Radford NR, Petersen RC. Physical exercise as prevention or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc. 2011;86:876–880. 34. Colcombe S, Kramer AF. Fitness effects as cognitive function of older adults: A meta-analysis study. Psychol Sci. 2003;14:125–130. 35. Muller J, Chan K, Myer JN. Association between exercise capacity and late onset of dementia. 2017;92. 36. Leon AS. Interaction of aging and exercise on the cardiovascular system of healthy adults. Am J Lifestyle Med. 2012;6:368–375.

100 CHAPTER

Aging Successfully: Predictors and Pathways Debra J. Rose, PhD

Key Points.................................................................................1147 100.1  Defining Successful Aging.............................................1147 100.2  Models of Successful Aging...........................................1148 100.3  Life-Course Approach to the Study of Aging...................1148 100.4  Determinants of Successful Aging..................................1149 100.5 Building Pathways to Successful Aging: The Results of Intervention Research................................................1149 100.5.1  Exercise or Physical Activity.............................1149 100.5.2  Cognitive Training and Stimulation...................1150

KEY POINTS • The older population (defined as individuals over the age of 65) is growing rapidly in the United States. By 2030 it is estimated that one in every five Americans will be 65  years or older. • The concept of “  successful aging”  has emerged and been strengthened over the last 20  years. This has resulted in a dramatic paradigm shift making research that used to be focused on negative aspects of aging to now emphasize positive aspects of aging. • Both environmental and lifestyle factors are important to successful aging. • Of all the lifestyle factors that impact on successful aging, regular physical activity plays the most important role. • Cognitive training and stimulation can also play an important role in maintaining mental function. • Dietary influences can also play an important role in successful aging. Dietary recommendations such as those contained in the Dietary Guidelines 2015– 2020 also apply to individuals over the age of 65. According to the Centers for Disease Control and Prevention,1  the United States is on the “ brink of a longevity revolution.”  This prediction is supported by statistics showing that by 2030, one in every five Americans will be 65  years or older. Mortality rates and longevity are also expected to improve with global life expectancy at birth projected to increase by at least 10  years, reaching approximately 76  years by 2050. As a consequence of this disproportionate growth in the older adult segment of the population, health care spending is also projected to increase by as much as 25% unless the health of the older adult population can be preserved or improved substantially. 2  Indeed, current estimates of the number of older

100.5.3  Dietary Influences............................................1151 100.5.4  Social Engagement and Volunteerism..............1151 100.6  It’ s Never Too Late: Fact or Fiction?...............................1152 100.7 Role of Health care Practitioners in the Promotion of Successful Aging.......................................................1152 100.8 Summary.......................................................................1153 Clinical Applications..................................................................1154 References...............................................................................1154

adults (65  years and older) in the United States who are considered to be aging “ successfully”  are alarmingly low. 3  Based on data derived from a national sample of older adults enrolled in the Health and Retirement Study, only 11.9% of older adults were categorized as aging “ successfully”  in any one year according to a similar set of criteria first established by Rowe and Kahn.4 , 5  Moreover, the odds of successful aging (SA) declined by as much as 25% over the 6-  year measurement period (1998–  2004) with the adjusted odds of SA being lower for adults 75  years and older, males, and those at a lower socioeconomic level.3  In this chapter, I will briefly explore the construct of SA, the many definitions and methods used to test various SA models, some of the predictors of SA as currently supported by research across multiple disciplines, and the results of intervention research focused on building pathways to SA. Finally, the role of the health care professional in promoting SA will be discussed and recommendations for implementing intervention strategies that have been shown to be effective in primary and secondary health care settings will be provided in the final section of this chapter.

100.1 DEFINING SUCCESSFUL AGING Both the concept of SA and the term itself is not universally accepted as noted in a review article by Depp and Jeste,6  who identified as many as 29 different definitions of SA during the course of reviewing 28 quantitative studies of SA. By far, the most often included component of SA in more than half of the studies reviewed was physical functioning/disability. Other components included, albeit in fewer study definitions, were cognitive ability, social functioning, life satisfaction, and absence of disease. As a result of the variability in how SA was defined, vastly 1147

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different proportions of study participants were categorized as aging successfully (1– 94%, median 35%). In other studies that have explored the construct of SA using qualitative methods of inquiry7  (i.e., older adult perceptions of SA) or mixed-method approaches that combine objective and subjective criteria of SA,8 –  10  the proportion of older adults categorized as aging successfully has again varied widely. Using the objective criteria set forth by Rowe and Kahn in their model of SA, Strawbridge et al.9  found that only 18.8% of the 867 older adults (65– 99  years) who comprised their sample would be categorized as successfully aging. In contrast, 50.3% of the same sample was similarly categorized on the basis of a single question that asked them to rate the extent to which they thought they were aging successfully. Moreover, when researcher-based criteria was compared with the perceptions of older adults as to what attributes they thought defined SA, a more encompassing definition emerged.7  While the majority of older adults who responded to a mailed survey considered two-thirds (13/20) of the already listed attributes to be important to SA, additional attributes were identified that could be broadly divided into four larger dimensions of health— physical, functional, psychological (mental), and social health. On the basis of these divergent findings, a number of researchers have argued that the perceptions of older adults need to be included in any definition of SA.7 , 11 , 12  McLaughlin et al.3  have also called for a broader definition of SA, particularly if the concept is to be used as a benchmark for assessing the health and functional status of the older adult population. The authors argue that if the term continues to be narrowly defined, “ we are likely to classify many older adults with good health and functioning as being in an unhealthy state for what might be relatively minor reasons.” By way of a compromise to the current controversy over how best to define SA, Depp et al.13  suggest that future research endeavors “ focus on the determinants of success as independent components and investigate the extent to which risk factors and interventions impact these components.”

100.2 MODELS OF SUCCESSFUL AGING To date, the most popular model of SA that has been used to guide gerontology research is one first conceptualized and collaboratively investigated by an interdisciplinary team of scholars assembled by the MacArthur Foundation and chaired by Dr. John Rowe,4 , 5  a geriatrician and physiologist at Mt. Sinai Medical Center. The development of this model was to herald a dramatic paradigm shift in aging research from one that focused on the negative aspects of aging such as disease and disability to one that emphasized the positive aspects of aging and the important role that lifestyle and other psychosocial factors play in helping older adults retain and/or enhance their ability to function well into their later years. The ability to maintain three key characteristics formed the basis of Rowe and Kahn’ s SA model: a low

risk of disease and disease-related disability, high mental and physical function, and active engagement with life.4  In order to be categorized as aging successfully, however, older adults needed to display high levels of all three of the aforementioned characteristics. A sample of 1189 older adults aged between 70 and 79  years who met the objective criteria established for SA (i.e., top 33rd percentile across all three domains) was subsequently followed for the next 8  years.4 , 5  In all, the many related studies that followed produced close to 100 scientific publications and a best-selling lay publication, 5  in which a number of myths previously associated with the aging process were successfully debunked. Baltes and Baltes14  developed a complementary model of SA known as the Selective Optimization with Compensation (SOC) model. The SOC model was based on findings emerging from the original Berlin Aging Study15  that followed a sample of 516 persons aged between 70 and 100  years between 1993 and 1998. In contrast to the Rowe and Kahn model of SA, the SOC model focuses more on describing the behavioral and psychological processes involved in adapting to age-associated reductions in physiological reserve and breadth of neural plasticity. The basic assumption of the SOC model is that individuals engage in behaviors that are aimed at optimizing their general reserves as they age while also compensating for restricted plasticity or adaptive potential. Subsequent research demonstrated that different combinations of the SOC mechanisms are used by adults of different ages to regulate their lives and that higher engagement in SOCrelevant strategies is associated with indicators of SA such as positive psychological functioning, life satisfaction, and emotional well-being, irrespective of age.16  More recently, Pruchno et al.17  have begun testing a two-factor model of SA. Central to their conceptual model of SA is the contention that adults can experience chronic disease and disability and still believe that they are aging successfully and that SA is a characteristic that should not be delimited by age. Unlike the two previous models of SA described, the assumptions of the two-factor model proposed by Pruchno et al. were tested in a large sample of middle-aged adults (50– 74  years). Using a mixed-method approach, wherein SA was defined using both objective and subjective criteria, the authors sought to understand how and to what extent the objective and subjective aspects of SA were related to each other, as well as the role of age and gender. Their preliminary results provide support for a model of SA that includes both objective and subjective criteria. Moreover, their findings further suggest that certain factors such as cognitive function, social engagement, and psychological well-being, previously identified as components of SA, might be better viewed as predictors or antecedents of SA, respectively.

100.3 LIFE-COURSE APPROACH TO THE STUDY OF AGING In recent years, a major shift toward the adoption of a lifecourse approach to studying aging has begun that capitalizes on data derived from historical and birth-cohort

100.5  Building Pathways to Successful Aging: The Results of Intervention Research  1149

studies. The life-course approach,18  as it is called, is being driven by a growing consensus that adult function has its roots in early life experiences and that aging is “ driven by the rate of accumulation of molecular and cellular damage.” According to Kuh et al.18  addressing two fundamental questions is central to a life-course research approach to aging. The first (question) seeks “ to identify what factors across the life course, from the molecular to the societal level, independently, cumulatively, or interactively influence whether people, as they age, maintain their physical and cognitive capability and stay intellectually and socially connected,”  whereas the second addresses the question of how best to “ transfer this knowledge to people themselves and the institutions that exist to improve human health.” It is worthy to note here that the first question being addressed specifically identifies two of the three components that Rowe and Kahn4 , 5  identified in their model of SA. Preliminary findings suggest that early movement experiences in childhood can predict changes in motor and cognitive abilities in mid- and later life as well as the risk of mortality.18 , 19 

100.4 DETERMINANTS OF SUCCESSFUL AGING Key determinants of SA that have been described in a number of review articles on the topic can be broadly divided into the following categories: genetic, biological, psychological, and social/environmental. As Depp and Jeste6  noted in their review, the predictors of SA appeared to vary as a function of the definition of SA used in each study. The strongest and most consistent predictor emerging was younger age (closer to 60  years) with other strong predictors being health-related (e.g., absence of arthritis, higher Activity of Daily Living levels, hearing problems, abstinence from smoking). Engaging in higher levels of physical activity, having fewer medical conditions, global cognitive function, absence of depression, and lower systolic pressure were moderately supported as predictors of SA with only minimal support being provided for higher levels of education and of income, being married, and being white. Although the once-prevalent belief that the secret to SA was to choose your parents wisely has since been found wanting as a result of the MacArthur studies of SA 5  and more recently published molecular genetic studies, 20  one’ s genetic makeup does play a role in the onset of disease21 –  23  and changes in mental function, 24  two important components of the Rowe and Kahn SA model. The good news is that as we age, the influence of genetics appears to become less influential, while environment and lifestyle factors become much more important. The aging process also results in a number of changes occurring at the cellular level that affect the rate at which cells multiply and how they function. These changes can result in compromised immune system responses, the onset of certain diseases (Alzheimer’ s disease and cancer), and an inability to regulate important body functions. Age-related dysregulation of the hypothalamic– pituitary– adrenal (HPA) axis, which

can result in the secretion of glucocorticoids (e.g., cortisol) and the subsequent damage to important brain structures such as the hippocampus, has also been reported. 25  This dysregulation of the HPA axis has been associated with decreased cognitive function and increased depression. 25  The influence of allostatic load 26  (AL) on indices of SA was first investigated during the course of the MacArthur studies of SA and conceptualized as an index of wear and tear on the body resulting from environmental challenges, both internal and external, that are repeatedly placed on the physiological systems of the body across the lifespan. Seeman et al. 27  found higher AL scores to be associated with poor physical and cognitive function as well as an increased risk for cardiovascular disease in a sample of older men and women. Cross-sectional and longitudinal studies have identified a number of psychological attributes that have been associated with SA. These include such things as intelligence and cognitive capacity or reserve, self-efficacy, affect (positive or negative), and attitudes toward the aging process. 28  Although less well studied, there is some evidence to support a role for positive spirituality in SA, 29 –  31  particularly as it relates to one’ s physical and mental health. Spirituality has been shown to be positively related to measures of physical and mental health, psychological well-being, and life satisfaction in older adulthood.31  Important social and environmental factors that have been cited in the literature as important for SA include such things as the physical environment and the level of social support available. Living in an environment that is safe, clean, and affords access to both desired and essential services is believed to be fundamental to aging successfully. Socioeconomic disparities also influence how well an older adult ages. Older adults with fewer financial resources available to them have less access to health care, healthy foods, opportunities for continued education, and a host of other services and/or resources required for aging successfully.32  While each of the variables described in this section have been shown to correlate, to a greater or lesser extent, with how well an older adult functions, it is likely that the complex interplay that occurs among these many variables, combined with the influence of individual lifestyle factors (e.g., physical and cognitive activity, nutrition, social engagement), best determines how older adults are and/or perceive that they are aging successfully.

100.5 BUILDING PATHWAYS TO SUCCESSFUL AGING: THE RESULTS OF INTERVENTION RESEARCH 100.5.1 Exercise or Physical Activity (See also Chapters 98 and 99) A mounting body of empirical evidence has demonstrated that exercise or physical activity plays an important role in shaping many of the physical, psychological, and cognitive changes that occur across the lifespan.

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Certainly, structured exercise- or physical activity-based interventions are at the core of most, if not all, attempts to prevent the onset of disability, slow the progression of disease or system impairments, or restore function to a level that optimizes independence following a traumatic event. Pope and Tarlov33  refer to these as the primary, secondary, and tertiary roles played by physical activity in promoting health. For each of the components identified in the SA model developed by Rowe and Kahn, physical activity has the potential to serve as the primary vehicle for enhancing and/or maintaining each of the three key characteristics identified. Indeed, a substantial amount of research has demonstrated an important primary role for physical activity in the prevention of a number of chronic diseases34  (e.g., cardiovascular disease, type II diabetes, osteoporosis, certain types of cancer), functional limitations, 35 , 36  and premature disability. 37 –  39  Moreover, regular engagement in physical activity is associated with the retention of substantially higher levels of cognitive health as characterized by preserved executive control function well into later adulthood.40 –  42  Finally, regular engagement in physical activity, particularly in socially supportive group environments, facilitates “ active”  engagement in life.43  This is particularly true for older women who are just beginning an exercise program.44 , 45  Despite the wealth of research evidence that has identified physical inactivity as a key risk factor for a number of chronic medical conditions that result in premature disability and/or mortality in the older adult years, only 51.2% of older adults (≥ 65  years) reported participating in the currently recommended level of physical activity (i.e., at least 150  min of moderate-intensity aerobic activity per week or 75  min of vigorous-intensity activity per week).46  Older adults aging with a disability are even less likely to engage in any type of leisure-time activity when compared with older adults without disability. This is a particularly troublesome finding given that individuals with disability who regularly engage in physical activity derive similar health benefits. A reduction in the level of functional impairment and improvements in perceived quality of life have also been demonstrated for individuals with disability who participate in physical activity, even at different levels of intensity.47 , 48  A review of the research investigating the efficacy of different types of physical activity interventions as they influence health in the older adult population, suggest that a “ one type suits all”  physical activity intervention is not effective.49 –  51 As the different roles for physical activity identified earlier in this chapter suggest, relatively healthy older adults can derive significant health benefits and/or a reduced risk for disability by participating in many different types of physical activity interventions (e.g., walking, cycling, structured exercise classes), whereas older adults living with one or more chronic diseases and/or system impairments that adversely affect their health and restrict their mobility appear to benefit more from a physical activity intervention that is more individually tailored to their needs and specifically addresses the impairments that are contributing to a more rapid decline in their health. While the overall intensity of the designed intervention may not differ between these two groups, how the major exercise

principles (i.e., overload and specificity) and related exercise variables (i.e., frequency, intensity, time, and type) are manipulated may be very different. Finally, for older adults who are frail or transitioning into frailty, individualized physical activity interventions that manipulate the major exercise principles and variables in yet another way and are delivered in combination with other intervention strategies (e.g., medication management, environmental modifications to living environment) appear to be a more effective intervention approach.52  Growing evidence also suggests the need for including a behavioral counseling or social-cognitive component within a physical activity intervention as a means of developing self-regulation skills and better long-term compliance with a physical activity intervention.45 , 52 , 53  The benefits of exercise on cognitive function among older adults, considered as important as maintaining physical capacity by Rowe and Kahn, have also been explored in a number of clinical trials over the past decade. Using meta-analytic techniques, Colcombe and Kramer54  evaluated the effects of 18 clinical trials that investigated the impact of different fitness interventions on cognitive function in healthy older adults ranging in age from 55 to 80  years. The benefits of exercise were most apparent for higher-order executive functions such as planning, abstraction, and the selection of relevant sensory information. Larger and more reliable improvements in cognitive function were noted for those fitness interventions that combined aerobic exercise with resistance training and were longer in duration (6  +  months). Of further note was the finding that clinical populations showed similar improvements with exercise as did the non-clinical populations studied. It is presumed that the mechanisms by which exercise exerts its primary influence on brain function lie in its promotion of neurotrophic factors and reduced oxidative stress and inflammation.55 , 56 

100.5.2 Cognitive Training and Stimulation Intervention strategies that specifically target higher-order cognitive processes have also demonstrated significant improvements in the cognitive function of both healthy older adults and those already experiencing mild cognitive impairment. 57 –  60  The Advanced Cognitive Training for Independent and Vital Elderly trial61  investigated both the short- and long-term benefits of a cognitive training program that targeted specific cognitive skills in a sample of 2000 healthy, community-dwelling older adults. Participants were randomly assigned to one of three different training groups (i.e., verbal episodic memory, inductive reasoning, or processing speed) or a no-contact control group. Immediate posttraining improvements in the specifically targeted cognitive skills were observed after only 10 training sessions and continued 2  years after completion of the initial training.57  Cognitive training interventions have also been shown to be effective in reversing intellectual decline with age. This was nicely demonstrated in the Seattle Longitudinal Study.62  Approximately two-thirds of study participants identified with declining cognitive function demonstrated significant improvements in multiple indices of executive

100.5  Building Pathways to Successful Aging: The Results of Intervention Research  1151

function, with approximately 40% of those who had experienced significant declines over the course of the 14-year period they were monitored returned to pre-decline levels of function. 58  Moreover, the positive training effects continued to be observed 14 years posttraining. 59  Other innovative cognitive training programs that have been tested include Senior Odyssey,63  a cognitive enrichment program that engages older adults in complex problem-solving activities in a team-like atmosphere that also promotes social connectedness. Participation in the program has been shown to enhance cognitive functions such as verbal fluency, speed of processing, and mindfulness.63 –  65  Studies investigating the benefits of computerbased cognitive training programs have also demonstrated positive effects on a number of important domains of executive function (e.g., processing speed, memory, selective attention) as well as improved performance in their everyday lives.66 , 67  Many of these programs are now commercially available and are widely used in rehabilitation, community, and retirement settings.

100.5.3 Dietary Influences (See also Chapter 9 on Optimal Nutrition for Older Adults) Both the adequacy and quality of food consumed by the older adult will influence their ability to age successfully. Numerous studies have demonstrated the impact of an inadequate diet on physical health,68 , 69  cognition,70 –  72  and the prevention or control of chronic disease69  in older adulthood. For optimal health across the lifespan, the consistent consumption of a healthy diet that is high in fruits and vegetables, dietary fiber, and essential vitamins and minerals while low in saturated fats is strongly recommended according to the recently published Dietary Guidelines for Americans, 2015–2020 .73  Adults over 50  years of age are also encouraged to consume foods fortified with vitamin B12 . Maintaining a healthy diet is also essential for weight reduction or maintenance. Research studies have shown that obese or overweight adults are at a higher risk for developing high blood pressure, diabetes, heart disease, arthritis, and certain forms of cancer.74  Decreased mobility and daily function are also negative outcomes associated with being overweight or obese. Unfortunately, maintaining a proper diet is not always easy for many older adults as a result of physiological changes that result in compromised organ function, difficulties with chewing or swallowing, or diminished interest in food as a result of sensory changes affecting taste and smell.74  Living alone has also been associated with an older adult’ s inability to meet his or her nutritional needs.75  In addition to the consumption of a well-balanced diet, findings from a small number of clinical and epidemiological trials have also demonstrated the benefits of calorie restriction (CR) and reduced food intake on multiple indices associated with SA. In addition to reducing the incidence of many age-related diseases,76  other favorable findings include reductions in blood pressure, body mass index, triglyceride levels, and improved cholesterol profiles.76 –  78  Improvements in memory have also been

demonstrated after relatively short periods (3  months) of caloric restriction.79  More recently, an alternative strategy to CR has become the focus of growing attention by a number of research groups.80  The development of CR Mimetics (i.e., compounds that target metabolic and stress-response pathways and, thereby, mimic the effects of CR) is underway. These drugs (e.g., metformin, resveratrol) are intended to mimic the metabolic, hormonal, and physiological effects of CR without the need to actually restrict caloric intake. Although more longitudinal studies are needed to more fully evaluate the long-term influences of CR Mimetics on the aging process, preliminary findings are promising with respect to CRM’ s enhancing and neuroprotective effects. Other nutrients that are essential to the physical health and cognitive function of older adults include calcium, which is critical for lowering the risk of bone loss and osteoporosis in both men and women,81  folic acid, omega-3 fatty acids, and other antioxidant vitamins.82  Some evidence also exists for the positive benefits of added vitamin D supplementation, particularly for older adults showing below-average baseline levels.83  Inadequate vitamin D levels have been associated with increased risk for falls and related fractures that will significantly undermine the older adults’  physical and emotional health.84  Finally, some evidence suggests that dietary supplements in the form of enriched drinks can have positive benefits on selected measures of cognition.85 

100.5.4 Social Engagement and Volunteerism The importance of being socially engaged and having a strong social support network in older adulthood has been frequently cited as an important characteristic4  or determinant of SA.13  Recent intervention research, in particular, has focused on the benefits of involving older adults in a variety of different productive activities (e.g., working for a salary, caregiving), including volunteering.86 –  91  One highly successful program that has been demonstrated to benefit both the older adult volunteers as well as those served is the Experience Corps (EC), a program that trains older adults to assist at-risk elementary school students with learning math and other skills in a school setting.86  In one of the first studies conducted to evaluate the program’ s efficacy, Fried et al. assigned 149 new older adult recruits to either an EC or control group. The older adult volunteers assigned to the EC group worked with elementary school students to improve their math and reading skills for a minimum of 15  h a week throughout the academic year. Outcomes at 1  year showed that the EC volunteers demonstrated significantly higher levels of physical activity, strength, cognition, and breadth of social support networks. What is perhaps most noteworthy about this program is that similar health benefits were derived by older adult volunteers categorized as being in only fair-to-good health.87  Having older adults engage in productive activities has also been shown to be positively associated with physical and psychological health as well as survival rates of older adults.89 –  91  Collectively, the results of these studies provide support for the value

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of older adults engaging in meaningful volunteer activities as a means of improving their level of physical, cognitive, and social health— all important determinants for SA.

100.6 IT’ S NEVER TOO LATE: FACT OR FICTION? While considerable research has demonstrated the negative effects of physical inactivity, obesity, smoking, excessive alcohol, and poor diet on morbidity and mortality,92 –  94  there is evidence to suggest that much can be done to reverse many of the adverse effects associated with unhealthy lifestyle behaviors.95  In fact, one of the many myths debunked as a result of the MacArthur Foundation studies was that it is too late for older adults to lower their risk for premature morbidity and mortality after decades of engaging in unhealthy (e.g., eating fatty foods, not exercising) or risky behaviors (e.g., smoking, excessive consumption of alcohol) once older adulthood is reached. 5  Research has also shown that most age-associated declines in physical performance can also be reversed with regular participation in even moderate levels of physical activity.96 , 97  For example, the Lifestyle Interventions and Independence for Elders pilot study, a multicenter, randomized clinical-controlled trial involving 424 sedentary persons aged between 70 and 89  years at risk for disability, has demonstrated both immediate97  and longerterm improvements (2- year follow-up)98  in physical performance and mobility disability following completion of a 12-month moderate-intensity physical activity intervention. As Rowe and Kahn5  aptly state, “ Physical activity is at the crux of SA, regardless of other factors.”  Research evidence also shows that smoking cessation, even in the case of previously heavy smokers, significantly lowers the risk for cardiovascular disease, lung cancer, and stroke.99 , 100  According to the American Lung Association, within a year of quitting, former smokers reduce their risk of coronary heart disease by 50% with the risk further declining with each passing year.99  The adverse effects of a poor diet can also be reversed through nutritional interventions that combine dietary screenings with individualized nutrition plans designed to address the specific needs of the older adult (e.g., malnourishment, obesity).101 , 102  Bowen and Beresford,103  following their review of 80 published dietary intervention studies, concluded that more intensive dietary interventions that set high goals for participants and recruited more selectively (i.e., more highly motivated participants) yielded better outcomes.

100.7 ROLE OF HEALTH CARE PRACTITIONERS IN THE PROMOTION OF SUCCESSFUL AGING Health care professionals can play an integral role in promoting SA among older adults. Health care providers are viewed by the majority of older adults as the primary

source of health information and, therefore, have the credibility needed to be an influential force in getting older adults to embrace a healthier lifestyle. The very fact that adults in the United States visit a physician’ s office an average of three times per year provides the opportunity needed to implement successful health-promoting practices.104  In spite of this knowledge, the percentage of older adults (65  years or older) who report receiving counseling about health-promoting behaviors such as regular physical activity are very low (approximately 31%).105  In this final section of the chapter, I will briefly review the research evidence that supports a role for the health care provider and the types of intervention strategies that have yielded successful outcomes. A number of research studies have explored the benefits of physician-based counseling of patients, particularly as it relates to physical activity,106  smoking cessation,107  alcohol consumption,108 and nutrition.109  Calfas et al.110  demonstrated that previously sedentary patients provided with in-office structured counseling sessions as short as 3– 5  min resulted in positive short-term changes in their patients’  physical activity levels as well as their readiness to adopt physical activity. Other studies that have individually tailored the PA counseling by matching it to a patient’  s stage of motivational readiness for physical activity111  (e.g., precontemplation, contemplation, preparation) have also proven effective, at least in the short term112 , 113  (see also Chapter 18 Transtheoretical Model). Patients enrolled in the Physically Active for Life project who received individually tailored PA (Physical Activity) counseling were more likely to be in more advanced stages of readiness for PA 6  weeks following their initial counseling appointment when compared with a group receiving standard care. Unfortunately, these gains were no longer evident after 8  months with no differences in physical activity levels evident between the two groups.113  In order to achieve more long-term behavior change among previously inactive older adult patients, Pinto et al.114  supplemented a brief PA counseling session (approximately 3  m in) delivered by the physician during the course of an office visit with regular telephone counseling by a health educator. Significantly higher levels of physical activity were reported for the group receiving the additional telephone counseling (additional hour/week) after 3  months when compared with a group receiving a single in-office counseling session (12.45  m in/week). More importantly, the physical activity gains were sustained in the extended counseling group through 6  months of follow-up. In addition to counseling, providing older adult patients with a motivational tool in the form of a pedometer may also prove to be an effective intervention strategy. Findings from a study conducted by Bravata et al.115  showed that pedometer use by adult outpatients resulted in higher physical activity levels and other health benefits (decreases in body mass index and blood pressure), at least in the short term. Given the knowledge that older adults can attenuate the progression of functional impairments by up to 55%, even by engaging in only moderate levels of physical activity,116  providing physical activity counseling to all older adult patients, irrespective of health status, should be a high priority for the health care professional.

100.8  Summary  1153

Physician-based counseling focused on alcohol consumption,108  smoking cessation,107 , 117  and improved nutritional practices109  has also yielded successful outcomes. The efficacy of physicians providing two brief (10– 15  min, 1  month apart) counseling sessions supplemented with follow-up phone calls from a nurse has been demonstrated to significantly lower alcohol use, episodes of binge drinking, and frequency of excessive drinking in groups of at-risk patients reevaluated at 1 and 2  years after the first counseling session.108  Similarly, physician counseling, often combined with nicotine replacement therapy or telephone quitlines, also constitutes effective smokingcessation strategies.107 , 117  Intervention strategies aimed at improving dietary behaviors have also yielded successful outcomes when delivered by health care providers in primary care settings. The most effective interventions appear to combine patient education, behavioral counseling, patient reinforcement, and follow-up. The interventions also tend to be more intensive, are conducted over a longer period of time, and are directed at patients at increased risk for chronic disease.109  Routine counseling of patients relative to the physical and cognitive benefits of social engagement as well as engaging in cognitively demanding activities should also be an integral component of the health care services provided to older adults. Encouraging older adults to add new cognitive, physical, and social activities into their daily routines and providing examples of appropriate types of activities will be important. As indicated earlier in this chapter, certain types of computer-based cognitive training programs have been demonstrated to improve multiple domains of cognition (e.g., processing speed, memory, visuospatial orientation) in controlled trials conducted with older adults.66  Although more controlled studies are needed, limited evidence also suggests that improvements in certain cognitive domains transfer to the performance of routine daily activities.118  Indeed, many communitybased centers and retirement communities have begun installing computer-based “ brain fitness”  training programs and other types of interactive video games (e.g., Nintendo Wii) aimed at improving the physical, cognitive, and social health of older adults. Older adults who report unusual changes in their physical or cognitive health concerns to their health care provider should undergo further testing to distinguish between changes that are associated with age versus pathology. Because age-associated changes in muscle and bone predispose older adults to injury, additional care needs to be taken when prescribing physical activity for older adults and referring them to community-based classes. In the case of those older adults who are already experiencing significant changes in their functional abilities and are at heightened risk for falls, it will be especially important to have the appropriate health care professional conduct a thorough assessment of their physical abilities so that the exercise prescription can be appropriately matched to their ability level. While referrals to local community-based physical activity programs or directions on how to begin a self-directed walking program may be sufficient for more healthy patients, others will require more tailored and multifactorial interventions. 52  While some hospitals and outpatient centers currently offer on-site

programs that include educational programs directed at improving chronic disease self-management skills as well as structured exercise programs focused on primary or secondary prevention of disease, many more are needed to address the growing needs of the middle-aged and older adult populations. What are the core ingredients necessary for implementing interventions aimed at enhancing the health of older adults? Haber119  recommends that in order to be successful, health promotion interventions aimed at older adults should include the following core elements: the development of short- and long-term health goals that are both modest and measurable, strategies for building and maintaining the patient or client’ s motivation, techniques for addressing barriers that have prevented success in the past and/or might become an issue in the future, fostering compliance so that the new behavior becomes a habit, and assisting the patient/client to garner the social support needed to continue in the face of adversity. To accomplish these outcomes, an interdisciplinary team approach is going to be necessary.

100.8 SUMMARY Despite the controversy that the term “ successful aging”  has sparked in the literature, both with respect to how it is defined and/or measured, research evidence strongly indicates that aging is not synonymous with an inevitable decline in one’ s physical and cognitive health. Modifiable lifestyle and behavioral factors clearly play a greater role in shaping the older adults’  overall quality of life, both as it is perceived and actually experienced, than one’ s genetic inheritance. While making healthy lifestyle and behavior choices early in life are clearly important to optimizing health and well-being in later adulthood, the research shows that it’ s never too late for an older adult to alter the trajectory of his or her lifespan. The health care professional has the potential to serve as both an important catalyst for change as well as a mediator of that change. Regularly counseling older adult patients about the benefits of physical activity, eating a balanced diet, not smoking, and avoiding excessive alcohol intake can do much to improve their physical health. Similarly, encouraging older adults to engage in stimulating cognitive and social activities on a daily basis will also benefit them psychologically and emotionally. The early identification of unusual physical and cognitive changes is an important first step in preventing or delaying the onset of more serious impairments that will threaten an older adult’ s ability to remain independent and socially engaged. This can be accomplished through regular screenings conducted by the appropriate health care provider and immediate referral for additional testing, if warranted, or to programs and/or services available in outpatient or community settings. In order to ensure long-term success, a systematic and collaborative team approach will be necessary because no single health care provider has the knowledge, skills, or resources available to address the many factors that contribute to whether an older adult does or does not age successfully. Building wellness teams that interface primary care physicians,

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physician assistants, physical and occupational therapists, and clinical nurse specialists with health educators and other community- and home-based service providers will be needed if long-term behavior change can be expected. Added incentives in the form of allocating time for health care providers to receive the necessary training, providing additional resources and personnel to implement effective interventions, and providing financial reimbursement linked to outcomes may be necessary to help primary care providers, in particular, overcome many of the barriers that currently exist to the implementation of regular health-promoting practices with their older-adult patients.

CLINICAL APPLICATIONS • It is possible to reverse many of the age-related declines in health and cognition with lifestyle factors.

• Health care practitioners play a key role in helping older individuals take positive steps to improve the aging process, but the likelihood that physicians will engage in this type of conversation is low (probably no more than 31%). • Physicians should counsel their older patients on physical activity and other types of positive lifestyle choices such as reducing alcohol consumption, improving overall diet, and smoking cessation. • Physicians should also counsel older individuals on the importance of social engagement as a key component of successful aging. • Counseling sessions as brief as 3– 5  minutes have been proven to be successful in helping older individuals improve lifestyle factors that contribute to successful aging. • Any sudden or significant decline in either cognitive or physical function should result in a thorough assessment before recommending lifestyle changes.

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Quality of Care and Outcomes Research. Circulation  2006;114:2739– 2752. Howe TE, Rochester L, Jackson A et al. Exercise for improving balance in older people (Review). Cochrane Database of Syst Rev  2007;(4):CD004963. DOI: 10.1002/14651858.CD004963.pub2. Rose DJ, Hernandez D. The role of exercise in fall prevention for older adults. Clin Geriatr Med  2010;26(4):607– 631. King AC. Interventions to promote physical activity by older adults. J Gerontol A Biol Sci Med Sci  2001;56:36– 46. Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: A meta-analytic study. Psychol Sci  2003;14:125– 130. Colcombe SJ, Erickson KI, Scalf PE et al. Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci  2006;61:1166– 1170. Kramer AF, Colcombe SJ, McAuley E et al. Fitness, aging and neurocognitive function. Neurobiol Aging  2005;26(Suppl 1):124– 127. Ball K, Berch DB, Helmers KF et al. Effects of cognitive training interventions with older adults: A randomized controlled trial. JAMA  2002;288:2271– 2 281. Schaie KW, Willis SL. Can intellectual decline in the elderly be reversed? Dev Psychol  1986;22:223– 232. Willis SL, Schaie KW. Training the elderly on the ability factors of spatial orientation and inductive reasoning. Psychol Aging  1986;1:239– 247. Willis SL, Tennstedt SL, Marsiske M et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA  2006;296:2805– 2814. Jobe JB, Smith DM, Ball K et al. ACTIVE: A cognitive intervention trial to promote independence in older adults. Control Clin Trials  2001;22(4):453– 479. Schaie KW. Developmental Influences on Cognitive Development: The Seattle Longitudinal Study . New York: Oxford University Press; 2004. Parisi JM, Greene JC, Morrow DG et al. The Senior Odyssey: Participant experiences of a program of social and intellectual engagement. Act Adapt Aging  2007;31:31– 49. Park DC, Gutchess AH, Meade ML et al. Improving cognitive function in older adults: Nontraditional approaches. J Gerontol B Biol Sci Psychol Sci  2007;62:45– 52. Stine-Morrow EAL, Basak C. Cognitive interventions. In Schaie KW, Willis SL (Eds.). Handbook of the Psychology of Aging , 7th edn. New York: Elsevier; 2011; 153– 170. Smith GE, Housen P, Yaffe K et al. A cognitive training program based on principles of brain plasticity: Results from the Improvement in Memory with Plasticity-based Adaptive Cognitive Training (IMPACT) study. J Am Geriatr Soc  2009;57(4):594– 603. Barnes DE, Yaffe K, Belfor N et al. Computer-based cognitive training for mild cognitive impairment: Results from a pilot, randomized, controlled trial. Alzheimer Dis Assoc Disord  2009;23(3):205– 210. Burke GL, Arnold AM, Bild DE et al. Factors associated with healthy aging:

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The cardiovascular health study. J Am Geriatr Soc  2001;49:254– 262. Shikany JM, White GL Jr. Dietary guidelines for chronic disease prevention. South Med J  2000;93(12):1138– 1151. Fillit HM, Butler RN, O’ Connell AW et al. Achieving and maintaining cognitive vitality with aging. Mayo Clin Proc  2002;77:681– 696. Mattson MP, Chan SL, Duan W. Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev  2002;82(3):637– 672. Gonzalez-Gross M, Marcos A, Pietrzik K. Nutrition and cognitive impairment in the elderly: Review. Br J Nutr  2001;86:313– 321. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2015–  2 020 . Washington, DC: U.S. Government Printing Office; 2015. Bobroff L. Nutrition and diet. In O’ Neil K, Peterson RL (Eds.). Optimal Aging Manual  (pp. 626– 6 41). Sarasota, FL: Optimal Aging LLC; 2004. Hays JC. Living arrangements and health status in later life: A review of recent literature. Public Health Nurs  2002;5:136– 151. Yu BP. Modulation of Aging Processes by Dietary Restriction . Boca Raton, FL: CRC Press; 1994. Heilbronn LK, de Jonge L, Frisard MI et al. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: A randomized controlled trial. JAMA  2006;295:1539– 1548. Masoro EJ. Overview of caloric restriction and ageing. Mech Ageing Dev  2005;126:913– 922. Witte A, Fobker M, Gellner R et al. Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci USA  2009;106:1255– 1260. Ingram DK, Zhu IM, Mamczarz IJ et al. Calorie restriction mimetics: An emerging research field. Aging Cell  2006;5:97– 108. Cumming RG. Calcium intake and bone loss: A quantitative review of the evidence. Calcif Tissue Int  1990;47:194– 201. Gomez-Pinilla F. Brain foods: The effects of nutrients on brain function. Nat Rev Neurosci  2008;9:568– 578. Bischoff-Ferrari HA, Willett WC, Wong JB et al. Fracture prevention with vitamin D supplementation: A meta-analysis of randomized controlled trials. JAMA  2005;293(18):2257– 2 264. Janssen HC, Samson MM, Verhaar HJ. Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr  2002;75(4):611– 615. Wouters-Wesseling W, Wagenaar LW, Rozendaal M et al. Effect of an enriched drink on cognitive function in frail elderly persons. J Gerontol A Biol Sci Med Sci  2005;60:265– 279. Fried LP, Carlson MC, Freedman M et al. A social model for health promotion for an aging population: Initial evidence on the Experience Corps model. J Urban Health  2004;81:64– 78.

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1156  Chapter 100  Aging Successfully 87. Barron JS, Tan EJ, Yu Q et al. Potential for intensive volunteering to promote the health of older adults in fair health. J Urban Health  2009;86(4):641– 653. 88. Jung Y, Gruenewald TL, Seeman TE et al. Productive activities and development of frailty in older adults. J Gerontol B Psychol Sci Soc Sci  2009;65B(2):256– 261. 89. Baker LA, Cahalin LP, Gerst K et al. Productive activities and subjective wellbeing among older adults: The Influence of number of activities and time commitment. Soc Indic Res  2005;73:431– 458. 90. Glass TA, Mendes de Leon CF, Marottoli RA et al. Population based study of social and productive activities as predictors of survival among elderly Americans. BMJ  1999;319:478– 483. 91. Hinterlong JE, Morrow-Howell N, Rozario PA. Productive engagement and late life physical and mental health: Findings from a nationally representative panel study. Res Aging  2007;29:348– 370. 92. Ferrucci LG, Izmirlian G, Leveille S et al. Smoking, physical activity, and life expectancy. Am J Epidemiol  1999;149:645– 653. 93. Reynolds SL, Hagedorn A, Yeom J et al. The impact of obesity on active life expectancy. Gerontologist  2005;45:438–  4 44. 94. Ebrahim E, Wannamethee SG, Whincup P et al. Locomotor disability in a cohort of British men: The impact of lifestyle and disease. Int J Epidemiol  2000;29:478– 486. 95. Morely JE, Flaherty JH. It’ s never too late: Health promotion and illness prevention in older persons. J Gerontol A Biol Sci Med Sci  2002;57A:M338– M 342. 96. Meisner BA, Dogra S, Logan AJ et al. Do or decline? Comparing the effects of physical inactivity on biopsychosocial components of successful aging. J Health Psychol  2010;15(5):688– 696. 97. Pahor M, Blair SN, Espeland M et al. Effects of a physical activity intervention on measures of physical performance: Results of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P)

study. J Gerontol A Biol Sci Med Sci  2006;61:M1157– M1165. 98. Rejeski WJ, Marsh AP, Chmelo E et al. The Lifestyle Interventions and Independence for Elders Pilot (LIFE-P): 2-Year follow-up. J Gerontol A Biol Sci Med Sci  2009;64A(4):M462– M467. 99. American Lung Association. Benefits of quitting smoking for older adults. http:​ //www​.lung​usa.o​rg/st​op-sm​oking ​/abou​ t-smo​k ing/​facts​-figu​res/s​mokin​g-and​- olde​ r-adu​lts.h​t ml. Accessed March 21, 2018. 100. Hermanson B, Omenn GS, Kronmal RA et al. Beneficial six-year outcome of smoking cessation in older men and women with coronary artery disease. N Engl J Med  1988;319:1365– 1369. 101. Meydani M. Nutrition interventions in aging and age-associated disease. Ann N Y Acad Sci  2001;928:226– 235. 102. Milne AC, Potter J, Vivanti A et al. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev  2009; CD003288. 103. Bowen DJ, Beresford SAA. Dietary interventions to prevent disease. Ann Rev Public Health  2002;23:255– 286. 104. Cherry D, Woodwell D. National Ambulatory Medical Care Survey: 2000 summary. Adv Data  2002;328:1– 32. 105. Glasgow RE, Eakin EG, Fisher EBN et al. Physician advice and support for physical activity: Results from a national survey. Am J Prev Med  2001;21:189– 196. 106. Eden KB, Orleans CT, Mulrow CD et al. Does counseling by clinicians improve physical activity? A summary of the evidence from the U.S. Preventive Services task Force. Ann Intern Med  2002;137:208– 215. 107. Ranney L, Melvin C, Lux L et al. Systematic review: Smoking cessation intervention strategies for adults and adults in special populations. Ann Intern Med  2006;145:845– 856. 108. Fleming M, Manwell LB, Barry KL et al. Brief physician advice for alcohol problems in older adults: A randomized community-based trial. J Fam Pract  1999;48(5):378– 384.

109. P ignone MP, Ammerman A, Fernandez L et al. Counseling to promote a healthy diet in adults. A summary of the evidence for the U.S. Preventive Services Task Force. Am J Prev Med  2003;24(1):75– 92. 110. Calfas KJ, Long BJ, Sallis JF et al. A controlled trial of physician counseling to promote the adoption of physical activity. Prev Med  1996;25:225– 233. 111. Prochaska, J, Marcus, BH. The transtheoretical model: Applications to exercise. In RK Dishman (Ed.). Advances in Exercise Adherence . Champaign, IL: Human Kinetics; 1994; 161– 180. 112. Marcus BH, Bock BC, Pinto BM et al. Efficacy of an individualized, motivationally-tailored physical activity intervention. Ann Behav Med  1998;20(3):174– 180. 113. G oldstein MG, Pinto BM, Marcus BH et al. Physician-based counseling for middle-aged and older adults: A randomized trial. Ann Behav Med  1999;21(1):40–  47. 114. Pinto BM, Goldstein MG, Ashba J et al. Randomized controlled trial of physical activity counseling for older primary care patients. Am J Prev Med  2005;29(4):247– 255. 115. Bravata DM, Smith-Spangler C, Sundaram V et al. Using pedometers to increase physical activity and improve health: A systematic review. JAMA  2007;298(19):2296– 2304. 116. Miller ME, Rejeski WJ, Reboussin BA et al. Physical activity, functional limitations, and disability in older adults. J Am Geriatr Soc  2000;48:1264– 1272. 117. Morgan GD, Noll EL, Orleans T et al. Reaching midlife and older smokers: Tailored interventions for routine medical care. Prev Med  1996;25(3):346– 354. 118. Willis SL, Tennstedt SL, Marsiske M et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA  2006;296(23):2805– 2814. 119. Haber D. Health Promotion and Aging , 4th ed. New York: Springer Publishing; 2007.

101 CHAPTER

Role of Physical Activity in the Health and Wellbeing of Older Adults Andiara Schwingel, PhD and Wojtek J. Chodzko-Zajko, PhD

Key points.................................................................................1157 101.1 Introduction...................................................................1157 101.2  Benefits of Physical Activity for Older Adults...................1158 101.3  Recommendations and Guidelines for Physical Activity...... 1159 101.3.1  Aerobic Activity for Older Adults.................................1159 101.3.2 Muscle-Strengthening Activities for Older Adults���� 1159 101.3.3  Balance Training for Older Adults...............................1159 101.3.4 Special Considerations for Prescribing Physical Activity for Older Adults�������������������������������������������� 1160 101.4 Motivating Older Adults to Initiate and Maintain a Physically Active Lifestyle..............................................1160 101.4.1  Social Support—Involving Friends and Family.......1160 101.4.2  Self-Efficacy—You Can Do It! We Can Help!......1160 101.4.3 Active Choices—Finding the Program That Works For You������������������������������������������������ 1160 101.4.4 Health Contract or Plan of Action—Making a Commitment����������������������������������������������� 1160 101.4.5  Perceived Safety—It’s Safe, It’s Fun.................1161 101.4.6 Regular Performance Feedback—How Are We Doing?����������������������������������������������������� 1161 101.4.7 Positive Reinforcement—Keep It Up, You’re Doing Great!��������������������������������������������������� 1161 101.5  Communicating about Exercise and Physical Activity........1161 101.5.1  Step 1—Getting Started...................................1161

KEY POINTS • Regular physical activity can reduce the risk of older adults developing a new chronic condition and reduce the risk of progression of the condition they already have, reduce their risk of falls and fallrelated injuries, and improve their physical function and quality of life. Physical activity can help older adults remain active and engaged within their families and communities. • Older adults should perform 150 min/week of moderate-intensity aerobic activity and muscle-strengthening activities 2 days/week. Balance exercise is recommended for all older adults as a way to prevent falls and fall injuries. • If health conditions prevent activity at the recommended amount, older adults should perform physical activities as tolerated so as to avoid being sedentary. Avoiding sedentary behavior is an

101.5.2 Step 2—Making Physical Activity Part of Your Life��������������������������������������������������������� 1161 101.5.3  Step 3—Keeping It Up, Stepping It Up..............1162 101.5.4  Step 4—Being Active for Life...........................1162 101.6 Answering Questions about Exercise and Physical Activity............................................................ 1162 101.6.1  Question: Why Should I Be Physically Active?......1162 101.6.2 Question: How Much Physical Activity Do I Need?���������������������������������������������������������� 1162 101.6.3 Question: What Is the Best Exercise for Older Adults?������������������������������������������������� 1163 101.6.4 Question: How Many Times a Week Should I Exercise?������������������������������������������������������� 1163 101.6.5 Question: I Have Not Exercised for Many Years, Where Should I Start?�������������������������� 1163 101.6.6 Question: Will Physical Activity Help to Reduce My Risk for Specific Diseases and Conditions?���� 1163 101.6.7  Question: Is Exercise Safe?..............................1164 101.6.8  Question: Am I Too Old to Exercise?..................1164 101.6.9 Question: Do I Need Special Clothing and Equipment?��������������������������������������������������� 1164 101.7 Summary.......................................................................1165 Clinical Applications..................................................................1165 References...............................................................................1165

important consideration when promoting health and wellbeing among older adults.

101.1 INTRODUCTION Is functional decline an inevitable and inescapable consequence of growing older? Or can we play an active role in determining the path that aging takes? There is a growing body of evidence to suggest that we may be able to postpone some of the negative consequences of growing older by maintaining an active lifestyle. Physical activity is shown to be an effective way of postponing the onset of functional decline, promoting independence, and maintaining quality of life in old age. During the past century, many countries have experienced an epidemiological transition in which the impact of communicable diseases has steadily declined and non-communicable diseases (NCDs) have become the leading causes of disease, disability, and death.1 1157

1158  Chapter 101  Role of Physical Activity in the Health and Wellbeing of Older Adults

Because NCDs typically take many years to develop, older adults are disproportionately affected; many of whom have increased risk of developing and dying from cardiovascular disease, type 2 diabetes, obesity-related NCDs, and certain cancers.1–4 Many NCDs share common preventable causes that are both lifestyle related (unhealthy diets, physical inactivity, smoking, and alcohol abuse) and biological (hypertension, obesity, and dyslipidemia). In addition, there are also a number of social determinants of health linked with NCDs, including education, availability, and affordability of healthy food, access to health services, and policies and infrastructures that support a healthy lifestyle. Despite the complex relationships among the many determinants of health, the World Health Organization (WHO) has identified physical activity as an effective means by which an individual can reduce the risk of developing NCDs and maintain independence and wellbeing in old age.5 Epidemiological research has consistently shown significant decreases in the relative risk of cardiovascular and all-cause mortality among persons who are classified as physically active compared with those in a similar age range who are classified as less active or sedentary.6 In agreement is the recently published 2018 Physical Activity Guidelines Advisory Committee Scientific Report,7 which confirms that physically active individuals sleep better, feel better, and function better. Strong evidence shows that regular physical activity can reduce the risk of older adults developing a new chronic condition and reduce the risk of progression of the condition they already have, reduce their risk of falls and fall-related injuries, and improve their physical function and quality of life. However, many older adults find it difficult to meet the targets proposed in the physical activity guidelines. Over the past decade, many studies have focused on the positive effects of smaller amounts of physical activity and/or the adverse consequences of sedentary behavior on health and wellbeing.7 Strong scientific evidence demonstrates that exposure to high amounts of sedentary behavior significantly increases the risk of developing NCDs (e.g. cardiovascular disease and diabetes) and death. For physically inactive individuals, replacing sedentary behavior with light intensity physical activities is likely to produce health benefits. Although not the focus of this book chapter, avoiding sedentary behavior is an important consideration when promoting health and wellbeing among older adults. In this chapter, we present an overview of current research and recommendations concerning the role of physical activity in the health and wellbeing of older adults. In the “Benefits of physical activity for older adults” section, we briefly review some of the benefits that accrue to older individuals who adopt a physically active lifestyle. In the “Recommendations and guidelines for physical activity” section, we summarize current guidelines regarding the frequency, intensity, duration, and type of physical activity recommended for older adults. Next, in the “Motivating older adults to initiate and maintain a physically active lifestyle” section, we focus on evidence-based strategies to help motivate older adults to initiate and maintain a physically active lifestyle. Finally, in the “Communicating about exercise and physical activity” section, we discuss how health professionals should talk to older adults about physical activity, focusing on the need to help them learn how to “be active their way.” We conclude by providing answers to frequently

asked questions about physical activity. Throughout the chapter, the Institute of Medicine definitions of physical activity and exercise and related concepts are adopted, where physical activity refers to body movement that is produced by the contraction of skeletal muscles and that increases energy expenditure. Exercise refers to planned, structured, and repetitive movement to improve or maintain one or more components of physical fitness.

101.2 BENEFITS OF PHYSICAL ACTIVITY FOR OLDER ADULTS Over the past 30 years, a number of studies have confirmed that there are many benefits for older adults who participate in regular physical activity. In 2008, the Department of Health and Human Services (DHHS) published, for the first time, official U.S. Government Physical Activity Guidelines (PAG).8 This book chapter presents findings from the 2008 PAG and from the 2018 PAG Advisory Committee Scientific Report.7 Both documents reiterate that, compared with less active persons, more active men and women have lower rates of all-cause mortality, coronary heart disease, high blood pressure, stroke, type 2 diabetes, metabolic syndrome, cancer (colon, breast, bladder, endometrium, esophagus, kidney, lung, and stomach), depression, sleep problems, falls and fall-related injuries, and dementia and other aspects of cognitive function. In addition to these biomedical benefits, there are many other reasons older adults should be encouraged to find a way to build physical activity into their everyday lives. Regular physical activity can help to improve quality of life in old age. Physical activity can help older adults remain active and engaged within their families and communities. A detailed review of the benefits of physical activity for older adults is beyond the scope of this chapter; however, several review articles are available, which provide excellent summaries of the existing evidence.7,9,10 For example, the American College of Sports Medicine (ACSM)’s Position Stand on Exercise and Physical Activity for Older Adults9 summarizes the benefits of both long-term exercise and physical activity and shorter-duration exercise programs on the health and well-being of older adults. The ACSM Position Stand concludes that, although no amount of physical activity can stop the biological aging process, there is evidence that regular physical activity can slow the physiological declines of an otherwise sedentary lifestyle and increase healthy life expectancy by limiting the development and progression of NCDs and other disabling conditions. Importantly, physical activity not only benefits our physical health but there is also strong evidence that it can improve psychological health and wellbeing. Ten years ago, the American Medical Association and the ACSM launched a major initiative called “Exercise is Medicine” (EIM).11 The goal of EIM is to make physical activity and exercise a standard part of a global disease prevention and treatment medical paradigm. The initiative recognizes that regular exercise can be an important element in the management of numerous medical conditions including coronary heart disease,12,13 hypertension,12,14,15 peripheral vascular disease,16 type 2 diabetes,17 obesity,18

101.3  Recommendations and Guidelines for Physical Activity  1159

elevated cholesterol,12,19 osteoporosis, 20 osteoarthritis, 21,22 claudication, 23 and chronic obstructive pulmonary disease. 24 A joint statement from ACSM and the American Heart Association10 concludes that physical activity is valuable in the treatment and management of depression and anxiety disorders, 25 dementia, 26 pain, 27 congestive heart failure, 28 syncope, 29 stroke, 30 back pain, 31 and constipation.32 In addition, there is some evidence that physical activity prevents or delays cognitive impairment33,34,35 and disability36,37,38 and improves sleep.39 EIM strongly advocates that physical activity should be considered by all health professionals as a vital sign in every patient visit and that all patients are effectively counseled and referred with respect to their physical activity needs. The World Health Organization (WHO) suggests that the benefits of physical activity for older adults can be divided into two broad categories: (1) benefits of physical activity for the individual and (2) benefits of promoting physically active lifestyles for society.40 Under the WHO schema, the individual benefits can be summarized in four general areas: physiological benefits; psychological benefits; social benefits; and the benefits for society. Among social benefits for the individual, participation in physical activity can help empower older individuals and assist them in playing a more active role in society. Physical activity programs, particularly when carried out in small groups and/ or in social environments, enhance social and intercultural interactions for many older adults. Society at large can benefit from physically active older adults. Physically active lifestyles can help postpone the onset of physical frailty and disease thereby significantly reducing health- and social-care costs. Older individuals have much to contribute to society. Physically active lifestyles help older adults maintain functional independence and optimize the extent to which they are able to actively participate in society. A society which promotes a physically active lifestyle for older adults is more likely to reap the benefits of the wealth of experience and wisdom possessed by the older individuals in the community. As long ago as 1996, the WHO was recommending that virtually all older persons should participate in physical activity on a regular basis and that society has a responsibility to advocate for broad-based participation in physical activity whenever possible. The WHO’s recommendations conclude that regular physical activity provides substantial benefits. In addition, it is cheap, safe, and readily available.

101.3 RECOMMENDATIONS AND GUIDELINES FOR PHYSICAL ACTIVITY The recommendations for the frequency, intensity, and duration of exercise and physical activity for older adults are summarized in the subsequent sections. Older adults should do 150 min/week of moderate-intensity aerobic activity. Additional benefits occur as the amount of physical activity increases through higher intensity, greater frequency, and/or longer duration. In addition, older adults should do muscle-strengthening activities 2 days/week. Participation in multicomponent activities should be considered, as they improve physical function of older adults.

The term “multicomponent” refers to physical activity interventions that include more than one type of physical activity, with common types being aerobic, musclestrengthening, and balance training. The following recommendation for older adults describes the amounts and types of physical activity including aerobic, musclestrengthening, and balance exercises.

101.3.1 Aerobic Activity for Older Adults Frequency: For moderate-intensity activities, accumulate at least 30 or up to 60 min/day (for greater benefit) to total 150–300 min/week or at least 20–30 min/day or more of vigorous intensity activities to total 75–150 min/week or an equivalent combination of moderate and vigorous activity. Intensity: On a scale of 0–10 for level of physical exertion, 5–6 for moderate intensity, and 7–8 for vigorous intensity. Duration: For moderate-intensity activities, accumulate at least 30 min/day or at least 20 min/day for vigorous intensity activities. Type: Any modality that does not impose excessive orthopedic stress, walking is the most common type of activity among older adults. Aquatic exercise and stationary cycle exercise may be advantageous for those with limited tolerance for weight-bearing activity.

101.3.2 Muscle-Strengthening Activities for Older Adults Frequency: At least 2 days/week. Intensity: Between moderate (5–6) and vigorous (7–8) intensity on a scale of 0–10. Type: Progressive power training or resistance training (8–10 exercises involving the major muscle groups of 8–12 repetitions each), stair climbing, and other strengthening activities that use the major muscle groups. The most commonly prescribed methods for increasing muscular strength, endurance, and power involve calisthenics (e.g., push-ups, sit-ups, chin-ups) or specific types of equipment, including weight machines, free weights, resistance bands, and similar devices.

101.3.3 Balance Training for Older Adults Balance exercise is recommended for all older adults. Balance training activities are movements that safely challenge postural control. If practiced regularly, they improve the ability to resist intrinsic or environmental forces that cause falls whether walking, standing, or sitting. Engaging in multicomponent training that includes balance training is safe and can reduce the risk of falls in older adults. Balance training is often combined with muscle-strengthening activities, with sessions about 3 times per week, for the prevention of falls and fall injuries among older adults. Examples of balance-training activities include standing on one foot, walking heel-to-toe, and using a wobble board. Most balance and fall-prevention programs include progressively more difficult postures that gradually reduce the

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1160  Chapter 101  Role of Physical Activity in the Health and Wellbeing of Older Adults

base of support (e.g., two-legged stand, semi-tandem stand, tandem stand, one-legged stand), dynamic movements that perturb the center of gravity (e.g., tandem walk and circle turns), stressing postural muscle groups (e.g., heel stands and toe stands), or reducing sensory input (e.g., standing with eyes closed).

101.3.4 Special Considerations for Prescribing Physical Activity for Older Adults If individuals are unable to meet the recommendations, they should be as physically active as their physical abilities and conditions allow. If older adults have been sedentary for many years, it may be necessary to start out slow when beginning a new exercise program, particularly for older adults who are frail or who have chronic conditions that affect their ability to perform physical tasks. Increases in exercise intensity and duration should be gradual and tailored to tolerance and preference. Taking it easy and being patient are good strategies for deconditioned seniors. For some older adults, multicomponent training that includes muscle-strengthening activities and/or balance training may need to precede aerobic training activities. If chronic conditions prevent activity at the recommended amount, older adults should perform physical activities as tolerated so as to avoid being sedentary.

101.4 MOTIVATING OLDER ADULTS TO INITIATE AND MAINTAIN A PHYSICALLY ACTIVE LIFESTYLE Developing the best, most well-rounded physical activity program is not going to be sufficient if we do not also pay attention to motivating older adults to participate in the program! In recent years, a great deal of attention has focused on the study of behavioral factors that increase the likelihood of an individual initiating and maintaining a regular program of exercise and/or physical activity. ACSM has summarized the Best Practices for Physical Activity Programs and Behavior Counseling In Older Adult Populations.41 The ACSM Best Practice Statement suggests that incorporating a comprehensive behavioral management strategy in physical activity interventions can help maximize recruitment, increase motivation for exercise progression, and minimize attrition. The following behavioral strategies can increase the likelihood a person will sustain a new physical activity behavior.

101.4.1 Social Support—Involving Friends and Family Social support from family and friends has been associated with long-term exercise adherence in older adults.42 Examples of social support strategies include peer support

(e.g., tell a friend and bring a friend, exercise buddy system) and professional health educator support (telephone counseling, mail follow-up).

101.4.2 Self-Efficacy—You Can Do It! We Can Help! For many seniors, aging is associated with a loss of perceived control.43 There is growing evidence that people are more likely to initiate and maintain physical activity if they feel confident about their ability to succeed and if they are afforded a variety of opportunities to actively participate in physical activity. Health contracts, practice/mastery experiences, modeling, and having choices enhance self-efficacy.

101.4.3 Active Choices—Finding the Program That Works For You As part of a comprehensive behavioral strategy, tailoring the exercise program to the needs and interest of participants has successfully motivated older adults to initiate and maintain a routine of regular physical activity.44 Therefore, physical activity leaders should work closely with individuals to design a physical activity regimen that reflects the person’s preferences and capabilities. There is growing evidence that providing choices concerning exercise program characteristics (such as group-based vs. individual activity programs and choice of exercise location) contributes to greater adherence. With the diversity of the growing older adult population, significant racial and ethnic disparities exist with regard to NCDs. Older adults from culturally and linguistically diverse backgrounds are less likely to be proactive in undertaking preventative measures to reduce risk of NCDs, such as physical activity. For many individuals, there are several constraints on activity participation beyond personal motivation.45 Cultural barriers, socioeconomic factors, psychological trauma relating to migration, perceptions of ill health and injury, and alternate health-seeking behaviors, to name a few. In an attempt to limit these constraints and positively influence the physical activity participation, it is necessary to carefully consider cultural diversity when developing and planning physical activity programs.

101.4.4 Health Contract or Plan of Action—Making a Commitment A health contract or plan of action is a written agreement, usually negotiated between older adults and their health professionals to accomplish a health goal.46 The contract usually includes challenging but realistic goal setting and a measurable, specific, time-delimited plan or course of action for reaching the health goals. The use of a health calendar to record physical activity provides a means for the participant to monitor the targeted physical activity and to reinforce a commitment to the exercise routine. Self-monitoring is most effective when completed

101.5  Communicating about Exercise and Physical Activity  1161

frequently (as it occurs or daily), focuses on the behavior (not absence of), and it is specifically defined.

101.4.5 Perceived Safety— It’s Safe, It’s Fun Concerns for safety have been identified as a barrier to exercise by many older adults.47 Physical activity programs can help alleviate inappropriate concerns about safety by educating participants about actual risks of physical activity and by helping individuals understand how to selfmonitor their exercise intensity levels.

in the “Be Active Your Way” guide provide an excellent framework for health-care provider–patient discussions around exercise and physical activity. Another important initiative mentioned earlier in this chapter that facilitates health-care provider–patient communication about active living is “Exercise is Medicine” (EIM) (http://www.exerciseismedicine.org). EIM encourages primary care physicians and other health professionals to include physical activity when designing treatment plans and to direct patients to evidence-based exercise programs and certified exercise professionals.

101.5.1 Step 1—Getting Started 101.4.6 Regular Performance Feedback— How Are We Doing? Providing regular and accurate performance feedback can assist older adults in developing realistic expectations of their own progress.48 Performance feedback should be positive and meaningful to the individual. Observation of meaningful positive changes in performance and success in achieving expected outcomes are associated with exercise adherence in older adults. Recent advances in self-monitoring technology, including step counters and smartphones and watches, have promise for helping people of all ages better track their physical activity behavior.

101.4.7 Positive Reinforcement—Keep It Up, You’re Doing Great! Positive reinforcement is any procedure introduced in an intervention that increases the likelihood of maintenance of the activity.49 Examples of effective reinforcement strategies in physical activity settings include recruitment incentives, rewards for reaching targeted goal, and public recognition for attendance and adherence. To maximize the effect of reinforcement, it should be valued by the individual being targeted.

101.5 COMMUNICATING ABOUT EXERCISE AND PHYSICAL ACTIVITY It is important to help older adults understand that there are many different ways for them to be physically active. For some individuals, structured exercise programs led by certified exercise professionals will be the preferred option, whereas others may wish to find other ways to build physical activity into their everyday lives. The notion that there is a single best way to exercise is no longer tenable, and it is increasingly clear that individuals will need to select the form of physical activity that works best for them. For example, the “Be Active Your Way” (http​s:// h​ealth​.gov/​pagui​delin​es/pd​f /adu​ltgui​de.pd​f) campaign invites individuals to select physical activities that meet their personal needs and preferences. The steps outlined

Before beginning an exercise or physical activity program, the “Be Active Your Way” guide recommends that older adults first focus on identifying a personally meaningful motive for increasing their activity levels. Health professionals should engage older adults in conversations about some physical activity goals that are personally meaningful to them. Among the possible reasons identified for increasing physical activity are the following: Be healthier Increase my chances of living longer Feel better about myself Have less chance of becoming depressed Sleep better at night Help me look good Be in shape Get around better Have stronger muscles and bones Help me stay at or get to a healthy weight Be with friends or meet new people Enjoy myself and have fun

101.5.2 Step 2—Making Physical Activity Part of Your Life Health professionals should encourage older adults who are considering a physical activity program to think about reasons why they have not been physically active in the past and to try to develop strategies for overcoming these barriers. The “Be Active Your Way” guide encourages people who have been sedentary for many years to choose something they already like to do and to try to build a physical activity component into the activity. For example, many people like to go shopping or to attend dances and other social events. By increasing the time they spend walking (or dancing), they can gradually combine their fun activity with a healthy dose of physical activity. Older adults should be encouraged to select an activity program that is personally meaningful. Among the strategies recommended are the following: Pick an activity you like and one that fits into your life. Find the time that works best for you. Be active with friends and family. Having a support network can help you keep up with your program.

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101.5.3 Step 3—Keeping It Up, Stepping It Up Once older adults have successfully integrated physical activity into their everyday lives, health professionals should encourage them to gradually increase the intensity and duration of physical activity until they are meeting the physical activity recommendations for older adults. This can be achieved in the following ways: By being active longer each time. Older adults already walking for 30 min, three times a week, could go longer—walking for 50 min, three times a week. By being active more often. If an older adult is biking lightly 3 days a week for 25 min each time, he or she could build up to riding 6 days a week for 25 min each time.

101.5.4 Step 4—Being Active for Life Once older adults are successfully meeting the physical activity recommendations, they should be encouraged to consider adding new elements to their physical activity regimen in order to keep physical activity interesting and fun. For example, once older adults are comfortable sustaining moderate-intensity activities on a regular basis, they could begin to add higher-intensity activities. The “Be Active Your Way” Guide lists a number of moderate and vigorous-intensity physical activity options for older adults’ consideration. Moderate-intensity physical activity options: Biking slowly Canoeing Dancing General gardening (raking, trimming shrubs) Tennis (doubles) Using your manual wheelchair Using hand cyclers—also called arm ergometers Walking briskly Water aerobics Vigorous-intensity physical activity options: Aerobic dance Basketball Fast dancing Jumping rope Martial arts (such as karate) Race walking, jogging, or running Riding a bike on hills or riding faster Team sports Swimming fast or swimming laps Tennis (singles)

101.6 ANSWERING QUESTIONS ABOUT EXERCISE AND PHYSICAL ACTIVITY For those of us who make our living advocating for physically active lifestyles, it may come as a surprise to realize

how little many older adults know about physical activity. However, many older adults were educated at a time and in a culture in which little was known about the health benefits of physical activity, and professionals and members of the public were skeptical about the need to remain physically active later in life. In the final section of this chapter, we consider some frequently asked questions that older adults ask about exercise and physical activity with the goal of assisting health professionals to provide succinct but accurate responses that will serve to motivate and inform older adults.

101.6.1 Question: Why Should I Be Physically Active? Response: There are many reasons you should build physical activity into your everyday life. Regular physical activity can help to improve quality of life in old age. Physical activity can help you stay active and engaged with your family and community. It can help you to manage or postpone some of the chronic diseases and conditions many of us have come to expect from old age. Aging does not have to be something that “happens to us”—on the contrary, being physically active can help us to play a more active role in our own aging. Physical activity can help us to live happier, healthier, and more productive lives. Additional comment: For many years, exercise professionals have tended to focus on the health or medical benefits of exercise and physical activity when trying to motivate sedentary individuals to become more active. For some individuals, motives such as decreasing cholesterol levels, improving cardiac output, and increasing bone mineral density are effective motivators, but for many seniors, they are not. It is equally important to mention that regular physical activity can be fun, can increase quality of life, and can help older adults continue to do the things that they like to do. It is doubtful that a single motivational strategy will work for all older adults. It is important that we expose older adults to a variety of different motivational strategies to help to find the technique that works best for them.

101.6.2 Question: How Much Physical Activity Do I Need? Response: Ideally, you should aim to do at least 150 min of moderate-intensity aerobic activity per week, as well as, 2 days/week of muscle-strengthening activities. However, start by doing what you can and gradually look for ways to do more. If you have not been active for a while, start out slowly. After several weeks or months, build up your activities—do them longer and more often. Additional comment: In this book chapter, we provide the best available scientific recommendations for physical activity. However, it is important to understand that, for many older adults, 150 min of moderate-intensity aerobic activity per week can be an extremely intimidating target that may leave them discouraged or unwilling to even try to increase their physical activity. It is important that health professionals help older adults understand that it is

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perfectly acceptable to gradually increase physical activity levels starting at easily achievable, nonthreatening levels, and slowly increasing as they become more comfortable with exercise and physical activity.

101.6.3 Question: What Is the Best Exercise for Older Adults? Response: There is no single best exercise that works for all older persons. Depending on how you define it, “old age” can cover as much as a 50-year age span, ranging from 50 to 100 years of age and older. For this reason, it is impossible to recommend single set of activities that is best for all older persons. Some seniors can run marathons or compete in triathlons, whereas others may be more comfortable walking or gardening. Still others will get their exercise in a chair or in bed! The most important thing is to do regardless of your age is to avoid inactivity. The specific type of physical activity will always vary from person-to-person. A good idea is to select activities you enjoy. If possible, mixing up activities that promote stamina, strength, and balance is a good idea. Additional comment: The best exercise or physical activity program is the one that older adults are willing and able to do regularly, that they enjoy, and that adds to their quality of life. For some individuals, this will be a structured group exercise program at the local senior center or YMCA; but for others, it will be something much less structured, possibly involving activities such as active commuting, gardening, or walking the dog. Many health professionals grew up enjoying games and sports and are extremely comfortable “working out” in traditional exercise environments. It is important to remember that not all older adults have enjoyed similar positive experiences with traditional exercise programs. Work with older adults to understand their goals, aspirations, and personal preferences. For some individuals, identifying options for active living may be a much more successful strategy than simply referring an individual to an exercise program at a local fitness center or community agency.

101.6.4 Question: How Many Times a Week Should I Exercise? Response: Generally, it is better to spread out physical activity throughout the week with a goal of being active on at least 3–5 days/week. By choosing activities that you enjoy, that are convenient and affordable, you may be able to find a way to be active on almost all days of the week. Try to mix up your physical activity program so you are not doing the same thing every day. On some days, you might go for a walk in your neighborhood with a friend or family member, on other days, you might take advantage of a more structured exercise program at the senior center or church. Many people find that wearing a step counter can help them keep track of their activity levels. On days where you have not accumulated many steps, an afterdinner walk can help you maintain your commitment to maintain an active lifestyle. Additional comment: As a health professional, one of the most important things you can do is to empower

older adults to be independently physically active and not to depend solely on you for advice about their physical activity. It is important to help older adults develop activities that they can do on their own time and in their own space. By helping seniors understand that there are many different ways to be active, health professionals can help them develop a well-rounded, personalized activity program that selects from a menu of physical activity choices and helps them to be active on most, if not all, days of the week.

101.6.5 Question: I Have Not Exercised for Many Years, Where Should I Start? Response: Forget the old saying “no pain, no gain”—it is simply not true! Too many of us learned in childhood that physical activity has to be painful or exhausting if it is going to do us any good. There are many excellent options for those of us who cannot or do not want to exercise vigorously. Walking is a wonderful way to increase your activity level. Stretching and water exercise are also good options. For example, the Arthritis Foundation offers excellent aqua exercise programs designed especially for those with arthritis and joint disorders. Gardening and working outdoors can also be a good form of physical activity. Remember—the most important thing is not what you do; rather, it is most important to avoid inactivity. Additional comment: Prescribing exercise and physical activity is as much an art as it is a science. The most successful health professionals are those that have mastered both of these elements. Simply informing patients about the current scientific guidelines may not be sufficient to motivate them to change their behavior. Understanding some of the principles of behavioral change, discussed earlier in this article, can help you develop greater insight into how to identify the right place for an individual to start on their journey toward an active lifestyle.

101.6.6 Question: Will Physical Activity Help to Reduce My Risk for Specific Diseases and Conditions? Response: Physical inactivity is a major risk factor for many physical and psychological conditions. Sedentary living is associated with heart disease, obesity, type 2 diabetes, and many other conditions. Inactivity is also linked to low self-esteem and psychological depression. Regular physical activity can positively influence all of the aforementioned conditions. Many studies have shown that activity can also help slow the loss of muscle and bone mass that often occurs with advancing age. In addition to these physical and psychological benefits, physical activity can often have significant social benefits. Many seniors enjoy group exercise programs where they have a chance to interact with fellow exercisers of all ages. Even for those individuals who prefer to be active alone or with a partner, physical activity can help them retain the strength and stamina necessary for playing an active role in everyday life. Additional comment: About 80 percent of older adults have at least one chronic condition, and 77 percent have

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at least two. Low levels of daily physical activity often coexist with chronic disease, thereby accelerating the risk of functional decline, disability, and mortality. One of the areas in which more scientific research is needed pertains to the specific mode, intensity, and duration of exercise and physical activity needed to bring about a particular clinical outcome. When approached by an older person with a specific disease or condition, it is especially important for a health provider to recommend an exercise or activity regimen that has been shown to be effective in the treatment and management of that particular condition. For example, when approached by an older woman with osteoporosis who was looking for an exercise program to increase her bone mineral density, it would probably not be optimal to recommend a low-intensity walking and calisthenics program conducted at the local senior center. Health professionals should familiarize themselves with the variety of exercise and physical activity options available in their community and be prepared to work together with older adults to help identify the most appropriate choice for each individual.

101.6.7 Question: Is Exercise Safe? Response: Yes! Almost everyone can find a safe and effective exercise program tailored toward his or her health status, physical activity goals, and personal preferences. It is far more risky to your health to be sedentary than it is to begin a program of light-to-moderate-intensity physical activity. The greatest risk is that your muscles will be sore in the first few weeks of an exercise program. There are some things that you can do to reduce these risks. Learn to read your body’s signals. On days that your body feels tired or weary—take it easy. On good days, take advantage of your body and enjoy yourself! Once we learn how to read our body’s signals and respect its needs, we get a better sense of how to adjust our activity programs as we grow older. Very few individuals will be able to (or would want to) run or dance as energetically in their seventies as they could in their twenties. Many believe that the secret of healthy aging is learning how to adjust to changing needs and circumstances while remaining an active and vibrant member of society. Additional comment: While there are some risks associated with participation in regular physical activity, the risks of being sedentary are much greater! Physical activity risks are related to level of intensity, with lower-intensity physical activity being associated with the lowest risk. Low-intensity physical activity reduces the risks of injury and muscle soreness and may be perceived as less threatening than moderate-to-high intensity routines. While lower risk is associated with lower-intensity exercise, the consensus is that moderate physical activity has a better risk/benefit ratio, and moderate-intensity physical activity should be the goal for older adults. Although speaking with a health care provider is always a good idea, the involvement of a primary care provider prior to beginning a program of physical activity may not always be necessary and depends on a person’s health condition and the level of intensity and mode of physical activity they plan to pursue.

101.6.8 Question: Am I Too Old to Exercise? Response: No! You are never too old to exercise! Strong evidence suggests that it is never too late in life to benefit from physical activity. Physical activity has been shown to be of benefit for individuals of all ages including persons as old as 90 and 100 years. Many people just like you are active on a daily basis. You can find a physical activity program that you will enjoy, that will make you feel better, and that will increase your quality of life. Think about what you most like to do in life and what you hope to gain from being active. Additional comment: It is increasingly clear that beneficial effects of regular physical activity can be observed at all stages of the life course, ranging from the very young to the oldest-old. In recent years, many excellent and well-publicized studies have focused our attention on the benefits of regular physical activity in those cohorts of seniors who were previously thought to be “too old” or “too frail” to partake in physical activity. There are a number of reasons why the frail and the oldest-old tend to be the most sedentary members of society. First, many of the oldest-old do not think of themselves as candidates for physical activity. They are unaware of the many benefits that can accrue to them if they increase their physical activity levels, and they do not realize that many people just like them enjoy activity on a regular basis. Second, for many years, exercise and physical activity professionals were reluctant to expose the oldest-old to the rigors of even the most modest physical activity regimens. It is only recently that professional organizations and Institutional Review Boards have begun to recognize that the benefits of physical activity are much greater than the very small risks they pose. Third, many of the exercise and physical activity programs traditionally employed with the middleaged and young-old are poorly suited for use with the frail and the oldest-old. However, there is now an ample number of evidence-based programs that have been proven to work in frail- and older-adult populations.

101.6.9 Question: Do I Need Special Clothing and Equipment? Response: No! Special clothing and equipment are seldom needed. Safe and effective physical activity can be performed wearing comfortable street shoes and loose fitting everyday clothes. Effective muscle-strengthening activities can be achieved with inexpensive equipment such as elastic bands, water-filled jugs, stairs, or simply using your bodyweight. Additional comment: Many older adults have significant discretionary income and are ready and willing to spend it on club memberships, exercise equipment, and clothing. However, many others are in less fortunate financial circumstances and do not have a lot of money to invest in physical activity. Health professionals should be sensitive to the resources available to their patients and tailor their advice and recommendations accordingly. Probably the most important equipment needed to maintain an active lifestyle is a well-fitting pair of shoes, which

References  1165

are both comfortable and provide adequate cushioning to minimize the risk of muscle and joint injuries.

101.7 SUMMARY Although no amount of physical activity can stop the aging process, there is strong evidence that regular physical activity can minimize the physiological effects of aging and increase active life expectancy by limiting the development and progression of non-communicable diseases and promote independence and quality of life in older age. A combination of aerobic, muscle-strengthening, and balance activities appear to be more effective than either form of training alone in counteracting the detrimental effects of a sedentary lifestyle on the health and functioning of the cardiovascular system and skeletal muscles. While there are clear fitness, metabolic, and performance benefits associated with high-intensity exercise training programs in healthy older adults, it is now evident that such programs do not need to be of high-intensity to

reduce the risks of developing chronic cardiovascular and metabolic disease. Social support, self-efficacy, perceived safety, and regular feedback are important behavioral factors that can help increase the likelihood of an individual initiating and maintaining a regular program of physical activity. Physical activity risks are often related to level of intensity, but the risks associated with a sedentary lifestyle far exceed them.

CLINICAL APPLICATIONS • Regular exercise can be an important element in the management of numerous medical conditions. • It is important to help older adults understand that there are many different ways for them to be physically active. • Health professionals should engage older adults in conversations about physical activity goals that are personally meaningful to them and help them find ways to make physical activity part of their lives.

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XVII PA RT

Health Promotion Dee W. Edington, PhD

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Health Promotion Introduction Dee W. Edington, PhD

102.1 Chapters and Authors....................................................1169

During the last half of the 20th century and now into the 21 st century, wellness and lifestyle medicine have become recognized as tools to identify early indicators and interventions to lower the possibility of chronic disease in individuals. In addition, the interventions increase wellness and quality of life of individuals and populations. Lifestyle medicine has been incorporated into physician practices and the impact is a powerful tool for early-stage treatment opportunities. The chapters in this section are designed to explore the role of risk factors and healthy behaviors as early modalities driving lifestyle medicine and the role it could play in the various areas of interest and the location of physician practices. The chapters are representative of the rising physician interest in wellness and lifestyle medicine, the quality of the work that can be done, and the widespread clinical and non-clinical areas where physician practice and thrive. Physicians can help their patients and populations by incorporating ways to listen and talk with their patients. Regardless of the place where physicians work or volunteer, there are opportunities to make a difference in the quality of life of people and communities. Lifestyle medicine gives the physicians another tool to intervene in the life of a patient and add to their quality of life.

102.1 CHAPTERS AND AUTHORS Michael Parkinson, MD presents a brief history and evolution of “health promotion” which blends public health, “wellness and well-being,” clinical preventive medicine, medical care, and now lifestyle medicine into a more comprehensive and effective model. He points out how 21st-century physicians can utilize new knowledge, perspectives, and frameworks to better partner with their patients and populations to improve health and reduce chronic diseases. Currently, he is Senior Medical Director for Health and Productivity at UPMC Health Plan and Work Partners. Dexter Shurney MD discusses much of the disconnect and potential solutions for closing the gap between traditional patient care and a lifestyle medicine approach to

care to prevent, treat, and reverse many common chronic conditions. Dr. Shurney is the Former Chief Medical Director/Executive Director of Global Health, Benefits and Wellness for Cummins, Inc. He is also the Presidentelect of American College of Lifestyle Medicine. Ron Loeppke, MD is Board certified in preventive medicine and has been highly successful in using the concepts of lifestyle medicine in teaching and treating patients in his medical practice. He also founded and was CEO of Health and Productivity Corporation of America—providing wellness programs for large populations—built on the pillars of prevention. Dr. Loeppke has led many innovative initiatives integrating medical practices with population health management strategies. Currently, he is Vice-Chairman of U.S. Preventive Medicine. Wayne N. Burton, MD recently retired as Global Corporate Medical Director at American Express. He successfully led the implementation of health and wellbeing programs in over 20 countries. Currently, he is Adjunct Professor of Environmental and Occupational Sciences at the University of Illinois School of Public Health and is an advisor and on the board of directors of many organizations. He has co-authored over 100 publications on employee health and productivity. Jane Ellery, PhD and Peter Ellery, PhD, M.L.A. are on the faculty at Ball State University, where they teach and conduct research at the intersection of health and place. Jane studies and teaches about community and population-based initiatives designed to enhance wellbeing across the lifespan. Peter’s landscape architecture work focuses on human-centered design and healthy community development practices. Both are part of the Placemaking Leadership Council, and Jane is a Senior Fellow at Project for Public Spaces. Jennifer S. Pitts is co-founder of Edington Associates and founder of the Institute for Positive Organizational Health. She has a doctorate in social psychology, a master’s degree in experimental psychology, a bachelor’s degree in behavioral sciences, and completed a two-year AHRQ postdoctoral fellowship in health policy and health services research at UCLA’s School of Medicine. She has 30 years of health and wellbeing research and consulting

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experience in academic and applied settings domestically and internationally. Alyssa Schultz, PhD presents her view of the future role of physicians in health promotion strategies and wellness tools. She discusses the evolving definition of health and how health promotion strategies and tools will persist

or change over time. Specifically, Dr. Schultz discusses how lifestyle medicine is impacted by other determinates of health, including the environment and culture, and the impact of new knowledge. Currently, she is working with several organizations designing and evaluating wellness programs.

103 CHAPTER

Health Promotion: History and Emerging Trends Michael Parkinson, MD, MPH, FACPM

Take Home Points.....................................................................1171 103.1 Introduction: Historical Schisms and a New Era of Integration.....................................................................1171 103.2  Integrated Models of Population Health..........................1171 103.3 Wellness, health promotion and disease management “ROI” and “VOI”........................................1172

TAKE HOME POINTS 1. Introduction: Historical schisms and a new era of integration 2. Integrated models of population health 3. Wellness, health promotion and disease management “ROI” and “VOI” 4. From wellness to well-being, health and productivity 5. Emerging trends and technologies 6. Accelerating health improvement going forward 7. Clinical applications

103.1 INTRODUCTION: HISTORICAL SCHISMS AND A NEW ERA OF INTEGRATION The roots of “health promotion” conceptually derive from the early 20th-century historical schism between clinical medicine (treatment of the individual patient) and public health (prevention of disease in populations).1 As defined in the 1979 Report of the Surgeon General, Healthy People, health promotion “seeks the development of community and individual measures which can help... [people] to develop lifestyles that can maintain and enhance the state of well-being.”2 The core scientific models of medicine are best represented by Koch’s Postulates which define a deterministic, linear proof for an organism to cause disease.3 Public health has at its core the paradigm of multifactorial interaction described by the Epidemiological Triad of “agent–host–environment” to understand disease causality. Similarly, the division between mental and physical health in the 20th century created a philosophical and

103.4  From Wellness to Well-Being, Health and Productivity........ 1172 103.5  Emerging Trends and Technologies................................1172 103.6  Accelerating Health Improvement Going Forward...........1173 Clinical Applications..................................................................1173 References...............................................................................1173

practice separation of the mind (behavioral and psychological health) from the body (medical specialties with ever-narrowing fields of expertise). The epidemiology of both medical-care costs and public health were historically uninformed by the principles and practice of the science of economics. Environmental, architectural, policy and social–psychological (how individuals impact and are impacted by groups) influences were similarly disconnected from an integrated framework which could explain why individuals and populations behave as they do (or don’t) with respect to health, care, costs, performance and productivity. Emerging science now provides new insights, and integrated models can define systematic approaches and best practices to improve “population health.”

103.2 INTEGRATED MODELS OF POPULATION HEALTH The goal of having the longest life possible without suffering premature death, disease or disability has been termed the “compression of morbidity.”4 It is a useful and compelling epidemiological construct which is understood broadly and sought by individuals and organizations who strive for a healthy and productive life. Both international and U.S. population-based studies and models acknowledge the primary contributory role of social determinants of health which traditionally were inadequately addressed in early health-promotion programs whether they be sponsored by private (employer) or public (health agency) entities. 5–8 The Robert Wood Johnson Foundation multi-year effort said it succinctly and best: “how long and well we live is determined by where and how we live, learn, work

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and play.”9 Early health-promotion programs emphasized an individually focused, behavioral and biometric riskbased approach which was often delivered largely out of context from the community, employer or organizational culture and determinants of health. As appreciation of the multifactorial causes of healthy and unhealthy behaviors grew, the terms “culture of health” and “well-being” emerged as better expressing the complexity, comprehensiveness and more person-centric vision of the goal of health promotion. As more research indicated that the root causes of poor health, excessive medical costs and lost productivity costs (absenteeism, injuries, disability, Worker’s Compensation) were similar and focused in sub-populations of individuals with elevated health risks, multiple chronic conditions and high cost-of-care diseases,10 the emergence of more integrated environmental, health promotion, disease prevention, care management, decision-making and productivity-focused models became predominant.11–13

103.3 WELLNESS, HEALTH PROMOTION AND DISEASE MANAGEMENT “ROI” AND “VOI” The ROI (“return on investment”) of wellness- and health-promotion programs to reduce health care costs (particularly in the near term) has intermittently moved from promising14–16 to pessimistic.17 Edington’s threedecades-long studies indicated that the healthiest and lower-risk individuals had the lowest near- and long-term costs and that moving moderate- and highest-risk groups to lower-risk levels showed a reduction in medical costs generally within 18–36 months after risk-level reduction.14,16 However, program costs were rarely considered in most ROI calculations or captured using any standard methodology. While the lack of standardization in methods also hampered analyses of disease management programs (optimizing self-care for common, expensive chronic diseases such as hypertension, hyperlipidemia, asthma, coronary artery disease, back pain and diabetes) due to the higher prescription and medical care utilization and costs, program interventions were more likely to demonstrate near-term medical cost savings (“positive ROI”). The RAND Health Workplace Wellness Programs Study,17 one of the largest systematic reviews of health promotion programs, demonstrated that while some health measures did improve, over a 5-year period there was no statistically significant reduction in total monthly medical costs, comparing companies with and without workplace wellness programs. Health promotion programs are increasingly being measured by a more comprehensive framework: the “value” of investment. “VOI” was more broadly defined as loyalty to the company; lower turnover, reduction in absenteeism; improvement in job performance (“presenteeism”); reduction in workrelated illnesses, injuries and safety incidents; earlier return-to-work and lower Worker’s Compensation claims and cost.

103.4 FROM WELLNESS TO WELL-BEING, HEALTH AND PRODUCTIVITY As health-promotion and disease-prevention programs evolved, more emphasis was placed on understanding and aligning environment, culture, policy, programs and incentives to be more integrated and to emphasize comprehensive health, well-being, personal performance and productivity. The federal government had already created the clinical- and patient-oriented U.S. Preventive Services Task Force18 and the population-focused U.S. Community Preventive Services Task Force,19 respectively, to review and rank evidence and make recommendations regarding interventions that improved health on either an individual or group level. The National Institute of Occupational Safety and Health (NIOSH), building on the Integrated Employee Health NASA IOM Report,11 similarly recognized the need for an integrated model of intervention that aligned health promotion with more traditional “health protection” (occupational safety and health), thus creating the Total Worker Health™ initiative. 20 New tools, frameworks and integrated metrics which are designed to be more comprehensive and impactful have been deployed to assess and improve the “environment” which can promote or detract from improving health and business performance. 21–24,12

103.5 EMERGING TRENDS AND TECHNOLOGIES New scientific and economic evidence is emerging and being applied to systems and technologies to initiate and sustain healthy behaviors for both individuals and populations. The clinical practice of lifestyle medicine, increasingly rooted in our rapidly evolving scientific understanding of epigenetics, represents a new front in the prevention, treatment and even reversal of common diseases. 25 Rapid protein expression by our genes in response to environmental and behavioral change creates a new clinical weapon to assist individuals and supplement population health and environmental strategies. Better understanding of the mind–body continuum, including the neuro-humoral science of “happiness” and the production of dopamine/endorphins by multiple stimuli have improved understanding of the chemistry and pathways to enhanced well-being. The power of social connection which underlies the phenomena of connection and contagion 26 and of intrinsic motivators which can be very personal and strongest (purpose, passion, mission) are also being described and deployed. 21 Built environments are becoming more mainstream in creating and sustaining a culture of health. Built environments design in healthy architectural and human support systems, which naturally promote productivity

References  1173

as well as the deployment of choice architecture. Choice architecture makes the “right thing to do the easy thing to do.” Re-connecting individuals and home, school, worksite and health care settings to the natural outdoor environment 27,28 has been shown to improve both public health and human functioning. Behavioral economics29,30 and the thoughtful alignment and application of incentives has increasingly informed the design and deployment of comprehensive health-management programs. Personal biomeasurement with real- or near-time feedback using wearable technologies tethered to social media support for ongoing behavior change and optimal self-care is promising and appeals to an increasingly “wired” generation. Physicians prescribing coaching using electronic medical records and the trusted “power of the white coat” to increase patient engagement and provider satisfaction are being implemented.31 Health care financing and delivery innovations occurring through the Affordable Care Act (ACA) and broader use of value-based incentivized health reimbursement arrangements and health savings accounts have further accelerated the adoption and impact of wellness strategies. The “volume to value transformation” being shaped by numerous employer and purchasing coalition initiatives as well as the ACA has led to the emergence of accountable population health care models designed to meet the “Triple Aim”32 of improving health, enhancing patient experience and reducing per capita cost of care. Growing consumerism and transparency in health care appropriateness, quality and costs can further accelerate the prevention, treatment and even reversal of disease vs “usual care” models characterized by ineffective, inefficient, overutilized and costly care. Consumer- and patient- activation to improve health and medical care can be measured using validated tools and deployed on a population basis. 33 And shared decision-making is increasingly accepted as foundational to producing better outcomes at lower cost using evidence-based decision aids. 34 Moving care and caring “forward” to onsite, near-site, homes, schools and worksites for both coaching and medical care delivery where it is more accessible, engaging, integrated and lower-cost is rapidly accelerating particularly among large, self-insured employers.

103.6 ACCELERATING HEALTH IMPROVEMENT GOING FORWARD Establishing trust is the sine qua non of effective health promotion efforts. Understanding and honestly meeting individuals, employees, patients, families and communities where they are as opposed to where policymakers, employers and stakeholders want them to be is a critical first step to improving health and engagement. By employing new insights, methods and technologies in epidemiology, economics, basic science, clinical medicine, public health, neuroscience, social psychology and comprehensive “environmental” design, future health-promotion efforts are much more likely to be successful than firstgeneration programs. Creating a culture of health is neither easy nor quick, particularly in social milieu which promotes unhealthy eating, sedentary lifestyles, obesity, stress, substance abuse and disturbed or inadequate sleep. Customizing next-generation health-promotion efforts to non-traditional sites and to meaningful sub-groups of people (or “tribes” of individuals who recognize and respect the experiences of others) in the home, school, workplace, medical setting and community will be required to ensure both the initiation and sustainment of a healthier culture.

CLINICAL APPLICATIONS Physicians, as still the most trusted agent in health care, will be expected by employers initially and other purchasers over time, to become competent in “lifestyle medicine” to prevent, treat and reverse common chronic disease. Clinicians increasingly will be expected not only to understand epigenetics in causing common, chronic inflammatory-mediated diseases but also to apply brief motivational-interviewing techniques to better engage patients in lifestyle interventions. Clinical practice workflows and EMRs will increasingly be linked to consumer-, employer- and communitycentric health behavior coaching programs; online tools; monitoring and feedback technologies; and support groups delivered outside the traditional office setting.

REFERENCES 1. White KL. Healing the Schism: Epidemiology, Medicine, and the Public’s Health. New York: Springer-Verlag; 1991. ISBN 0-387-97574-8. 2. U.S. Department of Health, Education, and Welfare, Public Health Service, Office of the Assistant Secretary for Health and Surgeon General. Healthy People: The Surgeon General’s Report on Health Promotion and Disease Prevention. Washington, DC; 1979. DHEW (PHS) Publication No. 79-55071. 3. Carson RA, Burns CK (Editors). Philosophy of Medicine and Bioethics: A Twenty-year Retrospective and Critical

Appraisal. New York/Boston/Dordrecht/ London/Moscow: Kluwer Academic Publishers; 2002. ISBN 0-79233545-7. p. 27. 4. Fries JF. Aging, natural death, and the compression of morbidity. N Engl J Med. 1980;303:130–135. . Evans RG, Barer ML, Marmor TR. 5 Why Are Some People Healthy and Others Not? The Determinants of Health Populations. New York: Aldine De Gruyter; 1994. ISBN-13: 978-0202304908. 6. Willcox BJ, Willcox C, Suzuki M. The Okinawa Program: How the

World’s Longest-Lived People Achieve Everlasting Health – And How You Can Too. New York: Clarkson Potter Publishers; 2001. 7. Willett WC et al. 2017. Health Professionals Follow-Up Study (Physicians, nurses, health professionals). https://content.sph.harvard.edu/hpfs/. Accessed 27 Oct 2017. . Buettner D. The Blue Zones: Lessons for 8 Living Longer from the People Who’ve Lived the Longest. 2008. ISBN13: 9781426202742. 9. Robert Wood Johnson Foundation 2009. Beyond Health Care: New Directions to

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a Healthier America. https​: //ww​w.rwj​ f.org ​/cont​ent/d​a m/fa​rm/re​ports​/repo​r ts/2​ 009/r​w jf40​483ns​on. Accessed 27 Oct 2017. Pronk N. An optimal lifestyle metric: four simple behaviors that affect health, cost and productivity. ACSMs Health Fit J. 2012;16(3):39–43. Institute of Medicine. Integrating Employee Health: A Model Program for NASA. Washington, DC: National Academy of Sciences; 2005. ISBN 0-309-09623-5 (pbk.)—ISBN 0-309-54955-8 (pdf) 1. Parkinson MD. Employer health and productivity roadmap™ strategy. J Occup Environ Med. 2013:55(Suppl): S46–51. Loeppke RR, Hohn T, Baase C et al. Integrating health and safely in the workplace: how closely aligning health and safety strategies can yield measurable benefits. J Occup Envir Med. 2015;57(5):585–597. Edington DW. Zero Trends: Health as a Serious Business Strategy. Ann Arbor, MI: University of Michigan Health Management Research Center; 2009. Baicker K, Cutler D, Song Z. Workplace wellness programs can generate savings. Health Affairs. 2010;29:304–311. Parkinson MD, Peele PB, Keyser DJ et al. UPMC MyHealth: Managing the health and costs of U.S. healthcare workers. Am J Prev Med. 2014;47(4):403–410. Mattke S, Kapinos KA, Caloyeras J et al. Workplace wellness programs: services offered, participation, and incentives. RAND Health Q. 2015;5(2):7. US Department of Health and Human Services Agency for Healthcare Research and Quality 2014. US Preventive Services

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Task Force Guide to Clinical Preventive Services. https​: //ww​w.ahr​q.gov​/site​s /def​ ault/​fi les​/wysi​w yg/p​rofes​siona​ls/cl​i nici​ ans-p​rovid​ers/g​u idel​i nes-​recom​menda​ tions​/guid​e /cps​g uide​.pdf.​ Accessed 27 Oct 2017. US Department of Health and Human Services Centers for Disease Control and Prevention. US Community Preventive Services Task Force 2017. Guide to Community Preventive Services. https:// www.thecommunityguide.org/. Accessed 27 Oct 2017. National Institute for Occupational Safety and Health (NIOSH). Total Worker Health™ https://www.cdc.gov/ niosh/twh/. Accessed 20 Oct 2017. Edington DW, Pitts JS. Shared Values, Shared Results: Positive Organizational Health as a Win-Win Philosophy. Middletown, DE; 2016. ISBN 978-0-692-56153-9. Health Enhancement Research Organization. HERO Health and Well-being Best Practices Scorecard in Collaboration with Mercer©. http:​//her​ o-hea​lth.o​rg/wp ​- cont​ent/u​pload​s /201​ 7/01/​U S-Sc​oreca​rd-V4​-writ​able_​1.201​ 7.pdf​. Accessed 23 Oct 2017. Lynch W, Gardner H. Who Survives? How Benefit Costs Are Killing Your Company. Cheyenne, WY: Health as Human Capital Foundation; 2011. Goetzel RZ, Fabius R, Fabius D et al. The stock performance of C. Everett Koop award winners compared with the Standard & Poor’s 500 Index. J Occup Environ Med. 2016;58(1):9–15. Bodai BI, Nakata TE, Wong WT et al. Lifestyle medicine: a brief review of its

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dramatic impact on health and survival. Perm J. 2018;22:17–25. Christakis NA, Fowler JA. Connected: The Surprising Power of Our Social Networks and How They Shape Our Lives. Little, Brown and Company; 2009. Jackson RJ, Sinclair S. Designing Healthy Communities. San Francisco: JosseyBass; 2012. ISBN 978111803366. Jennings VL, Larson CK, Larson LR. Ecosystem services and preventive medicine: a natural connection. Am J Prev Med. 2016;50(5):642–645. Volpp KG, Asch DA, Galvin R et al. Redesigning employee health incentives – lessons from behavioral economics. N Engl J Med. 2011;365:388–390. Asch DA, Volpp KG. Use behavioral economics to achieve wellness goals. Harvard Business Review, December 01, 2014. Maners RJ, Bakow E, Parkinson MD et al. UPMC Prescription for Wellness: a quality improvement case study for supporting patient engagement and health behavior change. Am J Med Qual. 2017. https://doi. org/10.1177/1062860617741670. Accessed 23 Nov 2017. Berwick DM, Nolan TW, Whittington J. The triple aim: care, health, and cost. Health Affairs. 2008;27(3):759–769. Duke CC, Lynch WD, Smith B, Winstanley J. Validity of a new patient engagement measure: the Altarum Consumer Engagement (ACE) measure. Patient. 2015;8(6):559–568. Lee OM, Emanuel EJ. Shared decisionmaking to improve care and reduce costs. N Engl J Med. 2013;368:6–8.

104 CHAPTER

The Employer’s Role in Lifestyle Medicine Dexter Shurney, MD, MBA, MPH

Key Takeaways.........................................................................1175 104.1 Introduction: Why Should Employers Care About a Healthy Workforce?........................................................1175 104.2  Best Business Practices.................................................1175 104.3  The Power of Lifestyle and Lifestyle Medicine................1176 104.4 Key Factors for Launching an Effective Lifestyle Medicine Program for Employers...................................1177

KEY TAKEAWAYS • Why employers should care about cultivating a healthy workforce • Best business practices for Lifestyle Medicine • The power of Lifestyle Medicine to prevent and reverse chronic health conditions • Key factors for launching an effective Lifestyle Medicine program for employers

104.1 INTRODUCTION: WHY SHOULD EMPLOYERS CARE ABOUT A HEALTHY WORKFORCE? There are numerous business advantages for companies to get the most out of every dollar spent on employee healthcare. The first reason, and certainly the most obvious, is the ever-rising cost of healthcare that falls on employers to pay. From 2006 to 2016, annual employer health care costs increased by 58 percent, including 3 percent from 2015 to 2016.1 Over time, the mounting financial cost of healthcare expenditures results in less corporate money available for raising workers’ wages and reinvesting in the business. If a company’s utility bills were to grow this much—without corresponding improvements in services or the delivery of those services—fiscal officers would scramble to solve the problem. In fact, in most industries outside of healthcare, improvements to service and technology typically result in lower costs. To the purchaser: think high-definition televisions, cellular phones, and computers are everyday examples of the return on investment within other industries. What compounds the problem in healthcare is how much of the cost is wasted on treating conditions that are, for the most part, avoidable. Another reason employers are concerned about employee health and the healthcare they receive pertains to

104.4.1 Differentiating Stakeholders and Finding the Right Partners������������������������������������������ 1177 104.4.2  Provider Training & Accountability....................1178 104.4.3 The Role of On-Site Clinics and Empowered Patients��������������������������������������������������������� 1178 104.4.4 Measuring Success & Return on Investment (ROI)����1178 104.5 Conclusion.....................................................................1178 References...............................................................................1179

productivity and worker retention, which have significant indirect costs to companies. A healthy employee is a more productive employee. What’s more, a healthy employee also tends to have a more positive outlook regarding the employer, which can foster greater levels of worker retention. 2 Companies benefit from a workforce that shows up feeling well, mentally and physically, prepared to work. Lost productivity comes in the form of absenteeism (sick leave and short- and long-term disability), and presenteeism, where an employee reports to work, but is less than fully engaged due to mental or physical distractions.3 Unhealthy employees, particularly those who don’t sleep well, may have issues that further inhibit efficiency. Case in point: According to a 2015 British sleep study, sleep deprivation can have the same effect on the body as being drunk.4 This level of exhaustion leads to accidents, manufacturing errors, and an overall decrease in productivity. Although these indirect costs are not as visible as other, more direct healthcare costs, they are just as important— if not more so—to the bottom lines of companies paying for health services on the behalf of their employees. Lastly, many forward-thinking employers care about employee health because it’s simply the right thing to do for their employees and their families. These employers see it as the proverbial “win–win” solution, should they get the balance right between care and costs.

104.2 BEST BUSINESS PRACTICES It’s simply good business for a company to improve quality and lower costs. So why should employee health be any different? To make improvements, companies must first identify the root cause of an issue. Businesses often use Lean or Six Sigma practices to pinpoint the root cause of a problem and resolve the issue to reduce waste and improve quality. For example, an engine manufacturer would want to know the reason its engines are failing: Are the ball bearings freezing? Does the belt break at a certain speed? Employers 1175

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are now starting to approach healthcare spending in much the same way by identifying the crux of the problem. Three-quarters of healthcare costs paid by employers are spent managing chronic conditions such as Type 2 diabetes, high blood pressure, and obesity—common health problems that are, in many instances, preventable through lifestyle changes.5 In a real sense, lifestyle-based health conditions are “defects” with a known root cause that can be averted. When an employer focuses on addressing the root cause of the problem, which is lifestyle in the case of health improvement, breakthrough results are inevitable.

104.3 THE POWER OF LIFESTYLE AND LIFESTYLE MEDICINE Employers are becoming more interested in lifestyle modifications as a remedy for poor population health and everrising healthcare costs because they are potential game changers in achieving outcomes that are seldom, if ever, realized through other means. A comprehensive lifestyle approach to health is a low-cost intervention that has been scientifically proven to prevent, treat, reverse, or cure many common chronic diseases and health conditions. Being able to look to a single low-cost solution as the answer to multiple employee health issues is quite appealing to businesses. The medical community has known for decades that at least 70 percent of chronic illnesses are preventable through adopting a healthy lifestyle. Lifestyle behaviors encompass many habits, which have been defined by large global employer Cummins, Inc. in terms of seven levers, as seen in Table 104.1 below. A comprehensive lifestyle approach focuses not only on the fundamentals of good nutrition and exercise, but includes other basic human health needs: access to clean water, exposure to sunshine and clean air, sound sleep, stress management, and the avoidance of tobacco, excess alcohol, and drugs. Indeed, these lifestyle changes can help prevent and treat a variety of common killers, including heart disease, Type 2 diabetes, and high blood pressure. Typically in chronic illness, one or more of these levers has been neglected. To illustrate the power of lifestyle, we’ll compare a human being to a garden plant. If provided with the right nutrients, the proper amount of water, and plenty of sunshine, the plant will flourish. The roots grow heartily, and likewise, the stem and the leaves follow suit, producing

robust blooms. The entire plant is healthy. On the other hand, deprive the plant of—or inundate it with—any one of the essential elements, and its whole being suffers. Much like the plant, the human organism responds similarly to what it is provided. When armed with the proper nutrients, the right amount of physical activity, sleep, stress, water, sunshine, and it is shielded from harmful substances, the human organism thrives and is better able to fight disease and resist infection. This isn’t limited to a single medical condition; all modifiable conditions improve high blood pressure, Type 2 diabetes, heart disease, depression, obesity, and so forth. This is the power of lifestyle and Lifestyle Medicine. If having one low-cost, effective intervention to address multiple conditions is not convincing enough on its own, the speed with which improvement occurs is also compelling for employers. Improved health outcomes can be seen within six to eight weeks of making lifestyle modifications. These behavioral improvements may include implementation of the Complete Health Improvement Program (CHIP),6 a community-based lifestyle education program used by several U.S. employers to teach their employees about healthy lifestyles and a whole-food, plant-based diet. CHIP is typically launched in groups over an eight-week period, often with significant results. For example, CHIP groups often report average total cholesterol reductions of 20 percent or more. This is encouraging to employers accustomed to running corporate health programs that rarely provide meaningful results (Figure 104.1). Employers are also taking notice of the science of epigenetics, a relatively new area of research supporting lifestyle management. Epigenetics suggests that environment and lifestyle can have a profound effect on DNA expression. That is to say, DNA doesn’t change due to lifestyle behaviors themselves, but the expression of that DNA may change based on what people are exposed to via their lifestyles.7 Exposure to tobacco smoke as it relates to lung cancer is a perfect example of how specific oncogenes (genes for cancer) are activated by the smoking lifestyle. Research suggests that if people who are genetically predisposed to lung cancer are not exposed to tobacco smoke, they are unlikely to develop lung cancer. This area of epigenetics research provides strong evidence that a person’s environment, along with lifestyle choices, can affect his or her health, even at the genetic level (Figure 104.2). It is no different with regard to Type 2 diabetes. The U.S. Centers for Disease Control and Prevention (CDC) recently launched a highly acclaimed diabetes-prevention program,

TABLE 104.1  Clinical Applications 1. Lifestyle-based health conditions are “defects” with a known root cause that can be identified, reversed, and prevented. 2. The majority of chronic illnesses are preventable through adopting a healthy lifestyle, which provides a low-cost, effective intervention to address multiple conditions and achieve improved results within six to eight weeks of behavior modifications. 3. Lifestyle choices can improve health, even at the genetic level. 4. A paradigm shift in healthcare reimbursement in which payers (employers) identify providers (physicians, hospitals, pharmacy companies, etc.,) willing to partner with them—and who share the values of a lifestyle approach to care—may achieve improved employee health. 5. Increased formalized training and certification in Lifestyle Management will provide more consistent and measurable results to bolster the success of this field. 6. On-site health clinics are a convenient way to empower employees to make positive behavior modifications for health and achieve their personal health goals. 7. A healthcare provider trained in lifestyle medicine understands and uses behavior modification as a critical tool in treating and reversing disease, and therefore is able to fully inform a patient about all healthcare options.

104.4  Key Factors for Launching an Effective Lifestyle Medicine Program for Employers  1177

104

Figure 104.1  The seven levers of a healthy lifestyle can prevent—and even reverse—many chronic diseases. Courtesy of Cummins, Inc.

Figure 104.2  Epigenetic differences arise during the lifetime of monozygotic twins living in different environments. (Source: Fraga et al 2005.)

the National Diabetes Prevention Program (National DPP),8 based on evidence that individuals who adopt a healthier lifestyle have a far lower incidence of Type 2 diabetes.

104.4 KEY FACTORS FOR LAUNCHING AN EFFECTIVE LIFESTYLE MEDICINE PROGRAM FOR EMPLOYERS 104.4.1 Differentiating Stakeholders and Finding the Right Partners Employers who want to improve the health of their employees are navigating within a healthcare environment

misaligned with their goals. For employers, the business imperatives are to keep their health costs down and maintain a healthy workforce. For healthcare providers, reimbursement is structured such that sicker patients generate the greatest profits. A good financial year for hospitals, surgeons, device makers, and pharmaceutical manufacturers is when they have performed more procedures, sold more products, and admitted more patients. However, it’s a completely different financial outcome for employers who pay the cost of this care. The traditional business model of treating sick people is at odds with the business goals of organizations outside the healthcare sector that are paying for these treatments. Resolving this contradiction will ultimately require a paradigm shift in approach regarding how healthcare is reimbursed. It may also require a reevaluation of the stakeholders involved in improving employee lifestyle choices. If payers (employers)

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can identify providers (physicians, hospitals, pharmacy companies, etc.) willing to partner with them—and who share the values of a lifestyle approach to care—then achieving improved employee health becomes a shared victory proposition.

104.4.2 Provider Training & Accountability Improving lifestyle behaviors is most successfully achieved under the supervision of healthcare providers trained in Lifestyle Medicine (LM). In 2010, a blue-ribbon panel of organized medical societies published a report questioning the lack of training recent graduates of U.S. medical schools received to practice LM successfully.9 The findings were a wake-up call, signalling the widespread need for more training. LM is largely practiced by primary care providers who are self-taught based on their particular interest in the field. However, this is gradually changing and we are now at a point where the practice of LM is more formalized. As of 2017, clinicians could become board certified in this area. Formalized training and certification will undoubtedly provide more consistent and measurable results in the form of medication reduction and disease reversal, for example, ultimately bolstering the success of this field.

104.4.3 The Role of On-Site Clinics and Empowered Patients Healthy behaviors must be reinforced by a supportive medical community. Along these lines, there is a strong case to be made for having on-site health clinics in the workplace. Not only can the convenience-factor motivate employees to stay on top of their wellness before small issues become big ones, but the employer can choose to staff a clinic with physicians who are sufficiently trained in lifestyle management and incentivized to keep patients healthy. One key to launching a successful on-site clinic is setting patients’ expectations appropriately. Clarifying to employees that the facility is a lifestyle clinic, and therefore will be treating employees’ lifestyle challenges, helps them understand how they can proactively take charge of their own health. This positions employees to leverage the on-site facility to achieve their personal health goals—be it reversing Type 2 diabetes or reducing medications—while simultaneously putting employers closer to their goal of improving the health of all employees. Similarly, an informed patient is an empowered patient. When a patient is presented with a prescription or treatment plan, a physician must first achieve “informed consent.” That means the patient is made aware of all available options—including the risks and benefits of those options—before receiving any treatment. Given that lifestyle interventions are some of the most effective approaches to good health, is a patient truly providing “informed” consent if a physician omits lifestyle changes from the treatment–option equation? It’s important for providers to carefully consider what they say—or don’t say—about lifestyle changes with patients. A healthcare

provider trained in lifestyle medicine understands and uses behavior modification as a critical tool in treating and reversing disease. Not only is this approach to care one of the most effective because it gets at the root problem of many diseases, but it also avoids the side effects that often accompany prescription medications or surgical interventions.

104.4.4 Measuring Success & Return on Investment (ROI) It’s not enough to judge the success of lifestyle management modifications based on basic screening and process parameters. Instead, measurable improvements in health outcomes are the target. Nearly all employers and healthcare plans rate a patient’s care using the Healthcare Effectiveness Data and Information Set (HEDIS). In cases of people with diabetes, HEDIS requires physicians to quantify and track data on a patient’s hemoglobin A1c levels, as well as the condition of the feet, eyes, urine, and kidneys. But this is often used as simply a “check the box” process; it does not measure whether the patient is any healthier over time. To really make an impact, it’s important to measure lifestyle behavior changes to identify actual outcomes of improved health—and ultimately, to tie them to employee performance as well as direct and indirect costs. Employers who measure disease reversals and reductions in medication use linked to improved health status for their employees will achieve greater impact from their programs than those who measure only clinic visits and screening parameters. The return on investment (ROI) for employers dedicated to creating a healthier workforce using lifestyle management pays dividends because healthy people use fewer healthcare resources such as medications, or services like hospital admissions, or clinical procedures. For instance, PCSK9 inhibitors—new medications for high cholesterol—cost an average of $15,000 per year per person. An employer who institutes lifestyle-change programs and assists 100 employees in improving cholesterol levels enough to move off these medications will save $1.5 million in annual healthcare costs. This is very realistic for a large employer and provides a tangible ROI that is easily understood by the company CFO.

104.5 CONCLUSION The current healthcare delivery model for treating the majority of lifestyle-related diseases in the United States is far from optimal since it largely ignores the root cause of these diseases. The inefficiencies resulting from underutilizing lifestyle medicine, combined with misaligned incentives and reimbursements for care, increase the waste and cost of providing healthcare for employees. Hence, the widespread desire among employers to find a better solution. Preventing, treating, and reversing chronic disease through a Lifestyle Medicine approach holds great promise and is very likely an important solution to addressing employer healthcare needs in the future.

References  1179

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2.

Kaiser Family Foundation. “2016 Employer Health Benefits Survey.” 14 Sept. 2016, http:​//www​.kff.​org/r​eport​ -sect​ion/e​hbs-2​016-s​ectio​n-one​- cost​- of-h​ ealth​-insu​rance​/ Health Enhancement Research Organization (HERO). Exploring the Value Proposition for Workforce Health: Business Leader Attitudes about the Role of Health as a Driver of Productivity and Performance. 2015:15–20.

3. 4.

5.

https​: //ww​w.ibi​web.o​rg/ma​rket-​persp​ ectiv​es/he​alth-​relat​ed-lo​st-pr​oduct​ivity​ -the-​f ull- ​cost- ​of-ab​sence​ Williamson A, Feyer A. “Moderate Sleep Deprivation Produces Impairments in Cognitive and Motor Performance Equivalent to Legally Prescribed Levels of Alcohol Intoxication”, Occupational and Environmental Medicine. 2000 October; 57(10):649–655. https​: //ww​w.cdc​.gov/​chron​icdis​ease/​ overv​iew/

6. 7.

8. 9.

https://www.chiphealth.com/ Fraga MF, et al. “Epigenetic differences arise during the lifetime of monozygotic twins”, Proceedings of the National Academy of Sciences of The United States of America. 2005;102:10604. https​: //ww​w.cdc​.gov/​d iabe​testv​/nati​onal-​ diabe​tes-p​reven​tion-​progr​a m.ht​m l Liana Lianov, Mark Johnson. “Physician Competencies for Prescribing Lifestyle Medicine”, JAMA. 2010;304(2):202– 203. doi:10.1001/jama.2010.903.

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105 CHAPTER

Why, How, and What in Leveraging the Value of Health Ron Loeppke, MD, MPH, FACOEM, FACPM

Key Points.................................................................................1181 105.1 Introduction...................................................................1181 105.2 Why...............................................................................1181 105.3 How...............................................................................1183 105.4  Shared Accountability....................................................1183 105.5 WHAT.............................................................................1184 105.6  USPM Program Outcomes..............................................1184

KEY POINTS • This chapter addresses why, how, and what to do in leveraging the value of health and the power of prevention with an evidence-based, trusted, third party to support a Lifestyle Medicine/Population Health Management (LM/PHM) Ecosystem. • It is important to find a third-party provider that has clinically proven, published studies demonstrating results that have been validated by an independent organization (like the Intel-GE Validation Institute). • There is an unparalleled opportunity for healthcare providers that practice Lifestyle Medicine to positively improve the health and reduce the burden of illness of populations down to the “population of one”—the individual person—through personalized preventive initiatives. • A key element of Lifestyle Medicine should be to focus on the health as much as the care in healthcare services, in order to help keep healthy people healthy. • Health and well-being is the new “green”—both at an organizational and a personal level. It is the ultimate sustainability strategy, because rather than only acknowledging the importance of protecting our external environment, it is dealing with the ultimate carbon footprint of our internal, personal environment. • Use published studies to estimate the total cost (medical/pharmacy and absenteeism/presenteeism costs) impact of poor employee health on employers. • Establish a business case for implementing Lifestyle Medicine/Population Health Management initiatives to present to employers as an investment to be leveraged rather than a cost to be justified.

105.6.1  Client Case Study Results................................1185 105.6.2 Intel-GE Validation Institute Recognition of U.S. Preventive Medicine������������������������������� 1187 105.7 Conclusions...................................................................1188 Clinical Applications..................................................................1188 References...............................................................................1189

105.1 INTRODUCTION The American healthcare system is on a collision course with several economic and demographic trends that have dire consequences for the nation. Healthcare costs are rising dramatically just at the time when the so-called “silver tsunami” is arriving in the form of millions of aging baby boomers who are exiting the workforce, no longer helping fund Medicare and Social Security, and beginning to utilize the healthcare system due to a growing burden of illness and health conditions. At the same time, the American workplace is at a crossroads. Global economic competition demands more productivity, technology is rapidly changing the dynamics of industries and marketplaces, and the American workforce is being transformed by major demographic shifts, by every measure declining in health. Therefore, there is an unparalleled opportunity for healthcare providers that practice lifestyle medicine to improve the health and reduce the burden of illness of populations down to the “population of one”—the individual person—through personalized Population Health Management (PHM) initiatives.

105.2 WHY Today’s healthcare cost crisis is largely a consequence of our health crisis—which drives an overwhelming and unrelenting demand on our healthcare system. We should focus on the health as much as the care in our healthcare system to help keep healthy people healthy—and to prevent them from falling in the river of illness in the first place.

1181

1182  Chapter 105  Why, How, and What in Leveraging the Value of Health

Over 150 million Americans are already fighting to survive in that river of illness—with one or more chronic diseases accounting for 75% of all healthcare costs and 70% of deaths in the United States. In fact, 96% of all Medicare expenditures are spent on these chronic conditions, all of which have lifestyle health risk factors impacting their development. In addition, the silver tsunami of the aging workforce from the baby boomer generation has significant implications on the demands of our healthcare system and those associated total costs.1–7 Ironically, it has been estimated that up to 40% of cancer cases—as well as 80% of diabetes and heart disease cases—could be prevented if Americans did not smoke, ate healthy, and exercised adequately.8 Ben Franklin offered this perspective more than 250 years ago when he said that “an ounce of prevention is worth a pound of cure,” but as a nation, we still don’t seem to be getting the message. Why is it that after all this time, preventive medicine has yet to be considered the best medicine? Former Surgeon General C. Everett Koop, M.D., stated that the United States could no longer afford the reparative, rehabilitative focus of our “sick” care system and that we needed a system focused on health that is undergirded by an ethic of prevention.9 In recent years, the healthcare reform discussion in the United States has focused increasingly on the dual goals of cost-effective delivery and better patient outcomes. Many new conceptual models for healthcare have been advanced to achieve these goals, including two that are well along in terms of practical development and implementation— the patient-centered medical home (PCMH) and accountable care organizations (ACOs). At the core of these two emerging concepts is a new emphasis on encouraging physicians, hospitals, and other healthcare stakeholders to be more accountable in the care system, emphasizing organizational integration and efficiencies coupled with outcome-oriented, performance-based medical strategies to improve the health of populations. The ACO model is meant to improve the value of healthcare services, controlling costs while improving quality as defined by outcomes, safety, and patient experience.10,11 This coordinated care system is then centered around the physician/patient relationship and linked by accountability through performance. In fact, healthcare is not immune to the era of consumerism in which we live. Patients are no longer satisfied with “Trust me, I’m your doctor.” They now respond by saying, “Show me, I’m your patient.”9 Ultimately, whatever organization is at financial risk for the health risk and clinical risk of a population needs to implement evidence-based Population Health Management initiatives in order to achieve the “triple aim” of Better Health (for the whole population), Better Healthcare (for those with medical conditions) and Better Value (higher quality and lower costs).12 In fact, these are the same goals that self-insured employers are seeking as they fund a significant portion our nation’s healthcare system. If the ultimate goals of ACOs and PCMHs are lowered healthcare costs and improved health outcomes, these growing care-delivery models and the employer community are well suited as partners. According to the U.S. Census Bureau, 55% of the nation’s population is covered by employer-based health plans—a total of 169 million people.10,11 The healthcare decisions of

these citizens are closely connected with their workplace, and in recent decades employers have become increasingly proactive as providers of programs and initiatives aimed at keeping their workforces healthier. A growing body of research shows an inextricable link between the health of the workforce and the productivity of the workforce, and enlightened employers are taking steps in response.13,14 In recent decades, more and more employers have identified employee health and safety as a key strategic business imperative. A significant body of research has established that investments in employee health and safety programming yield tangible returns that impact the bottom line.15–17 Researchers have also established that companies that adhere to best practices in health and safety programming tend to outperform their peers in the marketplace.18–21 Consequently, employers have become much more active participants in helping manage the health and safety of their employees—ranging from comprehensive wellness and preventive health programs to the use of on-site health clinics. The best and most effective of these are programs in which employer health and safety programs are well integrated and coordinated with each other.16 In its 2012 position statement on ACOs and PCMHs, the American College of Occupational and Environmental Medicine (ACOEM) noted the remarkable similarities in goals and methodologies that characterize integrated health and safety programming in the workplace and the ACO/PCMH models, and advocated for closer alignment between the two for the benefit of the nation’s patients.10 Furthermore, Medicare might become more sustainable if we could help employers graduate healthier retirees.1 Notable prevention frameworks for ACOs and PCMHs are as follows: • Programs for the healthy—not just the ill. Employers should strive to create a system that promotes and focuses on health—not simply a delivery system for the treatment of illness. A key to achieving this goal is the adoption of primary and secondary prevention approaches to help healthy workers maintain their good health. • Coordination of care for chronic disease. Individuals with chronic medical conditions (and more often, individuals with multiple comorbidities) need strong tertiary prevention/care management services, including health education, health coaching, and individualized treatment plans to reduce complications, comorbidities, and hospitalizations. These elements are vital to successful ACO/PCMH initiatives, and employers should deploy evidence-based benefit designs that foster them—such as zero co-pays for effective chroniccare medications to eliminate a financial barrier to controlling disease.11 Catherine Baase, MD, the former Global Medical Director of Dow Chemical Company, articulated four reasons that population health management has become a “C-Suite” issue for employers: (1) the inexorable rise in U.S. healthcare costs, with about one-third of those costs being waste; (2) the reality that prevention efforts could eliminate 30–50% of the illness burden that drives

105.4  Shared Accountability  1183

the majority of healthcare costs; (3) the massive safety and quality issues in the U.S. healthcare system, yielding 200,000–400,000 deaths per year as well as 10 to 20 times that number of sub-lethal error related safety/ quality events per year; and (4) the value of a healthy and safe workforce as a key driver of other corporate priorities such as employee engagement, quality of work output, employee loyalty, morale and attraction/retention—as well as corporate reputation, reliability, and sustainability. 22 Therefore, employers are keenly interested in “Lifestyle Medicine/Population Health Management (LM/PHM) strategies. In many ways, health and well-being is the new “green”—both at an organizational and a personal level. It is the ultimate sustainability strategy, because instead of acknowledging only the importance of protecting our external environment, it is dealing with the ultimate carbon footprint of our internal, personal environment.1

105.3 HOW How can lifestyle medicine leverage the power of prevention to empower and engage people by working with a trusted clinical third-party partner that provides comprehensive, evidence based Population Health Management (PHM) services? First, find third-party partners that have demonstrated that their PHM services/programs yield sustained positive impact on clinical (health risks and chronic conditions) and financial outcomes—ideally, that demonstration includes documented results that are published in peer-reviewed medical journals and/or are externally validated. Examples of externally validated third-party partners can be seen at the Validation Institute website. 23 An example of how a third-party partner could work with providers of lifestyle medicine is in support of the Medicare Annual Wellness Visit. Under the Affordable Care Act (ACA), Medicare started covering a new type of preventive visit in 2011—the annual wellness visit—with no cost to beneficiaries. This new type of visit differs from the Welcome to Medicare visit in that it can take place yearly, instead of just once upon entering the program, and thus all Medicare beneficiaries are eligible for it. In addition, the annual wellness visit can include many preventive services that Medicare previously did not cover. In 2011 the copayment required for the Welcome to Medicare visit was eliminated, and efforts were made to promote the expanded benefits to enrollees and practitioners. 24,25 Therefore, providers of lifestyle medicine have unique opportunities to deliver the Annual Wellness Visit to Medicare beneficiaries. In fact, lifestyle medicine providers should consider partnering with trusted clinical thirdparty vendors of evidence-based PHM services to support the Annual Wellness Visit with such services as an Online Wellness Portal with a National Committee for Quality Assurance (NCQA)-Accredited Personal Health Risk Assessment, a Personalized Annual Preventive Plan, Health Coaching, and Nurse-Based Disease/Care Management.26–28 Later in this chapter, other examples will be reviewed of how physicians practicing lifestyle medicine can partner with a trusted third-party provider of PHM services. There has been an ongoing debate by some in the ­industry about whether workplace wellness works. As with

most scientific questions, the answer is, “It depends.” If the workplace wellness programs are merely “random acts of wellness,” then that does not typically yield any significant positive clinical and financial outcomes. However, it has been shown that workplace wellness works and prevention pays—if they are implemented using evidence based approaches. 28,29 Studies have determined that the following are some of the most common characteristics found in best-performing wellness programs (i.e., those with documented evidence of success)29: • Executive management support and a culture of health; • Effective communication and implementation; • Incentives to motivate employees to participate in the program, leading to high engagement/participation rates; • Linking of wellness program to business objectives; • Multiyear strategic planning; • Employee input when developing goals and objectives; • Wide variety of program offerings; • Effective targeting, referral, and follow-up of highrisk individuals; • Evaluation of effectiveness. Ultimately, it is all about personal responsibility and how to support the person to become their own best coach for health management. The individual is the only one with themselves 24 hours a day, 365 days a year. That is one of the reasons why providers of lifestyle medicine will increasingly be in demand to empower individuals to live a healthier lifestyle.

105.4 SHARED ACCOUNTABILITY Integrated healthcare works best where accountability is shared by the stakeholders in the local healthcare system. This means shared accountability among the patients, providers, and purchasers of care. As physicians, we need to be more accountable about screening, diagnosis, and treatment guidelines, and we must demonstrate high-quality, cost-effective care by measuring our performance and documenting our outcomes. Patients need to take more responsibility for their personal health behaviors and for managing their risks, and they should have more appropriate expectations, improve their compliance, and become wiser consumers of healthcare services. At the same time, the purchasers (employers) need to be made more accountable. They should be required to invest in the well-being of their workers by providing safer, healthier workplaces. Employers should commit to a culture of health and offer workplace health and wellness programs. This is good for the employees as well as the employers—and it can help foster a corporate athlete mentality in workers.9 Shared accountability is very effective when implemented in conjunction with a physician-focused, patientcentered integrated health system strategy. However, to accomplish this it would be most helpful if we could align incentives among the key stakeholders to promote wellness,

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1184  Chapter 105  Why, How, and What in Leveraging the Value of Health

reduce health risk, enhance health, and improve the quality of care for those who already have a medical condition. The key stakeholders are as follows: patients/consumers; providers (physicians, hospitals, pharmacies, etc.), purchasers (employers), and payors (health plans, medical/disability insurance companies, and government entities).1,30,31 Aligning incentives around promoting health and wellness and improving quality of care among the key stakeholders would help manage both the demand side (consumer- and patient-appropriate utilization of healthenhancing services) as well as the supply side (physicianand provider-appropriate provision of health-enhancing services) in the healthcare value equation. Case studies of aligned incentives with the key stakeholders in integrated population health and productivity enhancement initiatives like these have demonstrated positive results.1,30,31 A case study example of a unique alignment of financial incentives among an employer, employees, providers, and a third-party population health management partner was around enhancing the health and wellbeing of a workforce as well as improving the quality of care provided to the employees/dependents of that employer. Such an arrangement allowed feedback and support to meet prevention and treatment evidence-based medicine guidelines that enhanced consistency in the quality of care provided. Based on analyzing claims and health coaching interaction data, if there were gaps in care, physicians were informed of the steps that a patient had yet to accomplish in an evidencebased treatment plan. Physicians and their patients received “quality” points according to how closely they followed certain evidence-based clinical and prevention guidelines and how well they closed gaps in care.5,32 The employer in this innovative case study communicated with their employees and the local physicians about the link between health, worker productivity and healthcare costs before the initiative began. They were also informed that the employer was willing to align financial incentives and share potential savings with the employees and physicians that participated in the program. Specifically, if the employer realized savings in the per member per year medical and pharmacy costs, then for every one dollar of medical/pharmacy costs saved, the bonus pool for the employees and physicians would also be credited with one dollar of health-related productivity savings.5,32 In fact, there were savings generated from this employer-based, integrated population health enhancement initiative, even after taking into account all program costs as well as taking into consideration estimated savings from benefit plan changes. A predetermined percentage of the program’s total cost savings for the employer were allocated—to only the employees and their physicians that participated in the program—in proportion to the “quality points” earned by each of them. To my knowledge, this was the first physician and employee/consumer pay-forperformance initiative to consider health-related productivity savings as part of the financial incentive. 5,32

Population Health Management (LM/PHM) Ecosystem that has published and externally validated results? U.S. Preventive Medicine (USPM) has created an innovative information technology solution for a personalized preventive solution, The Preventive Plan,® which provides a suite of evidence-based, innovative tools and services. The Preventive Plan’s offerings encompass an integrated high-tech, high-touch population health management program that has produced proven, published, and externally validated reductions in health risks, hospitalizations, ER visits, and costs. 23,26–28,33 U.S. Preventive Medicine is accredited in wellness and health promotion with performance reporting by the NCQA. The Preventive Plan Population Health Management Program focuses on consumer engagement for health risk reduction and disease prevention as well as management of chronic conditions—all based on the clinical science of preventive medicine: (1) Primary Prevention: Wellness and health promotion, (2) Secondary Prevention: Screenings for earlier detection and diagnosis, (3) Tertiary Prevention: Earlier intervention and disease/care management to reduce complications and disability. Preventive Plan members are able to complete an online Health and Well-being Assessment (HWA) and participate in lab and biometric screenings. The data are analyzed through the USPM preventive medicine algorithms to generate a personalized Preventive Plan which provides members with knowledge of their health risks and suggestions for reducing those risks through services and tools such as Health Coaching, health education videos, exercise/nutrition trackers/devices, and completion of social competitive challenges. Interventions also include recommended prioritized learning programs related to the risks identified from the HWA, lab testing, and biometric screening. The interventions are focused on identification of barriers, goal setting, and selfmonitoring activities aimed at increasing self-efficacy. In addition, members are provided with a suite of support tools, recommended risk reduction activities, and other information through their personalized Preventive Plan well-being portal that allows them to translate knowledge into action. U.S. Preventive Medicine also provides the Centers for Disease Control and Prevention (CDC) certified Diabetes Prevention Program (DPP) and chronic condition disease management programs for Medicaid recipients with a whole-person well-being approach. Furthermore, USPM is partnering with hospital/healthcare delivery systems to provide integrated solutions for their employee populations. It is also working in partnership through the health systems with regional employers. This strategy can help to facilitate and support value-based care and Accountable Care Organization (ACO) initiatives. This integrated symphony of evidence-based wellness, lifestyle management, and disease management programs, combined with technology and clinical human interventions, has led to significant return on investment (ROI) and value on investment (VOI).

105.5 WHAT

105.6 USPM PROGRAM OUTCOMES

What is an example of an evidence-based, trusted third party that can empower the stakeholders in a Lifestyle Medicine/

Published research studies in peer-reviewed journals have shown compelling health risk reductions of people

105.6  USPM Program Outcomes 

participating in The Preventive Plan from USPM after one year and also after two years of participation.26–28 The study published in the March 2013 issue of the Journal of Occupational and Environmental Medicine (JOEM) evaluated the impact of the Preventive Plan on health risks in a cohort of 7,804 individuals across 15 employers who were engaged in the Preventive Plan for two years. 28 Figure 105.1 shows the Edington Risk Model criteria of high risk levels for 15 health risk factors and the definitions of the Low, Medium, and High Health Risk Categories.28 The net result of the health risk transitions of those 7,804 individuals showed total population risk transition movement between baseline and two-year measurements as follows: the segment of the study population in the High Risk category was reduced from 11% to 6%; the segment in Medium Risk category was reduced from 29% to 23%, and the segment in Low Risk category was increased from 60% to 71%. Also, of those individuals who started in a High Risk Category at baseline, 46% moved down to Medium Risk, and 19% moved down to Low Risk Category. Equally impressive is the percent of individuals who started low risk and remained low risk (89%).28 Figure 105.2 shows the per cent of the population that was high risk at baseline across all 15 Edington individual health risk factors and then shows the per cent of the population segment in each risk factor sub-cohort group that reduced their risk out of the high risk level after Health Risk Measure

High Risk Criteria

Blood pressure

Systolic >139 mm Hg or

Body mass index

27.8 (men)

participating two years in their personal preventive plan. A few of the notable findings shown in Figure 105.2 are as follows: 81% lowered blood pressure; 79% improved physical activity; 64% reduced stress; 61% reported fewer health-related sick days; 58% lowered cholesterol; 54% improved perception of their health; 43% improved fasting blood glucose; and 35% quit smoking/tobacco use. A 12% decrease in high risk for body mass index was also seen in the population studied, which correlates with other improvements in high risk. 28 To determine whether health risk reductions were maintained over time, a cohort analysis was performed on 1,763 individuals who participated in the Preventive Plan for five consecutive years. Figure 105.3 shows the percentage of those individuals who had reduced their risk out of the high risk level and maintained that lower risk after five years—after starting at high risk in one or more of the 15 health risk factors at baseline. This is compelling evidence that health improvements can be sustained over a longterm time frame.

105.6.1 Client Case Study Results A Client Case Study of the Impact of the USPM Preventive Plan and Diabetes Care Management has further demonstrated compelling results, as follows:

Diastolic >89 mm Hg 27.3 (women) Cholesterol

>239 mg/dl

Existing medical problems

Heart problems, cancer, diabetes, or stroke

Fasting blood glucose

Fasting Glucose Borderline High (³100 and 2 miles/week

Males: a2 = 8%, c2 = 31%, e2 = 61%

Beunen & Thomis, 1999,37 Belgium

Adolescent twins, 43 MZ pairs (48.8% male), 61 DZ pairs (34.4% male), M age = 15

Number of hours spent on sports each week

Males: a2 = 83%e2 = 17% Females: a2 = 44%, c2 = 54%, e2 = 02%

Kujala et al., 2002,42 Finland

Adult same sex twins, 1772 MZ pairs, 3551 DZ pairs, ages 24 ~ 60

Dichotomous (YES/NO) participation in vigorous physical activity: either “alternatively walking and jogging”, “jogging”, or “running”

Males: a2 = 45% Females: a2 = 45%

Frederiksen and Christensen, 2003,43 Denmark

Elderly twins, 616 MZ pairs, 642 DZ pairs, ages 45 ~ 68

Dichotomous (YES/NO) sports participation. Participate in leisure time in any of: jogging, gym, swimming, tennis, badminton, football, handball, aerobics, rowing, table tennis, or volleyball

Males: a2 = 49%, e2 = 51% Females: a2 = 49, e2 = 51%

de Geus et al., 2003,45 Netherlands

Adolescent twins, 69 MZ pairs (50.7% male), 88 DZ pairs (34.1% male), ages 13 ~ 22 (M = 16.7, SD = 2)

Average weekly METh spent on sports or other moderate to vigorous voluntary exercise activities (with intensity of 4 MET or higher) in the last three months

Males: a2 = 79%, e2 = 21% Females: a2 = 79%, e2 = 21%

Adult twins, 93 MZ pairs (48.4% male), 115 DZ pairs (32.2% male), ages 35 ~ 62 (M = 44, SD = 7)

Average weekly METh spent on sports or other moderate to vigorous voluntary exercise activities (with intensity of 4 MET or higher) in the last three months

Males: a2 = 41%, e2 = 59% Females: a2 = 41%, e2 = 59%

Adult twins, 147 MZ pairs, 153 DZ pairs, M age = 50 (SD = 8)

Weekly hours spent on leisure time exercise at ages 12 ~ 18

Males: a2 = 18%, c2 = 37%, e2 = 45% Females: a2 = 18%, c2 = 37%, e2 = 45%

Weekly hours spent on leisure time exercise at ages 18 ~ 70

Males: a2 = 51%, e2 = 49% Females: a2 = 51%, e2 = 49%

The METh/week score was dichotomized into YES/ NO at a 4 METh/wk threshold, excluded obligatory Physical Education (PE) classes

Males: a2 = 0%, c2 = 84%, e2 = 16% Females: a2 = 0%, c2 = 84%, e2 = 16%

Simonen et al., 2004,46 Finland

Stubbe et al., 2005,39 Netherlands

Adolescent twins NTR, 276 MZ pairs (41.7% male), 370 DZ pairs (23.5% male), ages 13 ~ 14

Continued

111.4  Twin Studies on Voluntary Exercise Behavior  1241 TABLE 111.2  Twin Studies on Voluntary Exercise Behavior (Continued) Heritability Estimates

Study

Sample

Exercise Behavior Phenotype

Stubbe et al., 2005,39 Netherlands

Adolescent twins NTR, 321 MZ pairs (42.4% male), 442 DZ pairs (25.3% male), ages 15 ~ 16

The METh/week score was dichotomized into YES/ NO at a 4 METh/wk threshold, excluded PE

Males: a2 = 0%, c2 = 78%, e2 = 22% Females: a2 = 0,% c2 = 78%, e2 = 22%

Adolescent twins NTR, 248 MZ pairs (40.3% male), 395 DZ pairs (24.3% male), ages 17 ~ 18

The METh/week score was dichotomized into YES/ NO at a 4 METh/wk threshold, excluded PE

Males: a2 = 36%, c2 = 47%, e2 = 17% Females: a2 = 36,% c2 = 47%, e2 = 17%

Adolescent twins NTR, 250 MZ pairs (36.8% male), 326 DZ pairs (25.2% male), ages 19 ~ 20

The METh/week score was dichotomized into YES/ NO at a 4 METh/wk threshold, excluded PE

Males: a2 = 85%, e2 = 15% Females: a2 = 85%, e2 = 15%

Eriksson et al., 2006,47 Sweden

Young adult male twins, N = 1234

Volume of leisure time sports from a modified version of the Baecke questionnaire.

Males: a2 = 56%, e2 = 44%

Stubbe et al., 2006,48 Australia

Adult twins, 1260 MZ pairs (32.6% male), 1468 DZ pairs (18.3% male), ages 19 ~40 (M = 31.8)

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities with intensity > 4 MET

Males: a2 = 48%, e2 = 52% Females: a2 = 48%, e2 = 52%

Stubbe et al., 2006,48 Denmark

Adult twins, 3046 MZ pairs (43.3% male), 6410 DZ pairs (25.6% male), ages 19 ~40 (M = 31.1)

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities with intensity > 4 MET

Males: a2 = 52%, e2 = 48% Females: a2 = 52%, e2 = 48%

Stubbe et al., 2006,48 Finland

Adult twins, 2841 MZ pairs (43.8% male), 6001 DZ pairs (44.5% male), ages 19 ~40 (M = 26.9)

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities with intensity > 4 MET

Males: a2 = 62%, e2 = 38% Females: a2 = 62%, e2 = 38%

Stubbe et al., 2006,48 Netherlands

Adult twins NTR, 1266 MZ pairs (33.4% male), 1415 DZ pairs (20.8% male), ages 19 ~40 (M = 25.7)

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities with intensity > 4 MET

Males: a2 = 67%, e2 = 33% Females: a2 = 67%, e2 = 33%

Stubbe et al., 2006,48 Norway

Adult twins, 1502 MZ pairs (42.5% male), 2493 DZ pairs (21.8% male), ages 19 ~40 (M = 24.7)

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities with intensity > 4 MET

Males: a2 = 26%, c2 = 37%, e2 = 37% Females: a2 = 56%, e2 = 44%

Stubbe et al., 2006,48 Sweden

Adult twins, 3598 MZ pairs (45.4% male), 5329 DZ pairs (47.3% male), ages 19 ~40 (M = 28.6)

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities with intensity > 4 MET

Males:: a2 = 62%, e2 = 38% Females: a2 = 62%, e2 = 38%

Stubbe et al., 2006,48 UK

Adult female twins, 163 MZ pairs (0% male), 259 DZ pairs (0% male), ages 19 ~40 (M = 32.4)

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities with intensity > 4 MET

Females: a2 = 71%, e2 = 29%

de Moor et al., 2007,56 Netherlands

Adult NTR twins 156 MZ pairs (37.8% male), 326 DZ pairs (20.2% male), ages 18 ~ 50

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities with intensity > 4 MET

Males: a2 = 69%, e2 = 31% Females: a2 = 46%, e2 = 54%

de Moor et al., 2007,57 Netherlands

Adult twins NTR, 755 MZ pairs (26.9% male), 2306 DZ pairs (15.3% male), M age = 31 (SD = 7)

Trichotomy based on two METh/wk thresholds: 0 sedentary; 0–6METh/wk moderate; 6+ METh/wk vigorous

Males: a2 = 54%, e2 = 46% Females: a2 = 54%, e2 = 46%

McCaffery et al., 2009,50 USA

Vietnam Era Twin Registry, 2024 MZ pairs (100% male), 1566 DZ pairs (100% male), M ages = 41.07 (SD = 3.15)

Jog or run ≥10 miles/wk OR play strenuous racquet sports ≥ 5 h/wk OR ride a bicycle ≥ 50 miles/wk OR swim ≥ 2 miles/wk OR play other strenuous sports

Males: a2 = 10%, c2 = 18%, e2 = 72%

Continued

111

1242  Chapter 111  Genetic Influences on Regular Exercise Behavior TABLE 111.2  Twin Studies on Voluntary Exercise Behavior (Continued) Heritability Estimates

Study

Sample

Exercise Behavior Phenotype

Aaltonen et al., 2010,51 Finland

Baseline young adult twin data, N = 13556, ages 18 ~ 54

MET index defined as intensity (MET) × duration × frequency, and expressed as the sum score of METhours/day.

Males: a2 = 47%, e2 = 53% Females: a2 = 42%, e2 = 58%

Follow-up young adult twin data, N = 13822, ages 24 ~ 60

MET index defined as intensity (MET) × duration × frequency, and expressed as the sum score of METhours/day.

Males: a2 = 38%, e2 = 62% Females: a2 = 31%, e2 = 69%

Young twins NTR, 554 MZ pairs (38.1% male), 948 DZ pairs (21.2% male), ages 13 ~14 (M = 14.5, SD = 0.31)

Trichotomy based on two METh/wk thresholds:0–5 METh/wk; 5–20 METh/wk; 20+ METh/wk

Males: a2 = 85%, e2 = 15% Females: a2 = 38%, c2 = 46%, e2 = 16%

Young twins NTR, 662 MZ pairs (42.6% male), 969 DZ pairs (21.7% male), ages 15 ~16 (M = 16.2, SD = 0.61)

Trichotomy based on two METh/wk thresholds:0–5 METh/wk; 5–20 METh/wk; 20+ METh/wk

Males: a2 = 80%, e2 = 20% Females: a2 = 80%, e2 = 20%

Young twins NTR, 488 MZ pairs (34.6% male), 747 DZ pairs (20.9% male), ages 17 ~19 (M = 18.1, SD = 0.7)

Trichotomy based on two METh/wk thresholds:0–5 METh/wk; 5–20 METh/wk; 20+ METh/wk

Males: a2 = 72%, e2 = 28% Females: a2 = 72%, e2 = 28%

Mustelin et al., 2011,52 Finland

Young adult twins FinnTwin13, 59 MZ pairs, 92 DZ pairs, ages 23 ~ 31 (M = 27.4, SD = 2)

Baecke questionnaire: sport index (sports activities during leisure time)

Males: a2 = 56% Females: a2 = 56%

de Moor et al., 2011,49 Netherlands

Young twins NTR, 656 MZ pairs (23.3% male), 1628 DZ pairs (13.9% male), ages 13 ~18 (M = 16.4, SD = 1.1)

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET

Males: a2 = 42%, c2 = 44%, e2 = 14% Females: a2 = 36%, c2 = 52%, e2 = 12%

Adult twins NTR, 685 MZ pairs (42.6% male), 1223 DZ pairs (24.9% male), ages 30 ~65 (M = 39.9, SD = 9.4)

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET

Males: a2 = 42%, e2 = 58% Females: a2 = 42%, e2 = 58%

(Young) adult twins, N = 4604

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 22 ~ 36

Males: a2 = 13%, c2 = 27, e2 = 60 % Females: a2 = 37%, c2 = 6%, e2 = 57%

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 37 ~ 50

Males: a2 = 13%, c2 = 27%, e2 = 60% Females: a2 = 37%, c2 = 6%, e2 = 57%

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 19 ~ 33

Males: a2 = 47%, c2 = 1%, e2 = 52% Females: a2 = 27%, c2 = 15%, e2 = 58%

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 34 ~ 50

Males: a2 = 47%, c2 = 1%, e2 = 52% Females: a2 = 27%, c2 = 15%, e2 = 58%

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 19 ~ 27

Males: a2 = 57%, c2 = 3%, e2 = 40% Females: a2 = 56%, c2 = 3%, e2 = 42%

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 28 ~ 50

Males: a2 = 57%, c2 = 3%, e2 = 40% Females: a2 = 56%, c2 = 3%, e2 = 42%

van der Aa et al., 2010,19 Netherlands

Vink et al., 2011,54 Australia

Vink et al., 2011,54 Denmark

Vink et al., 2011,54 Finland

(Young) adult twins, N = 26298

(Young) adult twins, N = 23095

Continued

111.4  Twin Studies on Voluntary Exercise Behavior  1243 TABLE 111.2  Twin Studies on Voluntary Exercise Behavior (Continued) Heritability Estimates

Study

Sample

Exercise Behavior Phenotype

Vink et al., 2011,54 Netherlands

(Young) adult twins, N = 6753

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 19 ~ 25

Males: a2 = 64%, c2 = 3%, e2 = 32 % Females: a2 = 28%, c2 = 23%, e2 = 48%

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 26 ~ 50

Males: a2 = 64%, c2 = 3%, e2 = 32% Females: a2 = 28%, c2 = 23%, e2 = 48%

Vink et al., 2011,54 Norway

Young adult twins, N = 9066

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 19 ~ 31

Males: a2 = 35%, c2 = 29%, e2 = 36% Females: a2 = 54%, c2 = 3%, e2 = 44%

Vink et al., 2011,54 Sweden

(Young) adult twins, N = 27414

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 19 ~ 35

Males: a2 = 53%, e2 = 46% Females: a2 = 54%, e2 = 46%

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 36 ~ 50

Males: a2 = 53%, e2 = 46% Females: a2 = 54%, e2 = 46%

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 19 ~ 40

Females: a2 = 57%, c2 = 9%, e2 = 42%

Exerciser (YES/NO) dichotomy based on spending at least 60 minutes each week on exercise activities > 4 MET at ages 41 ~ 50

Females: a2 = 57%, c2 = 9%, e2 = 42%

Vink et al., 2011,54 UK

(Young) adult female twins, N = 2451

Mustelin et al., 2012,53 Finland

Young adult twins FinnTwin12, 229 MZ pairs (42.4% male), 347 DZ pairs (25.4% male), ages 20 ~26 (M = 22.4, SD = 0.7)

Regular sports activities are scored as 1,3, or 5 according to their intensity

Males: a2 = 64%, e2 = 36% Females: a2 = 64%, e2 = 36%

Huppertz et al., 2012,35 Netherlands

Young twins NTR, 648 MZ pairs (45.8% male), 1320 DZ pairs (26.1% male), M age = 7.45 (SD = 0.32)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 24%, c2 = 71%, e2 = 6% Females: a2 = 22%, c2 = 67%, e2 = 11%

Young twins NTR, 620 MZ pairs (45.8% male), 1141 DZ pairs (26.1% male), M age = 10.1 (SD = 0.33)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 66%, c2 = 25%, e2 = 10% Females: a2 = 16%, c2 = 72%, e2 = 11%

Young twins NTR, 1540 MZ pairs (46.7% male), 2746 DZ pairs (24.3% male), M age = 12.3 (SD = 0.4)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 38%, c2 = 50%, e2 = 11% Females: a2 = 36%, c2 = 50%, e2 = 11%

Adolescent twins FinnTwin16, 769 MZ pairs (38.1% male), 1743 DZ pairs (24.6% male), M age = 16.2 (SD = 0.1)

Trichotomy: 1: exercising less than once a week; 2: exercising one to three times per week; 3: exercising four or more times per week

Males: a2 = 52%, c2 = 19%, e2 = 29 % Females: a2 = 52%, c2 = 24%, e2 = 24%

Adolescent twins FinnTwin16, 724 MZ pairs (36.3% male), 1614 DZ pairs (24.7% male), M age = 17.1 (SD = 0.1)

Trichotomy: 1: exercising less than once a week; 2: exercising one to three times per week; 3: exercising four or more times per week

Males: a2 = 44%, c2 = 24%, e2 = 32% Females: a2 = 50%, c2 = 26%, e2 = 24%

Young adult twins FinnTwin16, 715 MZ pairs (35.9% male), 1603 DZ pairs (24.2% male), M age = 18.6 (SD = 0.2)

Trichotomy: 1: exercising less than once a week; 2: exercising one to three times per week; 3: exercising four or more times per week

Males: a2 = 46%, c2 = 23%, e2 = 31% Females: a2 = 51%, c2 = 21%, e2 = 28%

Young adult twins FinnTwin16, 613 MZ pairs (37.8% male), 1351 DZ pairs (23.2% male), M age = 24.5 (SD = 0.9)

Trichotomy: 1: exercising less than once a week; 2: exercising one to three times per week; 3: exercising four or more times per week

Males: a2 = 34%, c2 = 43%, e2 = 23% Females: a2 = 31%, c2 = 49%, e2 = 20%

Aaltonen et al., 2013,36 Finland

Continued

111

1244  Chapter 111  Genetic Influences on Regular Exercise Behavior TABLE 111.2  Twin Studies on Voluntary Exercise Behavior (Continued) Heritability Estimates

Study

Sample

Exercise Behavior Phenotype

Huppertz et al., 2014,55 Netherlands

Adult twins NTR, 701 MZ pairs (27% male), 572 DZ pairs (14.2% male), ages 18 ~50 (M = 30.5, SD = 7)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 50%, e2 = 50% Females: a2 = 43%, e2 = 57%

Huppertz et al., 2016,34 Netherlands

Young twins NTR, 1262 MZ pairs (47.9% male), 2384 DZ pairs (27.1% male), M age = 7.52 (SD = 0.34)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 14%, c2 = 80%, e2 = 6% Females: a2 = 12%, c2 = 80%, e2 = 8%

Young twins NTR, 1384 MZ pairs (48.3% male), 2582 DZ pairs (26.1% male), M age = 9.84 (SD = 0.43)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 26%, c2 = 69%, e2 = 7% Females: a2 = 26%, c2 = 65%, e2 = 8%

Young twins NTR, 2615 MZ pairs (46.4% male), 4589 DZ pairs (24.9% male), M age = 12.25 (SD = 0.4)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 31%, c2 = 62%, e2 = 7% Females: a2 = 27%, c2 = 65%, e2 = 8%

Young twins NTR, 1451 MZ pairs (39.4% male), 2333 DZ pairs (21.4% male), M age = 14.61 (SD = 0.6)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 43%, c2 = 36%, e2 = 21% Females: a2 = 40%, c2 = 43%, e2 = 17%

Young twins NTR, 959 MZ pairs (39.9% male), 1305 DZ pairs (21.2% male), M age = 16.87 (SD = 0.45)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 56%, c2 = 27%, e2 = 17% Females: a2 = 49%, c2 = 31%, e2 = 20%

Young twins NTR, 458 MZ pairs (30.6% male), 572 DZ pairs (18.5% male), M age = 18.77 (SD = 0.51)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 79%, c2 = 4%, e2 = 17% Females: a2 = 49%, c2 = 19%, e2 = 33%

Young twins NTR, 114 MZ pairs (50.9% male), 111 DZ pairs (32.4% male), M age = 17.1 (SD = 1.1)

The METh/week score based on the summed MET*time/wk score over all exercise and sports activities performed

Males: a2 = 80%, e2 = 20% Females: a2 = 80%, e2 = 20%

Nederend et al., 2016,58 Netherlands

NB: A number of studies reported on overlapping samples, most notably the Dutch sample in Stubbe et al. (2005) overlaps with that in Vink et al. (2011), and the samples of van der Aa (2010) and Huppertz et al.(2012) with that of Huppertz et al. (2016), although different exercise phenotypes and age categories were used across these studies on overlapping samples.

behavior. The largest changes occur during childhood and adolescence.19,34,35 Huppertz et al.34 used a combination of univariate modeling on a very large cross-sectional set of Dutch twins (birth year ranged between 1986 and 2004) and a genetic simplex model on the subset of twins that had longitudinal data across multiple ages. Heritability was found to be low in seven-year-olds (14% in males and 12% in females) but gradually increased up to age 18 (79% in males and 49% in females). In contrast, the initially very high relative contribution of the shared environment to the variance in childhood exercise behavior rapidly waned when children grew into adolescence and young adulthood (from 80% to 4% in males and from 80% to 19% in females). This decrease in the shared environmental variance, which is stronger in males than in females, occurred in parallel to a large increase in the genetic variance. The genetic effects in males remained largely the same from childhood to late adolescence (although their relative importance increased), whereas in females, the contribution of novel genetic effects as a function of age was more profound.

Twin studies in Finland, Sweden, and Belgium have shown that the age-moderation of the genetic and shared environmental effects on exercise behaviors hold in these countries, too, 36–38 and further confirmed that shared environmental factors seem more important in young adolescent girls than in boys. The clear age moderation seen by Huppertz et al.34 in twins born between 1986 and 2004 was already observed by Stubbe et al. 39 in an earlier birth study of Dutch adolescent twins born between 1971 and 1987. Taken together, these results imply that family-based interventions are useful to increase this health behavior in children, whereas individually based interventions might be better suited for adolescents. Studies conducted in adult twins between 19 and 68 years17,36,39–58 show that variation in exercise behavior is influenced by genetic factors, with heritability estimates ranging between 10% and 85% of the variance in exercise. Most of these studies included twins of a wide age range, for example, 19 to 40 years48 or 18 to 60 years. 51 A large study by Vink et al. 54 investigated in seven different countries whether the heritability of exercise behavior

111.4  Twin Studies on Voluntary Exercise Behavior  1245 TABLE 111.3  Family Studies on Regular Exercise Behavior Spousal, Sibling and Parent-Offspring Correlations

Heritability Estimates

Regular sports participation (YES/NO)

Spousal: 0.49 Father-son: 0.37, Mother-son: 0.32, Father-Daughter: 0.29, Mother-Daughter: 0.30

a2 = 45% c2 = 44% e2 = 11%

N = 9500, Fathers(2375): M age = 45.4 SD = 5.8 Mothers(2375): M age = 42.9 SD = 5.5 Sons(2425): M age = 16.1 SD = 4 Daughters(2325) M age = 16 SD = 4

Baecke et al. questionnaire: sport index

Spousal: 0.29 Female siblings: 0.25, Male siblings: 0.23 Female-male siblings: 0.24 Father-son: 0.19, Mother-son: 0.15 Father-daughter: 0.18, Mother-daughter: 0.18

a2 = 19% e2 = 81%

Choh et al., 2009,61 USA

N = 518, Fathers(219) Mothers(302): aged 18 ~ 86

Baecke et al. questionnaire: sport index

Not reported

a2 = 26% c2 = 13% e2 = 61%

de Moor et al., 2011,49 Netherlands

N = 3663 Fathers(1488): M age = 45.5 SD age = 4.6 Mothers(1650): M age = 45.5 SD age = 4.6 Sons(1636): M age = 16.4 SD age = 1.2 Daughters(1889): M age = 16.4 SD age = 1.2

The METh/wk score was dichotomized into YES/NO regular exercise participation at a > 4 METh/ wk threshold

Spousal: 0.41, Father-son: 0.36, Mother-son: 0.18 Father-daughter: 0.21, Mother-daughter: 0.21

a2 = 64% c2 = 0% e2 = 36%

Seabra et al., 2014,60 Portugal

N = 9500 Fathers (2375): M age = 45.4 SD age = 5.8 Mothers (2375): M age = 42.9 SD age = 5.5 Sons (2425): M age = 16.1 SD age = 4 Daughters(2325): M age = 16 SD age = 4

From Baecke et al. questionnaire: Sports Participation

Spousal: 0.23, Female siblings: 0.31, Male siblings: 0.29 Female-male siblings: 0.23 Father-son: 0.16, Mother-son: 0.11 Father-daughter: 0.14, Mother-daughter: 0.14

a2 = 50% e2 = 50%

From Baecke et al. questionnaire: Intensity of exercise

Spousal: 0.12, Female siblings: 0.39, Male siblings: 0.51 Female-male siblings: 0.18 Father-son: 0.15, Mother-son: 0.15 Father-daughter: 0.1Mother-daughter: 0.1

a2 = 40% e2 = 60%

From Baecke et al. questionnaire: Weekly amount of exercise

Spousal: 0.46 Female siblings: 0.52, Male siblings: 0.37 Female-male siblings: 0.22 Father-son: 0.14, Mother-son: 0.21 Father-daughter: 0.23, Mother-daughter: 0.23

a2 = 46% e2 = 54%

From Baecke et al. questionnaire: Proportion of the year exercising

Spousal: 0.48 Female siblings: 0.52, Male siblings: 0.22 Female-male siblings: 0.27 Father-son: 0.22, Mother-son: 0.08 Father-daughter: 0.4, Mother-daughter: 0.4

a2 = 49% e2 = 51%

Study

Sample

Phenotype

Koopmans et al., 1994,44 Netherlands

N = 6470 Fathers: M age = 48 SD age = 5.7 Mothers: M age = 46 SD age = 5.2 Siblings: M age = 18 SD age = 2.3

Seabra et al., 2008,59 Portugal

111

1246  Chapter 111  Genetic Influences on Regular Exercise Behavior

Figure 111.1  Path Diagram. Path diagram depicting correlated latent additive genetic (A) and shared environmental (C) factors that can cause twin resemblance in voluntary exercise behavior, as well as unique environmental (E) factors that are uncorrelated in the twins. We set the correlation of the latent genetic factors for MZ twins to 1, and for DZ twins to 0.5. The correlation of shared environmental factors is set to 1 for both types of twins. The latent unique environmental factors are (per definition) uncorrelated. Unobserved latent variables have no scale: their variance is arbitrarily set to 1 (the double arrows that start and end in the latent factors). Path coefficients a, c, and e represent the factor loadings of exercise on the latent factors.

during adulthood (19 to 50 years) changes with age. In four of the seven countries (Denmark, Finland, Sweden, and the Netherlands), a significant decrease in heritability was observed with age (from 60–90% at age 19 to 13–40% at age 50). In the other three countries (Australia, Norway, and United Kingdom), the heritability of exercise was found to be stable during adulthood. The results from the twin studies in Table 111.2 demonstrate convincingly that heritable factors are present at all ages. The heritability of voluntary exercise behavior peaks during late adolescence and young adulthood.

111.5 FAMILY STUDIES ON VOLUNTARY EXERCISE BEHAVIOR The heritability estimates obtained from twin studies are valid only if the assumptions underlying the twin method hold. An important assumption is the equal environment assumption, which states that environmentally caused similarity in the trait or behavior of interest (i.e., voluntary exercise behavior) is the same in MZ and DZ twin pairs.32 Only one twin study has explicitly tested the equal environment assumption for a set of relevant traits.47 It was tested whether twin pairs with higher contact frequency were more similar in their total physical activity, physical activity at work, or in leisure-time separately, and whether this effect depended on zygosity status. No evidence for violation of the equal environment assumption was found for any of the physical activity measures. Other assumptions of the twin method include absence of assortative mating and the independence of genes and environment. If phenotypic assortative mating on exercise behavior is present, the correlation between genetic factors influencing exercise behavior is higher than the theoretical 50% in DZ twins and full siblings, which can cause underestimation of heritability and overestimation of the shared environmental effects. If there is cultural

transmission, that is, the parents’ exercise behavior is a part of the relevant shared environment by the twins and acts as a “role-model” for the exercise behavior of the children, then the genetic and the shared environmental effects on exercise behavior are no longer independent. Correlation of an exercise-inducing family environment with a genetic propensity to exercise will inflate estimates of C in the twin model. The presence of assortative mating and cultural transmission and how they impact heritability estimates can be tested by adding data from more types of relatives to the twin design, such as data from parents, grandparents, spouses, and siblings. Spouse correlations inform on the presence of assortative mating. Parent-offspring correlations enable testing for the effects of cultural transmission. Table 111.3 lists the five studies that employed extended family designs to report on the familial resemblance of voluntary exercise behavior among adolescent offspring (age range 13 to 20 years) and their parents.44,49,59–61. The spouse correlation for exercise behavior was significant in all these studies and ranged from 0.16 to 0.48. De Moor et al.49 analyzed twin-spouse pairs and demonstrated that the significant spouse correlation for exercise was best explained by phenotypic assortment (i.e., that partners choose each other because they are similar in their exercise behavior) rather than by social homogamy (i.e., that partners similar in exercise behavior meet and marry because they come from similar social backgrounds) or social interaction processes (i.e., that partners resemble each other because they spend time together and mutually influence each other). Importantly, an extended twin-family model that took assortative mating into account led to nearly the same heritability estimates as the twin-only model. Parent-offspring correlations have ranged from 0.13 to 0.25 and are generally somewhat lower than the full sibling correlations (0.24 to 0.31). De Moor et al.49 estimated in a sample of 3,525 adolescent twins and their siblings (13 to 18 years) and 3,138 parents from 1,736 families that 42% of variation in adolescent exercise behavior in

References  1247

boys could be explained by genetic factors, and 52% could be explained by environmental factors shared by family members of the same generation but not with the parents. In girls, 36% of the variance in exercise was explained by genetic factors and 41% by generation-specific environmental effects. Cultural transmission effects from parents to offspring were not significant in adolescence, that is, adolescents do not simply “copy” the exercise behaviors they see in their parents. Taken together, the results of extended twin family studies suggest that heritability estimates for exercise behavior obtained from studies using only twins are not overly biased.

for regular exercise behavior, that is, the biology that makes exercisers exercise but keeps non-exercisers from doing the same. Knowledge of these pathways may further help resolve causality in the well-known association of exercise with other lifestyle behaviors such as overeating and smoking, or with physical health problems like cardiovascular and metabolic disease42 and mental health problems, including depression.70 More importantly, such understanding may be exploited in stratified or personalized interventions that take innate biological differences into account.64,71,72 Future large-scale meta-analytic GWA efforts can therefore be expected to render important clues to improve the success of interventions on this crucial health behavior.

111.6 GENE-FINDING STUDIES

CLINICAL APPLICATIONS

The heritability of exercise behavior has been well established, but less is known about the genetic variants that are associated with this trait. Candidate gene studies in single small-sized cohort studies are now widely distrusted as a reliable source of replicable association, because most complex behavioral traits are highly polygenic, with only a very low percentage of the variance in the trait explained by a single genetic variant. The first genome-wide association (GWA) study on voluntary exercise behavior that we conducted in 2009 was, in retrospect, also heavily underpowered.62 It tested 1,607,535 observed and imputed SNP markers that passed stringent quality controls for their association with leisure-time exercise behavior in two independent samples comprising 1,644 Dutch and 978 American subjects. The most promising finding was in the PAPSS2 gene (37 SNPs with pooled p-values 150 min/week moderate activity or 75 min/week of vigorous activity). • For safety reasons, inactive patients at risk should undergo a medical checkup before starting moderate-to-vigorous physical activity.

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1278  Chapter 113  Physical Activity and Anxiety 13. Morgan, A.J., Jorm, A.F. 2009. Outcomes of self-help efforts in anxiety disorders. Expert Rev Pharmacoecon Outcomes Res 9(5):445–59. 14. Olthuis, J.V., Watt, M.C., Bailey, K., Hayden, J.A., Stewart, S.H. 2016. Therapist-supported Internet cognitive behavioural therapy for anxiety disorders in adults. Cochrane Database Syst Rev (12);3:CD011565. doi: 10.1002/14651858.CD011565.pub2. 15. Bandelow, B., Michaelis, S., Wedekind, D. 2017. Treatment of anxiety disorders. Dialogues Clin Neurosci 19(2):93–107. 16. Fu, J., Peng, L., Li, X. 2016. The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis. Neuropsychiatr Dis Treat 12:951–9. 17. Pull, C.B. 2007. Combined pharmacotherapy and cognitive-behavioral therapy for anxiety disorders. Curr Opin Psychiatry 20:30–5. 18. Zwanzger, P., Diemer, J., Jabs, B. 2009. Comparison of combined psycho- and pharmacotherapy with monotherapy in anxiety disorders: controversial viewpoints and clinical perspectives. J Neural Transm 116:759–65. 19. Hofmann, S.G., Sawyer, A.T., Korte, K.J., Smits, J.A. 2009. Is it beneficial to add pharmacotherapy to cognitive-behavioral therapy when treating anxiety disorders? A meta-analytic review. Int J Cogn Ther 2(2):160–75. 20. Bandelow, B., Reitt, M., Rover, C., Michaelis, S., Gorlich, Y. Wedekind, D. 2015a. Efficacy of treatments for anxiety disorders: a meta-analysis. Int Clin Psychopharmacol 30(4):183–92. 21. Bandelow, B., Lichte, T., Rudolf, S., Wiltink, J., Beutel, M. 2015b. The German guidelines for the treatment of anxiety disorders. Eur Arch Psychiatry Clin Neurosci 265(5):363–73. 22. Flatten, G., Gast, U., Hofmann, A., Knaevelsrud, C., Lampe, A., Liebermann, P. 2011. S3 – Leitlinie Posttraumatische Belastungsstörung. Trauma & Gewalt 3:202–10. 23. Hohagen, F., Wahl-Kordon, A., LotzRambaldi, W., Muche-Borowski, C. 2015. S3-Leitlinie Zwangsstörungen. Berlin, Heidelberg: Springer. 24. van der Watt, G., Laugharne, J., Janca, A. 2008. Complementary and alternative medicine in the treatment of anxiety and depression. Curr Opin Psychiatry 21:37–42. 25. Chen, K.W., Berger, C.C., Manheimer, E., Forde, D., Magidson, J., Dachman, L., Lejuez, C.W. 2012. Meditative therapies for reducing anxiety: a systematic review and meta-analysis of randomized controlled trials. Depress Anxiety 29(7):545–62. 26. Saeed, S.A., Antonacci, D.J., Bloch, R.M. 2010. Exercise, yoga, and meditation for depressive and anxiety disorders. Am Fam Physician 81(8):981–6. 27. Manzoni, G.M., Pagnini, F., Castelnuovo, G., Molinari, E. 2009. Relaxation training for anxiety: a tenyear systematic review with meta-analysis. BMC Psychiatry 8:41. 28. Gotink, R.A., Chu, P., Bussschbach, J.J., Benson, H., Fricchione, G.L., Hunink, M.G. 2015. Standardised mindfulnessbased interventions in healthcare: an overview of systematic reviews and

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114 CHAPTER

Physical Activity and Depression Kayla N. Fair, DrPH and Chad D. Rethorst, PhD

Take Home Points.................................................................... 1281 114.1  Prevalence and Burden of Depression........................... 1281 114.1.1 Cross-sectional and Longitudinal Studies of Exercise�������������������������������������������������������� 1282 114.1.2  Randomized Controlled Trials of Exercise........ 1282 114.1.2.1 Efficacy of Aerobic Exercise in Reducing Depressive Symptoms�����1282 114.1.2.2 Efficacy of Resistance Training Exercise in Reducing Depressive Symptoms������������������������������������ 1282 114.1.2.3 Meta-Analyses Examining the Efficacy of Exercise in Reducing Depressive Symptoms������������������ 1282 114.1.2.4 Exercise vs. Established Treatments����������������������������������� 1283 114.1.2.5 Exercise as an Adjunctive / Augmentative Therapy������������������ 1283 114.1.3  Exercise Prescription...................................... 1283 114.1.3.1  Session Frequency and Duration.......1283 114.1.3.2  Exercise Intensity........................... 1283 114.1.3.3  Intervention Duration..................... 1283 114.1.3.4  Exercise modality.......................... 1284

TAKE HOME POINTS • Evidence indicates physical activity can be utilized in the treatment and prevention of depression • This may be particularly relevant in diseased populations where the depression comorbidity results in significantly poorer outcomes • Several potential biological mechanisms underlie the antidepressant effects of exercise. Understanding these mechanisms may facilitate matching patients to effective treatment of depression. • Future research must continue to evaluate strategies for implementing exercise as a treatment in realworld clinical settings

114.1 PREVALENCE AND BURDEN OF DEPRESSION Depressive disorders annually affect approximately 10% of the population in the United States with a lifetime prevalence of 10% in men and 15% in women. Costs associated

114.1.3.5 Adherence to Exercise Interventions��������������������������������� 1284 114.1.4 Reduction of Depressive Symptoms in Diseased Populations������������������������������������ 1284 114.1.4.1  Cardiovascular Disease.................. 1284 114.1.4.2  Type II Diabetes............................. 1284 114.1.4.3 Cancer........................................... 1284 114.1.4.4  Other Diseases.............................. 1285 114.1.5 Mechanisms of the Antidepressant Action of Exercise����������������������������������������������������� 1285 114.1.5.1 Serotonin....................................... 1285 114.1.5.2  Brain Derived Neurotrophic Factor.....1285 114.1.5.3 Hypothalamic-Pituitary-Adrenal Axis���������������������������������������������� 1285 114.1.5.4 Endocannabinoids......................... 1285 114.1.5.5  Psychosocial Factors..................... 1286 114.1.6 Predictors of the Antidepressant Action of Exercise�������������������������������������������������������� 1286 114.1.7  Future Directions............................................ 1286 Clinical Applications................................................................. 1287 References.............................................................................. 1287

with depressive disorders have grown, as the annual economic burden of depressive disorders is estimated at $210 billion.1  Even in individuals who do not meet diagnostic criteria for Major Depressive Disorder (MDD), depressive symptoms have negative influences on health. Elevated depressive symptoms are associated with an increased risk of MDD,2  functional impairment,3 –  5  higher rates of disability,6  and increased social dysfunction.4 , 7  Further increasing the burden of depressive disorders is the limited accessibility and effectiveness of treatments. Only 55% of people with a depressive disorder receive treatment, and only 32% of those receiving treatment experience alleviation of symptoms.8  Randomized controlled trials (RCTs) have shown the efficacy of three classes of treatment in reducing depressive symptoms: antidepressants, psychotherapy, and neurostimulation.9  Despite the empirical evidence demonstrating the efficacy of these treatments, response rates indicate that a significant portion of individuals do not respond to these treatments.10 –  14  These data highlight the need for more cost-effective, accessible and alternative treatments for depressive disorders. Exercise is one potential treatment that has been supported through research. 1281

1282  Chapter 114  Physical Activity and Depression

114.1.1 Cross-sectional and Longitudinal Studies of Exercise The relationship between physical activity and depressive disorders was first identified in epidemiological work. Higher levels of physical activity and cardiorespiratory fitness have consistently been associated with lower depressive symptoms and risk on depression onset.15 –  18  Although there is strong evidence that there is an inverse relationship between symptoms of depression and physical activity, the complex and multi-faceted nature of the relationship requires that researchers gain a better understanding of how other factors may moderate or influence this relationship. Recent studies have identified that this inverse relationship exists in low-to middle-income countries,19  exists as we age, 20  and may even exist with as little as one hour of physical activity per week. 21 

114.1.2 Randomized Controlled Trials of Exercise 114.1.2.1 Efficacy of Aerobic Exercise in Reducing Depressive Symptoms Building on the findings from epidemiological studies, a number of RCTs have examined the treatment effects of aerobic exercise on depressive symptoms in individuals with MDD. Dunn et al. 22  randomized 80 adults, age 20– 45, to either high dose aerobic exercise (17.5 kilocalories per kilogram of weight (KKW) at a self-selected intensity), low dose aerobic exercise (7 KKW at a self-selected intensity) or an exercise placebo group (i.e. stretching). Following 12  weeks, the mean Hamilton Rating Scale for Depression (HRSD) score was reduced by 47% in the high exercise group, which was significantly greater than the reductions in HRSD score observed in the low dose exercise (30%) and placebo groups (29%). Blumenthal et al.23  randomized adults, age 40 and older, with MDD to one of four treatment groups: home-based aerobic exercise, supervised aerobic exercise, SSRI (sertaline) or placebo pill. Following 16  weeks of treatment, greater remission rates were observed in the home-based (45%) and supervised exercise (40%) compared to a pill placebo (31%). The Regassa study 24 randomized 946 patients with depression into one of three treatment groups: 12- week exercise intervention, 12-week internet-based cognitive behavioral therapy and 12 weeks of treatment as usual that was delivered by their primary care physician. These exercise classes were held hourly three times a week for a total of 12  weeks. At the conclusion of the trial, patients who participated in the exercise classes both had significantly reduced MontgomeryAsberg Depression Rating scores than those in the treatment as usual group. Building on previous reports of positive longterm effects of exercise as a treatment for depression,25 , 26  long-term follow-up data from the Regassa study, reported that light and vigorous exercise groups had experienced reduced Montgomery-Asberg scores compared to treatment as usual and moderate exercise, though all groups experience either stable or reduced depressive symptoms.27 

114.1.2.2 Efficacy of Resistance Training Exercise in Reducing Depressive Symptoms Another group of studies have examined the effect of resistance training exercise on depressive symptoms. A 10-week study found resistance training significantly reduced depressive symptoms compared to an attentionalcontrol group. Furthermore, 59% of the resistance training group had achieved a clinically meaningful response compared to only 26% in the control group. 28  After the 10-week assessments, participants in the resistance training group were instructed to continue engaging in twice-weekly, unsupervised resistance training sessions for another 10   weeks. Depressive symptoms remained significantly lower in the resistance training group after this phase and the percentage of participants classified as “ non-depressed”  was 73% compared to 36% in the control group. The significant difference in depressive symptoms between the groups remained at a 26-month follow-up. 29  In another trial, older adults were randomized to one of three conditions: high dose resistance training, low dose resistance training or standard care. At the end of 8  weeks, the high dose group had significantly greater reductions in depressive symptoms compared to the other two groups and there was no significant difference between the low dose and standard care groups. Participants in the high dose group were also more likely to achieve a clinical response, as 61% of the high dose participants achieved a clinical response compared to 29% of the low dose group and 21% of the standard care group. 30 

114.1.2.3 Meta-Analyses Examining the Efficacy of Exercise in Reducing Depressive Symptoms In addition to the studies referenced above, several other trials have examined the effect of exercise interventions in patients with depressive disorders. The results of these studies have been summarized in a number of meta-analyses.31 –  34  These meta-analyses report significant effect sizes for the reduction of depressive symptoms following an exercise intervention. The effect sizes reported in these meta-analyses range from 0.83 to 1.39, indicating a large treatment effect. The latest Cochrane Review reported a smaller effect size and recommended further research to clearly illustrate a clear relationship between exercise as a treatment for depression.35  However, an additional meta-analysis36  and a critical appraisal highlighted methodological limitations of the Cochrane review and made arguments for including additional studies in the report37 . Both the critical appraisal and the meta-analysis reported larger effect sizes for exercise as a treatment for major depressive disorder. In addition to evaluating depression symptoms, meta-analyses have also explored other secondary outcomes associated with depression, such as quality of life and other psychosocial indicators. One meta-analysis explored the impact that exercise has on quality of life indicators among depressed patients and found that exercise improved overall quality of life, physical and psychosocial quality of life.38 

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114.1.2.4 Exercise vs. Established Treatments The studies described above compare exercise to some version of control group. Further studies have compared exercise to established treatments for MDD. Results of two studies conducted by Blumenthal et al. 23 , 39  indicated no significant difference in treatment response to exercise versus SSRI in older adults. However, evaluation of long-term outcomes in these studies suggest a benefit to exercise compared to SSRI. 25 , 26  Klein et al.40  found no significant difference in changes in depressive symptoms between exercise and group psychotherapy, while. Hallgren et al. 24  found no difference between three exercise intensity groups and internet-based cognitive– behavioral therapy. These findings are further supported by the Rethorst et al.31  meta-analysis, which also included the results of unpublished studies and reported no difference in effect size in studies comparing exercise to SSRI or psychotherapy.

114.1.2.5 Exercise as an Adjunctive / Augmentative Therapy As previously mentioned, Blumenthal et al.39  examined exercise as an adjunctive treatment by including a group that received both SSRI and aerobic exercise. While this group demonstrated significant reductions in depressive symptoms, this reduction was not significantly different from those who received only SSRIs or aerobic exercise. Two RCTs to date have examined exercise as an augmentative treatment for non-remitted MDD. Mather et al.41  randomized older adults, who had received at least 6  weeks of antidepressant medications without a sustained response, to either aerobic exercise or health education classes. Following a 10-week intervention, the exercise group had a significantly higher response rate compared to the health education group. Trivedi et al.42  compared the efficacy of two doses of aerobic exercise as augmentation for non-remitted MDD. Following the 12-week intervention, both groups had significant increases in remission rates and there was a trend toward higher remission rates in the high dose exercise group, though the difference between the two groups was not significant.

114.1.3 Exercise Prescription While there is substantial evidence supporting the use of exercise in the treatment of MDD, research has not provided a clear indication of the proper dose of exercise needed to elicit an antidepressant effect. Complicating the matter is the fact that several aspects of the exercise intervention could potentially influence the efficacy of the intervention including: session frequency, session duration, exercise intensity, intervention duration and exercise modality.43 

114.1.3.1 Session Frequency and Duration Exercise intervention trials in participants with MDD have varied in frequency of exercise sessions (i.e. the number of sessions per week). Dunn et al. 22  found no difference in effect between groups exercising three times per

week versus five times per week. This finding is supported by meta-analytic results demonstrating no difference in effect sizes across trials with different session frequency.31  Typically, exercise has been prescribed in terms of session duration, in which participants exercise for a set amount during each session. The session duration used in trials for MDD has usually ranged between 30– 60  minutes. To date, no trial has directly compared interventions of differing session duration. However, examination of moderating variables in the Rethorst et al.31  meta-analysis suggest that sessions lasting 45– 59  minutes are most effective. Another approach to prescribing exercise has been through calculation of caloric expenditure. Dunn et al.22  compared low dose (7 KKW) to high dose (17.5 KKW). In this trial, 17.5 KKW resulted in greater reductions in depressive symptoms, suggesting that there is a minimum dose of exercise needed to elicit an antidepressant response and that the total amount of exercise dose completed may be more important in determining the optimal exercise dose than session frequency or session duration.

114.1.3.2 Exercise Intensity One shortcoming in previous research in this area is the lack of adequate monitoring of exercise intensity. Some trials have not monitored exercise intensity or have allowed participants to “  self-select”  exercise intensity. Exercise intensity has ranged from 50% to 85% of HRmax among trials that did monitor intensity. No trial has compared exercise intensities in reducing depressive symptoms, though the Rethorst et al. meta-analysis found no difference in effect size across trials based on exercise intensity. For resistance training, both trials conducted by Singh et al. 28 , 30  prescribed resistance training at 80% of 1-RM, though Singh et al.30  compared this intensity of resistance training to a group of lower intensity resistance training at 20% of 1-RM. The results of this trial suggest a dose response relationship between resistance training intensity and changes in depressive symptoms as the high dose group had significantly greater reductions in depressive symptoms compared to the low dose group. A recent randomized control trial evaluated the effect of exercise intensity on depression symptoms.24  Helgadó ttir, Hallgren, Ekblom, & Forsell44  randomized adults between the ages of 18– 67 into one of four groups for a 12-week intervention which targeted depression symptoms: light exercise (yoga), moderate exercise, vigorous exercise and treatment as usual. There were no significant difference between the exercise groups; however, each of the three exercise groups had significantly lower post-treatment scores when compared to treatment as usual.

114.1.3.3 Intervention Duration Previous trials have reported significant reductions in depressive symptoms in as little as 4  weeks, though most trials have treatment periods of several months. Metaanalytical results suggest that longer intervention durations may be more efficacious in reducing depressive symptoms in patients with MDD. Rethorst et al. 31  report larger effect sizes in trials of 10  weeks or longer compared to those trials with intervention durations of 4– 9  weeks.

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114.1.3.4 Exercise modality The majority of trials examining the antidepressant effects of exercise have used aerobic exercise activities. Though as previously noted, other trials have shown the efficacy of resistance training in reducing depressive symptoms. 28 , 30  There are no indications currently that one modality of exercise is more efficacious in treating MDD. One trial has directly compared differing modalities, finding no difference between an aerobic exercise group and a resistance training group,45  while metaanalytic results have revealed no difference in effect size between the two modalities. 31 

114.1.3.5 Adherence to Exercise Interventions Ultimately, the aim of prescription of exercise as a treatment for MDD is to individualize treatments to optimize patient outcomes. This requires identification of factors that may influence response to treatment. One of the largest influences on treatment efficacy is treatment adherence. It has been postulated that exercise may be unsuccessful as a treatment for MDD due to the belief that patients with MDD will not adhere to an exercise program. However, in studies that have compared exercise interventions to SSRIs there are no statistical differences in treatment adherence between the two treatments. 23 , 39  Furthermore, the Rethorst et al.31  meta-analysis calculated the adherence rates of trials included and found a dropout rate of 14.6%. This rate is comparable to dropout rates observed in groups receiving SSRIs and psychotherapy.46 , 47  Additional strategies can be used in conjunction with an exercise intervention to improve adherence. First, the intervention itself can be modified to improve adherence. For example, Blumenthal et al. 23  found better adherence to a home-based exercise compared to laboratory-based exercise. In another study, Dunn et al. 22  found altering session frequency (3/week vs. 5/week) resulted in no difference in adherence. A meta-analysis conducted by Stubbs et al.48  reported that both patients who are recruited to supervised exercise sessions and recruited out of an inpatient setting, are less likely to drop out.

114.1.4 Reduction of Depressive Symptoms in Diseased Populations In addition to trials examining the effect of exercise in individuals with MDD, another group of trials have examined the effect of exercise on depressive symptoms in diseased populations. Comorbid depressive disorders are commonly observed among individuals with chronic diseases. In addition to the burden associated with a MDD, the comorbidity of MDD is often associated with poorer disease outcomes due to a reduction in treatment adherence associated with the presence of a depressive disorder.

114.1.4.1 Cardiovascular Disease Given the role of exercise in the prevention and treatment of cardiovascular disease, there have been several trials that have examined the effects of an exercise program on

depressive symptoms in cardiovascular disease patients. A randomized control trial that was conducted in 82 medical centers in the United States, France and Canada concluded that heart failure patients randomized to receive supervised aerobic exercise sessions and follow up home exercise sessions experienced a statistically significant decrease in their Beck Depression Inventory Score (BDI II). Blumenthal et al.49  found that participants with ischemic heart disease randomized to a 16-week aerobic exercise intervention had significantly lower BDI scores compared to participants receiving usual care. In another trial, participants with chronic heart failure randomized to an aerobic exercise intervention had significantly lower BDI scores compared to the treatment as usual (TAU) group.50  Similarly, Kulcu et al. 51  found a significant decrease in BDI scores following 8  weeks of aerobic exercise in patients with congestive heart failure compared to TAU.

114.1.4.2 Type II Diabetes Individual with Type II Diabetes are at increased risk for developing depression. Given there increased risk of reporting depression symptoms, 52  this population can benefit from both the physical and mental health benefits associated with physical activity. A cross-sectional study by Craike et al. 53  not only found that physical activity explained 22% of the variance in depression symptoms among people with Type II Diabetes, but also found differences in the effect of exercise intensity when stratifying the sample by weight status. Normal weight and overweight individuals with Type II Diabetes experienced a negative association between symptoms of depression and vigorous physical activity; however, people classified as obese experienced a negative association for both moderate and vigorous physical activity.

114.1.4.3 Cancer In patients with cancer, trials have examined the effects of exercise both during and following treatment. The outcomes of these trials are not always focused on depressive symptoms and the results of those trials that did assess depressive symptoms are equivocal.54  However, there are clear psychological benefits from exercise in cancer patients including decreased fatigue, increases in positive mood, and improved quality of life. 55  A few studies have explored the effect of exercise on depression in patients undergoing treatment for cancer or cancer survivors. A meta-analysis that explored the relationship between cancer- related fatigue and exercise measured depression as a secondary outcome and reported that exercise had a moderate effect on depression symptoms. 56  Another study randomized breast cancer patients into either high dose aerobic exercise, standard aerobic exercise or combination of aerobic exercise and resistance training.57  This trial reported among all patients, higher doses and combination of aerobic and resistance training was not superior to standard aerobic group. However, patients who reported symptoms of depression at baseline were more responsive to being randomized into combination group. Although patients who reported baseline depression and were assigned to the high dose group did

114.1  Prevalence and Burden of Depression  1285

not have statistically significant reductions in depression symptoms compared to those assigned to the standard group, the authors did report meaningful effect sizes for those in the high dose group. 57 

114.1.4.4 Other Diseases While the number of trials in other diseased populations is not as large as in cardiovascular disease, research has examined the effects of exercise on depressive symptoms in patient populations. 58  As an example, patients with fibromyalgia display lower levels of depressive symptoms following exercise interventions. 59 , 60  Similarly, patients with COPD have reductions in depressive symptoms following an exercise intervention.61 , 62 

114.1.5 Mechanisms of the Antidepressant Action of Exercise Several mechanisms have been proposed to explain the antidepressant action of exercise. These mechanisms typically fall into one of two categories: neurobiological markers and psychosocial factors.

114.1.5.1 Serotonin Serotonin is the neurobiological marker most commonly associated with MDD. Low levels of plasma serotonin have been widely observed in patients with MDD63 , while SSRI are the most commonly prescribed medication for the treatment of MDD. SSRIs inhibit 5-HT transport,64  ultimately reducing plasma, serum, and whole-blood serotonin levels.65 , 66  Results of animal studies indicate that exercise increases the neural discharge of serotonin,63 , 67  tryptophan levels in the raphe nucleus68 –  70  and hippocampus,67  and serotonin metabolism.71 –  73  In animal models, exercise-induced alterations have been linked to reductions in depression-like behavior. Kim et al.74  induced a depressive state through a series of foot shocks, which also reduced expression of serotonin in the dorsal raphe and reduced expression of 5-HT1A receptors. Subsequent treadmill exercise increased 5-HT and 5-HT1A expression. These increases were associated with reduced depressive symptoms. Exercise prior to stress exposure also protects against detrimental reduction in serotonergic functioning. Ten weeks of swimming exercise prior to foot shock increased 5-HT in the hippocampus and reduced behavioral consequences of stress exposure. A study by Otsuka et al.75  suggests intensity alters the effects of exercise on serotonergic functioning. Treadmill running at a low speed (15/m/min) increased c-Fos expression in 5-HT dorsal raphe nucleus neurons and reduced depression and anxiety behaviors. However, running at a faster speed (25  m /min) did not significantly alter serotonergic functioning or depression/anxiety behaviors. Less evidence exists of the effects of exercise on serotonergic functioning in humans. Acute exercise increases plasma tryptophan, while exercise training increases plasma prolactin, 5-HTT, and 5-HT2A receptors,76  but decreased serum serotonin levels.77 

114.1.5.2 Brain Derived Neurotrophic Factor Research indicates that brain derived neurotrophic factor (BDNF) is thought to play a role in the development and treatment of MDD. Compared with health adults, serum BDNF is lower in untreated MDD patients compared to health adults, serum BDNF levels are inversely correlated with symptom severity and increase following treatment.78  Exercise appears to increase peripheral BDNF level. Two meta-analyses report moderate increases in BDNF following an acute bout of exercise.79 , 80  Both analyses found this effect to be moderated by sex, as the post-exercise increase in BDNF was larger in males than females, and Dinoff et al.79  report greater increases in BDNF following exercise sessions of longer duration. These metaanalyses summarized studies of primarily in healthy adults, but similar effects have been observed in studies of patients with MDD.81 –  83  BDNF levels also increase in response to exercise training.80 , 84  Only one study included in these analyses was conducted in a sample of patients with MDD. In this study, no significant effect of exercise training on serum levels of BDNF was observed. It is worth noting, that in this study participants had been treated with an SSRI of adequate dose and duration prior to enrollment, which may confound the observed effects on BDNF as SSRI treatment increases peripheral BDNF.85 

114.1.5.3 Hypothalamic-Pituitary-Adrenal Axis Patients with MDD demonstrate elevated levels of cortisol in plasma and urine,86 –  88  increased corticotrophin releasing factor (CRF) in cerebral spinal fluid,89 , 90  and increased size and activity of the pituitary and adrenal glands.91  Patients with MDD also demonstrate increased HPA reactivity to psychological stress.92  HPA-axis function normalizes in response to MDD treatment.93 , 94  Evidence also suggests alterations in the HPA-axis in response to exercise. Bouts of acute aerobic exercise result in increased cortisol excretion, while chronic aerobic exercise is associated with reduced cortisol excretion.95  Acute aerobic exercise also reduced cortisol response to the Montreal Imaging Stress Test.96  Furthermore, physical fitness is associated with reduced cortisol response to stress in the form of exercise97  and psychological stress.98  These findings are supported by a wealth of animal research demonstrating altered HPA-axis response to stressors following chronic exercise training.99 –  102  There is also evidence that these exercise-induced alterations in HPA-axis response to stress lead to improvement in depression. Liu et al.103  induced depression-like behavior in rats through chronic uncontrolled foot shock. Physiologically, this stress increased serum corticosterone. Four weeks of swimming exercise reduced serum corticosterone, which was associated with reductions in depression-like behavior.

114.1.5.4 Endocannabinoids Recent research has implicated endocannabinoids in the etiology and treatment of MDD.104 , 105  Patients with MDD demonstrate lower levels of endocannabinoid ligands serum 2-arachidonylglycerol (2-AG) and anandamide,106 , 107 

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while the level of 2-AG is negatively correlated with the duration of the current depressive episode.107  Studies in rats indicate that endocannabinoid receptor CB1  antagonists produce antidepressant effects,108 , 109  while administration of fluoxetine results in a decrease in CB1  gene expression.110  A single bout of aerobic exercise in humans increases anandamide, suggesting that exercise activates the endocannabinoid system.111  Increases in AEA following an acute bout of exercise is negatively correlated with depression, tension, and total mood disturbance factors on the Profile of Mood States and positively correlated with vigor.112  The acute increase of endocannabinoids may be dependent on the intensity of the exercise. Raichlen et al.113  observed increases in endocannabinoids following moderate intensity exercise but no change following high or low intensity exercise. Evidence of chronic effects of exercise on endocannabinoids is limited to animal models. CB1  gene expression is reduced with chronic aerobic exercise,114  mirroring the effect of fluoxetine of CB1  gene expression. Exercise also alters CB1  receptor sensitivity, which provides a protective effect against exposure to stress.115 

114.1.5.5 Psychosocial Factors In addition to the neurobiological mechanisms described above, psychosocial factors may also play a role in the antidepressant effects of exercise. Low self-efficacy is often associated with depressive symptoms.116  It has been proposed that self-efficacy can be improved through physical activity.117 , 118  Trials in patients with MDD consistently report an increase in self-efficacy following chronic exercise119 –  121  and these increases in self-efficacy are associated with a decrease in depressive symptoms.119  Another construct proposed as a mechanism for the antidepressant action of exercise is distraction. It has been postulated that exercise can serve as a distraction from stress and therefore reduce depressive symptoms.122 , 123 However, Craft119  found no significant difference in distraction following an aerobic exercise intervention in women with MDD.

114.1.6 Predictors of the Antidepressant Action of Exercise Ultimately, the study of the antidepressant effects of exercise will inform how exercise can most effectively be used as a treatment. As described previously, the heterogeneity in treatment response indicates the need to tailor treatments to individual patients. One approach to tailor treatments is to attempt to predict treatment response based on pre-treatment patient characteristics. Recent studies have aimed to identify predictors of treatment response to antidepressant medications and psychotherapy.124 –  126  A similar approach could inform which patients are most likely to benefit from exercise as a treatment. A recent review by Schuch et al.127  summarized the previous research efforts to identify predictors of treatment response to exercise. In the TREAD study,42  biological factors associated with better treatment response to exercise included higher baseline levels of BDNF128  and

TNF-a.129  Lavebratt et al.130  also report elevated baseline inflammation, specifically IL-6, predicted better treatment response to exercise. Pre-treatment clinical characteristics associated with better response to exercise treatment include better physical health,131 lower anxiety,131  and the presence of hypersomnia,132  and atypical depressive symptoms.133  The eventual utility of these predictors will be to differentiate exercise as a treatment among the variety of treatment options available. For example, exercise appears to be most effective as a treatment for individuals with elevated inflammation.129 , 130  In contrast, higher levels of inflammation have typically been associated with poorer treatment response to SSRIs.134 , 135  This suggests it may be possible for clincians to choose between different treatments based on patient characterstics. However, it should be noted that the effects of these individual predictors may not be large enough to inform clincial decision-making. As a result, more recent research has attempted to combine multiple factors to predict MDD treatment response.136 

114.1.7 Future Directions Several areas for research will further clarify and define the role of exercise in the treatment of MDD. First, while there is evidence for a dose-response relationship, the combination of time, frequency, and intensity of exercise required for the optimal reduction of depressive symptoms has not been identified. Not only will this maximize the treatment effect, but identifying the appropriate dose of exercise is also important to allow physicians to provide a clear exercise prescription to patients. Current exercise prescription recommendations are based on summaries of previous studies.43  It should also be noted that there is likely individual variation in response to exercise. Therefore, there is not likely to be a “ one size fits all”  exercise prescription. Few studies have directly compared multiple exercise doses or intensities, though results of those studies do suggest different patients respond differently to different exercise programs. This evidence corresponds with studies of physiological mechanisms differential neurobiological response to varying exercise stimuli. For example, Otsuka et al.75  report increases in c-Fos expression in 5-HT neurons following low speed treadmill running but not high speed running. Conversely, c-Fos increased in corticotrophin-releasing factor neurons following high speed treadmill running but not low speed running. Researchers should continue to explore the role of exercise as an adjunctive or augmentation treatment. Integrating exercise with established treatments has the potential to maximize treatment in a population that typically has modest response to treatment. Results from previous trials suggest that exercise may be especially effective in maintaining treatment effects25 , 31  and as a treatment for individuals who do not fully respond to initial SSRI treatment.41 , 137  Finally, despite epidemiological evidence suggesting the protective effect of physical activity on future MDD, no trial has prospectively examined the preventive effects of exercise. The role of exercise in the treatment of MDD will ultimately depend on treatment professionals being

References  1287

willing and properly educated to prescribe exercise to their patients. Recent data indicate that only 5% of general practitioners include exercise as one of their most recommended treatments for MDD, compared to 92% for antidepressant medications. This disparity is likely due to the fact that only 41% of general practitioners believe exercise to be   “very effective”  or  “quite effective”  in treating MDD.138  Based on the existing evidence, several professional organizations, including the American Psychiatric Association,139  the Canadian Network for Mood and Anxiety Treatments,140  the National Institute for Health and Clinic Excellence,141  and the Royal Australian & New Zealand College of Psychiatrists,142  now recommend exercise as a treatment for MDD. However, significant shortcomings remain in the recommendation of exercise as a treatment for MDD.143  Strengthening the evidence

supporting exercise as a viable treatment option for depression will require demonstration of effectiveness in real-world settings. As such, researchers have called for a shift from well-controlled randomized controlled trials to pragmatic trials conducted in clinical settings.144 

CLINICAL APPLICATIONS Exercise is an efficacious in the treatment of depressive disorders as either a monotherapy or as an augmentation to another antidepressant treatment. For patients interested in exercise as part of their treatment, evidence indicates a weekly goal of approximately 150  minutes of moderateintensity physical activity per week. Aerobic activities and resistance training have both proven effective in reducing depressive symptoms.

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receptor activity elicits an antidepressantlike response in the rat forced swim test. Eur. neuropsychopharmacol . 2005;15:593– 599. 105. Hill MN, Gorzalka BB. Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressantlike response in the rat forced swim test. Eur. Neuropsychopharmacol . 2005;15(6):593– 599. 106. Hill MN, Miller GE, Carrier EJ, Gorzalka BB, Hillard CJ. Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology . 2009;34(8):1257– 1262. 107. Hill MN, Miller GE, Ho W-SV, Gorzalka BB, Hillard CJ. Serum endocannabinoid content is altered in females with depressive disorders: a preliminary report. Pharmacopsychiatry . 2008;41:48– 53. 108. Shearman LP, Rosko KM, Fleischer R, et al. Antidepressant-like and anorectic effects of the cannabinoid CB1 receptor inverse agonist AM251 in mice. Behav. Pharmacol . 2003;14(8):573– 582. 109. Griebel G, Stemmelin J, Scatton B. Effects of the cannabinoid CB1 receptor antagonist rimonabant in models of emotional reactivity in rodents. Biol. Psychiatry . 2005;57(3):261– 267. 110. Oliva JM, Uriguen L, Perez-Rial S, Manzanares J. Time course of opioid and cannabinoid gene transcription alterations induced by repeated administration with fluoxetine in the rat brain. Neuropharmacology . 2005;49(5):618– 626. 111. Sparling PB, Giuffrida a, Piomelli D, Rosskopf L, Dietrich A. Exercise activates the endocannabinoid system. Neuroreport . 2003;14:2209– 2 211. 112. Brellenthin AG, Crombie KM, Hillard CJ, Koltyn KF. Endocannabinoid and mood responses to exercise in adults with varying activity levels. Med. Sci. Sports Exerc . 2017;49(8):1688– 1696. 113. Raichlen DA, Foster AD, Gerdeman GL, Seillier A, Giuffrida A. Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ’ r unner’ s high’ . J. Exp. Biol . 2012;215(Pt 8):1331– 1336. 114. Yan ZC, Liu DY, Zhang LL, et al. Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta. Biochem. Biophys. Res. Commun . 2007;354(2):427– 433. 115. De Chiara V, Errico F, Musella A, et al. Voluntary exercise and sucrose consumption enhance cannabinoid CB1 receptor sensitivity in the striatum. Neuropsychopharmacology . 2010;35(2):374– 387. 116. Bandura A. Self-efficacy: The exercise of control . New York: Worth Publishers; 1997. 117. Folkins CH, Sime WE. Physical fitness training and mental health. Am. Psychol . 1981;36(4):373– 389. 118. Bandura A. Self Efficacy. 2000. 119. Craft L. Exercise and clinical depression: examining two psychological mechanisms. Psychol Sport Exer .  2005;6:151– 171. 120. Ossip-Klein DJ, Doyne EJ, Bowman ED, Osborn KM, McDougall-Wilson IB, Neimeyer RA. Effects of running or weight lifting on self-concept in clinically

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XIX CHAPTER

Injury Prevention David A. Sleet, PhD, FAAHB

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115 CHAPTER

Injuries and Lifestyle Medicine David A. Sleet, PhD, FAAHB

Key Points................................................................................ 1293 115.1 Introduction.................................................................. 1293 115.2 Injury as a Public Health Problem.................................. 1294 115.3 Burden of Injuries......................................................... 1294 115.3.1 Costs.............................................................. 1294 115.3.2 Community Impact......................................... 1295 115.3.3 Global Impact................................................. 1295 115.4 Trends and Variations.................................................... 1295 115.5 Disproportionate Impact................................................ 1296 115.6 Injury or Accident?........................................................ 1296

KEY POINTS • Injuries are a huge public health problem, domestically and globally, placing an enormous burden on individuals, families, communities, and the health care system. • Injuries in the United States are the leading cause of death to those ages 1–44, with unintentional injuries as the main cause. • Most unintentional injuries are predictable and preventable. • Acute exposure to energy at levels beyond human tolerance or the absence of essentials such as oxygen are root causes of injury. • Injury rates vary by socio-demographics, age, sex, race, income, and geography. • Injuries are costly to society, and such costs can be averted through the use of inexpensive devices such as seat belts, smoke alarms, bicycle helmets, and improving the safety of products and environments. • Lifestyle medicine practitioners can play an important role in injury prevention by working with patients and communities to improve behaviors, laws, enforcement, and products. • Several axioms for injury prevention can help guide efforts of lifestyle medicine practitioners. • Clinical applications of strategies for reducing unintentional injuries are available and promising.

115.1 INTRODUCTION Injuries, which include both unintentional injuries and violence, are a major public health problem affecting patients, families, and the communities in which they

115.7  Causes of Injury.......................................................... 1297 115.8  Injury Control.............................................................. 1297 115.9  Axioms in Injury Prevention......................................... 1297 115.10 How Lifestyle Medicine Practitioners Can Help Prevent Injuries........................................................... 1298 115.11 Future Directions........................................................ 1299 115.12 Conclusions................................................................ 1299 Clinical Applications................................................................. 1299 References.............................................................................. 1300

live.1 This chapter will focus on unintentional injuries, which account for two-thirds of the public health injury burden. Public health shares a common goal with the Lifestyle Medicine Association: to increase awareness of lifestylebased causes of disease and injury and to assist in the integration of health professionals working in lifestyle-related disease and injury management and prevention. 2 In addition to the many preventable diseases that are seen in the practice of lifestyle medicine, there is one health threat that the public still accepts as a fait accompli: injuries. We have not yet fully integrated injury prevention into lifestyle medicine, and patients are not as educated on how to lower the risks of injury as they are on how to lower the risks of cancer or heart disease. Perhaps this is in part due to the belief by the public that injuries are “accidents,” acts of fate, random events, or acts of God. The science of injury prevention teaches us that injuries are not accidents—they are predictable, and they are preventable.3 Lifestyle medicine can be an important source to dispel the myth of “accidents” and help patients and the public recognize that injuries are preventable only if certain steps are taken to reduce the risks at home, on the road, at work, and in the community. The ways we drive, walk, use alcohol and drugs, play sports, organize our home environment, select a car, use playground equipment, take prescription and over-thecounter medications, and supervise our children at play all affect the likelihood of injury. A growing body of scientific evidence has demonstrated that lifestyle interventions for injury can and do work to lower risks.4 – 6 Effective interventions may include education and behavior change but also environmental supports such as legislation/enforcement, technology, engineering, and environmental change.7 Specific interventions that support prevention include using individual protective devices such 1293

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as helmets and seat belts; reducing risky driving behaviors such as texting and driving; purchasing and using safety equipment such as smoke alarms; promoting regulations and legislation such as requiring alcohol interlock devices in the vehicles driven by convicted drunk drivers; supporting enhanced enforcement such as random roadside breath testing for alcohol; and improving practices of physicians, providers, and other health care workers such as counseling and brief interventions.

115.2 INJURY AS A PUBLIC HEALTH PROBLEM The National Academy of Sciences in 1985 pronounced that “injury is the most under-recognized public health problem facing the nation today.”8 The science of injury control demonstrates that using public health and health promotion approaches can be effective in injury prevention.9,10 Injuries, like diseases, result from interactions between persons (host factors), agents or vectors (e.g., energy exchange), and the environment (physical and social environmental factors). This approach is the foundation for understanding injury prevention.11,12 Despite this, injury prevention receives relatively little attention from legislators, teaching institutions, journal editors, and, most strikingly, the health care system when compared with other public health issues. In addition to focusing on physical activity, nutrition, tobacco, hypertension, and sexually transmitted diseases, lifestyle medicine practitioners can add preventing injury as part of a comprehensive public health approach to lifestyle change. Lifestyle medicine can prevent injuries by supporting legislation, advancing medical advocacy, providing community education, and linking clinical care with injury prevention.13

115.3 BURDEN OF INJURIES Injuries are a large, predictable, and preventable national and global problem. In the United States, unintentional injuries are the fourth leading cause of death for people of all ages, the leading cause of death for children and adolescents,14 and the leading cause of years of potential life lost (YPLL) before age 65 years17—twice that of Heart Disease and 1.6 times that of Malignant Neoplasms (Table 115.1). Injuries, including all causes of unintentional and violence-related injuries combined, account for 59% of all deaths among people ages 1–44 years of age in the United States—that is more deaths than non-communicable diseases and infectious diseases combined. Each year, millions more are injured and survive. In fact, 2.5 million people are hospitalized, 26.9 million people are treated in emergency departments and released each year. One in four Americans will suffer a potentially preventable injury serious enough to require medical attention.17 The consequences of injuries can be extensive and wide-ranging. Injured victims are often faced with lifelong mental, physical, and financial problems and in the case of

TABLE 115.1   Years of Potential Life Lost (YPLL) before Age 65, United States, 2016, All Races, Both Sexes, All Deaths Cause of Death All Causes

YPLL

Percent

11,928,107

100.0%

Unintentional Injury

2,739,490

23.0%

Malignant Neoplasms

1,715,904

14.4%

Heart Disease

1,349,164

11.3%

Suicide

895,466

7.5%

Perinatal Period

745,134

6.2%

Homicide

607,886

5.1%

Congenital Anomalies

421,944

3.5%

Liver Disease

301,329

2.5%

Diabetes Mellitus

252,804

2.1%

Cerebrovascular

228,104

1.9%

2,670,882

22.4%

All Others

Source:  CDC. Web-Based Injury Statistics Query and Reporting System. National Center for Injury Prevention and Control (NCIPC). Centers for Disease Control and Prevention, Atlanta,GA.

disabling injuries, the consequences are often enduring. In 2016, 161,374 people died from unintentional injuries in the United States (crude rate = 49.94), and in 2015, one in ten persons (29,608,581 persons) experienced a nonfatal unintentional injury serious enough to require a visit to the emergency department.17 Approximately one-third of all emergency department visits15 and 6% of all hospital stays16 are due to injuries.

115.3.1 Costs The costs of injuries are staggering. The total lifetime medical and work-loss costs of injuries and violence in the United States was $671 billion in 2013, including the costs of fatal injuries ($214 billion) and nonfatal injuries (over $457 billion).17 Nearly $130 billion of the fatal injury costs were attributable to unintentional injuries, followed by suicide ($50.8 billion) and homicide ($26.4 billion). Drug poisonings, including prescription drug overdoses, accounted for 27% of fatal injury costs; falls, 37%; and transportation-related fatal injuries, 21% (Figure 115.1). To offset these expenses, many low-cost safety devices and practices are available and can return large benefits with small investments. For example:18,19 For every dollar spent on a child safety seat, society can save $100 in direct medical costs. For every dollar spent on a bicycle helmet, society can save $440 in direct medical and other costs. For every dollar spent on a smoke alarm, society can save $15 in direct medical costs. For every dollar spent on poison control centers, society can save $6.70 in medical costs.

115.4  Trends and Variations  1295

Figure 115.1 Medical and Work Loss Costs of Injury – United States, 2013. Source: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2013. https​ ://ww​ w.cdc​.gov/​injur ​y/wis​qars/​overv​iew/c​ost_o​f_inj​ury.h​tml.

115.3.2 Community Impact The burden of injuries on communities is equally large and multidimensional, especially among child injury deaths. In 2015, almost 13,000 children and adolescents died from unintentional or violence-related injury—almost 36 every day, and another 22,200 children a day on average were seen in emergency departments (ED) seeking treatment for nonfatal injuries.14 Not only do communities suffer the emotional and psychological impacts of injury-related deaths (consider the drowning death of a young child or the death of a teen driver) but there are also the effects on employers and the social strain injuries cause in the community. The loss of a job, care for the injured person, costs of rehabilitation, family disruption, medical care visits, insurance claims, marital difficulties, and so on, all have enormous community and social consequences.

115.3.3 Global Impact Injuries are also a huge global problem and cause 5.8 million deaths every year—one death every five seconds—1.7 times more than number of deaths from malaria, TB, and HIV/AIDS combined. 20 An update to the Global Burden of

Disease (GBD) study21 calculated that in 2013 almost one billion people (973 million) sustained injuries that required medical attention, accounting for 10% of the global burden of disease. Major causes included car crashes, which made up 29% of the total, followed by self-harm (17.6%), falls (11.6%), and violence (8.5%). Among those whose injuries required some form of health care, around 6% were hospitalized. The largest category of injury requiring hospital admission was a fracture (38.5%). 21 On any one day, more than 15,000 people will die from an injury, worldwide, including 2,600 children. Unintentional injuries account for almost 90% of these cases and are the leading cause of death for children age 10–19. Around 95% of these injuries occur in low- and middle-income countries and to the poorest populations. 20 Once children reach five years of age, unintentional injuries are the biggest threat to their survival. The majority of these injuries are the result of road traffic crashes, drowning, burns, falls, or poisoning. 22 Road traffic injuries alone are the leading cause of death among 15- to 19-yearolds and the second leading cause among 10- to 14-yearolds. 23 Road traffic injuries are also the number one killer of healthy Americans living, working, or traveling overseas. 24 The 2015 UN Sustainable Development Goal 3.6 (“by 2020, half the number of global deaths and injuries from road traffic accidents”) and Sustainable Cities Goal 11.2 (“by 2030 provide safe, affordable…transportation systems for all”) are among the 17 goals and 169 targets for all countries to achieve by 2030. 25 (http​s://w​w w.un​ .org/​ s usta​ i nabl​ e deve​ lopme​ nt/su​ s tain​ able-​ d evel​opmen​ t-goa​ls/)

115.4 TRENDS AND VARIATIONS Incident rates for injuries, like those for diseases, demonstrate long-term trends and geographic, socioeconomic, and seasonal variations. Injury rates also vary according to characteristics among individuals (e.g., age, sex, income) and environments (e.g., neighborhood, workplace, home). Injury epidemiology is an important tool to help explain these variations, identify groups at higher risk for injury, and target specific interventions to reduce the burden. 26 Figure 115.2 compares the ten leading causes of death in 2015 by age grouping. In the United States, unintentional injuries are among the top ten causes of death in each age group throughout the life span. Injuries represent the first, second, and third leading causes of death among ages 15–24 and 25–34. Within the 15- to 24-year-old age group, the top three leading causes of death (unintentional injuries, homicide, and suicide) accounted for more deaths than the other seven causes combined. Unintentional injuries dominate as the leading cause of death across all age groups from ages 1–44, with motor vehicle injuries predominating among ages 5–34.17 Deaths are only a small part of the problem. Non-fatal injuries place a heavy burden on the health care system and expend valuable pre-hospital, hospital, and rehabilitation resources. Falls, for example, are the leading cause of injury-related emergency department visits for people of all ages, accounting for an estimated 9.3 million visits

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Figure 115.2  Ten Leading Causes of Death by Age Group, United States, 2015.

in 2015 or about 32% of all injury visits. Another four million visits are for being struck by or against, four million more seek treatment in an emergency department for a transportation-related injury, and an estimated 114 million visits are to physicians’ offices to treat an injury.17

115.5 DISPROPORTIONATE IMPACT As with many public health problems, injury disproportionately affects those who can least afford to suffer from it. In the United States, Native Americans 19 years and younger are at greater risk of preventable injury-related deaths than other populations in the same age group. Compared with blacks and whites, this group had the highest injury-related death rates for motor vehicle crashes, pedestrian events, and suicide. Rates for these causes were two to three times greater than rates for whites of the same age. In 2016, injuries and violence caused the deaths of 3,335 Native Americans.17 In 2016, American Indians/Alaska Natives (AI/AN) had the highest age-adjusted rate (76.49) of all injury deaths in the United States. Blacks have the second highest rate at 72.14, while whites had an age-adjusted rate of 70.94.17 The combination of high injury rates, high poverty rates, and high rates of uninsured people among AI/ANs has led to the development of targeted interventions and implementation of capacity building programs for tribes and communities to reduce and prevent injuries.

115.6 INJURY OR ACCIDENT? An injury is distinct from an accident. Although the word “accident” is in common use, it describes only the event and not its consequences. Using the word “injury,” (as in a traffic injury), more clearly connotes the medical consequences of the event, which are both predicable and preventable. Accidents, unlike injuries, are not usually considered predictable or preventable. In fact, the Oxford English Dictionary defines the word accident as “an unusual event, which proceeds from some unknown cause … unexpected … happening by chance or fortune.”27 The word injury has its root in the Latin term injuris, which literally means “not right.” The dictionary defines injury as “harm of any kind, done or sustained.”28 Since most injuries can be prevented through changes to products, behaviors, and environments, using terms such as injury prevention rather than accident prevention helps make clear that injuries are controllable and can be prevented. Former U.S. Surgeon General C. Everett Koop underscored this distinction when he said:29 We must accept that the injuries associated with motor vehicles are not ‘accidents’ and that much can be done to reduce them. …An informed and aroused public can change the behavior of each of us, but more importantly it must lead to community outrage and action in regard to unsafe playgrounds,

115.9  Axioms in Injury Prevention  1297

automobiles, highways, work places, toys, homes and use of handguns.

115.7 CAUSES OF INJURY In public health, injury is defined as “unintentional or intentional damage to the body resulting from acute exposure to thermal, mechanical, electrical, or chemical energy or from the absence of such essentials as heat or oxygen.”30 These exposures are affected by lifestyle choices. The specific cause of injury is the transfer of energy to a person at rates and in amounts more than the tolerance of human tissue.31 The amount of the energy concentration outside the tolerance of tissue usually determines the severity of the injury. The terms injury and trauma are often used interchangeably. Although there are many kinds and causes of injury, two main categories prevail; 1. Acute exposure to energy refers to injuries resulting from falls, motor vehicle crashes, and sports injury (kinetic energy); fires and burns (thermal energy); poisonings (chemical energy); electrocution (electrical energy); and from radiation. 2. Absence of essentials includes lack of oxygen (as in asphyxiation, strangulation, or drowning) and lack of heat (as in hypothermia or frostbite). According to Gordon in 194932 “A significant disturbance of (the) equilibrium (between man and his environment) is the basis for disease or injury. The disturbance may occur either through principal action of the agent, because of a characteristic of the host, or as a function of environment, but most often through some combination of the three” (p 507). In the case of a sports injury, damage to the host (the person harmed) is brought about through a rapid transfer of kinetic energy which can come from, for instance, colliding with another player or with a goal post. This exchange of energy can be modified in several ways—by making the host more resistant to the damage (by increasing human injury tolerance through training), by reducing the kinetic energy exchanged (for example, interposing protective equipment between the host and the energy source, such as with goal post padding or a helmet on the player), or by eliminating the source of the energy exchanged (banning contact sports or removing goal posts).

115.8 INJURY CONTROL Control of injuries requires preventing the occurrence or reducing the severity of the injury event. In the case of an injury to an older adult falling, damage to the host (the person harmed) is brought about through a rapid transfer of kinetic energy as the faller hits the ground. Changing this pattern of energy transfer can be modified in many ways: (1) by making the host more resistant to it (by increasing injury tolerance through exercise and diet), (2) by reducing the amount of energy transferred to the

host (by landing on a softer surface or wearing hip protectors), or (3) by creating a safer home environment (by removing trip hazards and installing proper lighting on stairs or installing grab bars in the bathroom). These are lifestyle changes within reach of most patients, manufacturers, homebuilders, governments, and caregivers. The application of lifestyle change and health promotion strategies can modify individual and population risks, reduce exposure to hazardous environments, and remove or modify harmful products from the marketplace.33 Individual and community actions are required for these strategies to succeed, and they are fostered by education, stimulated by social and organizational change, and encouraged through public policy, legislation, and enforcement activities. 34 Injury prevention counseling can be an effective intervention.35 But despite strong recommendations from the American Academy of Pediatrics,36 only one in five adults who visit a health care provider reported receiving counseling on any injury topic, only one in ten was counseled on seat belt use, and one in 17 received counseling on home smoke alarms.37 Pediatricians have had the greatest compliance with patient and family injury counseling. Yet, pediatricians are still more likely to council patients and families on injury prevention than other medical providers.38 An online survey of 1,088 health care providers who saw patients at or near driving age found that nearly all providers (92.9%) reported addressing one or more driving safety factors (seat belt use, nighttime driving, fatigue, teen passengers, alcohol/drug use, speeding/reckless driving, and cell phone use/texting) with adolescent patients and/or their parents. Discussions on seat belt use was reported most often (83.7%). 39 Counseling for injury prevention has probably increased substantially since 2012, when ICD-9-CM V65.43 became a billable medical code for counseling on injury prevention that can be used to indicate a diagnosis on a reimbursement claim; however, it is only used for claims with a date of service on or before September 30, 2015.40 Thereafter, the equivalent in ICD-10-CM code is ICD-10-CM Z71.89 and has been in use since October 1, 2015 for billable purposes (http​://ww​w.icd​9data​.com/​ 2012/​Volum​e1/V0​1-V91​/ V60-​V69/V​65/V6​5.43.​htm).​

115.9 AXIOMS IN INJURY PREVENTION Several axioms for injury prevention can help guide efforts in controlling injuries.12,33,34 1. Injury results from interactions between people and the environment: There are both human and environmental determinants of injury. The agent of injury will cause relatively little damage if the amount reaching tissues is within the limits of human tolerance. Tap water can scald in seconds (or not at all) depending on its temperature and skin conditions. The importance of this interaction is recognized in approaches that control the environment by reducing hot water temperatures at the tap and approaches that simultaneously target parents

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of small children and the elderly about hot water scald risks (including the need for reduced tap water temperatures). 2. Injury-producing interactions can be modified through changing behavior, products, or environments: Injuries can be reduced by modifying the weakest or most adaptable link in the chain of causation. Unsanctioned swimming in a home swimming pool is more easily reduced by placing an isolation fence or barrier between a child and the pool than by supervising a child’s behavior at all times. During sanctioned swimming, while in the pool, close supervision is the most important strategy. Changing the environment, the laws, the person, or the product can all lead to reductions in injuries. 3. Environmental changes have the potential to protect the greatest number of people: Changes to the environment that automatically provide protection to every person have the potential to prevent the most injuries. This includes automatic protection built into roads (such as barriers), into buildings (such as fire sprinkler systems), into automobiles (such as rollover protection), into homes (such as electrical fuses), and into products (such as childresistant packaging on medicines). Few “passive” interventions succeed without an active behavioral component (such as replacing lids on medicines) and succeed better when the public is informed and convinced of their need and benefit. 4. Effective injury prevention requires a mixture of strategies and methods: Three primary strategies— education/behavior change, technology/engineering, and legislation/enforcement—are widely recognized as effective in preventing injuries. Individual behavior change, product engineering, public education, legal requirements, law enforcement, and changes in the physical and social environment work together to reduce injuries. The challenge in intervention planning is to select the most effective combination of strategies to produce the desired result. 5. Public participation is essential for community action: Effective public policy requires the support and participation of people. Local problems and resource availability often determine the direction of injury prevention programs. Factors influencing success in injury prevention are best identified by public feedback and participation in the process. Without public support, effective laws designed to protect the public (such as mandatory motorcycle helmet use laws) may be ignored, or even worse, repealed. 6. Intersectoral collaboration is necessary: Injury prevention requires coordinated action by many groups. Participation by community leaders (in addition to health officers, physicians, hospital administrators, and others) is necessary in planning and implementing injury prevention programs. Different sectors can play different roles—ranging from identifying problems to mobilizing community action, evaluating intervention effectiveness, and advocating for change. Identifying and building a constituency and shifting or sharing resources require collaboration across many different sectors.

115.10 HOW LIFESTYLE MEDICINE PRACTITIONERS CAN HELP PREVENT INJURIES As injury prevention and lifestyle medicine become more closely aligned, the potential benefits of comprehensive injury prevention strategies will become clearer and more widely accepted.41,42 Lifestyle medicine physicians often see patients and their families after an injury has occurred, but yet have the opportunity to go “upstream” too, to uncover the root causes, collect injury surveillance data on specific causes, design preventive interventions for specific populations in the clinical environment, testify on behalf of prevention policies, or help improve injury prevention programs in their community. There are also opportunities in patient care to implement interventions such as screening and brief interventions for alcohol or opioid abuse, and to screen and counsel older patients on fall prevention.43 Physicians can also influence decision makers by providing evidence that prevention policies work or to set health care and reimbursement policies that promote and incentivize prevention. Health care professionals who serve on medical school or nursing faculties and teach courses on trauma prevention can also help prepare their students with material related to injury prevention. Reducing injuries will also require a shift in how society thinks about hazards, the environment they live in, their personal risk behaviors, and the value of prevention. Lifestyle medicine can contribute to this shift by engaging in a variety of actions in the community to protect the public, such as: • Supporting efforts to reduce injuries, such as primary seat belt laws, stronger teen driving policies, smoke alarm installation policies, and motor cycle safety. • Informing decision makers about the potential public health effects of repealing effective injury prevention legislation. • Supporting drowning prevention strategies such as the use of four-sided fences around residential swimming pools and the use of life jackets while boating. • Collecting data on the clinical and health care costs and consequences of the injuries treated. • Strengthening collaboration with local coalitions, such as Safe Kids, a local drowning prevention coalition; the National Safety Council; or state public health departments and state offices of highway safety. • Supporting efforts to build injury prevention into health care reform. • Testifying at hearings and town meetings about evidence-based strategies that work. • Supporting research on risk factors, protective factors, and interventions to reduce all forms of injury and trauma, including injury prevention on and off the job. • Encouraging built environment strategies that prevent injuries to pedestrians and cyclists.

Clinical Applications  1299

115.11 FUTURE DIRECTIONS The National Academy of Sciences/Institute of Medicine report Reducing the Burden of Injury44 reemphasized the importance of using a scientific approach to injury prevention and called on public health agencies and others to work with medical care organizations, health care providers, states and communities, businesses, and other federal agencies to pursue alliances that would help reduce injuries. Injury epidemiologists, behavioral scientists, and lifestyle medicine practitioners should work side-by-side to identify, prevent, and control injuries, and to explore ways to strengthen data systems, identify risk and protective factors, test interventions, and conduct evaluations of existing injury prevention efforts. Translating successful strategies for use in primary care settings is more challenging (even in traditional prevention arenas such as cancer prevention and women’s health),45,46 but it is critical in injury control where using known and effective interventions can save lives almost immediately. The challenge now is to stimulate lifestyle medicine and primary care physicians to become more engaged in using and adapting best practices with patients and families to save lives and prevent injuries. 2 Among the most urgent priorities is the area of motor vehicle injury prevention, where more than 35% of the injury deaths occur. The drastic reductions in motor vehicle injury deaths during the past 20 years shows what can be accomplished when data are used for decision making and action.47,48 Examples of evidence-based strategies to prevent motor vehicle occupant injuries can be found in the Guide to Community Preventive Services (Community Guide).49 The guide summarizes what is known about the effectiveness, economic efficiency, and feasibility of interventions to promote community health and prevent disease, and it makes recommendations for the use of various interventions based on the evidence gathered in the rigorous and systematic scientific reviews of published studies. Reductions in motor vehicle deaths and hospitalizations in military service members provide another illustration of what is achievable when there is a focus on the prevention of a specific injury problem in a defined population. 50 As we learn more from data about injury patterns, trends, and vulnerable populations, this new knowledge, if acted upon, can lead to: (1) identifying new and unique injury problems, such as the prescription drug overdose epidemic, (2) improving the quality and timeliness of injury data, (3) helping federal and state agencies, and their partners, define and implement research agendas to close the gaps in existing knowledge, (4) translating injury prevention priorities into prevention programs, (5) evaluating prevention efforts in various settings and among vulnerable populations, and (6) delivering quality injury prevention programs that affect the widest cross section of the population, including individuals, families, and communities. Lifestyle medicine practitioners can be important partners in this effort. It’s time to add injuries to the broad range of conditions resulting from lifestyle choices and engage the primary caregivers and other gatekeeper health

care professionals in advocating for lifestyle choices that reduce injuries from all causes.

115.12 CONCLUSIONS Although injuries have plagued societies since the beginning of time, preventive and lifestyle medicine have only recently recognized these events as important public health problems that are both predictable and preventable. Injuries are seldom distributed randomly—they are concentrated in physical space and time, and they affect definable populations. Using ecological public health approaches that are based on sound epidemiology, 51 human factors research52 and behavioral and social science theories53 stand the best chance of succeeding in identifying problem areas and reducing injuries. Targeting the host, agent, and environmental factors, including hazardous products that contribute to injury, will help reduce overall injury rates. Approaches will need to be adapted to different populations, lifestyles, and life stages. Because there are so many different injuries with varied causes, tailored strategies are necessary. Reductions in injury and their costs to the health care system, to patients and their families are possible, but will need support, collaboration, and partnering from policy makers, clinicians, and health care practitioners. Lifestyle medicine and primary care family practitioners are important allies in encouraging lifestyle choices that reduce injuries. Primary caregivers and other health care professionals can help reduce injuries from all causes using clinical-based prevention skills and advocating in the community for changes in environments and for policies that reduce the potential for injury.

CLINICAL APPLICATIONS • Include injury prevention in all health promotion and disease prevention activities with patients • Expand record keeping to collect and monitor patient risk factors for injuries (e.g., chart reminders for teens about texting and driving or about opioidrelated overdose among middle-aged adults). • Assess the safety practices of patients and their families (e.g., working smoke alarms; wearing seat belts; using helmets; avoiding alcohol (and texting) while driving; using life jackets). • Set goals for patients to change risky lifestyles that predispose to injuries. • Have information available on how patients can access resources in the community for injury prevention (e.g., local safety council, state health departments, SafeKids, local bicycle helmet programs). • Screen for alcohol misuse, using existing tools such as brief intervention and motivational interviewing. • Screen for use of age-appropriate child safety seats and booster seats. • Support improvements in prehospital and hospital care for injured victims and support comprehensive trauma care systems in the community.

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• Talk to parents of teenage drivers about the importance of graduated driver licensing. • Endorse passage and support for statewide primary seat belt laws.

• Maximize the use of Electronic Health Records for injury data and use Prescription Drug Monitoring Programs to manage potential patient addiction.

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Control. Injury Prevention: Meeting the Challenge. New York: Oxford University Press. (Supplement to American Journal of Preventive Medicine, 5(3), 1989, 1–303. National Committee for Injury Prevention and Control. Injury Prevention: Meeting the Challenge. New York: Oxford University Press. (Supplement to American Journal of Preventive Medicine, 5(3): 1–303, 1989. De Haven H. Mechanical Analysis of Survival in Falls from Heights of Fifty to One Hundred and Fifty Feet. War Medicine, Vol 2: 586–596, 1942. Gordon JE. The Epidemiology of Accident. Am J Public Health, Vol 39: 504–515, 1949. Sleet DA, Rosenberg ML. Injury control. In: Scutchfield DF, Keck CW, eds. Principles of Public Health Practice. New York: Delmar Publishers; pp. 337–349, 1997. Sleet DA, Gielen A. Injury prevention. In SS Gorin and J Arnold, (Eds). Health Promotion Handbook. St Louis, MO: Mosby; pp. 247–275, 1998. Gielen AC. Injury and Violence Prevention: A Primer. Patient Educ Couns, Vol 46: 163–168, 2002. Gardner HG; American Academy of Pediatrics Committee on Injury, Violence, and Poison Prevention. Office-Based Counseling for Unintentional Injury Prevention. Pediatrics, Vol 119(1): 202–206, 2007. Dellinger AM, Chen J, Vance A, Breiding M, Simon T, Ballesteros MF. Injury Prevention Counseling for Adults: Have We Made Progress? Fam Community Health, Vol 32(2): 115–122, 2009. Chen J, Kresnow MJ, Simon TR, Dellinger A. Injury Prevention Counseling and Behavior among US Children: Results from the Second Injury Control and Risk Survey. Pediatrics, Vol 119: e958–965, 2007. Dellinger AM, West BA. Health Care providers and Teen Driving Safety: Topics Discussed and Educational Resources Used in Practice. Am J Lifestyle Med, Vol 9(6): 451–456, 2015. American Academy of Pediatrics. Counseling on injury prevention. http:​// www​.icd9​data.​com/2​012/V​olume​1/V01​ -V91/​V60-V​69/V6​5/V65​.43.h​t m. Gielen A, Girasek D. Integrating perspectives on the prevention of unintentional injuries. In N Schneiderman, M Speers, J Silva, H Tomes, JH Gentry, (Eds). Integrating Behavioral and Social Sciences with Public Health. Washington, DC: American Psychological Association, pp. 203–227, 2001. Sleet DA and A Gielen. Injury prevention and behavioral science: opportunities to impact population health. Monograph. In Behavioral & Social Science contributions to Population Health. Bethesda, MD: NIH, Office of Behavioral and

References  1301 Social Science. Printed by US Gov’t Printing Office, September, 2015. 43. Houry D, Florence C, Baldwin G, Stevens J, McClure R. CDC Injury Center’s Response to the Growing Public Health Problem of Falls Among Older Adulta. Am J Lifetyle Med, Vol 10(1): 74–77, 2016. 4. Bonnie RJ, Fulco CD, Liverman CT, eds. 4 Reducing the Burden of Injury: Advancing Prevention and Treatment. Washington, DC: National Academy Press; 1999. 45. Graham AI, Kerner JF, Quinlan KM, Vinson C, Best A. Translating Cancer Control Research into Primary Care Practice: A Conceptual Framework. Am J Lifestyle Med, Vol 2: 241–249, 2008.

46. Zapka JG. Prevention Research and Reality: Narrowing the Quality Chasm. Am J Lifestyle Med, Vol 2: 260–262, 2008. 47. Dellinger A, Sleet DA. Preventing Traffic Injuries: Strategies that Work. Am J Lifestyle Med, Vol 4(1): 82–89, 2010. 48. Dellinger A, Sleet DA. From Modest Beginnings to Winnable Battle: 20 years of Road Safety efforts at CDC’s Injury Center. J Saf Res (Special issue), Vol 43(4): 279–282, 2012. 49. Zaza S, Briss PA, Harris KW, eds. The Guide to Community Preventive Services: What Works to Promote Health? New York: Oxford University Press; 2005.

50. Sleet D, Jones B, Amoroso P. Military Injuries and Public Health: An Introduction. Amer J Prevent Med, (Special Issue on Injuries in the U.S. Armed Forces), Vol 18(3S): 1–3, 2000. 51. Allegrante JC, Hanson D, Sleet DA, Marks R. Ecological Approaches to the Prevention of Unintentional Injuries. Ital J Public Health, Vol 7 (2): 24–31, 2010. 52. Porter BE, Bliss JP, Sleet DA. Human Factors and Injury Prevention. Am J Lifestyle Med, Vol 4: 90–97, 2010. 53. Sleet DA, Branscum P, Knowlden AP. Advancing Theory in Health Promotion and Community Health. Fam Community Health, Vol 40(1): 1–2, 2017.

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116 CHAPTER

Traffic Injury Prevention: Strategies That Work Ann M. Dellinger, PhD, MPH, David A. Sleet, PhD, FAAHB, and Merissa A. Yellman, MPH

Key Points................................................................................ 1303 116.1  Traffic Injury and Lifestyle............................................. 1303 116.2 Epidemiology................................................................ 1304 116.3  Effective Interventions.................................................. 1306 116.3.1  Alcohol-Impaired Driving................................. 1306 116.3.2  Occupant Protection....................................... 1308 116.3.3  Motorcycle Helmets........................................ 1309 116.3.4  Bicycle Helmets.............................................. 1309 116.3.5  Graduated Driver Licensing Systems.............. 1309 116.3.6  Parental Monitoring of Young Drivers.............. 1309 116.3.7 Automated Enforcement: Speed and Red Light Cameras����������������������������������������������� 1309

KEY POINTS • Traffic injuries are a leading cause of death in the United States and a major public health problem. • Effective evidence-based strategies are available but not universally implemented. • Primary prevention approaches hold the most promise for reducing the traffic injury burden. • Practitioners of lifestyle medicine have an important role in prevention by supporting patient education in clinical settings or by supporting evidence-based public policy. Traffic-related injuries have only recently been recognized as a fundamental part of public health practice. Primary care providers can have a positive influence on their patients’ behavior and help prevent one of the leading causes of death in America. There are many effective strategies that are closely related to lifestyle factors and can be used to address these preventable deaths and injuries and that can be incorporated into clinical practice. For example, clinicians can support primary prevention by implementing screening and brief intervention for excessive alcohol consumption and by counseling patients about drinking and driving, and they can also support secondary prevention by counseling patients about the need for seat belts for themselves and child safety seats for their young children. This chapter will describe the current traffic environment and the epidemiology of traffic-related deaths and injury, and will also review what

116.4  Interventions with Limited Evidence Of Effectiveness.....1310 116.4.1 Legislation to Restrict Cell Phone Use While Driving����������������������������������������������������������� 1310 116.4.2  Designated Driver Programs............................1310 116.5  Emerging Considerations...............................................1310 116.5.1 The Changing Age Distribution of the U.S. Population����������������������������������������������������� 1310 116.5.2  Drug-Impaired Driving.....................................1310 116.6  Implications for Primary Care Practice...........................1311 Clinical Applications..................................................................1311 References...............................................................................1311

is known about effective prevention strategies, with an emphasis on strategies that are most applicable to lifestyle medicine.

116.1 TRAFFIC INJURY AND LIFESTYLE Traffic-related injury and lifestyle are inextricably linked. Our culture values independence, and for many people independence comes with the ability to drive. The motor vehicle dominates all other modes of travel in the United States. In the span of 100 + years, the number of registered automobiles grew from 8,000 in 1900 to 263 million in 2015.1 In 2016, 20% of households reported three or more vehicles, and only 9% reported zero vehicles. 2 A high degree of mobility is integral to our lifestyle. There are more than 221 million licensed drivers in the United States, and they drive an average of 14,000 miles per year on over four million miles of roads.3 Figure 116.1 indicates that while exposure to the road environment has increased, there has been a long-term decline in the rate of traffic-related deaths, over 90% since 1925.1 This is primarily due to advances in the safety of vehicles and roads, and due to improvements in driver behavior,4 which have mitigated the negative effects of increased motorization. In spite of these declines, traffic crashes remain a leading cause of death among all age groups in the United States. 5 A 2016 Centers for Disease Control and Preventon (CDC) report compared the United States to 19 other high-income countries and revealed that 1303

1304  Chapter 116  Traffic Injury Prevention: Strategies That Work 20 VMT

3000

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16 2500

14 12

2000

10 1500

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3500

4 500

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0 0 1925 1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 Year (1925-2015)

Figure 116.1  Annual Vehicle Miles Traveled (VMT) and Motor Vehicle-Related Deaths, United States, 1925–2015. Data Source: National Safety Council, Injury Facts, 2017.

the United States had the highest number of motor vehicle crash deaths per 100,000 people, and per 10,000 registered vehicles.6

116.2 EPIDEMIOLOGY Traffic crashes result in more than 30,000 deaths and more than three million nonfatal injuries treated in hospital emergency departments each year. 5,7 The risk of death or injury varies by many factors, including sex, age, race/ ethnicity, type of road user (e.g., occupant, pedestrian, motorcyclist, cyclist [non-motorized]), and location (e.g., state, urban/rural setting). There is a significant risk difference by sex. Males have death rates at least twice that of females overall—for vehicle occupants, motorcyclists, pedestrians, and cyclists; and for all age groups after the age of licensure (age groups 15–19 years and older). The difference is especially high for motorcyclists (death rate 11 times higher among males) and cyclists (six times higher among males). For nonfatal injuries, males have higher injury rates than females except in the case of motor vehicle occupants where the injury rate among females is 1.3 times that among males. 5 Death rates vary widely by age, with the lowest rates among children aged 0–14 years, and the highest rates among those aged 15–24 years and 80 years and older. 5 In 2015, young drivers (16–20 years of age) represented 5.4% of all licensed drivers; however, 9% of all drivers involved in fatal crashes were young drivers.8 Young drivers have higher crash involvement rates than any other age group; this holds true for fatal crashes, injury crashes, and

property-damage-only crashes.7 Novice teen drivers have especially high death rates given their lack of experience driving and their risk-taking behaviors. Defined later in this chapter, graduated driver licensing (GDL) systems are an effective crash prevention strategy for teen drivers. In 2006, 30% of 16-year-olds were licensed drivers compared to 26% in 2016, among 17-year-olds the decline was from 51% to 47%, and among 18-year-olds, the decline was from 67% to 62%.9,10 Older drivers, age 65 years and older, represent a fast growing segment of the driving population. In just ten years, from 2006 to 2016, the number of older licensed drivers grew 38% to almost 42 million, nearly 19% of the driving population in the country.9,10 The proportion of the population who are licensed drivers has also increased in this age group; in 2006, 89% of 65- to 69-year-olds were licensed drivers, and in 2016, this had increased to 92%.9,10 Similar increases were seen in all older age groups, including those aged 85 and older, who increased from 51% to 61%.9,10 Per mile traveled, fatal crash rates increase notably starting at age 70–74 years and are highest among drivers 85 years of age and older. This is largely due to an increased susceptibility to injury and medical complications among older drivers rather than an increase in crash involvement.7,11 However, age-related declines in vision and cognitive functioning, as well as physical changes, may affect some older adults’ driving abilities. The American Medical Association has collaborated with the National Highway Traffic Safety Administration (NHTSA) to create resources for physicians to assess and counsel their patients on their ability to drive safely.12

116.2  Epidemiology 

There are also racial and ethnic differences in crashrelated deaths. Generally, American Indian and Alaska Native populations have the highest death rates, while Asian and Pacific Islander populations have the lowest; African American, white (Non-Hispanic), and Hispanic populations (of all races) have similar death rates.5 However, when adjusting for time on the road, or vehicle miles traveled, vehicle occupants who are African American and Hispanic have higher death rates than whites.13 Some racial and ethnic minority groups are disproportionately affected by motor vehicle crashes; approximately 4.3% of all deaths among American Indian and Alaska Native populations are due to crashes, and 3.3% of all deaths among Hispanics are due to crashes, while less than 1.7% of all deaths among African American, white, and Asian/Pacific Islander populations are crashrelated.14 Figure 116.2 shows age-adjusted motor vehicle-related deaths rates by race/ethnicity and sex. For all racial/ethnic groups, males have higher death rates than females; American Indian and Alaska Native males have higher deaths rates than all other groups. 5 Death rates vary by road user type. Motor vehicle occupants (drivers and passengers) represent the majority of crash deaths (67%), motorcyclists represent 14%,

1305

pedestrians 16%, cyclists 2%, and others 1%.7 However, these unadjusted statistics do not incorporate exposure to the road environment into their calculation. For example, motorcyclists represent 14% of the crash deaths but only 3% of all registered vehicles and 0.6% of all vehicle miles traveled.15 Per vehicle mile traveled in 2015, motorcyclist fatalities occurred nearly 29 times more frequently than passenger car occupant fatalities.15 Alcohol is also prevalent in fatal crashes among motorcyclists. The percentage of motorcyclists involved in fatal crashes who had a blood alcohol concentration (BAC) of ≥ 0.08 g/dL (25%) was higher than the percentage of passenger car drivers (21%), light truck drivers (20%), and large truck drivers (2%) who died in fatal crashes.16 Among cyclists killed in crashes, 22% had a BAC of 0.08 g/dL or higher.17 Among pedestrians killed in crashes, 34% had a BAC of 0.08 g/dL or higher.18 States vary in the number and rate of traffic crash deaths, the use of seat belts, the incidence of self-reported drinking and driving, the proportion of urban versus rural area, the coverage of level one trauma care centers, and many other factors related to the risk of a crash and the risk of death or injury given a crash has occurred. Consequently, as shown in Figure 116.3, there is almost a sixfold difference in motor vehicle traffic death rates. 5

40

Age-adjusted death rate per 100,000 popula on

35

30

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20 Male Female

15

10

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Black

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Figure 116.2  Age-Adjusted Motor Vehicle Death Rates by Race/Ethnicity and Sex, United States, 2016. Data Source: CDC WISQARS, available at: https://www.cdc.gov/injury/wisqars/fatal.html Data for White, Black, American Indian/ Alaska Native, and Asian/Pacific Islander only include Non-Hispanic Ethnicity. Data for Hispanic Ethnicity include all races. Rates are standardized to the 2000 U.S. population.

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Figure 116.3  Age-Adjusted Motor Vehicle Death Rates by U.S. State, 2016. Data Source: CDC WISQARS available at: https://www.cdc.gov/injury/wisqars/fatal.html Rates are per 100,000 population and are standardized to the 2000 U.S. population.

116.3 EFFECTIVE INTERVENTIONS While this chapter focuses primarily on individual behaviors, it also includes some information on vehicle safety devices and other strategies. The intent is to provide a practical review of interventions designed to reduce traffic crash deaths and injuries that can be supported by clinicians, whether through patient education in clinical settings or by partnership engagement and policy.

116.3.1 Alcohol-Impaired Driving In 2016, 28% of all traffic deaths (around 10,500) involved a driver with a blood alcohol concentration (BAC) of ≥ 0.08 g/dL, a level illegal in every state.16 Each year millions of adults admit to an estimated 121 million episodes of alcohol-impaired driving,19 yet only a small proportion, 1.02 million, are arrested for this offense. 20 Moreover, 85% of drinking and driving episodes are reported by binge drinkers, and the 4.5% of the adult population who reported binge drinking at least four times per month accounted for 55% of all alcohol-impaired driving episodes.19 Progress has stalled in this area; while the number of alcohol-related traffic deaths has declined with the overall decline in all traffic deaths, the proportion of traffic deaths that are alcohol-related has remained constant. Figure 116.4 shows that since the late 1990s this proportion has hovered around 30%. 21 Interventions to reduce alcohol-impaired driving include: Zero tolerance laws. These laws make it illegal for persons under age 21 to drive after any drinking, but the threshold is usually set at 0.02 g/dL BAC because

of the possibility for slight imprecision in breathalyzer testing. These laws have been associated with declines in alcohol-related deaths. 22,23 Voas, Tippetts, and Fell found declines from 19–24% in underage drinking drivers in fatal crashes. 24 All states have passed zero tolerance laws for young drivers. Minimum Legal Drinking Age Laws. Age 21 minimum legal drinking age (MLDA) laws are effective in reducing alcohol-related crashes and injuries. 23,25 This type of law is especially important given the high crash and death rates of young drivers. 24,26–28 At the same blood alcohol level, crash risk is higher for young drivers than older drivers. 29 All states have increased their MLDA to 21 years, up from 18 years. NHTSA estimates 552 lives saved in 2016 due to MLDA laws.30 Lowering the MLDA so that younger people can legally purchase alcohol has been associated with an increase in alcohol-impaired crashes by a median of 10%. 23 Sobriety checkpoints. Alcohol roadside checkpoints, whether randomly or selectively implemented, can be an effective law enforcement intervention. Sobriety checkpoints have been shown to decrease fatal and non-fatal injury alcohol-involved crashes by a median of 9%.31 Sobriety checkpoints are generally paired with media efforts to publicize the effort, which helps to increase the perceived risk of arrest. Lower BAC. Blood alcohol concentration (BAC) laws make it illegal to operate a motor vehicle at or above a specified BAC. Originally set at 0.10 or 0.15, these laws have had their maximum limits lowered over time; 0.08 g/dL BAC laws have been found effective in reducing alcohol-impaired driving. 22,23,28 As

116.3  Effective Interventions  1307

116

Figure 116.4  Proportion of Persons Killed, by Highest Blood Concentration (BAC) in the Crash, United States, 1982–2015. Data Source: National Highway Traffic Safety Administration

of 2004, all states have passed 0.08 g/dL BAC laws that place the legal limit for driving after drinking (for adults age 21 and older) below 0.08 g/dL. One state, Utah, has recently passed a 0.05 g/dL limit, which is expected to go into effect at the end of 2018. The United States lags behind many other countries that have reduced their legal BAC limit for drivers to under 0.05 g/dL.32 Ignition interlocks. These devices prevent a drinking driver from starting the vehicle by requiring the driver to provide a breath sample before starting the vehicle. If the breath sample exceeds a specified BAC, the ignition is locked and the vehicle will not start. State programs can range from strictly judicial (i.e., judges decide on the interlock requirements), administrative (e.g., operated through the department of motor vehicles), or a hybrid of the two. Reports that have combined data from multiple studies estimate that interlocks account for 65% reductions in driving while impaired (DWI) recidivism, a beneficial effect that is usually limited to the period of installment. 33–35 An innovative study in Florida paired ignition interlocks with treatment for alcohol use disorder. The interlock plus treatment group experienced 32% lower recidivism than the non-treatment group. This level of effectiveness translated into an estimated 41 fewer rearrests and 13 fewer crashes. 36 Because drivers with a prior DWI violation are seven

times more likely to have a subsequent violation than drivers without a history of DWI, 37 ignition interlocks could be considered for all convicted DWI offenders, including first-time and repeat offenders. Server intervention training. Server intervention and training programs are designed to prevent patron intoxication and alcohol-impaired driving by offering food with drinks, delaying service to rapid drinkers, and refusing service to intoxicated patrons. Evidence for effectiveness comes from studies of establishments that volunteered to participate in training servers; therefore, management support was well established, and server training was intensive, high-quality, and face-to-face (not video-training). Questions remain, however, about whether server training is effective as a standalone intervention. 23 A related issue is dram shop liability, which holds the owner(s) or server(s) at the location that provided the last alcoholic drink to a patron responsible for harms inflicted by that patron on others. Dram shop liability has been shown to be effective in reducing alcohol-related crash fatalities. 38 Alcohol screening and brief intervention. Screening for excessive alcohol use and subsequent brief intervention has been found effective in emergency departments, 39 trauma centers,40 and primary care settings.41 The outcome measures of interest vary

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across studies but have included reduced alcohol intake, reduced excessive drinking, reduced injury frequency, and other outcomes. 39–41 A study by Fleming et al. found that two 15-minute sessions with a physician followed by two five-minute telephone calls from an office nurse resulted in sustained effects over a 48-month period. The treatment group had significant reductions in seven-day alcohol use, number of binge drinking episodes, and frequency of excessive drinking compared to controls. In addition, the treatment group had fewer days of hospitalization and fewer emergency department visits. The largest cost benefit was due to fewer motor vehicle-related events.41 These results indicate that a modest investment in time and resources can have a clinically important effect that is maintained over years. Alcohol Pricing Strategies. Alcohol pricing strategies can be implemented at the state and federal levels, and are beverage-specific (i.e. they differ for beer, wine, and spirits). Studies have shown that increasing alcohol taxes and higher alcohol prices raise revenue. They also reduce excessive drinking and alcohol-related harms (such as fewer deaths from liver cirrhosis and all-cause mortality) as well as alcohol-impaired driving and motor vehicle crash fatalities.42–45 Some studies have also shown effects for reducing outcomes of violence, sexually transmitted diseases, and alcohol dependence.46 Despite the strong evidence showing that increased alcohol taxes reduce a wide variety of alcohol-related harms, the revenue from these taxes does not cover alcohol-related costs to society and have declined in inflation-adjusted terms (at both the federal and state levels).42,43,46,47

116.3.2 Occupant Protection Occupant restraints, including lap and shoulder belts, child safety seats (CSS), and booster seats, are among the most effective injury prevention interventions available. Seat belts reduce the risk of death and serious injury in a crash by about half.48 CSS are 71% effective in reducing fatalities among infants and 54% effective among toddlers.49 An estimated 328 children under five years of age were saved in 2016 by CSS.30 Booster seats are 45% more effective than adult seat belts alone in reducing injury among age- and size-appropriate children. 50 Interventions to increase occupant protection include: Seat Belts. Seat belts provide the greatest protection available to drivers and occupants. The National Safety Council estimates that seat belts saved almost 14,000 lives in the United States in 2015, and that almost 350,000 lives have been saved since 1975.1 In 2015, 48% of passenger vehicle occupants (among occupants for whom restraint use was known), who died in car crashes were unrestrained; in contrast, among occupants who survived fatal crashes, only 14% were unrestrained.1 The National Occupant Protection Use Survey (NOPUS) conducted in 2016

found seat belt use to be 90% nationwide. 51 To date, 49 states, the District of Columbia, Puerto Rico, and all U.S. territories have adult seat belt use laws in place. Primary enforcement laws allow a law enforcement officer to stop a motorist based on a seat belt violation alone, while secondary enforcement laws require another reason to stop a motorist other than a seat belt infraction. Both primary and secondary enforcement laws are effective in increasing belt use and reducing fatal and nonfatal injury, with primary laws showing the greatest effectiveness. 52–54 State primary enforcement laws were effective from 1984 through 2015; however, as of January 2018, 16 states do not have primary enforcement laws. 55 Enhanced enforcement programs of seat belt laws, through more officers on patrol, or by increasing the number of citations issued, are also effective in reducing fatal and nonfatal injuries, and in increasing belt use. 52 Child safety seats. All states require children to be restrained, although the specifics of coverage vary. 55 CSS laws require children to be restrained in federally approved safety seats appropriate for the child’s age, height, and weight. CSS laws decrease fatal and nonfatal injury, and increase child safety seat use. CSS education programs combined with distribution of CSS have been found to decrease fatal and nonfatal injury, increase CSS use, and increase possession of CSSs. Community-wide information plus enhanced enforcement campaigns have also been found to increase CSS use. 55,56 Finally, incentive plus education programs (including rewards for either parents or children for correctly using CSS) have been shown to increase CSS use. 56,57 Booster Seats. Booster seats are designed to raise a child so that the vehicle lap and shoulder belts fit properly. The American Academy of Pediatrics recommends that all children use a booster seat until they reach four feet, nine inches in height, which usually occurs between eight and 12 years of age. 58 A systematic review of the impact of various legislative, educational, and promotional interventions among children aged four to eight years found that interventions that combined education with distribution of booster seats or incentives such as discounted coupons had the greatest positive impact. 59 Moreover, booster seat legislation has been shown to increase booster seat use, reduce injury, and save costs.60–63 Rear Seating Position. The number of children sitting in the front seat is declining. By 2008, 95% of infants, 98% of toddlers, and 88% of children four to seven years of age rode in the rear seating position. 58 Although the catalyst for moving children to the rear seat was the danger from passenger-side air bags, rear seating position is still the safest place for children whether or not there is a passenger-side air bag present.64–66 Studies have found that children in the rear row(s) of the vehicle are 40% to 70% less likely to sustain injury than those in the front, depending on the specific characteristics of each study. 58,67

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116.3.3 Motorcycle Helmets Motorcycle helmets are estimated to be 42% effective in preventing fatal injury to motorcyclists and 69% effective in reducing head injury.68 Helmet use is especially important since, per vehicle mile traveled, motorcyclists are about 29 times more likely to die in a crash than passenger car occupants.15 Motorcycle helmet use laws are effective in increasing helmet use among riders. In states with mandatory or universal (covers riders of all ages) helmet use laws, 76% of motorcyclists wear them—without a law, use is 40%. In states that repealed universal helmet laws, helmet use declined (a median of 39 percentage points), and deaths increased (a median of 42 percentage points).69 In 2018, 19 states plus the District of Columbia required helmet use by all operators and passengers, 28 states required some motorcyclists to wear helmets, and three states had no helmet use law.70 An estimated 71% of motorcyclists wore helmets in 2000, compared with only 65% in 2016.71

116.3.4 Bicycle Helmets Bicycle helmets are effective in preventing head injury, brain injury, facial injury, and death.72–74 However, only about half of children ages five to 14 years always wear their helmets when riding,75 and 21 states in the United States have laws in place that require young riders to wear helmets. No state law requires adults to wear helmets.76 Interventions designed to increase bicycle helmet use generally target children and adolescents, as does legislation requiring helmet use. Legislation with supporting helmet promotional activities has successfully increased observed helmet use and reduced injury and death in the United States and abroad.77–80 Community-based interventions that included free helmets and an educational component had the strongest evidence of effectiveness, along with school-based interventions and those that subsidized helmets.81

116.3.5 Graduated Driver Licensing Systems Motor vehicle crashes are the leading cause of death among teenagers in the United States. Graduated drivers licensing (GDL) systems address the high risks faced by new drivers by requiring an apprenticeship of planned and supervised practice (learner’s permit stage), followed by a provisional license that places temporary restrictions on unsupervised driving.82 Two commonly imposed restrictions are limits on nighttime driving and passenger limits for the number of teen passengers allowed to ride with the new driver. These restrictions are lifted as new drivers gain experience and teenage drivers mature (full licensure). Although the specific requirements for advancing through the three stages of GDL vary across jurisdictions, they provide a protective environment while new drivers become more experienced. GDL has proven effective in reducing new driver crash risk, and the stronger the system the stronger the effect.83–87 The most comprehensive GDL systems were associated with a 38% reduction in

fatal crashes among 16-year-old drivers.88 All states have some form of GDL system, but the strength of the system varies greatly by state.89 An issue related to GDL and teen driver safety is driver education resulting in early licensure. Early licensure can lead to increased exposure of inexperienced drivers and to more crashes. School-based driver education training can often lead to earlier licensure, which in turn can lead to increased exposure.90 Studies by Levy, Vernick et al., and Roberts and Kwan90–92 have consistently indicated that young drivers who take driver education tend to get their licenses earlier than young drivers who do not. Any potential safety benefit from the driver training may be offset by the increase in exposure of teens to unsupervised driving.90–92

116.3.6 Parental Monitoring of Young Drivers Although not definitive, there are studies of the effect of parental monitoring (i.e., parents highly involved in their children’s learning to drive process) of young driver safety. Results have varied, from indicating no effect to modest effects on risky driving behaviors.93 However, parents are in a strong position to delay licensure and to restrict driving under higher-risk conditions such as nighttime driving and driving with teenage passengers,94,95 whether these restrictions are part of their states’ GDL system or not. Research has shown that teens whose parents set and maintain strict limits are less likely to engage in risky driving behaviors, have traffic violations, or to crash during the first year of licensure.95 Parents are the Key to Safe Teen Driving is a campaign from the Centers for Disease Control and Prevention that provides materials for parents, pediatricians, and community groups to help keep teen drivers safe on the road (https://www.cdc.gov/ parentsarethekey/).

116.3.7 Automated Enforcement: Speed and Red Light Cameras Speed affects both the likelihood of a crash and the severity of a crash. Crashes at higher speeds are more severe and therefore the risk of injury is greater. In 2016, 27% of traffic fatalities were among persons killed in crashes where at least one driver was speeding.96 For vulnerable road users such as pedestrians and cyclists, this is especially problematic. Automated enforcement (using speed and red light cameras) is one way to supplement conventional enforcement, which requires law enforcement officers to stop drivers and issue citations. Automated speed enforcement has been shown to reduce speeds and speeding violations.97,98 Reviews of the effectiveness of speed cameras have found decreases in both crashes and injuries in the United States and around the world.72,97–99 As of January 2018, 422 communities in the United States have red light camera programs.100 A recent study101 looked at the effectiveness of red light cameras in two ways: they measured the effect of turning on the cameras and the effect of turning off existing red light cameras. The investigators found that the cameras were effective

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in preventing crash deaths; fatal crashes were reduced when cameras were turned on, and higher when they were turned off.

116.4 INTERVENTIONS WITH LIMITED EVIDENCE OF EFFECTIVENESS 116.4.1 Legislation to Restrict Cell Phone Use While Driving Research has shown that drivers using cell phones are four times more likely to be involved in a serious crash.102 Research by the American Automobile Association (AAA) Foundation found that 81% of drivers view texting and emailing as very serious threats to safety, yet 40% of drivers admitted to having read a text or email message, and 31% admitted to typing or sending a text message or email while driving in the past 30 days.103 Cell phone legislation varies, with some states or localities banning hand-held devices, some banning use among young drivers or bus drivers, and some states banning texting while driving. Although most people agree that using a cell phone while driving is unsafe, the effectiveness of legislation to address this problem has yielded inconsistent results at this time.93,104 Technological approaches, such as automatic disabling of cell phones when the vehicle is moving, may hold promise.

116.4.2 Designated Driver Programs A designated driver is a person who agrees to either abstain or limit alcoholic consumption and drive others home. Designated driver promotion programs run by restaurants or drinking establishments encourage individuals to act as designated drivers by offering incentives such as free nonalcoholic drinks, food, or free admission. Despite their widespread use in the United States, relatively few programs have been thoroughly evaluated. A systematic review of designated driver programs in drinking establishments found insufficient evidence of their effectiveness in reducing alcohol-impaired driving or alcohol-related crashes.105 A review by Nielson and Watson found that while awareness and use of designated drivers may increase, evidence of a reduction in drinking and driving or alcohol-related crashes has not been well documented.106 More recent communication activities by the National Highway Traffic Safety Administration have encouraged planning ahead and designating a sober driver to address the problem of designating the seemingly leastimpaired driver as the designated driver.107

116.5 EMERGING CONSIDERATIONS 116.5.1 The Changing Age Distribution of the U.S. Population Some of the highest crash death rates occur among those in the oldest age groups. When paired with an aging population, the duel needs of safety and mobility emerge as

public health concerns. Beginning in 2011, 10,000 people in the United States reach the age of 65 every day, and this trend will hold for 20 years (http://pewresearch.org/ databank/dailynumber/?NumberID=1150). This aging of the Baby Boomer generation has important implications for our nation in a variety of ways, including our ability to meet the mobility needs of an increasing older adult population. People reaching age 65 today will, on average, live another 19 years.108 Some emerging changes that will have direct effects on mobility and transportation needs are apparent now. For example, in 1996, 12% of people age 65 + participated in the civilian labor force; in 2016, this proportion had risen to 19%, and by 2026 it is estimated to reach 22%.109 More participation in the labor force could result in more exposure to the traffic environment among older adults. Older adults frequently choose to age in place; one consequence of this is the proportion of older adults living alone, 29% or 13.3 million older people in 2015. This differs between men, 20% living alone, and women, 36% living alone.108 People age 65 + are less likely to change their residence than any other age group; between 2014 and 2015 just 4% moved versus 13% for those younger than 65.108 Living alone can make driving critical for meeting everyday needs. For those older adults who are not able to drive safely due to physical and/or cognitive impairments, few mobility options may exist in their neighborhood.

116.5.2 Drug-Impaired Driving Drugs other than alcohol are involved in about 16% of motor vehicle crashes.110,111 Marijuana-impaired driving has become an issue of increasing concern, especially with the recent expansion of legal marijuana use (both medical and recreational) within many states.112 As of January 2018, 30 states and the District of Columbia (DC) have legalized marijuana in some form, and eight states and DC have legalized marijuana for recreational use (http:// www.governing.com/gov-data/state-marijuana-lawsmap-medical-recreational.html). The effects of alcohol on driving performance are well understood. Alcohol metabolizes at a relatively steady rate and can be measured by the concentration of alcohol in the blood (BAC). In addition, level of impairment corresponds reasonably well with BAC; therefore, BAC can be used to measure impairment. In contrast, the primary psychoactive substance in marijuana is delta-9-tetrahydrocannabinal (THC). It is fat-soluble and stores in fatty tissues in the body. THC can be released back into the blood long after ingestion and long after the psychoactive effects can be felt; therefore, blood levels of THC are not a good measure of impairment.113 However, like alcohol, marijuana impairs an individual’s ability to drive safely, including slowing reaction time and reducing coordination.114 Despite the negative effects of marijuana use on driving performance, there are currently no known effective strategies to address this issue. Driving under the influence of opioids is another issue of increasing concern in the field of injury prevention, especially because the United States is in the midst of an opioid overdose epidemic. More than 42,000 Americans

References  1311

died from opioid-involved overdose in 2016.115 Studies exploring the effects of opioid use on driving ability and motor vehicle crash risk are limited, including the effects of prescription opioid use for managing pain or treating substance use disorder, as well as illicit opioid use. In recent literature, a 2013 Canadian case-control study found that among drivers who were prescribed opioids, those prescribed opioids in a dosage ≥ 20 morphine milligram equivalents per day had increased odds (between 21% and 42% higher, depending on dose) of road trauma resulting in an emergency department visit compared to those prescribed lower dosages.116 A 2017 self-report study of medical and nonmedical prescription opioid use and crash history found that medical use of prescription opioids was associated with a 62% increase in odds for a motor vehicle collision.117 Given available evidence, CDC has published a guideline which recommends that clinicians discuss with patients the effects that opioids might have on ability to safely operate a vehicle, particularly when opioids are initiated, when dosages are increased, or when other central nervous system depressants, such as benzodiazepines or alcohol, are used concurrently.118

116.6 IMPLICATIONS FOR PRIMARY CARE PRACTICE Despite the great success in reducing motor vehicle-related death rates in the past 50 years, motor vehicle crashes remain a leading cause of injury-related death in the United States. Primary care practitioners have the opportunity to reduce death and injury using a variety of strategies, including screening and counseling.119–121 Practitioners also can help patients understand the importance of reducing their exposure to risk on the road, and the importance of safety behaviors. In clinical practice, traffic injury prevention can become a regular part of the practice of lifestyle medicine and integrated into care and preventive services. Injury prevention science has demonstrated that traffic injuries are not “accidents”—they are predictable and preventable. Through efforts to educate and change behaviors, have strong safety laws and enforcement, and encourage more effective use of technology and engineering, lifestyle medicine can contribute to reducing traffic injuries and help promote a culture of safety.122

CLINICAL APPLICATIONS Actions

Available Tools

Comments

Patient education regarding risk and protective factors such as alcohol and cell phone use while driving, seat belts, and child safety seat use Support for statewide evidenced-based policies and practices

CDC Injury Center resources available at https://www.cdc.gov/ motorvehiclesafety/index.html Parents are the Key to Safe Teen Drivers available at https://www.cdc. gov/parentsarethekey/ National Highway Traffic Safety Administration resources for road safety available at https://www.nhtsa.gov/ Safe Kids Worldwide resources available at https://www.safekids.org/ American College of Preventive Medicine health information available at https://www.aap.org/en-us/Pages/Default.aspx

Clinicians can integrate traffic safety into routine lifestyle counseling as they would for other noncommunicable issues such as exercise, nutrition, and mental health.

Policy and enforcement support

National Conference of State Legislatures resources available at http://www.ncsl.org/research/health.aspx

Clinicians can support state policies and programs that lead to reductions in traffic injuries and state initiatives that reduce risky driving.

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1314  Chapter 116  Traffic Injury Prevention: Strategies That Work driver problem. Am J Prev Med. 2008;35(3S):S294–S303. 95. Simons-Morton B, Quimet MC. Parent involvement in novice teen driving: a review of the literature. Inj Prev. 2006;12(Suppl I):i30–i37. 96. National Highway Traffic Safety Administration. Traffic Safety Facts. Speeding. US Department of Transportation, Washington, DC, 2018 Report No. DOT HS 812 480. 97. Retting RA. Two decades of photo enforcement in the United States: a brief summary of experience and lessons learned. ITE Journal. 2010;80(11):20–9. 98. Pilkington P, Kinra S. Effectiveness of speed cameras in preventing road traffic collisions and related casualties: systematic review. BMJ. 2005;330:331–4. 99. Decina LE, Thomas L, Srinivasan R, Staplin L. Automated Enforcement: A Compendium of Worldwide Evaluations of Results. US Department of Transportation, Washington, DC, 2010. Report No. DOT HS 810 763. Available from: https://www.nhtsa.gov/ DOT/NHTSA/Traffic%20Injury%20 Control/.../HS810763.pdf. 100. Insurance Institute of Highway Safety. Automated enforcement. (Online). Insurance Institute for Highway Safety, Highway Loss Data Institute, Arlington, Virginia, 2018. Available at: http://www. iihs.org/iihs/topics/laws/automated_ enforcement?topicName=speed 101. Hu W, Cicchino J. Effects of turning on and off red light cameras on fatal crashes in large U.S. cities. J Safety Res. 2017;61:141–8. 102. McCartt AT, Hellinga LA, Braitman KA. Cell phones and driving: review of research. Traffic Inj Prev. 2006;7:89–106. 103. AAA Foundation for Traffic Safety. 2016 Traffic Safety Culture Index. Washington, DC, February, 2017. Available at: https://aaafoundation. org/2016-traffic-safety-culture-index/. 104. Insurance Institute for Highway Safety. Cellphones and texting. (Online). Insurance Institute for Highway Safety, Highway Loss Data Institute, Arlington, Virginia, 2018. Available at: http://www. iihs.org/iihs/topics/laws/cellphonelaws?to picName=distracted-driving.

105. Ditter SM, Elder RW, Shults RA, et al. Effectiveness of designated driver programs for reducing alcohol-impaired driving: a systematic review. Am J Prev Med. 2005;28(5S):280–7. 106. Nielson AL, Watson B. The effectiveness of designated driver programs. J Australasian College of Road Safety. 2009;29(2):32–7. 107. National Highway Traffic Safety Administration. Drunk driving. (Online). US Department of Transportation, Washington, DC. Available at: https://www.nhtsa.gov/risky-driving/ drunk-driving. 108. Administration on Aging, Administration for Community Living. A profile of older Americans: 2015. (Online). US Department of Health and Human Services. Available at: https://www.acl. gov/sites/default/files/Aging%20and%20 Disability%20in%20America/2015Profile.pdf. 109. Bureau of Labor Statistics. Employment projections. (Online). US Department of Labor. Civilian labor force participation rate, by age, sex, race, and ethnicity. Table 3.3. Accessed January 18, 2018. Available from: https://www.bls.gov/emp/ ep_table_303.htm. 110. National Highway Traffic Safety Administration. Drug and alcohol crash risk. US Department of Transportation, Washington, DC, 2018 Report No. DOT HS 812 117. Available from: https://www. nhtsa.gov/staticfiles/nti/pdf/812117Drug_and_Alcohol_Crash_Risk.pdf. 111. Centers for Disease Control and Prevention. Impaired driving: get the facts. (Online). Available from: https://www.cdc. gov/motorvehiclesafety/impaired_driving/ impaired-drv_factsheet.html. 112. Compton, R. P. & Berning, A. (2015, February). Drug and alcohol crash risk. (Traffic Safety Facts Research Note. DOT HS 812 117). Washington, DC: National Highway Traffic Safety Administration. Available from: https://www.nhtsa.gov/ staticfiles/nti/pdf/812117-Drug_and_ Alcohol_Crash_Risk.pdf. 113. National Highway Traffic Safety Administration. Marijuana-Impaired Driving, A Report to Congress. US Department of Transportation,

Washington, DC, 2017 Report No. DOT HS 812-440. Available from: https:// www.nhtsa.gov/sites/nhtsa.dot.gov/files/ documents/812440-marijuana-impaireddriving-report-to-congress.pdf. 114. Centers for Disease Control and Prevention. What you need to know about marijuana use and driving. (Online). Available from: https://www. cdc.gov/marijuana/pdf/marijuana-driving-508.pdf. 115. Hedegaard H, Warner M, Miniño AM. 2017. Drug overdose deaths in the United States, 1999-2016. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. Available from: https://www.cdc.gov/nchs/data/ databriefs/db294.pdf, see Table. 116. Gomes T, Redelmeier DA, Juurlink DN, Dhalla IA, Camacho X, Mamdani MM. Opioid dose and risk of road trauma in Canada: a population-based study. JAMA Int Med. 2013;173(3):196–201. 117. Wickens CM, Mann RE, Ialomiteanu AR, Rehm J, Fischer B, Stoduto G, Callaghan RC, Sayer G, Brands B. The impact of medical and non-medical prescription opioid use on motor vehicle collision risk. Transp Res Part F Traffic Psychol Behav. 2017;47:155–62. 118. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain – United States, 2016. MMWR Recommen Rep. 2016;65:1–49. 119. Chen J, Kresnow M-j, Simon TR, et al. Injury prevention counseling and behavior among U.S. children: results from the second Injury Control and Risk Survey. Pediatrics. 2007;119:e958–e965. 120. Dellinger AM, Chen J, Vance A, et al. Injury prevention counseling for adults: have we made progress? J Fam Community Health. 2009;32:115–22. 121. B allesteros MF, Gielen AC. Patient counseling for unintentional injury prevention. Am J Lifestyle Med. 2010;4:38–41. 122. Sleet DA, Dinh-Zarr BT, Dellinger AM. Traffic Safety in the Context of Public Health and Medicine. In: Traffic Safety Culture in the United States: The Journey Forward. Washington, DC: AAA Foundation for Traffic Safety, 2007.

117 CHAPTER

Review and Implementation of the CDC Guideline for Prescribing Opioids for Chronic Pain LeShaundra Cordier, MPH, CHES and Helen Kingery, MPH

Key Points.................................................................................1315 117.1 Introduction...................................................................1315 117.2  Guideline Development..................................................1315 117.3  Recommendations from the Guideline...........................1316

KEY POINTS • From 1999 to 2016, more than 200,000 people have died in the United States from overdoses related to prescription opioids.1 • We now know that overdoses from prescription opioids are a driving factor in the 16-year increase in opioid overdose deaths. • The Centers for Disease Control and Prevention (CDC) developed the Guideline for Prescribing Opioids for Chronic Pain to provide recommendations for prescribing opioids to patients 18 and older in primary care settings, outside of cancer treatment, palliative care, and end-of-life care. • Improving the way opioids are prescribed can ensure patients have access to safer, more effective pain management. • Recommendations focus on when to initiate or continue opioid use; opioid selection, dosage, duration, follow-up, and discontinuation; and assessing risk and addressing harms of opioid use. • Resources are available with additional tools to guide clinicians in implementing the recommendations.

117.1 INTRODUCTION An estimated one out of five patients with non-cancer pain or pain-related diagnoses are prescribed opioids and nearly two million Americans, aged 12 or older, either abused or were dependent on prescription opioids in 2014. According to the CDC: 2 • An estimated 11% of adults experience daily pain. • Millions of Americans are treated with prescription opioids for chronic pain.

117.3.1 Determining when to Initiate or Continue Opioids for Chronic Pain�������������������������������������� 1316 References...............................................................................1317

• Primary care providers are concerned about patient addiction and report insufficient training in prescribing opioids. Improving the way opioids are prescribed through clinical practice guidelines can ensure patients have access to safer, more effective chronic pain treatment while reducing the number of people who misuse, abuse, or overdose from opioids.

117.2 GUIDELINE DEVELOPMENT The CDC developed and published the CDC Guideline for Prescribing Opioids for Chronic Pain to provide recommendations for the prescribing of opioid pain medication for patients 18 and older in primary care settings. 2 The guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care, and addresses (1) when to initiate or continue opioids for chronic pain; (2) opioid selection, dosage, duration, follow-up, and discontinuation; and (3) assessing risk and addressing harms of opioid use. The CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation. The CDC also obtained input from experts, key stakeholders, the public, peer reviewers, and federal partners. It is important that patients receive appropriate pain treatment with careful consideration of the benefits and risks of treatment options. The CDC Guideline addresses patient-centered clinical practices, including conducting 1315

1316  Chapter 117  Review and Implementation of the CDC Guideline for Prescribing Opioids for Chronic Pain

thorough assessments, considering all possible treatments, closely monitoring risks, and safely discontinuing opioids. This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death. The CDC has provided a checklist for prescribing opioids for chronic pain (http:// stacks.cdc.gov/view/cdc/38025) as well as a website (http:​ //www​.cdc.​gov/d​r ugov​erdos​e /pre​scrib​i ngre​sourc​es.ht​m l) with additional tools to guide clinicians in implementing the recommendations. The 12 recommendations featured in the Guideline focus on the appropriate prescribing and use of opioids in treating chronic pain (pain lasting longer than three months or past the time of normal tissue healing).

117.3 RECOMMENDATIONS FROM THE GUIDELINE 117.3.1 Determining when to Initiate or Continue Opioids for Chronic Pain 1. Nonpharmacologic therapy and non-opioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and non-opioid pharmacologic therapy, as appropriate. 2. Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and should consider how opioid therapy will be discontinued if benefits do not outweigh risks. Clinicians should continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety. 3. Before starting, and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy as well as patient and clinician responsibilities for managing therapy. Clinical applications for determining when to initiate or continue opioids for chronic pain: • Opioids are not first-line or routine therapy for chronic pain. • Establish and measure goals for pain and function. • Discuss benefits and risks and availability of non-opioid therapies with patient. Opioid selection, dosage, duration, follow-up, and discontinuation 4. When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids

instead of extended-release/long-acting (ER/LA) opioids. 5. When opioids are started, clinicians should prescribe the lowest effective dosage. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when considering increasing dosage to > 50 morphine milligram equivalents (MME)/day, and should avoid increasing dosage to > 90 MME/ day or carefully justify a decision to titrate dosage to > 90 MME/day. 6. Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days or less will often be sufficient; more than seven days will rarely be needed. 7. Clinicians should evaluate benefits and harms with patients within one to four weeks of starting opioid therapy for chronic pain or of dose escalation. Clinicians should evaluate benefits and harms of continued therapy with patients every three months or more frequently. If benefits do not outweigh harms of continued opioid therapy, clinicians should optimize other therapies and work with patients to taper opioids to lower dosages or to taper and discontinue opioids. Clinical applications for opioid selection, dosage, duration, follow-up, and discontinuation: • Use immediate-release opioids when starting. • Start low and go slow—use the lowest effective dose. • Prescribe short durations for acute pain. • Do not prescribe ER/LA opioids for acute pain. • Follow-up and reevaluate risk of harm; reduce dose or taper and discontinue, if needed. Assessing risk and addressing harms of opioid use 8. Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Clinicians should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose, such as history of overdose, history of substance use disorder, higher opioid dosages (≥50 MME/day), or concurrent benzodiazepine use are present. 9. Clinicians should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or dangerous combinations that put him or her at high risk for overdose. Clinicians should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every three months.

References  1317

10. When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs. 11. Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible. 12. Clinicians should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

Clinical applications for assessing risk and addressing harms of opioid use: • Evaluate risk factors for opioid-related harms. • Check Prescription Drug Monitoring Program (PMPD) data for high dosages and prescriptions from other providers. • Use urine drug testing to identify prescribed substances and undisclosed use. • Avoid concurrent benzodiazepine and opioid prescribing. • Arrange treatment for opioid use disorder if needed.

REFERENCES 1. Seth P, Rudd R, Noonan, R, Haegerich, T. Quantifying the Epidemic of Prescription Opioid Overdose Deaths. American Journal of Public Health, 2018;108(4),e1–e3. DOI:10.2105/ AJPH.2017.304265.

2. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recommendations and Reports, 2016;65(No. R R-1),1–49. DOI:http:// dx.doi.org/10.15585/mmwr.rr6501e1.

117

118 CHAPTER

Improving the Care of Young Patients with Mild Traumatic Brain Injury: CDC’s EvidenceBased Pediatric Mild TBI Guideline Kelly Sarmiento, MPH, Angela Lumba-Brown, MD, Matthew J. Breiding, PhD, CDR, US, Wayne Gordon, PhD, ABPP/Cn, David Paulk, PA-C, EdD, DFAAPA, Kenneth Vitale, MD FAAPMR, and David A. Sleet, PhD, FAAHB

Key Points.................................................................................1319 118.1 Introduction...................................................................1319 118.2  Mild TBI in Children....................................................... 1320 118.2.1  Clinical Presentation....................................... 1320 118.2.2 Indications of Deteriorating Neurological Function�������������������������������������������������������� 1320 118.2.3  Management of Mild TBI in Children............... 1321 118.3  Improving Care for Children with Mild TBI..................... 1321 118.3.1 CDC’s Evidence-Based Pediatric Mild TBI Guideline������������������������������������������������������� 1321

KEY POINTS • Mild Traumatic Brain Injury (TBI) is caused by a blunt force or direct blow to the head or elsewhere in the body, with an impulsive transmission to the brain resulting in acceleration/deceleration, translational, rotational, and/or angular forces. Mild TBI triggers a complex pathophysiological cascade involving ionic and neurometabolic changes and microstructural axonal dysfunction, resulting in somatic symptoms, cognitive and sleep impairment, and behavioral changes. • Mild TBI is especially concerning in children due to their anatomical differences. Mild TBI symptoms are typically nonspecific and similar to other conditions, and patients can deteriorate over time, so children need to be closely monitored. Most symptoms resolve within a couple of weeks, and children should undergo a gradual, stepwise return to activity to minimize symptom recurrence and prolonged recovery. • Diagnosis of mild TBI is primarily clinical and should be based on a validated symptom severity scale. Most patients have a good recovery, but premorbid conditions and risk factors can delay recovery and should be assessed to determine a potential poor prognosis. Treatment includes cognitive and vestibular rehabilitation as needed, sleep hygiene, and non-narcotic analgesia.

118.3.2 Key Recommendations in CDC’s Pediatric Mild TBI Guideline������������������������������������������ 1321 118.4  Dissemination and Implementation of the Guideline...... 1324 118.4.1  Educational Tools............................................ 1324 118.4.2  Outreach Efforts............................................. 1324 118.5  Next Steps.................................................................... 1324 Clinical Applications................................................................. 1325 References.............................................................................. 1325

• Individualized educational tools for various audiences (parents, schools, sports, and partner organizations) and healthcare providers encountering mild TBI can improve awareness and effective implementation of the Centers for Disease Control and Prevention’s (CDC’s) Pediatric Mild TBI Guideline evidence-based diagnosis, prognosis, and management/treatment recommendations. Medical organizations can help disseminate the Guideline and integrate it in clinical systems and medical decisionmaking tools to help the Guideline recommendations become widespread and serve as the standard of care. • In the era of increasing concussion and mild TBI awareness, diagnosis and treatment of this injury are also evolving with new evidence. Guidelines and implementation tools have to be continually updated to reflect the latest research.

118.1 INTRODUCTION Traumatic brain injury (TBI) is a serious public health problem, contributing to one-third of all injury-related deaths in the United States each year.1. Caused by a blunt force applied to the head or body or a penetrating head injury, a TBI can cause a wide range of functional short- or long-term changes affecting thinking (i.e., memory and reasoning), 1319

1320  Chapter 118  Improving the Care of Young Patients with Mild Traumatic Brain Injury

sensation (i.e., sight and balance), language (i.e., communication and understanding); and/or emotion (i.e., depression, personality changes, and social inappropriateness).2,3 The severity of a TBI may range from “mild,” (i.e., a brief change in mental status or consciousness as with a concussion) to “severe,” (i.e., an extended period of unconsciousness or amnesia after the injury with significant associated brain hemorrhage).4 A TBI not only can be devastating for an individual and their loved ones but can also take a large societal and economic toll. According to health economists5 and the Centers for Disease Control and Prevention (CDC),6 the lifetime adjusted economic cost of TBI, including direct and indirect medical costs, was estimated to be approximately 76.5 billion (in 2010 dollars). According to data from the CDC, among children age 17 and under there were almost 840,000 TBI-related emergency department visits, hospitalizations, and deaths (1,343.3 per 100,000) in 2014.7 Of those, approximately 97% were emergency department visits. The most common principal mechanisms of injury for TBI-related emergency department visits and hospitalizations were falls (539.8 per 100,000 and 10.8 per 100,000, respectively). Motor vehicle crashes were the leading cause of TBI-related death for children age 17 and under (0.8 per 100,000).7 Current estimates of TBI among children do not include patients seen in primary care offices, specialty clinics, or those who do not seek medical care.8,9 This results in a significant underestimate of the number of children who sustain a TBI—making it challenging to capture the full burden of this injury. Approximately two-thirds of TBIs in patients seeking medical care are classified as mild, including concussions.10 A mild TBI is associated with a force or impact to the head or body that causes the brain to accelerate and decelerate with translational, rotational, and/or angular forces. Injury can result on the side of the force (coup) or on the side opposite the force (contrecoup). These direct or indirect forces are believed to lead to a wave of energy that passes through the brain tissue, injuring it and triggering neuronal dysfunction involving a complex cascade of ionic, metabolic, and physiologic events (Figure 118.1). This cascade, as well as microscopic axonal dysfunction, results in the presence of some clinical signs and symptoms. In most cases, this process will generally correct itself, and the majority of patients will have a good recovery.

118.2  MILD TBI IN CHILDREN Children are at particular risk for TBI given their developing nervous system, thinner cranial bones, lack of musculature to absorb transmitted forces, including weaker necks, larger heads in proportion to their bodies, and inherent risk-taking behaviors.11 Mild TBI is of particular concern for children due to inherent differences in a child’s developing brain and their increased susceptibility to chemical and metabolic changes that occur in the brain when concussion occurs. Furthermore, because axons in a child’s developing brain are not as wellmyelinated, this may also predispose them to traumatic injury.

118.2.1 Clinical Presentation Children with mild TBI commonly present with one or more signs or symptoms that generally fall into four categories (see Table 118.1). These categories or subtypes are not mutually exclusive:

1. Somatic (i.e., headache and balance disruption); 2. Cognitive (i.e., amnesia and disorientation); 3. Mood/Affective (i.e., irritability and fatigue); and 4. Sleep (i.e., trouble falling asleep).

Diagnosing a mild TBI can be challenging, as symptoms of mild TBI are common to those of other medical conditions, such as depression, pain, and headache syndromes. Thus, it is essential to assess each patient completely and systematically, including evaluation for other common conditions such as dehydration (especially following sports-related injuries) or early signs of viral infection.

118.2.2 Indications of Deteriorating Neurological Function Children presenting with potential TBI should be carefully observed over the first 24–48 hours and transported for immediate medical attention if there is an increase in the severity or number of their signs and symptoms,

Figure 118.1  Mechanism of mild TBI results from an impact to the head or body which leads to a complex cascade of ionic, metabolic and physiologic events. Source: Centers for Disease Control and Prevention, www.cdc.gov/HEADSUP.

118.3  Improving Care for Children with Mild TBI  1321 TABLE 118.1  Clinical Presentation of Mild TBI Somatic

Cognitive

Mood/Affective

Sleep

• Headache • Dizziness • Balance disruption • Nausea/Vomiting • Visual disturbances (photophobia, blurry/double vision) • Phonophobia

• Confusion • Anterograde amnesia • Retrograde amnesia • Loss of consciousness • Disorientation • Feeling mentally “foggy” • Vacant stare • Inability to focus • Delayed verbal and motor responses • Slurred/incoherent speech • Excessive drowsiness

• Emotional lability • Irritability • Fatigue • Anxiety • Sadness

• Trouble falling asleep • Sleeping more than usual • Sleeping less than usual

or indications of deteriorating neurological function. Examples may include: • Decreasing levels of consciousness or any loss of consciousness • Focal neurologic deficit such as weakness or numbness in the upper or lower extremities and slurred speech • Increasing severity of headaches, especially in the setting of other symptoms • Repeated vomiting • Increasing confusion, unusual behavioral change, or irritability • Seizures • Significant cervical pain with tenderness and/or loss of range of motion, paresthesias, or weakness

118.2.3 Management of Mild TBI in Children Among children, most mild TBI symptoms resolve within a couple of weeks, but the length of recovery is unique to the characteristics of the injury and person. Longitudinal studies suggest that 30% of children will have persistent symptoms at one month post-injury, 10% at three months post-injury, and less than 5% at one year post-injury.12–16 Children who have a history of repeat mild TBIs or concussions may experience prolonged periods of recovery and may be at risk for health problems later in life.17–24 Other factors that might delay recovery include neurological or mental health disorders, learning difficulties, and family and social stressors. Current clinical research recommends a gradual return to physical and cognitive activity for children after a mild TBI. Such activity must be customized to a patient’s particular needs. 25–27 Return to activity should first begin with a period of rest and light activity and then gradually progress to complete recovery where the child participates in regular activity as long as the child remains free of symptoms (Figure 118.2). This gradual approach aims to help mitigate the reemergence or significant worsening of symptoms and to avoid actions that may put a child at risk for a prolonged recovery or more serious injury.

118.3 IMPROVING CARE FOR CHILDREN WITH MILD TBI Despite the public health burden of mild TBI, no evidencebased clinical guidelines on the diagnosis and management of pediatric mild TBI (inclusive of non-sports injury and younger age groups) has been available in the United States. Yet clinical guidance for healthcare providers on the identification, diagnosis, and management of pediatric mild TBI is critical to improving the health and safety of this vulnerable population.

118.3.1 CDC’s Evidence-Based Pediatric Mild TBI Guideline To address this critical need, the CDC’s National Center for Injury Prevention and Control published an evidence-based guideline on pediatric mild TBI. 28 The Guideline used a modified Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology, based on the American Academy of Neurology process, and reviewed scientific literature published over a 25-year period (for all causes of pediatric mild TBI). 29 Recommendations included in the CDC Pediatric Mild TBI Guideline provide guidance to health care providers who care for children in primary care, outpatient specialty, inpatient, and emergency care settings.

118.3.2 Key Recommendations in CDC’s Pediatric Mild TBI Guideline The Guideline contains 19 sets of recommendations for healthcare providers that cover diagnosis, prognosis, and management and treatment of mild TBI. Through the modified GRADE process, CDC assigned one of the action levels to each recommendation: • Level A: (Must do) Almost all patients in almost all circumstances would want the recommendation followed. • Level B: (Should do) Most patients in most circumstances would want the recommendation followed.

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1322  Chapter 118  Improving the Care of Young Patients with Mild Traumatic Brain Injury

Figure 118.2  Stepwise return to activty plan for children following mild TBI. Source: Centers for Disease Control and Prevention, www.cdc.gov/HEADSUP.

TABLE 118.2  Recommendations for the Diagnosis of Mild TBI in Children NEUROIMAGING: Clinical evaluation of a child with possible mild TBI includes balancing the likelihood of potentially devastating complications of a more severe injury against the risks associated with head computed tomography (CT). • Healthcare providers should not routinely obtain head CT for diagnostic purposes in children with mild TBI. (Level B) • Healthcare providers should use validated clinical decision rules to identify children at low risk for intracranial injury (ICI), in whom head CT is not indicated, and identify children who may be at higher risk for significant ICI and therefore may need head CT. Existing decision rules combine a variety of factors which might indicate higher risk, including the following: • Age  40 kg/m 2) and very severe obesity (BMI > 50 kg/m 2) have grown disproportionately rapidly during this period of time.9 Obesity not only carries adverse health consequences in and of itself, but it is also strongly associated with multiple other metabolic abnormalities. For example, obesity is strongly and independently associated with cardiovascular disease (CVD), the leading killer of both men and women in the United States.10,11 Moreover, obesity is also associated with a number of risk factors for CVD including hypertension, dyslipidemia, diabetes, physical inactivity, and poor nutrition.12,13 It is estimated that 80–85% of all type 2 diabetes is related to obesity.14 Obesity is associated with over 35% of cancers and it is predicted to become the leading lifestyle-related risk factor associated with cancer in the next decade surpassing even cigarette smoking.15–17 According to data from the Framingham Heart Study, over 50% of hypertension is associated with obesity18 and approximately 50% of lipid abnormalities are associated with obesity.19 The metabolic syndrome, which is strongly associated with obesity, is currently estimated to affect 25–35% of the adult population in the United States. 20 Moreover, 35–40% of the adult population has glucose intolerance, which is also a strong predictor of diabetes and closely associated with obesity. 21 Obesity is, in many ways, the quintessential lifestyle disease. It is abundantly clear that obesity is a complicated multi-factorial problem resulting from numerous internal and external influences which impact on the obese individual. It has been argued that, in the United States and most of the Western world, we live in an obesogenic (some have even called it a “toxic”) environment for weight gain. In addition to individual choices related to nutrition and physical activity, there are also significant impacts on the risk of developing obesity from family, culture, community, government, and world food policies.22 Genetic influences clearly play a role since some individuals are more likely to gain weight than others and some ethnic groups (e.g., Hispanic and Black women)5 are much more affected than others, although all ethnicities and both genders are affected by obesity. The fact that obesity represents an urgent national health imperative has been underscored by numerous evidence-based documents. For example, the Dietary Guidelines for Americans 2015 characterizes obesity as the “leading nutritional health problem” facing the United States. 22 The Healthy People 2010 document originally set a goal of limiting obesity to no more than 15% of the adult population. 23 This lofty goal can now be seen in retrospect to be wishful thinking. In the United States, we are moving rapidly away from this goal rather than toward it. The goal of reducing obesity prevalence to 15% of the adult population has also been incorporated into the Healthy People 2020 Guidelines. 24 With all this as background, it is no longer a viable option for healthcare professionals to remain on the sidelines both as individual practitioners and community

leaders when it comes to the urgent problem of both adult and childhood obesity. In this chapter, we will summarize some of the known evidence linking obesity to adverse health consequences. We will also briefly discuss potential initiatives and frameworks-seeking solutions. The chapter will close with recommendations for individual healthcare professional involvement to help stem the epidemic of obesity, with a particular emphasis on the interaction of healthy eating and active living as key components of energy balance.

126.2 DEFINITIONS OF OVERWEIGHT AND OBESITY 126.2.1 Adults Overweight and obesity in adults are generally defined using body mass index (BMI), which is a measure of weight related to height and is also correlated to total body fat and health outcomes. The National Heart, Lung, and Blood Institute defines healthy weight for adults as a BMI of 19–24.9 kg/m 2 , overweight as a BMI of 25–29.9 kg/m 2 , obesity >30 kg/m 2 and extreme obesity >40 kg/m 2 . 25 It is important to note that body fat distribution also impacts the risk of chronic disease, 26–29 with abdominal obesity particularly strongly correlated with the risk of diabetes and heart disease. For this reason, both waist circumference and waist to hip ratio are added in some guidelines.

126.2.2 Children and Adolescents Several different criteria are utilized in children and adolescents up to the age of 20 to define “overweight” or “obese.” The Centers for Disease Control and Prevention (CDC) use the term “overweight” for children and adolescents with BMI at or above the 95th percentile for sexspecific BMI for age values from the 2000 CDC Growth Charts.30 The CDC uses the term “at risk” for overweight for children and adolescents who are between a BMI of 85th and 95th percentiles. The American Medical Association and other organizations have recommended that this terminology be changed so that children and adolescents who are over the 85th percentile for BMI values be classified as “overweight” and over the 95th percentile classified as “obese.”31 It has been reported that when children entered kindergarten (age 5–6 years) 12.4% were obese and another 14.9% were overweight. By the eighthgrade 20.8% were obese and 17.0% were overweight. These data suggest that obesity in children between the ages of 5 and 14 years seems more likely to have occurred at younger ages, particularly among children who entered kindergarten overweight.32 Epidemiologic data related to obesity in the United States are based almost exclusively on BMI derived from measured height and weight. The National Center for Health Statistics of the Centers for Disease Control and Prevention conducts standardized physical examinations on large representative samples of children, adolescents, and adults through the National Health and Examination Survey Program (NHANES). NHANES

126.2  Definitions of Overweight and Obesity  1393

includes oversampling of African Americans, Mexican Americans, as well as other groups to improve estimates for these groups. The description of obesity rates and trends in the United States presented in this chapter is based on NHANES data. Rates of overweight and obesity have risen dramatically over the last thirty years in the United States (see Figure 126.1). During this timeframe, the prevalence of obesity more than doubled in adults (from 15% to 33%) while the prevalence of obesity and overweight in children tripled (from 6% to 19%). 5,8 Estimates from 2010 indicate that 36.5% of adults are obese and that 17% (or 12.5 million) children and adolescents are obese.5,8 (see

Figure 126.2) The population rates of obesity in some segments are substantially higher, which may be a result of interactions between culture, environment, and genetics. A particularly alarming trend is the increase in extreme obesity (Grade 3; BMI > 40 kg/m 2).8 Over a most recent 7–8-year span the percent of extreme obesity in adults 20 years of age or older has increased from 4.7% to 5.7%, which equates to about two million additional people in the extreme obesity category in the United States.8 There are also demographic characteristics associated with overweight and obesity. Age-adjusted prevalence rates of obesity are generally higher in older versus younger cohorts, women versus men, and in racial/ethnic groups

Figure 126.1  Trends in Adult Overweight and Obesity Ages 20–74 Years. (Source: The National Center for Health Statistics.)

Figure 126.2  Trends in Childhood Overweight. (Source: National Centre for Health Statistics.)

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1394  Chapter 126  Obesity and Health

compared to Caucasians. Approximately 35.5% of women (16.0% of female children and adolescents) and 32% of men (18.2% of male children and adolescents) were obese according to NHANES 2007–2008.5,8 The odds of being obese are higher in adult women than men, but not related to gender in children and adolescents. Mexican Americans and Non-Hispanic Blacks display higher rates of obesity compared to Caucasians. The most extreme example is found in women where non-Hispanic Black women had a rate of obesity exceeding adult Caucasian women by 24% (53.9% vs 30.2%). 5,8 Age also brings about increases in obesity, particularly for non-Hispanic Caucasian men and Hispanic females.7 For example, the prevalence of obesity for Caucasian males between 20 and 30 years of age is 26.3% but increases to 38.4% after the age of 60.

and obese women respectively and 2.4 times and 6.7 times for overweight and obese men.43 The relationship between obesity and diabetes in children is also potent. In the SEARCH for Diabetes in Youth Study, it was estimated that approximately 3,700 adolescents per year are now diagnosed with T2DM and that this number is increasing.44 T2DM is now the most prevalent form of diabetes diagnosed in adolescents.45 Insulin, fasting insulin, and insulin-to-glucose ratio are significantly higher in obese versus control 7–11-year-olds, and impaired insulin sensitivity becomes more apparent as the duration of obesity increases. 27,46–48 A detailed discussion of the relationship between obesity and diabetes is found in Chapter 28 and has been reviewed extensively elsewhere.49

126.3 THE HEALTH EFFECTS OF OBESITY

126.4.2 Obesity and Heart Disease

126.3.1 The Role of Adipocytes Historically, adipocytes were thought to be primarily storage sites for excess fat. Research over the past two decades, however, has demonstrated that adipocytes are, in fact, highly complicated, inflammatory endocrine and metabolic cells. Thus, adipose tissue essentially serves as a complex endocrine organ and a potent source of inflammatory molecules such as tumor necrosis factor-α (TNF  α), interleukin-6, and many others. 26,33–36 These complex properties of adipocytes may underlie the strong linkage between obesity and chronic metabolic conditions such as diabetes, coronary heart disease, and the metabolic syndrome. Adipocytes located in the abdominal region appear to be particularly complicated and active from a metabolic and inflammatory point of view. 26–29

126.4 HEALTH EFFECTS OF OBESITY IN ADULTS 126.4.1 Obesity and Diabetes An estimated 9.3% of Americans (26 million individuals) have diabetes and over 79 million adults display evidence of “pre-diabetes”.37 There is a clear association between obesity and type 2 diabetes (T2DM). Individuals with a BMI of >35 kg/m 2 have 42.1 times the risk of type 2 diabetes in men and 93.2 times the risk in women compared to normal BMI controls. The risk of developing T2DM is elevated the longer one is obese.38–40 A meta-analysis pooling data from 32 studies between 1966 and 2004 found that the relative risk of T2DM was 1.87, 1.87, and 1.88 per standard deviation of BMI, waist circumference and waist-to-hip ratio respectively.41 The Nurses’ Health Study, which followed over 80,000 female nurses over a 16-year span, demonstrated that being overweight or obese is the single most important predictor of T2DM.42 In another meta-analysis that studied BMI across categories (normal to overweight to obese) relative risks were 3.9 times and 12.4 times for overweight

Multiple large-scale studies have linked obesity to risk of cardiovascular disease. In a recent meta-analysis, the relative risk among obese men and women compared to normal weight men and women was 2.4 times for coronary heart disease (CHD), 2.1 times for hypertension, 1.5 times for stroke, 1.8 times for congestive heart failure, and 3.5 times for pulmonary embolism.39 Longitudinal data from the Framingham Heart Study found that age-adjusted relative risk for cardiovascular disease was 1.64 times in women and 1.46 times in men comparing obese to normal-weight individuals.50 Obesity is also associated with multiple other established risk factors for CHD including hypertension, dyslipidemia, diabetes, and an inactive lifestyle. The multiple links between obesity and heart disease as well as the risk factors for CHD are beyond the scope of the current chapter and have been reviewed extensively elsewhere.51 A recent study shows that factors for CVD track with severity of obesity in children and young adults. This study reported that, in multivariable models, controlling for age, race and ethnic group, and sex showed that the greater the severity of obesity, the higher the risks of low HDL, cholesterol level, high systolic and diastolic blood pressures, and high triglyceride and glycated hemoglobin levels.52

126.4.3 Obesity and Cancer Multiple prospective studies have established a significant association between obesity and cancer.16,53–56 In one large, 16-year longitudinal study involving nearly one million subjects, all-cause mortality for all cancers was 62% higher in women and 52% higher in men with a BMI > 40 kg/ m 2 compared to subjects with a normal BMI.53 In another study involving 1.2 million women between the ages of 50 and 64, obesity was associated with significantly higher rates of 10 out of the 17 most common types of cancer. 54 The International Agency for Research on Cancer (IARC) reported that there was a significant association between BMI and cancer risk, with positive dose-relationship in multiple cancers, particularly those of the gastrointestinal tract including colon, rectum, stomach, liver, gallbladder, pancreas, and kidney. IARC also reported that waist circumference was generally consistent associated with those

126.5  Economic Impact of Obesity  1395

reported for BMI.16 Current evidence suggests that obesity prevention may be more advantageous than weight loss in reducing the incidence of obesity-related cancer.16,55 The relationship between obesity and cancer has been extensively reviewed elsewhere. 56

126.4.4 Obesity and the Metabolic Syndrome The metabolic syndrome (MetS), which represents a clustering of risk factors related to impaired glucose and lipid metabolism, is strongly associated with obesity in general and abdominal obesity in particular. 26,27,57–59 MetS is a significant risk factor for both diabetes and heart disease. Current estimates suggest that MetS is present in 25–35% of the adult population in the United States. 20 Weight reduction by itself or occurring in combination with lifestyle changes such as increased exercise is associated with a significant drop in the prevalence of MetS.60,61 Even moderate amounts of weight loss (20 lbs.) result in a significant reduction in the prevalence of MetS.61 The pathophysiology of metabolic syndrome and its linkage to obesity has been extensively reviewed elsewhere.62

126.4.5 Obesity and Arthritis There are strong linkages between obesity and multiple forms of arthritis but particularly osteoarthritis.63,64 Obesity is the leading cause of osteoarthritis in women and the second leading cause of osteoarthritis in men.64 The linkage between obesity and arthritis appears to be partially mediated through increased pressure on weight-bearing joints but also may relate to the systemic inflammation that often accompanies obesity.64 The linkage between obesity and arthritis has been extensively reviewed elsewhere.65

126.4.6 Obesity and Other Medical Conditions Obesity is significantly associated with multiple other risk factors and diseases in both men and women.66 A partial listing of these conditions is found in Table 126.1. Obesity is related to multiple maternal and fetal problems in pregnancy.67–69 Obese individuals are also at increased risk of depression and other psychiatric disorders.70–72 Obesity is strongly related to the increased prevalence of gallbladder disease73,74 and obstructive sleep apnea.75 NHANES data suggest that individuals with a BMI of > 35 kg/m 2 lose an average of 9–13 years of life compared to normal-weight individuals.76 Obesity is also related to a number of disease risk factors and diseases in children and adolescents.52,77 Obesity is strongly related to MetS in children and adolescents, 59 as well as a variety of cardiovascular complications including hypertension, left ventricular hypertrophy, dyslipidemia, and sleep apnea.78–83 Obese children and adolescents also experience more psychological abnormalities including loneliness, poor self-perception, depression, and

TABLE 126.1  Medical conditions associated with obesity • Metabolic Conditions • Type 2 diabetes • Metabolic Syndrome • Glucose Intolerance • Cardiovascular Disease • Coronary Heart Disease • Stroke • Heart Failure • Deep Venous Thrombosis • CHD Risk Factors • Dyslipidemia • Hypertension • Inflammation • Hypercoagulability • Pulmonary Diseases • Obstructive Sleep Apnea • Hypoventilation Syndrome • Asthma • Cancers • Colorectal • Esophageal • Endometrial • Breast (post-menopausal) • Kidney • Gastrointestinal Diseases • Non Alcoholic Fatty Liver Disease • Gallstones (Cholecystitis) • Gastroesophogeal Reflux • Other Conditions • Gout • Kidney Stones • Osteoarthritis • Psychological Disorders • Fertility and Pregnancy Complications • Erectile Dysfunction

anxiety disorders.84–87 Furthermore, obesity in adolescent years carries a significantly increased risk of severe obesity in adulthood.88

126.5 ECONOMIC IMPACT OF OBESITY In addition to the enormous health toll attributed to obesity, substantial costs are being driven by the obesity epidemic. For example, in the United States it is estimated that obesity may cost as much as $147 billion per year.89 Some of the burden of these expenditures is shared by the government (i.e., taxpayers) while the rest is largely paid through private insurers.90 Thus, taxes and employee insurance premiums (which are paid by all employees regardless of weight) finance most of the cost of treating obesity or its related conditions. It is estimated that an obese individual costs a health plan 47% more in healthcare expenditures, and an overweight individual generates 16% more costs than healthy weight individuals.91 During the period between 1998– 2006, direct annual medical costs associated with obesity increased from 6.5% to 9.2% of total health costs.92,93 This computes to obese individuals spending an average of $1,429 annually in 2006 for medical care, which equates to more than 42% more annual costs compared to individuals of average weight.94

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1396  Chapter 126  Obesity and Health

For all of these reasons, multiple stakeholders including taxpayers, the government, employers, and employees all have significant motivation to restrain the rising costs of obesity if only for its financial impact.

126.6 PUBLIC HEALTH IMPLICATIONS Obesity was first recognized as a public health issue by the National Institutes of Health in 1985.95 Data for the Centers for Disease Control and Prevention indicate that obesity in the United States remains a major health problem.66,92,93 Obesity now outranks both smoking and drinking alcohol in its adverse effects on morbidity and mortality as well as health costs. Obesity is associated with a 36% increase in in-patient and out-patient healthcare costs compared to a 21% increase in spending for smoking and excessive alcohol consumption.96 As already indicated, the Healthy People 2010 objectives related to obesity stated the goal of reducing the prevalence of obesity in adults in the United States to 15%.23 This goal has been carried over to the Healthy People 2020 objectives.24 However, no state in the United States has achieved this objective.31 One significant public health concern related to obesity is the increased risk of premature mortality. A number of investigations have clearly demonstrated that as body weight increases so does mortality from diabetes, cancer, and heart disease.97–99 If the American population were able to lose its excess body weight, mortality would be reduced by 15%, which corresponds to three years in average life expectancy for every citizen in the United States.98 As already indicated, obesity is a complicated chronic disease with multiple underlying causes including lifestyle, culture, genetics, and socioeconomic and psychological factors all contributing. For this reason, obesity should be viewed as a chronic disease similar to heart disease and diabetes, and its treatment must be multi-factorial,

focusing not only on the individual level but also from the public health perspective of the community and national level. A comprehensive and coordinated approach will be required to reverse the epidemic of obesity in the United States, including policy and environmental changes to transform communities to support and promote healthy lifestyle choices for all U.S. citizens. The CDC convened an expert panel which identified 24 recommended strategies for obesity prevention together with suggested measurements for each strategy that communities can utilize to track progress.98 A list of these strategies is found in Table  126.2. To help accomplish this, the strategies – together with the implementation and measurement guide – will be published and made available through the CDC website: http:​//www​ .cdc.​gov/n​ccdph​p/dnp​ao/pu​blica​tions​/inde​x.htm​l. In addition to the CDC initiative, multiple other private and governmental initiatives have been announced in an attempt to reduce the health impact of obesity in general and childhood obesity in particular. For example, First Lady Michelle Obama’s “Let’s Move” campaign established the goal of ending childhood obesity within the next generation.99 Other efforts such as the collaboration between the William J. Clinton Foundation and numerous healthcare and commercial organizations in the “Partnership for Healthy America” have articulated similar goals and an increased sense of urgency.100 The Affordable Care Act (ACA) has a number of obesity-prevention measures in place, including the menu-labeling provision, which requires restaurant chains with more than 20 locations to list calories on their menus. This represents a start in addressing one environmental risk factor: basically, the consumption of foods away from home which are typically higher in calories and fats.101 While additional results from studies involving menu labeling and caloric consumption have been elusive, it is anticipated that other interventions will build on this aspect of the ACA.102

TABLE 126.2  CDC task force recommendations for steps that communities could take to help combat obesity • Increase Availability of Healthier Food and Beverage Choices in Public Service Venues. • Improve Availability of Affordable Healthier Food and Beverage Choices in Public Service Venues. • Improve Geographic Availability of Supermarkets in Underserved Areas. • Provide Incentives to Food Retailers to Locate in and/or Offer Healthier Food and Beverage Choices in Underserved Areas. • Improve Availability of Mechanisms for Purchasing Foods from Farms. • Incentives for the Production, Distribution, and Procurement of Foods from Local Farms. • Restrict Availability of Less Healthy Foods and Beverages in Public Service Venues. • Institute Smaller Portion Size Options in Public Service Venues. • Limit Advertisements of Less Healthy Foods and Beverages. • Discourage Consumption of Sugar-Sweetened Beverages. • Increase Support for Breastfeeding. • Require Physical Education in Schools. • Increase the Amount of Physical Activity in PE Programs in Schools. • Increase Opportunities for Extracurricular Physical Activity. • Reduce Screen Time in Public Service Venues. • Improve Access to Outdoor Recreational Facilities. • Enhance Infrastructure Supporting Bicycling. • Enhance Infrastructure Supporting Walking. • Support Locating Schools within Easy Walking Distance of Residential Areas. • Improve Access to Public Transportation. • Zone for Mixed-Use Development. • Enhance Personal Safety in Areas Where Persons Are or Could Be Physically Active. • Enhance Traffic Safety in Areas Where Persons Are or Could Be Physically Active. • Communities Should Participate in Community Coalitions or Partnerships to Address Obesity.

126.7  Public Policy and Environmental Strategies  1397

126.7 PUBLIC POLICY AND ENVIRONMENTAL STRATEGIES Policies and policy-informed environmental supports will all be required on a national, state, and local level to promote active living, healthy eating, and the prevention of obesity. These strategies have been discussed by Heath elsewhere.103 Heath divides these public policy and environmental initiatives into the following four areas: • Agricultural and food supply policies that support healthy eating • Healthcare service policies • Educational and school-based policies • Urban design, land use, and transportation policies for active living/healthy eating Initiatives in all these areas will be required to improve energy-balance behaviors for active living and healthy eating to help combat the obesity epidemic.

126.7.1 Searching for Solutions Given the complexity of underlying causes for the obesity epidemic, comprehensive solutions will be required to ameliorate this problem. Such approaches must involve multiple levels of influencers and involve multiple areas of intervention. One framework for approaching obesity

and weight management has been proposed by the Centers for Disease Control.104 Figure 126.3 depicts the socioeconomic framework offered by the CDC for approaching the obesity epidemic. This framework stresses that maintaining proper energy balance is complicated and factors influencing this issue are multiple and interconnected, thus mandating a multi-faceted approach to amelioration.

126.7.2 The Food Environment A comprehensive approach to the modern food environment will clearly be required to help solve the global obesity problem. In the United States, for example, the average caloric consumption has dramatically increased over the past 40 years.105 As depicted in Figure 126.4, the average daily caloric consumption in the United States has increased from 2,057 kcals in 1970 to 2,674 kcals in 2008. While significant increases have occurred in virtually every category of food, the increases are particularly prominent in the areas of added fats and oils, flour, and cereal products.105 It has been argued by Swinburne106 and others that increased caloric consumption in the United States during the past four decades alone is more than sufficient to explain the U.S. epidemic of obesity. Other investigators, however, have challenged this notion and argue that other aspects of the environment such as diminished physical activity have also contributed significantly to the obesity epidemic.107,108 It is clear, however, that individuals in the United States are not adhering to the guidance from various

Figure 126.3  Factors Influencing Obesity and Weight Gain Centers of Disease Control and Prevention. Division of Nutrition, Physical Activity, and Obesity. State Nutrition, Physical Activity and Obesity Program: Technical Assistance Manual. January 2008. Accessed: March 20, 2017 http:​//www​.cdc.​gov/o​besit​y/dow​nload​s/TA_​Manua​l_1_3​1_08.​pdf – pg 41 of the document.

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Figure 126.4  Average Daily Per Capita Calories from the U.S. Food Availability in 1970, 1990 and 2008, Adjusted for Spoilage and Other Waste. (Source: ERS Food Availablity (per Capita) Data System http:​//www​.ers.​usda.​gov/D​ata/F​oodCo​nsump​tion/​.)

iterations of the Dietary Guidelines21,22 or the Physical Activity Guidelines of Americans 2008.109 As shown in Figure  126.5, the American population falls far short when it comes to fruit and vegetable and dairy consumption compared to MyPyramid recommendations.110 It has also been argued that both the increased number of meal occasions and increase in portion sizes both play significant roles in the obesity epidemic in the United States.111 While the number of meal occasions appears to be relatively stable over the last 25 years,112 the number of calories consumed in snacking has increased by approximately 25% during this period of time.113 There is ongoing debate about whether snacking per se

significantly contributes to weight gain in the American population.113–115 There is general agreement, however, that increases in portion size have contributed significantly to an overall increase in caloric consumption.116 As demonstrated in Table 126.3, portion sizes of common foods sold in the United States have increased between 100% and 1,000% over the past 50 years.116 While these data support that the food environment does not currently support healthy eating patterns in the United States, solutions to this issue will require the participation of many stakeholders in the food system, including not only individuals themselves but also supermarkets, the commercial food industry, and farmers.

Figure 126.5 The Loss-Adjusted Per Capita Food Availability in Comparison to MyPyramid Recommendations for a 2,000-Calorie Diet. Availability of grains (128%) and meat (121%) were above recommendations, while availability of vegetables (71%), dairy (60%), and fruit (44%) were below recommendations. (Note: Based on a 2,000-calorie diet. Source: USDA, Economic Research Service, Food Availability (Per Capita) Data System. Available at http:​//www​.ers.​usda.​gov/A​mberW​aves/​March​10/PD​F/Tra​cking​ACent​ury.p​df.)

126.8  The Need for Healthcare Professional Involvement  1399 TABLE 126.3  Changes over time in the average portion size of selected food items sold in the U.S. marketplace Food item Portion size (year)

Portion size (year)

Percent increase

Beer, can

12 oz (1936)

8–24 oz (2002)

33% - 100%

Beer, bottle

7 oz (1976)

7–40 oz (2002)

0% - 471%

Chocolate bar, milk chocolate

0.6 oz (1908)

1.6–8 oz (2002)

167% - 1233%

French fries

2.4 oz (1955)

2.4–7.1 oz (2002)

0% - 196%

Hamburger

3.9 oz (1954)

4.4–12.6 oz (2002)

13% - 223%

Soda, fountain

7 oz (1955)

12–42 oz (2002)

71% - 500%

Soda, bottle and can

6.5 oz (1916)

8–34 oz (2002)

23% - 423%

Adapted from: Report of the DGAC on the Dietary Guidelines for Americans, 2010

126.7.3 Physical Activity

126.7.6 Small Steps Approach

The United States population remains far too sedentary. The Dietary Guidelines for Americans 2010 and 2015 both concluded that there was “strong, consistent evidence” that physically active people are at reduced risk for becoming overweight or obese. 21,22 In addition to the benefits related to prevention of obesity and assistance in long-term weight maintenance, multiple other benefits accrue to physically active people. These have been summarized in detail in the Physical Activity Guidelines for Americans 2008.109

A recent task force report from the American Society of Nutrition concluded that current initiatives designed to combat obesity have not succeeded in reversing the obesity epidemic.122 An alternative strategy was presented by this panel based on promoting small changes in physical activity and nutrition to prevent further weight gain rather than focusing on weight loss. Such approaches are supported by a variety of lines of evidence and appear to hold some promise to help combat obesity.

126.7.4 Genetics There is no question that genetics play an important role in the modern obesity epidemic. Most investigators conclude that about 40% of obesity may be related to an individual’s genetic make-up.117–119 The interaction between genetic make-up and the environment plays a particularly prominent role. A detailed discussion about obesity and genetics is beyond the scope of the current chapter and has been reviewed extensively elsewhere.118–120 While specific areas of the genome controlling food intake, physical activity, and weight gain are under active investigation, this work is far from ready for clinical application. Researchers anticipate, however, a time when genetic research may yield important information to help make issues of weight control more individualized and precise.

126.7.5 Closing the Energy Gap It has been argued by Blackburn that healthcare professionals should focus first on individuals with extreme obesity (BMI of > 40 kg/m2) since this is the segment of the obese population which is most rapidly increasing.121 These investigators have put forth the concept that interventions for obese individuals should address the “energy gap.” By their estimates, an energy gap of approximately 400 kcals per day exists currently in the United States which was not present in the 1970s. These investigators further suggest that an approach involving improved dietary composition, calorie restriction, and increased physical activity as key components of a comprehensive lifestyle intervention to close this energy gap.

126.8 THE NEED FOR HEALTHCARE PROFESSIONAL INVOLVEMENT Given the severity of the obesity epidemic and its potentially significant adverse health consequences, it is critically important that healthcare professionals become actively involved and knowledgeable in multiple aspects of this issue. Clearly, this is an area where components of lifestyle medicine will play critically important roles. After all, the goal of Lifestyle Medicine is to help people understand how their daily habits and practices impact on their short- and long-term health and quality of life and their likelihood of developing chronic diseases such as obesity. As we have already indicated, obesity represents the quintessential lifestyle disease. It carries a significant health risk both to individuals and to our population as a whole. It is, therefore, incumbent upon healthcare providers to take actions now. Some specific steps that individuals and clinicians can take are outlined by Utter et al.,123 who offer the following recommendations: Health care providers and medical clinicians should counsel their patients to: • Eat more fruits and vegetables and fewer foods high in fat and sugar. See http://www.choosemyplate.gov/. • Drink more water instead of sugary drinks. • Limit TV watching in children to less than 2 hours a day and don’t put a TV in their room at all. • Support breastfeeding. • Promote policies and programs at school, at work, and in the community that make the healthy choice

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the easy choice. This includes policy and environmental supports for both healthy eating and active living. • Try going for a 10-minute brisk walk three times a day, five days a week.

126.9 SUMMARY/CONCLUSIONS There is no longer any serious doubt that we are in the midst of a worldwide pandemic of obesity. Both adult and childhood obesity represent health problems for all

nations. Obesity is strongly linked to a variety of comorbidities including diabetes, heart disease, cancer, the metabolic syndrome, and arthritis. Obesity also results in an enormous psychological and financial burden both for its individual sufferers and for the health of every nation. For all of these reasons, it is incumbent for healthcare professionals to become knowledgeable about and assist in the treatment not only of individual patients who are obese but also help influence public health, public policy, and environmental changes to provide a multi-faceted approach to this major health problem.

CLINICAL APPLICATIONS Action

Tools

Comments

Assess weight and obesity in all patients.

Body mass index (BMI), weight and waist circumference

Unfortunately, 40% of individuals who are obese are never counseled in physician visits concerning their weight.

Counsel overweight or obese individuals on effective strategies for weight reduction.

Multiple materials are available from the NIH, Obesity Society, etc.

Effective weight loss strategies will involve both portion control and increased physical activity.

Work on public health initiatives in addition to individual counseling

Multiple materials to create a less “obesogenic” environment are available through the Centers for Disease Control.

Obesity requires both a public health approach as well as an individual approach since the ability to lose weight may be impacted by both the food and physical environment.

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Index α  motor neurons (α MNs), 1129 α -Tocopherol β -Carotene Study (ATBC), 412 1990 National Nutrition Monitoring and Related Research Act, 102 1993 International Consensus Conference on Physical Activity Guidelines for Adolescents, 434 1996 Report of the Surgeon General, 182 1998 American Psychological Convention, 230 2004 Fourth Report vs.  2017 Clinical Practice Guideline, 944 2007 Expert Committee Guidelines, 913 2008 Physical Activity Guidelines Advisory Committee Report, 474, 475– 476, 1158 2009 Family Smoking Prevention and Tobacco Control Act, 24 2012– 2015 National Prescription Audit database, 492 2013 AHA/ACC/TOS Guidelines for the Management of Overweight and Obesity in Adults, 59– 60 2013 Lifestyle Work Group, 65 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults, 65 2015–2020 Dietary Guidelines for Americans , 101– 110, 130, 269, 891 additional resources, 110 aligning with, 109 expanding guidance, 109– 110 implementation by health professionals, 106– 108 supporting nutrition education, 108– 109 overview, 103– 106 calorie needs per day, 104– 105 guidelines, 103 healthy-eating patterns, 104 key recommendations, 104 shifts in food choices, 106 2016 ACC consensus document, 55, 57 2016 US Report Card on Physical Activity for Children and Youth, 342 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults, 65, 66, 67, 69, 71 2017 Clinical Practice Guidelines, 943– 944 2018 Standards of Care for Diabetes, 508 1.5-mile test, 169 12-step facilitation (TSF), 1116 1-repetition maximum (1-RM), 171 1-RM, see  1-repetition maximum (1-RM) 3-D Automated Whole Breast Ultrasound (ABUS), 333 6-minute walk test, 169

A AA, see  Alcoholics Anonymous (AA) AAA, see  American Automobile Association (AAA) AAAP, see  American Academy of Addiction Psychiatry (AAAP) AACE, see  American Association of Clinical Endocrinologists (AACE) AACI, see  American Association for the Cure of Inebriety (AACI) AAMI, see  Age-associated memory impairment (AAMI) AAP, see  American Academy of Pediatrics (AAP) AAR, see  Anticipated affective reactions (AAR) ABCD, see  Adiposity-based chronic disease (ABCD) Abdominal obesity, 9 ABLM, see  American Board of Lifestyle Medicine (ABLM) ABMS, see  American Board of Medical Specialties (ABMS) ABPM, see  Ambulatory blood pressure monitoring (ABPM) ABPTS, see  American Board of Physical Therapy Specialties (ABPTS) Absolute worth, 209 Abstinence Model, see  Minnesota Model ABUS, see  3-D Automated Whole Breast Ultrasound (ABUS) ACA, see  Affordable Care Act (ACA) Academy of Nutrition and Dietetics (AND), 116, 384, 890 Acamprosate, 1054 ACC, see  American College of Cardiology (ACC) Acceptable macronutrient distribution ranges (AMDR), 86, 113 Acceptance, 209 Acceptance and Commitment Therapy (ACT), 853 Accountable Care Act, 306 Accountable Care Organization (ACO), 20, 32, 1182, 1184, 1188– 1189, 1358, 1360 Accredited Exercise Physiologists (AEP), 159 ACC Task Force on Health Policy Statements and Systems of Care, 742, 746 Accurate empathy, 209 ACE, see  American College of Endocrinology (ACE); American Council on Exercise (ACE) Acetazolamide, 617 A-CHESS, see  Alcohol-Comprehensive Health Enhancement Support System (A-CHESS) ACHOIS, see  Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS)

ACIP, see  Advisory Committee on Immunization Practices (ACIP) ACL, see  Anterior cruciate ligament (ACL) injuries ACLM, see  American College of Lifestyle Medicine (ACLM) ACLS, see  Aerobics Center Longitudinal Study (ACLS) ACO, see  Accountable Care Organization (ACO) ACOEM, see  American College of Occupational and Environmental Medicine (ACOEM) ACOG, see  American College of Obstetrics and Gynecology (ACOG); American Congress of Obstetrics and Gynecology (ACOG) ACOs, see  Accountable care organizations (ACOs) ACP, see  American College of Physicians (ACP) ACPM, see  American College of Preventive Medicine (ACPM) ACQ, see  Asthma Control Questionnaire (ACQ) ACS, see Acute coronary syndromes (ACS); American Cancer Society (ACS); American Community Survey (ACS) ACSM, see  American College of Sports Medicine (ACSM) ACSM Guidelines for Exercise Testing and Prescription, 38 ACSM Recommendations for Exercise Pre-participation Health Screening, 158 ACSM Walking Equation, 165 ACT, see  Acceptance and Commitment Therapy (ACT); Asthma Control Test (ACT) ACTH, see  Adrenocorticotropic hormone (ACTH) Action and coping planning, 244– 245 overview, 244– 245 practical application, 245 Activating and Guiding the Engagement of Seniors through Social Media (AGES) 2.0 project, 319 Active vs.  Avoidant coping, 1004 Acupuncture, 1080 Acute coronary syndromes (ACS), 768 Acute mountain sickness (AMS), 617 AD, see  Alzheimer disease (AD) ADA, see  American Diabetes Association Diabetes (ADA) Adaptive coping strategies, 291– 292 teaching patients to change mind, 291– 292 Added sugar intake, 128 Addiction, 1047– 1049 treatment (see also  Smartphone-based technologies)

1405

1406  Index adverse effects of legal and societal changes on, 1053 in America, 1053– 1054 Addiction Research Center, 1054 Addiction Society of Addiction Medicine (ASAM), 1080 Adenosine triphosphate (ATP), 282, 448 Adequate intake (AI), 86 ADH, see  Alcohol dehydrogenase (ADH) ADHD, see  Attention deficit hyperactivity disorder (ADHD) Adipex, see  Phentermine Adipocytes, 9, 1394 Adipose tissue modulation, 564 Adiposity-based chronic disease (ABCD), 517– 524 alcohol moderation, 523 antibiotic use and microbiome, 522– 523 endocrine disruptors, 522– 523 in farming, 522 by humans, 522 community engagement, 523– 524 consequences, 518 lifestyle intervention, 518– 520 mood, 523 overview, 517– 518 sleep hygiene, 520– 521 stress reduction, 521 transculturization, 524 Adiposity measurement and obesity, 455– 458 bioelectrical impedance (BIA), 458 body mass index (BMI), 456– 457 computed tomography (CT), 458 densitometry, 456 dual-energy X-ray absorptiometry (DEXA), 456 sagitta abdominal diameter (SAD), 458 skinfolds, 458 ultrasound technique (UT), 458 waist circumference (WC), 457 waist-to-height ratio (WHtR)/waiststature ratio (WSR), 457– 458 waist-to-hip ratio (WHR), 457 Adolescent Brain Cognitive Development Study, 1094 Adrenocorticotropic hormone (ACTH), 282, 1232 Adult Treatment Panel Guidelines (ATP III), 7, 11, 21, 24– 25, 55, 116 Advanced Cognitive Training for Independent and Vital Elderly trial, 1150 Advanced glycated end products (AGE), 360, 654, 707 Advisory Committee on Immunization Practices (ACIP), 635 AEP, see  Accredited Exercise Physiologists (AEP) Aerobic and anaerobic fitness, 163– 164 Aerobics Center Longitudinal Study (ACLS), 47, 478 AF, see  Atrial fibrillation (AF) Affirmation, 209, 211 Affordable Care Act (ACA), 24, 32, 531, 1173, 1183, 1221, 1357– 1358, 1359, 1360, 1362, 1388, 1396

AGE, see  Advanced glycated end products (AGE) Age and CVD risk, 11 Age-associated memory impairment (AAMI), 1142 AGEs, see  Advanced glycation end products (AGEs) AGES, see  Activating and Guiding the Engagement of Seniors through Social Media (AGES) 2.0 project Aging and cognitive decline, 1141– 1146 age-associated memory impairment (AAMI), 1142 Alzheimer disease (AD), 1142– 1143 atrial fibrillation (AF), 1144 B vitamins, 1144 cognition definition, 1142 CVD risk factors, 1144 dementia, 1142 dietary habits, 1144 effects on brain, 1142 mild cognitive impairment (MCI), 1142 overview, 1141 physical activity, 1145 psychological disturbances, 1143 reduced cognitive reserve, 1143 traumatic brain injury (TBI), 1143 vitamin D, 1144– 1145 and lifestyle medicine, 1123– 1125 and PA, 1157– 1165 benefits, 1158– 1159 communication, 1161– 1162 frequently asked questions, 1162– 1165 motivation, 1160– 1161 overview, 1157– 1158 recommendations and guidelines, 1159– 1160 successful, 1147– 1154 adverse effects, 1152 cognitive training and stimulation, 1150– 1151 defining, 1147– 1148 determinants, 1149 dietary influences, 1151 exercise/physical activity, 1149– 1150 life-course approach, 1148– 1149 models, 1148 overview, 1147 role of health care practitioners, 1152– 1153 social engagement and volunteerism, 1151– 1152 AGS, see  American Geriatrics Society (AGS) AHA, see  American Heart Association (AHA) AHA Nutrition Committee, 118 AHA Nutrition Guidelines, 27 AHA Strategic Plan, 6, 10– 11, 31, 112, 119 AHEI2010, see  Alternative Healthy Eating Index 2010 (AHEI2010) AHI, see  Apnea-hypopnea index (AHI) AI, see  Adequate intake (AI); Artificial intelligence (AI) AICR, see  American Institute of Cancer Research (AICR)

Airway hyperresponsiveness, 591 Airway inflammation, 590– 591 Ajzen, I., 198 ALA, see  Alpha linoleic acid (ALA) Alcohol, 13, 117 consumption, 31, 69 impaired driving, 1306– 1308 misuse, 511 moderation, 523 pricing strategies, 1308 screening, 1307– 1308 Alcohol and opioid use, 1051– 1055 addiction treatment adverse effects of legal and societal changes on, 1053 in America, 1053– 1054 overview, 1051– 1052 Alcohol-Comprehensive Health Enhancement Support System (A-CHESS), 1107, 1109 Alcohol dehydrogenase (ADH), 414 Alcoholics Anonymous (AA), 1053, 1054, 1079 Alcohol Review,  1011 Alcohol use disorder (AUD), 511, 1069– 1081 case presentation, 1069 detoxification, 1076– 1077 inpatient vs.  outpatient setting, 1076 withdrawal symptoms and timeframe, 1076 diagnosis, 1072– 1075 college students, 1075 Diagnostic and Statistical Manual of Mental Disorders,  1072– 1073 elderly, 1073– 1075 physicians, 1075 screening tools, 1073 epidemiology, 1069– 1070 maintenance of sobriety and relapse prevention, 1077– 1080 acupuncture, 1080 behavioral treatments, 1078– 1079 herbal remedies, 1080 pharmacologic treatments, 1078 transcutaneous electrical acupuncture stimulation, 1080 medical comorbidities, 1075 neurobiology, 1070– 1072 dopaminergic pathways, 1072 GABA A  receptors, 1072 pharmacology of alcohol, 1070– 1071 stages of addiction, 1071– 1072 overview, 1069 referrals and consultations, 1080 smartphone-based intervention in, 1107 Alcohol Use Disorders Identification Test (AUDIT), 511, 1073, 1074 Aldehyde dehydrogenase 2 (ALDH2), 414 ALDH2, see  Aldehyde dehydrogenase 2 (ALDH2) Allergen immunotherapy, 594 AlliTM , see  Orlistat Allopathic Medicine, 965 Alpha linoleic acid (ALA), 57– 58, 1144 Altered carbohydrate metabolism, 442 Altered fat metabolism, 442– 4 43

Index  1407 Alternative Healthy Eating Index 2010 (AHEI2010), 773 Alzheimer disease (AD), 1142– 1143, 1254 AMA, see  American Medical Association (AMA) Ambulatory blood pressure monitoring (ABPM), 940 AMDR, see  Acceptable macronutrient distribution ranges (AMDR) American Academy of Addiction Psychiatry (AAAP), 1054 American Academy of Breastfeeding Medicine, 680 American Academy of Geriatrics, 154 American Academy of Orthopedic Surgeons, 154 American Academy of Pediatrics (AAP), 343, 530, 673, 679, 865, 914, 915, 1308 American Association for the Cure of Inebriety (AACI), 1052 American Association of Clinical Endocrinologists (AACE), 45, 56, 368, 387, 395, 767 American Automobile Association (AAA), 1310 American Board of Lifestyle Medicine (ABLM), 306, 967, 971 American Board of Medical Specialties (ABMS), 967 American Board of Physical Therapy Specialties (ABPTS), 149 American Cancer Society (ACS), 434, 449, 717 American College of Cardiology (ACC), 20, 21, 25, 27– 28, 55, 112, 130, 348, 735, 741, 752, 767, 772, 773, 984, 985 American College of Endocrinology (ACE), 56, 387, 395 American College of Lifestyle Medicine (ACLM), 20, 961, 962, 969, 970, 971, 978, 1324 American College of Obstetrics and Gynecology (ACOG), 185, 347, 663, 673, 717, 721 American College of Occupational and Environmental Medicine (ACOEM), 1182, 1188 American College of Physicians (ACP), 24 American College of Preventive Medicine (ACPM), 20, 154, 962, 969, 971 American College of Radiology, 333 American College of Sports Medicine (ACSM), 10, 37– 38, 44, 67, 148, 149, 154, 159, 163, 165, 170, 183, 186, 187, 264, 344, 434, 474, 475, 560, 763, 981, 987, 1158, 1160 American Community Survey (ACS), 1070, 1351 American Congress of Obstetrics and Gynecology (ACOG), 697 American Council on Exercise (ACE), 148 American Diabetes Association (ADA), 30, 31, 316, 367, 368, 384, 387, 395, 508, 984 American Diabetes Association Guide of Managing Diabetes, 21

American Geriatrics Society (AGS), 1327, 1330, 1331 American Heart Association (AHA), 3, 5, 7, 9, 10, 12, 13, 14, 20, 21, 25, 27– 28, 31, 32, 40, 55, 95, 112, 116, 117, 130, 149, 173, 348, 735, 741, 752, 767, 772, 773, 796, 806, 842, 962, 984, 1158– 1159, 1387 diet and lifestyle recommendations, 118– 120 avoiding tobacco products, 119 consuming overall healthy diet, 118 desirable lipid profile, 119 healthy body weight, 118– 119 normal blood pressure, 119 physical activity, 119 specific, 119– 120 American Heart Association Scientific Statement on Implementing Pediatric and Adult Nutrition Guidelines, 6 American Holistic Nurses Credentialing Corporation, 307 American Institute of Cancer Research (AICR), 409, 410– 411, 412, 413, 420, 434 American Journal of Cardiology,  762 American Journal of Lifestyle Medicine,  969 American Journal of Obstetrics and Gynecology,  654, 708 American Lung Association, 1152 American Medical Association (AMA), 150, 154, 264, 530, 1052, 1053, 1158, 1214, 1304 American Medical Temperance Association (AMTA), 1052 American Osteopathic Academy of Addiction Medicine (AOAAM), 1054 American Physical Therapy Association (APTA), 149 American Planning Association, 1202 American Psychiatric Association (APA), 1011, 1054, 1094, 1109 American Psychological Association, 1006 American Public Health Association, 1202 American Society for Metabolic and Bariatric Surgery, 505 American Society of Addiction Medicine (ASAM), 1054, 1076, 1116 American Society of Clinical Oncology (ASCO), 427 American Society of Nutrition, 1399 American Temperance Society, 1052 American Thoracic Society (ATS), 597 AMH, see  Anti-mullerian hormone (AMH) AMP-activated protein kinase (AMPK), 427 AMPM, see  Automated Multiple-Pass Method (AMPM) AMS, see  Acute mountain sickness (AMS) AMTA, see  American Medical Temperance Association (AMTA) AND, see  Academy of Nutrition and Dietetics (AND) Anderson, James, 400 Angiogenesis, 1257– 1258 Animal dander, 643

Annual Wellness Visit, 1183 Anorexia of aging, 1135 ANP, see  Atrial natriuretic peptide (ANP) Antenatal care, 653– 658 autism, 657– 658 exercise in pregnancy, 658 fetal impacts of maternal lifestyle, 656– 657 maternal mortality, 655 overview, 653 ovulatory infertility, 653– 654 preeclampsia, 655– 656 pregnancy outcomes, 654 Anterior cruciate ligament (ACL) injuries, 343– 344 Anthropometry, 879– 880 Antibiotic use and microbiome, 522– 523 endocrine disruptors, 522– 523 in farming, 522 by humans, 522 Anticipated affective reactions (AAR), 248 Anti-mullerian hormone (AMH), 708 Antioxidants, 13, 358– 359 Antiretroviral therapy (ART), 555, 557, 703 Anti-Saloon League, 1053 Antithrombotic Therapy for VTE Disease,  626 Antonovsky, Aaron, 1203, 1204 Anxiety and PA, 1271– 1277 anxiolytic effect in healthy, 1275 definitions and diagnoses, 1271– 1272 agoraphobia, 1271 generalized anxiety disorder (GAD), 1272 incidence and impact, 1272 obsessive-compulsive disorder (OCD), 1272 panic disorder (PD), 1272 post-traumatic stress disorder (PTSD), 1272 social anxiety disorders (SAD), 1272 specific phobias, 1272 endurance training, 1275– 1276 mechanisms of anxiolytic activity, 1276– 1277 biological, 1276– 1277 psychological, 1276 meta-analytical findings, 1276 one-time, 1275 overview, 1271 prevalence and incidence, 1274– 1275 treatment, 1272– 1274 combination of pharmacotherapy and psychotherapy, 1273 complementary methods and addons, 1273– 1274 pharmacological, 1273 psychotherapeutic, 1272– 1273 Anxiolytic activity mechanism, 1276– 1277 biological, 1276– 1277 psychological, 1276 AOAAM, see  American Osteopathic Academy of Addiction Medicine (AOAAM) APA, see  American Psychiatric Association (APA) Apnea-hypopnea index (AHI), 585 Apo B-containing lipoprotein particles, 55



1408  Index Apo C-II, 54 Apolipoprotein E (APOE)-Ɛ 4 carriers, 1262 Apoptosis, 1129– 1130 Appalachian Mountain Club, 150 APTA, see  American Physical Therapy Association (APTA) AR, see  Augmented reality (AR) Archives of Physical Medicine and Rehabilitation,  196 Arginine vasopressin (AVP), 136 ARIC, see  Atherosclerosis Risk in Community (ARIC) Aromatase, 420 ART, see  Antiretroviral therapy (ART) Arteriovenous malformations (AVMs), 579 Arthritis, 188 and obesity, 1395 Artificial intelligence (AI), 321 Artificial sweeteners, 361 ASAM, see  American Society of Addiction Medicine (ASAM) Asbestos-related lung disease, 613– 614 clinical presentation and diagnosis, 614 epidemiology, 614 ASCO, see  American Society of Clinical Oncology (ASCO) ASCVD, see  Atherosclerotic cardiovascular disease (ASCVD) ASD, see  Autism spectrum disorders (ASD) ASLM, see  Australasian Society for Lifestyle Medicine (ASLM) Aspen Institute, 343 Asthma, 589– 606 clinical features, 590 management, 598– 606 allergy testing and immunotherapy, 601– 602 complications, 600– 601 exercise-induced asthma (EIA), 602– 603 food hypersensitivity, 604 gastroesophageal reflux, 605 issues, 600 medication-induced, 604– 605 obesity, 604 occupational asthma, 603– 604 pregnancy, 605– 606 stress, 604 overview, 589– 590 pathophysiology, 590– 593 airway hyperresponsiveness, 591 airway inflammation, 590– 591 management, 591– 592 monitoring disease activity, 592– 593 variable airflow obstruction, 590 pharmacologic therapy, 595– 598 benralizumab, 597 biologic therapies, 596 bronchial thermoplasty, 597 chronic controllers, 595– 596 long-acting beta-2 agonist, 596 long-acting muscarinic antagonists, 596 mepolizumab, 597 omalizumab, 596– 597 quick-relief medications, 598 reslizumab, 597 treatment, 593– 595

environmental control, 593– 594 indoor allergens, 594 outdoor allergens, 594– 595 Asthma Control Questionnaire (ACQ), 599 Asthma Control Test (ACT), 599– 600 Asthma Therapy Assessment Questionnaire (ATAQ), 599 ATBC, see  α -Tocopherol β - Carotene Study (ATBC) Atherosclerosis, 922 pathophysiology, 4– 5 Atherosclerosis Risk in Community (ARIC), 13 Atherosclerotic cardiovascular disease (ASCVD), 25, 387, 767, 890– 891, 984 Atkins, Robert, 449 ATP, see  Adenosine triphosphate (ATP) ATP III, see  Adult Treatment Panel Guidelines (ATP III) Atrial fibrillation (AF), 1144 Atrial natriuretic peptide (ANP), 136 ATS, see  American Thoracic Society (ATS) Attention deficit hyperactivity disorder (ADHD), 942 AUD, see  Alcohol use disorder (AUD) AUDIT, see  Alcohol Use Disorders Identification Test (AUDIT) Auditory Verbal Learning Test (AVLT), 1258 Augmented reality (AR), 320– 321 Aurin, Marcus, 1052 Australasian Society for Lifestyle Medicine (ASLM), 962 Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS), 867 Autism, 657– 658 Autism spectrum disorders (ASD), 657– 658 Automated Multiple-Pass Method (AMPM), 83 Autonomous motivation, 1212 Autonomy support, 209 Avian influenza, 634 AVLT, see  Auditory Verbal Learning Test (AVLT) AVMs, see  Arteriovenous malformations (AVMs) AVP, see  Arginine vasopressin (AVP)

B Baase, Catherine, 1182 BAC, see  Blood alcohol concentration (BAC) Backus, W., 1004 Bacon, Francis, 193 BAI, see  Beck Anxiety Inventory (BAI) Bandura, Albert, 194, 197, 230 Bariatric surgery, 916 dietary changes, 508 and PA barriers, 510 benefits in postoperative, 510 levels, 510 recommendations, 510 prevention of micronutrient deficiencies, 508– 509 procedures, 505

weight regain, 513 Barnard, R. J., 393 Barry, Mike, 962 Bassler hypothesis, 793 BAT, see  Brown adipose tissue (BAT) Baumeister, Roy, 1213 BCT, see  Behavioral couples therapy (BCT); Behavior Change Technique (BCT) Taxonomy BDI-II, see  Beck Depression Inventory II (BDI-II) BDNF, see  Brain-derived neurotrophic factor (BDNF) “ B e Active Your Way”  guide, 1161 Beck Anxiety Inventory (BAI), 1012 Beck Depression Inventory II (BDI-II), 1012 Beecher, Lyman, 1052 Behavioral approaches to manage stress, 281– 294 building resilience, 282, 284 mind-body therapies, 284– 293 overview, 281 stress response and relaxation responses, 281– 282 technology in, 293– 294 nutrition prescription and, 269– 279 basics, 270– 271 counseling techniques, 273– 274 cultural sensitivity, 272– 273 education in group medical visit model, 274– 276 nutrients for wellness, 272 overview, 269– 270 portion control, 271– 272 practical culinary skills, 276– 279 whole foods, 271 Behavioral couples therapy (BCT), 1113– 1114 Behavioral economics, 1173 Behaviorally-based lifestyle treatment, 913– 914 family-based behavioral treatment (FBT), 913 mind, exercise, nutrition… do it! (MEND), 913– 914 overview, 913 Behavior and pediatric lifestyle medicine in children, 855 economics, 857– 858 family-based treatment, 855– 856 models, 852– 853 functional contextualism, 853 social-ecological, 852 principles, 853– 855 Behavior change, 32, 193– 196, 314, 435– 436 CVD patients and, 781– 785 coaching, 783 elements, 783– 785 engagement, 782– 783 key points, 781 theories, 781– 782 determinants, 32 digital health technology for, 311– 322 assistive mobility devices, 321 big data and machine learning, 321 digital therapeutics, 319– 320 mobile applications, 315– 316

Index  1409 multiomics, 320 overview, 311– 313 sensors and form factors, 321 social media, 318– 319 text messaging, 313– 315 virtual and augmented reality, 320– 321 wearables, sensors, and devices, 316– 318 and HWC, 299– 309 assimilation of coaches, 308 client and patient populations and care settings, 304– 305 client/patient privacy, 308 evaluation and research, 306– 307 as field and profession, 300– 304 future of health care, 308 hiring coaches, 307– 308 overview, 299– 300 payment models, 305– 306 physician referrals, 307 professional coaches, 307 visit structures and delivery methods, 305 physical activity, 435– 436 cancer populations, 436 healthy populations, 435– 436 Behavior Change Coding Taxonomy, 261 Behavior Change Technique (BCT) Taxonomy, 256 Behavior Risk Factor Surveillance System (BRFSS), 30 Be He@lthy, 315 Bé hier, Louis-Jules, 1052 BeLPT, see  Beryllium lymphocyte proliferation test (BeLPT) Belviq XRTM , see  Lorcaserin Be Mobile program, 315 Benedict, Peter, 1351 Bé né zet, Antoine, 1051 Benralizumab, 597 Benson, Herbert, 286, 1008 Benson-Henry Mind Body Medical Institute (MBMI), 825, 829, 1021 Benzodiazepines, 1076 Benzphetamine, 493 Berryman, Jack, 153 Berwick, Don, 1182 Berylliosis, 615– 616 clinical presentation and diagnosis, 615– 616 epidemiology, 615 treatment and prevention, 616 Beryllium lymphocyte proliferation test (BeLPT), 615– 616 Beryllium sensitization (BeS), 615 Beta-Carotene and Retinol Efficacy Trial (CARET), 412 Better Life Index, 1207 BGS, see  British Geriatrics Society (BGS) BIA, see  Bioelectric impedance analysis (BIA) Bicycle helmets, 1309 Big data and machine learning, 321 Bile acid sequestrants, 930 Biliopancreatic diversion (BPD), 505, 507 Biliopancreatic diversion with duodenal switch (BPDDS), 505, 507

Binns, A., 961 Bioelectric impedance analysis (BIA), 458, 985 The Biology of Belief,  333 Biomarkers for Nutrition in Development, 84 Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia, 84 Blood alcohol concentration (BAC), 1306, 1310 Blood lipid profile, 827– 828 Blood pressure, 478– 479 and PA, 348 resistance exercise training and, 41 Blue Zones, 1007 BMD, see  Bone mineral density (BMD) BMI, see  Body mass index (BMI) Body composition, 171– 173 body mass index (BMI), 173 hydrodensiometry/underwater weighing, 171– 173 overweight and obesity, 171 Body mass index (BMI), 9, 173, 442, 456– 457, 491, 802, 888, 1194 Body Scan, 286, 288 Body surface area (BSA), 427 Bone health and PA, 348 Bone mineral density (BMD), 345, 348 Bontril, see  Phendimetrazine Booster seats, 1308 BPCI, see  Bundled Payments for Care Improvement (BPCI) BPD, see  Biliopancreatic diversion (BPD) BPDDS, see  Biliopancreatic diversion with duodenal switch (BPDDS) Brain derived neurotrophic factor (BDNF), 1255– 1256, 1261– 1262, 1277, 1285 Breast cancer, 334– 338, 715– 719 epidemiology/risk factors, 715– 716 intervention/prevention, 719 lifestyle, 717– 719 obesity and, 334– 338 clean eating, 335 CoQ10, 337 exercise and recreational activity, 336 folate, 337 lifestyle evaluation and modifications, 336 nutrition, 336 prevention, 338 retinol and β - carotene, 337 selenium, 338 sleep, 335– 336 stress reduction, 336– 337 vitamin D, 337 vitamin E and vitamin C, 337 vitamins, antioxidants, and minerals, 337 zinc, 338 and PA, 348– 349 screening, 716– 717 Breast-feeding, 673– 682 anatomy, 674 benefits, 675– 678 infant, 676– 678 maternal, 675– 676

hormonal influences, 674– 675 milk content, 675 overview, 673– 674 practical management, 678– 680 assessment of intake adequacy, 679– 680 contraindications, 680 problems related to, 680– 681 engorgement, 680 mastitis, 680 medications and lactation, 681 prior breast surgery, 680– 681 support, 681– 682 pumping breast milk, 681– 682 weaning, 682 Breast health, 331– 338 epidemiology, 331– 332 genetics, 332 epigenetics, 332– 333 hormone therapy, 333 obesity, 334– 338 cancer prevention, 338 clean eating, 335 CoQ10, 337 exercise and recreational activity, 336 folate, 337 lifestyle evaluation and modifications, 336 nutrition, 336 retinol and β - carotene, 337 selenium, 338 sleep, 335– 336 stress reduction, 336– 337 vitamin D, 337 vitamin E and vitamin C, 337 vitamins, antioxidants, and minerals, 337 zinc, 338 overview, 331 prevention, 334 protective life choices, 332 risk assessment, 332 risk factors, 334 alcohol, 334 screening, 333– 334 Breath awareness, 286 BRENDA approach, 1091 Brent, Charles Henry, 1053 Brent Commission, 1053 BRFSS, see  Behavior Risk Factor Surveillance System (BRFSS) Brief interventions, 1115– 1116 British Association of Sport and Exercise Medicine, 157 British Geriatrics Society (BGS), 1327, 1330, 1331 Bronchial thermoplasty, 597 Brown adipose tissue (BAT), 443 Brownell, Kelly, 764 BSA, see  Body surface area (BSA) Buetner, Dan, 1007 Bundled Payments for Care Improvement (BPCI), 1360 Buprenorphine, 1054 office-based treatment (OBT), 1087 advantages, 1087 disadvantages, 1087 Bupropion, 1058



1410  Index Burton, Wayne N., 1169 Bush, George W., 342, 529 B vitamins, 1144

C Calcium, 127, 953– 954 California Department of Public Health, 645 Calorie restriction (CR), 1151 CAM, see  Complementary and Alternative Medicine (CAM) Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE), 754 Cancer, 130– 131, 187– 188, 1284– 1285 and depression, 691 nutrition therapy for patient, 441– 4 49 complementary and restorative therapeutic treatment, 446– 4 49 malnutrition and cancer cachexia, 441–  4 42 metabolic alterations, 442– 4 43 overview, 441 screening, 443–  4 44 treatment and side effect management, 444 obesity and, 419– 427, 1394– 1395 body surface area (BSA), 427 lifestyle modifications for primary cancer prevention, 423– 425 mechanisms, 420– 422 overview, 419– 420 PA and, 431– 437 behavior change, 435– 436 defining “ health-enhancing,”  433– 435 growing burden, 431 limitations, 437 overview, 431 prevention, 431– 433 strategies for interventions, 436– 437 secondary prevention in survivors, 425– 426 strategies to disrupt, 422 type 2 diabetes mellitus, 426– 427 prevention and diet, 409– 415 alcohol, 414– 415 dietary fiber, 412– 413 fruits and vegetables, 409– 410 meat intake, 413– 414 micronutrients and phytochemicals, 410– 412 overview, 409 Cancer Exercise Trainer (CET), 149 Cancer Intervention and Surveillance Modeling Network, 716 Cannabis use disorder, 1093– 1099 adolescent exposure, 1094 adult exposure, 1094– 1096 mortality and fatal overdose, 1094 psychiatric comorbidity, 1095– 1096 withdrawal, 1095 assessing, 1096 childhood exposure, 1094 overview, 1093 during pregnancy, 1099 prenatal exposure, 1093 screening, 1096

treatment, 1096– 1098 pharmacological interventions, 1098 psychosocial interventions, 1098 use for pain, 1098 use for psychiatric conditions, 1098– 1099 Cannon, W. B., 1006 CAR, see  Cortisol awakening rise (CAR) CARA, see  Comprehensive Addiction and Recovery Act (2016) (CARA) Carbamazepine, 1076 Carbohydrate metabolism, 356– 357 Carbon monoxide, 641– 642 Cardiac rehabilitation (CR) delivery and impact, 833– 837 behavioral lifestyle change counseling, 835 challenges and solutions, 835 models, 834– 835, 836 overview, 833– 834 Cardiac Rehabilitation Outcomes Study (CROS), 774 Cardiac Wellness Program, 825, 1021 Cardiometabolic risk factor (CMRF), 875– 876, 876– 879 Cardioprotective medications, lifestyle modification effects on, 771– 777 nutrition, 772– 773 overview, 771– 772 physical activity, 773– 775 psychosocial health, 775– 776 smoking cessation, 775 Cardiorespiratory fitness (CRF), 773– 775, 880– 881 non-exercise test estimates, 170 testing, 985– 986 walk tests for, 169– 170 CardioSmart, 746 Cardiovascular activity, 474 Cardiovascular disease (CVD), 130, 478– 479, 1284; see also  CVD risk factor reduction and bone density, 691 effects on risk factors for, 478– 479 blood pressure, 478– 479 inflammatory markers, 479 lipids, 479 nutrition and, 111– 120 AHA diet and lifestyle recommendations, 118– 120 alcohol, 117 chocolate, 118 coffee and caffeine, 117 dairy products, 116– 117 dietary patterns, 112– 114 eggs, 117 fish, 116 fruits and vegetables, 116 garlic, 117– 118 heart healthy nutrition plans, 120 meat, 116 nuts, 116 overview, 111– 112 salt and sodium, 118 soy, 117 sugar sweetened beverages (SSBs), 117 tea, 117

vitamin D, 118 vitamins E and C, 118 whole grains and dietary fiber, 116 patients and behavior change, 781– 785 coaching, 783 elements, 783– 785 engagement, 782– 783 key points, 781 theories, 781– 782 physical activity and, 37– 47 central adiposity and inflammation, 43– 4 4 diabetes, 41– 42 heart failure, 41 hypertension, 40– 41 lipids, 44– 45 metabolic syndrome, 45– 47 obesity, 42– 43 overview, 37– 38 physical fitness vs.,  38 recommendations, 38– 39 stroke, 40 women and CHD, 39– 40 and positive psychology factors, 231– 232 prevention and treatment, 811– 820 dietary supplements, 814– 817 folic acid, 812 multivitamins, 811– 812 niacin, 812– 813 over-the-counter (OTC) dietary supplement selection, 817, 819 overview, 811 vitamin C, 813 vitamin D, 813– 814 vitamin E, 814 primordial/primary prevention, 841– 846 family-based approaches, 842– 843 family-focused interventions, 843– 845 life course approach, 841– 842 overview, 841 secondary prevention and, 751– 757 addressing depression, 753– 756 anger/hostility, 753 anxiety, 753 complementary and alternative medicine approaches, 757 effects of antidepressants, 757 overview, 751 patient, 751– 752 psychosocial factors, 752– 753, 756– 757 social support, 753 Cardiovascular health integrated lifestyle diet-1 (CHILD-1&2), 891, 893, 926 Cardiovascular health integrated lifestyle diet-2-low-density lipoprotein (CHILD-2-LDL), 926 CARET, see  Beta-Carotene and Retinol Efficacy Trial (CARET) Carotid intima-media thickness (CIMT), 13 Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Study (CREST-2), 749 CAS, see  College Alcohol Study (CAS)

Index  1411 CA-125 serum level, 721 CAT, see  COPD assessment test (CAT) CATCH, see  Coordinated Approach to Child Health (CATCH) Catheter-directed thrombolysis (CDT), 627 Caya Contoured Diaphragm, 698 CBT, see  Cognitive behavioral therapy (CBT); Core body temperature (CBT) CBTI, see  Cognitive behavioral therapy for insomnia (CBTI) CCARE, see  Center for Compassion and Altruism Research and Education (CCARE) CCEP, see  Certified clinical exercise physiologist (CCEP) CCM, see  Chronic care model (CCM) CDC, see  Center for Disease Control and Prevention (CDC) CDC Guideline for Prescribing Opioids for Chronic Pain,  1315 CDO, see  Combined dyslipidemia of obesity (CDO) CDT, see  Catheter-directed thrombolysis (CDT) Cell mediated immunity (CMI), 565 Center for Compassion and Altruism Research and Education (CCARE), 1214 Center for Disease Control and Prevention (CDC), 6, 10, 37, 150, 163, 293, 306, 383, 435, 475, 529, 556, 632, 633, 635, 663, 688, 726, 763, 888, 1147, 1176, 1184, 1203, 1303, 1315, 1319, 1320, 1321, 1324, 1327, 1341, 1386, 1387, 1392, 1396, 1397 Centers for Medicare and Medicaid Services (CMS), 825, 1358 Central adiposity and CVD, 43– 4 4 “ fitness vs. fatness” debate, 43 PA and sustained weight loss, 43– 4 4 preventing weight gain, 43 recommendations, 44 resistance training and weight loss, 44 Centre for Bhutan Studies, 1207 CEPA, see  Clinical Exercise Physiology Association (CEPA) CEPT, see  Cholesterol ester transfer protein (CEPT) CER, see  Comparative effectiveness research (CER) Cerebral vascular changes and aging, 1143 Certified clinical exercise physiologist (CCEP), 149 Certified exercise physiologist (EP-C), 149 Certified Medical Exercise Specialists, 148 Certified personal trainer (CPT), 148 Certified Strength and Conditioning Specialist (CSCS), 148 Cervical cancer, 726– 728 epidemiology/risk factors, 726– 727 intervention/prevention, 728 lifestyle, 727– 728 screening, 727 Cervical intraepithelial neoplasia (CIN), 727– 728 CET, see  Cancer Exercise Trainer (CET)

CETP, see  Cholesterylester Transfer Protein (CETP) Chancroid, 705 Change talk, 214 “ C hange Talk: Childhood Obesity ,”  914 Changing for Good,  226, 301 Changing to Thrive,  226, 301 CHD, see  Coronary heart disease (CHD) Chemoprophylaxis, 635– 636 Chemotherapy and radiation therapy, 444 CHILD-1&2, see  Cardiovascular health integrated lifestyle diet-1 (CHILD-1&2) Childhood and adolescence chronic disease in, 867 physical activity, 184– 185 Childhood and adolescent obesity, 888– 890 balanced hypocaloric reduction, 914 traffic light diet, 914 bariatric surgery, 916 clinical applications, 889– 890 USDA dietary guidelines, 890 USDA MyPlate, 890 comorbid conditions, 911 definitions, 910 diet, 889 etiology and pathophysiology, 888, 910– 911 family climate, 889 ideal macronutrient composition, 914 meal replacement products, 914 very low-calorie diets (VLCD), 914 motivational interviewing, 914 overview, 909– 910 physical activity, 915 physical activity and sleep time, 889 prevention interventions, 911 risk and protective factors, 911 screen time and screening, 889, 911 sedentary behavior, 915 and sleep, 901– 905 assessment, 903 diet, 902 epidemic, 901 influence on health behavior patterns, 903 overview, 901 pediatric obstructive sleep apnea, 903 physical activity and screen time, 903 poor sleep health, 901– 902 treatment of disorders, 904– 905 sleep interventions, 915 treatment, 911– 914 2007 Expert Committee Guidelines, 913 behaviorally-based lifestyle, 913– 914 clinical weight loss, 911, 913 interpreting effects, 913 overview, 911 weight loss medications, 915– 916 CHILD-2-LDL, see  Cardiovascular health integrated lifestyle diet-2-low-density lipoprotein (CHILD-2-LDL) Children’ s Health Insurance Reauthorization Act, 24 Child safety seats (CSS), 1308

CHIP, see  Complete Health Improvement Program (CHIP) Chlamydia, 700– 701 Chocolate, 118 Cholesterol acyltransferase (LCAT), 54 Cholesterylester Transfer Protein (CETP), 7, 54 Cholinergic anti-inflammatory pathway, 564– 565 Choose My Plate, 90 Christoffel, Katherine Kaufer, 1387 Chronic care model (CCM), 987– 990 components, 988– 989 sample effective programs, 989– 990 Chronic Contemplation, 194 Chronic disease life course approach to prevention, 861– 867 childhood and adolescence, 867 early exposures, 865– 866 endocrine disrupting chemicals (EDCS), 864– 865 infancy, 867 overnutrition, 863– 864 overview, 861– 862 physical activity, 864 pre-conception, 866 pregnancy, 866– 867 smoking, 864 undernutrition, 862– 863 and sleep, 995– 996 cancer, 996 cardiovascular diseases, 996 excessive BMI and metabolic disorders, 995– 996 inflammatory disorders, 996 mood disorders, 996 Chronic exercise and immunity, 547– 552 effect on leukocyte number and function, 547 efficacy of vaccines, 552 excessive training, 549– 551 Th1/Th2 balance, 549– 550 toll-like receptors, 550 URS and URTI, 550– 551 inflammation, 551 monocytes and tissue macrophages, 547– 548 natural killer cells, 548 neutrophils, 548 overview, 547 T and B lymphocytes, 549 wound healing, 551– 552 Chronic inflammation and PA, 539– 540 Chronic kidney disease (CKD), 941 Chronic obstructive pulmonary disease (COPD), 574, 612– 613, 1193 clinical presentation and diagnosis, 612– 613 epidemiology, 612 non-pharmacologic therapy, 613 pharmacologic therapy, 613 prevention and treatment, 613 CHS, see  Clalit Health Services (CHS) CIMT, see  Carotid intima-media thickness (CIMT) CIN, see  Cervical intraepithelial neoplasia (CIN)



1412  Index Circles of Recovery: Self-help Organizations for Addictions,  1079 CIWA-Ar, see  Clinical Institute Withdrawal Assessment, revised iteration, (CIWA-Ar) CKD, see  Chronic kidney disease (CKD) Clalit Health Services (CHS), 1038 Cleveland, Minot, 1386– 1387 Clifton, Donald, 230 Clinical Exercise Physiology Association (CEPA), 149 Clinical Institute Withdrawal Assessment, revised iteration, (CIWA-Ar), 1076 Clinical Opiate Withdrawal Scale (COWS), 1088 Clinical Practice Guideline for Treating Tobacco Use and Dependence, 1108 CLOCC, see  Consortium to Lower Obesity in Chicago Children (CLOCC) CM, see  Contingency management (CM) CMDLD, see  Coal mine dust lung disease (CMDLD) CME, see  Continuing Medical Education (CME) CMI, see  Cell mediated immunity (CMI) CMRF, see  Cardiometabolic risk factor (CMRF) CMS, see  Centers for Medicare and Medicaid Services (CMS) CMV, see  Cytomegalovirus (CMV) Coal mine dust lung disease (CMDLD), 616 clinical presentation and diagnosis, 616 epidemiology, 616 prevention and treatment, 616 Coal workers’  pneumoconiosis (CWP), 616 COC, see  Combined oral contraceptive (COC) pills Cockroaches, 644 Code of Medical Ethics, 1214 CODIACS, see  Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS) Coenzyme Q10 (CoQ10), 337, 814– 815 Coffee and caffeine, 117 Cognitive behavioral therapy (CBT), 291, 523, 754, 776, 1008, 1091, 1098, 1114– 1115 Cognitive behavioral therapy for insomnia (CBTI), 1000 Cognitive reappraisal, 291 College Alcohol Study (CAS), 1075 Combined dyslipidemia of obesity (CDO), 931 Combined oral contraceptive (COC) pills, 688– 689 initiation and administration, 689 mechanism of action, 688 myocardial infarction and stroke, 689 venous thromboembolism (VTE), 689 Communicator’ s Guide, 108 Communities Putting Prevention to Work project, 1387 Community Guide, 371, 373 Community Preventive Services Task Force, 1369

Community reinforcement approach (CRA), 1115 Community support, 989 Comparative effectiveness research (CER), 1359 Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS), 754 Compassion, 209 Complementary and Alternative Medicine (CAM), 441, 446– 4 47, 965 Complete Health Improvement Program (CHIP), 1025, 1176 Complex reflection, 211 Comprehensive Addiction and Recovery Act (2016) (CARA), 1054 Comprehensive Alcoholism Prevention and Treatment Act (1970), 1054 Comprehensive Primary Care Plus (CPC+), 1358 Comprehensive Primary Care Program, 1358 Computed tomography (CT), 458 Computerized-tailored intervention (CTI) treatment, 223, 224, 225– 226 Condyloma acuminata,  704 Congestive heart failure, see  Heart failure (HF) Congress in the Agricultural Act (2014), 110 Connected Health model, 836 Consciousness raising, 221– 222 Consortium to Lower Obesity in Chicago Children (CLOCC), 1387 Consumer Product Safety Commission (CPSC), 642 Contemplation and prayer, 220, 289 Contemplation Ladder, 225 Contingency management (CM), 1115 Continuing Medical Education (CME), 156– 157 Continuous positive airway pressure (CPAP), 645– 646, 646 Continuous Update Project (CUP), 409 Contraception, 687– 695 combined oral contraceptive (COC) pills, 688– 689 initiation and administration, 689 mechanism of action, 688 myocardial infarction and stroke, 689 venous thromboembolism (VTE), 689 depot-medroxyprogesterone acetate (DMPA), 690– 692 cancer and depression, 691 cardiovascular disease and bone density, 691 clinical considerations, 691 on future fertility, 691– 692 lactation and, 691 mechanism of action, 690– 691 side effects, 691 emergency contraception (EC), 693– 694 clinical considerations, 694 efficacy, 693– 694 options, 693 long-acting reversible contraception (LARC), 692– 693

intrauterine contraception (IUDs), 692– 693 Nexplanon implant, 692 overview, 687– 688 postpartum, 694– 695 combined contraception methods, 694 LARCs, 694 sterilization, 694– 695 progesterone-only pills, 690 transdermal contraceptive patch, 689– 690 contraceptive vaginal ring, 690 mechanism of action and clinical considerations, 689– 690 Contraceptive vaginal ring, 690 Contrave, see  Naltrexone ER-bupropion SR Controlled motivation, 1212– 1213 Cooper 12-minute test, 169 Coordinated Approach to Child Health (CATCH), 1370– 1371 COPD, see  Chronic obstructive pulmonary disease (COPD) COPD assessment test (CAT), 613 COPE, 1004 CoQ10, see Coenzyme Q10 (CoQ10) Core body temperature (CBT), 1000 Corollary discharges, 576 Coronary artery bypass surgery, 761– 765 counseling patients, 763 developing positive mind-set, 765 eating healthy food, 764 exercise regularly, 763– 764 healthy changes, 765 managing stress, 764– 765 overview, 761 smoking, 763 teachable moment, 761– 763 Coronary heart disease (CHD), 25 women and, 39– 40 Coronary patients and obesity, 801– 807 epidemiology, 802 measuring, 802 MHO, 802– 803 modifying lifestyle, 805– 807 overview, 801– 802 paradox, 803– 805 physiologic effects, 805 Corticosteroids, 595 Corticotrophin-releasing hormone (CRH), 282 Cortisol awakening rise (CAR), 999 Cough, 580– 583 acute, 581 chronic cough with abnormal chest X-ray, 582– 583 clinical causes, 581 definition and physiology, 580 subacute and chronic, 581– 582 Cough variant asthma, 582 Counter conditioning techniques, 223 COWS, see  Clinical Opiate Withdrawal Scale (COWS) COX, see  Cyclooxygenase (COX) CPAP, see  Continuous positive airway pressure (CPAP) CPC+, see  Comprehensive Primary Care Plus (CPC+)

Index  1413 CPSC, see  Consumer Product Safety Commission (CPSC) CPT, see  Certified personal trainer (CPT) CR, see  Calorie restriction (CR); Cardiac rehabilitation (CR) CRA, see  Community reinforcement approach (CRA) C-reactive protein (CRP), 43, 442, 539, 563– 564 CREATE, see  Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) CREST-2, see  Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Study (CREST-2) CRF, see  Cardiorespiratory fitness (CRF) CRH, see  Corticotrophin-releasing hormone (CRH) CROS, see  Cardiac Rehabilitation Outcomes Study (CROS) Cross-Stressor Adaptation Hypothesis (CSAH), 1232– 1233 CRP, see  C-reactive protein (CRP) CSAH, see  Cross-Stressor Adaptation Hypothesis (CSAH) CSCS, see  Certified Strength and Conditioning Specialist (CSCS) Csikszentmihalyi, Mihaly, 230 CSS, see  Child safety seats (CSS) CT, see  Computed tomography (CT) CTI, see  Computerized-tailored intervention (CTI) treatment Culture of Health, 1202 CUP, see  Continuous Update Project (CUP) CVD, see  Cardiovascular disease (CVD) CVD risk factor reduction, 3– 14, 1144; see also  Cardiovascular disease (CVD) alcohol, 13 concept, 5 depression, 13 emerging, 12 hemostatic factors, 12 high sensitivity C-reactive protein (hs-CRP), 12 homocysteine, 12 LDL subclasses and particle size, 12 lipoprotein (a), 12 markers of inflammation, 12 evidence-based vs.  risk-based strategies, 6 implementing guidelines, 6 levels of antioxidants, 13 lifestyle strategies for prevention and treatment, 19– 32 assessment, 21 cigarette smoking cessation, 21– 24 classifying interventions, 21 determinants of behavior change, 32 diabetes and glucose intolerance, 29– 30 dyslipidemias, 24– 26 hypertension, 26– 28 lifestyle medicine in clinical practice, 32 moderate alcohol consumption, 31

nutritional counseling, 31 obesity, 28– 29 overview, 19– 21 pharmaceutical measures, 28 physical inactivity, 30– 31 post menopausal estrogen therapy, 31 prediction, 21 psychological risk factors and counseling, 31 metabolic syndrome and multiple, 11– 12 modifiable, 6– 11 diabetes and glucose intolerance, 8 dyslipidemias, 7 hypertension, 7– 8 inactive lifestyle, 9– 10 obesity, 9 poor nutritional habits, 10– 11 tobacco use, 6– 7 nonmodifiable, 11 age, 11 family history, 11 gender, 11 overview, 3– 5 pathophysiology of atherosclerosis, 4– 5 primary vs.  secondary prevention, 5 primordial prevention and “ ideal”  health, 5– 6 relative risk vs.  absolute risk, 5 scientific basis, 6 stress and type A personality, 13 trends in assessment, 13– 14 direct plaque imaging, 13 genomic approaches, 13– 14 reduction strategies, 14 scoring systems, 14 CWP, see  Coal workers’  pneumoconiosis (CWP) Cycle ergometer protocols, 168 Cyclooxygenase (COX), 57, 605 Cytomegalovirus (CMV), 549, 565

D DAAT, see  Depression and Anxiety Assessment Test (DAAT) Daily Value (DV), 93 Dairy products, 116– 117 DALYs, see  Disability-adjusted life years (DALYs) Danish Health Examination Survey, 362 DASH, see  Dietary Approaches to Systolic Hypertension (DASH); Dietary Approach to Stop Hypertension (DASH) DASH-Sodium Trial, 69, 1024 DASI, see  Duke Activity Status Index (DASI) DATA, see  Drug Addiction Treatment Act (2000) (DATA) Data security, 315 DBCD, see  Dysglycemia-based chronic disease (DBCD) DCCT, see  Diabetes Control and Complications Trial (DCCT) Dean Ornish Program for Reversing Heart Disease, 1021 Deci, Edward, 230, 1212

Decision support, 989 Deep vein thrombosis (DVT), 627 de la Haye, Kayla, 530 Delay discounting, 857 Delayed-type hypersensitivity (DTH), 566 Delivery system design, 988– 989 Delta-9-tetrahydrocannabinal (THC), 1310 Dementia, 1142 Dementia and PA, 349 Densitometry, 456 Dentition and associated senses, 130 Denver Learning Landscapes Alliance, 1368 Department of Health and Human Services (DHHS), 24, 44, 90, 102, 108, 178, 315, 826, 828, 890, 1040, 1063, 1116, 1158, 1350, 1375 Depot-medroxyprogesterone acetate (DMPA), 690– 692 cancer and depression, 691 cardiovascular disease and bone density, 691 clinical considerations, 691 on future fertility, 691– 692 lactation and, 691 mechanism of action, 690– 691 side effects, 691 Depression, 13 Depression and Anxiety Assessment Test (DAAT), 1012, 1013 Depression and PA, 1281– 1287 cross-sectional and longitudinal studies, 1282 mechanisms of antidepressant action, 1285– 1286 brain derived neurotrophic factor (BDNF), 1285 endocannabinoids, 1285– 1286 hypothalamic-pituitary-adrenal axis, 1285 psychosocial factors, 1286 serotonin, 1285 overview, 1281 predictors of antidepressant action, 1286 prescription, 1283– 1284 adherence to interventions, 1284 intensity, 1283 intervention duration, 1283 modality, 1284 session frequency and duration, 1283 randomized controlled trials, 1282– 1283 aerobic exercise, 1282 efficacy of resistance training exercise, 1282 exercise as adjunctive/augmentative therapy, 1283 exercise vs.  established treatments, 1283 meta-analyses, 1282 symptoms in diseased populations, 1284– 1285 cancer, 1284– 1285 cardiovascular disease, 1284 fibromyalgia and COPD, 1285 type II diabetes, 1284 Designated driver programs, 1310 Designing Healthy Communities,  1202 Detoxification, 1076– 1077



1414  Index inpatient vs.  outpatient setting, 1076 Clinical Institute Withdrawal Assessment, revised iteration, (CIWA-Ar), 1076 medications in acute withdrawal, 1076– 1077 withdrawal symptoms and timeframe, 1076 Developmental Origins of Health and Disease theory, 861 DEXA, see  Dual-energy X-ray absorptiometry (DEXA) DGA, see  Dietary Guidelines for Americans (DGA) DHA, see  Docahexaenoic acid (DHA) Diabetes, 41– 42 and glucose intolerance, 8, 29– 30 glycemic control, 42 management, 383– 391 diagnosis, 384 gestational diabetes, 389– 391 lifestyle medicine in, 391 overview, 383– 384 type 1 diabetes, 384– 387 type 2 diabetes, 387– 389 metabolic syndrome and CVD, 41– 42 and obesity, 1394 and PA, 348 and positive psychology factors, 232 strength training, 42 Diabetes Control and Complications Trial (DCCT), 385 Diabetes mellitus (DM), 186– 187, 941 Diabetes Prevention Program (DPP), 29, 150, 306, 319, 362, 373, 374, 377, 395, 524, 866, 990, 1027, 1184 Diabetes Prevention Study (DPS), 373, 374 Diabetes Self-Management Education and Support (DSMES), 383, 387 Diagnostic and Statistical Manual 5 (DSM5), 344 Diagnostic and Statistical Manual of Mental Disorders  (DSM), 1057, 1072– 1073, 1084, 1094– 1095 Di Clemente, C. C., 782 Didrex, see  Benzphetamine Diehl, Hans, 961 Diener, Ed, 230 Diet and cancer prevention, 409– 415 alcohol, 414– 415 dietary fiber, 412– 413 fruits and vegetables, 409– 410 meat intake, 413– 414 micronutrients and phytochemicals, 410– 412 carotenoids, 412 folate, 411– 412 garlic and allium vegetables, 410– 411 overview, 409 Dietary Approaches to Systolic Hypertension (DASH), 11 Dietary Approach to Stop Hypertension (DASH), 27, 31, 112, 114, 486, 519, 773, 892, 895, 1023, 1144 Dietary assessment error in, 82– 83 methods, 81

for weight management, 484– 485 energy expenditure, 484– 485 energy intake, 485 intervention, 485 Dietary biomarkers, 84 Dietary fiber, 926 Dietary Guidelines Advisory Committee 2015– 2020, 89, 90, 127 Dietary Guidelines for Americans (DGA), 6, 10, 14, 27, 29, 31, 32, 88, 89, 90, 95, 112, 1399 Dietary reference intake (DRI), 78, 85– 86, 90, 125– 126 challenges of updating, 88– 89 framework for chronic disease risk, 87– 88 limitations, 88 Dietary risk assessment, 88 Dietary Supplement Ingredient Database (DSID), 82 Diethylpropion, 493 Diffusion limitation of carbon monoxide (DLCO), 574 Digital Health Innovation Plan, 311 Digital health technology, 311– 322 assistive mobility devices, 321 big data and machine learning, 321 digital therapeutics, 319– 320 mobile applications, 315– 316 multiomics, 320 overview, 311– 313 sensors and form factors, 321 social media, 318– 319 text messaging, 313– 315 virtual and augmented reality, 320– 321 wearables, sensors, and devices, 316– 318 Digital health technology-enabled CVD risk reduction, 741– 749 case study, 746– 749 healthcare transformation, 746 home-based alternative cardiac rehabilitation and secondary prevention delivery models, 743– 744 lifestyle intervention and secondary prevention, 744– 745 overview, 741– 742 Digital therapeutics, 319– 320 Direct costs, 464 Disabilities, 188 Disability-adjusted life years (DALYs), 4, 1191 Disease Management Purchasing Consortium, 1187 Division of Nutrition, Physical Activity, and Obesity, 529 DLCO, see  Diffusion limitation of carbon monoxide (DLCO) DM, see  Diabetes mellitus (DM) DMPA, see  Depot-medroxyprogesterone acetate (DMPA) Docahexaenoic acid (DHA), 57– 58, 815, 1144 Doctorate of Physical Therapy (DPT), 149 Dole, Vincent, 1054 DOT, see  US Department of Transportation (DOT)

DPP, see  Diabetes Prevention Program (DPP) DPS, see  Diabetes Prevention Study (DPS) DPT, see  Doctorate of Physical Therapy (DPT) Dr. Dean Ornish Program for Reversing Heart Disease (ORN), 825 Dramatic relief, 222 DRI, see  Dietary Reference Intake (DRI) Drug Abuse Office and Treatment Act, 1054 Drug Addiction Treatment Act (2000) (DATA), 1054, 1087 Drug-impaired driving, 1310– 1311 DSID, see  Dietary Supplement Ingredient Database (DSID) DSM, see Diagnostic and Statistical Manual of Mental Disorders  (DSM) DSM5, see  Diagnostic and Statistical Manual 5 (DSM5) DSMES, see  Diabetes Self-Management Education and Support (DSMES) DSS-II, see  Second Diabetes Surgery Summit (DSS-II) DTH, see  Delayed-type hypersensitivity (DTH) Dual-energy X-ray absorptiometry (DEXA), 171, 345, 456, 985, 1128 Duke Activity Status Index (DASI), 170 Dunn, Halbert, 1204 Duraimani, S., 1008 Dust mites, 643 DV, see  Daily Value (DV) DVT, see  Deep vein thrombosis (DVT) Dysglycemia-based chronic disease, 355– 363 dietary patterns, 361– 362 Mediterranean diets, 361– 362 New Nordic Diet (NND), 362 Ornish diet (OD), 362 metabolic components, 356– 361 advanced glycated end products, 360 antioxidants, 358– 359 artificial sweeteners, 361 carbohydrate metabolism, 356– 357 endocrine disruptors, 361 fructose, 357– 358 lipid metabolism, 358 omega-3 fatty acids, 358 plant polyphenols, 359– 360 starch, fiber and sugar, 357 systemic inflammation, 360– 361 overview, 355– 356 physical activity, 362– 363 Dysglycemia-based chronic disease (DBCD), 355– 356 Dysinger, Wayne, 962, 971 Dyslipidemias, 890– 893 CHILD-2 diet, 893 children with, 921– 934 clinical case 1, 924 evaluation for secondary causes, 923– 924 familial combined hyperlipidemia, 925– 926 familial hypertriglyceridemia, 931– 932 heterozygous familial hypercholesterolemia, 924– 925 laboratory studies, 922– 923

Index  1415 lifestyle-related, 931 normal lipid values, 922 overview, 921– 922 therapy for hypertriglyceridemia, 932– 933 therapy for pure hypercholesterolemia, 926– 931 universal screening, 922 clinical strategies, 53– 61 elevated total and LDL cholesterol, 53– 54 high density lipoprotein, 54 lifestyle role in management, 57– 59 lipid classification and treatment targets, 55– 57 non-HDL cholesterol and apo B, 55 overview, 53 triglycerides, 54– 55 weight management, 59– 60 dietary and lifestyle approaches, 891– 893 hypercholesterolemia and hyperlipidemia, 7 hypertriglyceridemia, 7 lifestyle therapy, 890– 891 low levels of HDL cholesterol, 7 management, 24– 26 Dyspnea, 576– 580 acute vs.  chronic, 578– 579 definition, 576 night vs.  day, 579 palliative management, 580 physiology, 576– 577 position, 579– 580 qualities, 577

E EAPs, see  Employee Assistance Programs (EAPs) EAR, see  Estimated average requirement (EAR) EARS, see  Elaborate Affirmations Reflect Summarize (EARS) EBM, see  Evidence-based medicine (EBM) EBV, see  Epstein Barr virus (EBV) EC, see  Emergency contraception (EC); Experience Corps (EC) Ecological Momentary Assessment (EMA), 258, 1106 ED, see  Endothelial dysfunction (ED) EDC, see  Endocrine disrupting chemicals (EDC); Endocrine disrupting compounds (EDC) Edington Risk Model, 1185 EEG, see  Electroencephalography (EEG) EF, see  Enhance Fitness (EF); Executive function (EF) Efferent-afferent/neuromechanical dissociation, 576 EFSA, see  European Food Safety Authority (EFSA) Egger, Gary, 961, 962 Eggs, 117 EIA, see  Exercise-induced asthma (EIA) EIB, see  Exercise-induced bronchoconstriction (EIB) Eicosapentaenoic acid (EPA), 57– 58, 815, 1144

Eighteenth Amendment to the United States Constitution, 1053 EILO, see  Exercise-induced laryngeal obstruction (EILO) EIM, see  Exercise Is Medicine®   (EIM) Elaborate Affirmations Reflect Summarize (EARS), 215 Electroencephalography (EEG), 1228, 1252 Electronic cigarettes, 645, 1064 Electronic Medical Record (EMR), 157, 312, 1222 Electronic nicotine delivery systems (ENDS), 645 Electronic Preventive Services Selector (ePSS), 978 Elicit-provide-elicit model, 212 Ellery, Jane, 1169 EMA, see  Ecological Momentary Assessment (EMA) Emergency contraception (EC), 693– 694 clinical considerations, 694 efficacy, 693– 694 options, 693 Emergency Evacuation Planning Guide for People with Disabilities, 1351 Emerging Risk Factor Collaboration, 12 Emler, 1004 Emotional health, 1003– 1013 assessment, 1006 depression and anxiety, 1012 effective screening, 1012 factors affecting, 1004– 1005 positivity and happiness, 1005 improving happiness, 1005– 1006 dealing anger, 1005– 1006 gratitude journal, 1005 journal thankfulness, 1005 leaving past, 1005 optimism, 1005 management, 1012– 1013 overview, 1003 and stress response, 1006 tools for managing, 1007– 1012 unhealthy lifestyles, 1006 well-being, 1004 adaptive mechanisms, 1004 Emotional response, 248– 249 overview, 248– 249 practical application, 249 Emotions, 1004 Employee Assistance Programs (EAPs), 1193 Employer’ s role, 1175– 1178 business practices, 1175– 1176 lifestyle power and lifestyle medicine, 1176– 1177 measuring success & ROI, 1178 on-site clinics and empowered patients, 1178 overview, 1175 provider training & accountability, 1178 stakeholders and right partners, 1177– 1178 EMR, see  Electronic Medical Record (EMR) ENCORE, see  Exercise and Nutritional Interventions for Cardiovascular Health (ENCORE)

Endocannabinoids, 1230, 1285– 1286 Endocrine disrupting chemicals (EDC), 864– 865 Endocrine disrupting compounds (EDC), 361, 522– 523 Endocrine disruptors, 522– 523 Endocrine Society, 890 Endometrial cancer, 723– 726 epidemiology/risk factors, 723– 724 intervention/prevention, 726 lifestyle, 725– 726 screening, 724– 725 Endometriosis, 720 Endothelial dysfunction (ED), 1132, 1143 ENDS, see  Electronic nicotine delivery systems (ENDS) Engorgement, 680 Enhance Fitness (EF), 150 ENhancing Recovery In Coronary Heart Disease (ENRICHD), 752, 754 Environmental Protection Agency (EPA), 639, 641 Environmental reevaluation, 222 Environmental tobacco smoke (ETS), 639 Environmental Working Group (EWG), 335 EPA, see  Eicosapentaenoic acid (EPA); Environmental Protection Agency (EPA) EP-C, see  Certified exercise physiologist (EP-C) EPIC, see  European Prospective Investigation into Cancer and Nutrition (EPIC) EPOCH, see  Exploring Perinatal Outcomes among Children (EPOCH) ePSS, see  Electronic Preventive Services Selector (ePSS) Epstein Barr virus (EBV), 565 Epworth Sleepiness Scale (ESS), 585 ERN, see  Error-related negativity (ERN) ERPs, see  Event-related potentials (ERPs) Error-related negativity (ERN), 1228 ERS, see  European Respiratory Society (ERS) ESC, see  European Society for Cardiology (ESC) ESS, see  Epworth Sleepiness Scale (ESS) ESSA, see  Exercise and Sports Science of Australia (ESSA) Esselstyn, C. B. Jr., 1021 Estimated average requirement (EAR), 85– 86 ET, see  Exercise training (ET) ETS, see  Environmental tobacco smoke (ETS) European Association for the Study of Diabetes, 387 European Food Safety Authority (EFSA), 136 European Joint Task Force, 21 European Prospective Investigation into Cancer and Nutrition (EPIC), 722 European Respiratory Society (ERS), 597 European Society for Cardiology (ESC), 772 Event-related potentials (ERPs), 1228, 1252 Evidence-based medicine (EBM), 965 Evocation, 209



1416  Index EVS, see  Exercise vital sign (EVS) EWG, see  Environmental Working Group (EWG) Executive function (EF), 246– 248, 1228 Exercise and Nutritional Interventions for Cardiovascular Health (ENCORE), 70 Exercise and Sports Science of Australia (ESSA), 159 Exercise-induced asthma (EIA), 602– 603 Exercise-induced bronchoconstriction (EIB), 602 Exercise-induced laryngeal obstruction (EILO), 584 “ E xercise is Medicine: A Historical Perspective,”  153 Exercise Is Medicine®   (EIM), 148, 149, 151, 154, 157, 264, 1158– 1159, 1161 Exercise Management for Persons with Chronic Disease and Disabilities,  560 Exercise physiologist, 148– 149 Exercise prescription, 147– 151 arthritis, 188 cancer, 187– 188 children and adolescents, 184– 185 diabetes mellitus, 186– 187 Diabetes Prevention Program (DPP), 150 disabilities, 188 Enhance Fitness (EF), 150 Exercise is Medicine®  (EIM), 151 exercise physiologist, 148– 149 flexibility training, 183– 184 health coach, 149– 150 National Park Rx Initiative, 150– 151 older adults, 185 OutdoorsRx, 150– 151 overview, 147– 148 personal trainer, 148 physical activity adherence, 184 recommendations, 178– 179 physical fitness parameters, 179 physical therapist, 149 pregnancy and postpartum, 185– 186 referral guides, 150 resistance training, 182– 183 frequency, 183 rate of progression, 183 repetitions and sets, 183 type, 182– 183 SilverSneakers, 150 training principles, 179– 182 cardiorespiratory endurance training, 180 duration, 181 frequency, 181– 182 intensity, 180– 181 progressive overload, 179 rate of progression, 182 reversibility, 180 specificity, 179 type, 180 volume, 182 warm-up and cool-down, 184 Exercise training (ET), 805– 806 Exercise vital sign (EVS), 264

Experience Corps (EC), 1151 Exploring Perinatal Outcomes among Children (EPOCH), 865

F Facebook, 258 Facts Up Front label, 95 FADS2 gene, 678 FAI, see  Functional aerobic impairment (FAI) Fair Labor Standards Act, 681 FAME, see  Fractional Flow Reserve vs.  Angiography for Multivessel Evaluation (FAME) Familial Combined Hyperlipidemia (FCHL), 891, 925– 926 Familial hypercholesterolemia (FH), 891 Familial hypertriglyceridemia (FHTG), 931– 932 Family-based approaches and CVD prevention, 842– 843 family characteristics and cardiovascular health, 842 shared family environment, 842– 843 Family-based behavioral treatment (FBT), 855– 856, 913 Family history, 11 Family therapy, 1114 Fasting diet, 448– 4 49 Fasting lipid panels (FLPs), 922– 923 Fasting-mimicking diet (FMD), 1030 Fat-free mass (FFM), 345 FBT, see  Family-based behavioral treatment (FBT) FCHL, see  Familial Combined Hyperlipidemia (FCHL) FDA, see  Food and Drug Administration (FDA) FDA-approved obesity drugs, 492– 498 benzphetamine, 493 diethylpropion, 493 liraglutide, 497– 498 lorcaserin, 494– 495 naltrexone ER-bupropion SR, 496– 497 orlistat, 494 phendimetrazine, 493– 494 phentermine, 492– 493 phentermine-topiramate ER, 495– 496 Federal Drug Administration (FDA), 754 Federation of State Physician Health Programs, 1075 Female athlete triad (Triad), 344– 345 FENO, see  Fraction of exhaled nitric oxide (FENO) Fetal heart rate (FHR), 667 FEV, see  Forced expiratory volume (FEV) FFM, see  Fat-free mass (FFM) FFQ, see  Food frequency questionnaire (FFQ) FH, see  Familial hypercholesterolemia (FH) FHR, see  Fetal heart rate (FHR) FHTG, see  Familial hypertriglyceridemia (FHTG) Fiber, 127 Finnish Diabetes Prevention Study, 362 Fish, 116 Fishbein, M., 198 Fish oil, 815– 816

Fitness Registry and the Importance of Exercise National Database (FRIEND), 166 Fleming, M. F., 1073 Flexibility, 876– 877 FLPs, see  Fasting lipid panels (FLPs) FMD, see  Fasting-mimicking diet (FMD) FNDDS, see  Food and Nutrient Database for Dietary Studies (FNDDS) Folate, 337 Folic acid, 812 Follicle-Stimulating Hormone (FSH), 707 Food, Drug and Cosmetic Act (1938), 92 Food and Drug Act (1906), 1053, 1054 Food and Drug Administration (FDA), 24, 92, 94, 95, 116, 311, 318, 319, 492, 494, 532, 645, 812, 1054, 1058, 1087, 1377, 1378 Food and Nutrient Database for Dietary Studies (FNDDS), 82 Food and Nutrition Board, 95, 113, 125 Food and supplement databases, 82 Food frequency questionnaire (FFQ), 81, 83 Food groups vs.  nutrients, 89 Food labels, 92– 95 Facts Up Front, 95 health claims, 94 Heart Check, 95 label claims, 94 nutrient claims, 94 Nutrition Facts label, 93– 94 Smart Choices program, 95 structure/function claims, 94 supermarket scoring systems and icons, 95 voluntary and Front of Package (FOP) labeling, 94– 95 Food Marketing Institute, 95 Food4Me study, 96 Food Safety and Information Service (FSIS), 95 FOP, see  Front of Package (FOP) labeling Forced expiratory volume (FEV), 575, 592, 612 Forced vital capacity (FVC), 574– 575, 592, 612 Fractional Flow Reserve vs.  Angiography for Multivessel Evaluation (FAME), 738 Fraction of exhaled nitric oxide (FENO), 593 Framingham Heart Study, 5, 6, 7, 11, 21, 26, 56 Framingham Risk Assessment, 984 Framingham Risk Scoring System, 5, 14 Frank, Erica, 1036, 1042 Frankl, Victor, 230, 231 Fredrickson, Barbara, 291 Freestanding devices, 317 Frieden, Thomas, 529 Friedmann, Peter, 1078 FRIEND, see  Fitness Registry and the Importance of Exercise National Database (FRIEND) Front of Package (FOP) labeling, 93, 94– 95 Fructose, 357– 358 Fruits and vegetables, 116

Index  1417 FSH, see  Follicle-Stimulating Hormone (FSH) FSIS, see  Food Safety and Information Service (FSIS) Functional aerobic impairment (FAI), 559 Functional contextualism, 853 Functional medicine, 966 FVC, see  Forced vital capacity (FVC)

G GABA A  receptors, 1072 GAD, see  Generalized Anxiety Disorder (GAD) Gallup-Healthways, 1207 Gallwey, Tim, 301 Garlic, 117– 118 Gastro-esophageal reflux disease (GERD), 581– 582, 605 GBD, see  Global burden of disease (GBD) GDL, see  Graduated driver licensing (GDL) systems GDM, see  Gestational diabetes mellitus (GDM) GEI, see  Group Exercise Instructors (GEI) Gender and CVD risk, 11 Generalized Anxiety Disorder (GAD), 983, 1012 Generalized resistance deficits (GRDs), 1204 Generalized resistance resources (GRRs), 1204 Genital warts, see Condyloma acuminata  Genome-wide association (GWA), 1247 Genomic approaches, 13– 14 Geographic information system (GIS), 1202 GERD, see  Gastro-esophageal reflux disease (GERD) German Cancer Research Center, 645 Gestational diabetes mellitus (GDM), 384, 389– 391, 664– 665 education/counseling and support, 391 medical nutrition therapy (MNT), 390– 391 physical activity, 391 psychosocial care, 391 GH, see  Growth hormone (GH) GINA 2018, see  Global Initiative for Asthma guidelines in 2018 (GINA 2018) Girls on the Run (GOTR), 342– 343 GIS, see  Geographic information system (GIS) GLAGOV, see  Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV) Glanz, Karen, 193– 194 Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV), 767 Global burden of disease (GBD), 1295 Global Initiative for Asthma guidelines in 2018 (GINA 2018), 595, 597 Global Initiative for Obstructive Lung Disease (GOLD), 574, 613

Global Observatory for Physical Activity (GoPA), 154 Global Positioning Systems (GPS), 1105, 1106 Glucocorticoids, 1258– 1259 Glucose intolerance, 8, 29– 30 and type 2 diabetes, 130 monitoring, 317 GLUT-4 glucose transporters, 370 Glycemic control, 42 GOLD, see  Global Initiative for Obstructive Lung Disease (GOLD) Gonorrhea, 701 Google Fit, 316 GoPA, see  Global Observatory for Physical Activity (GoPA) Gordon, J. R., 782 GOTR, see  Girls on the Run (GOTR) GPS, see  Global Positioning Systems (GPS) GRADE, see  Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework Graded Activity Program, 826 Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, 1315, 1321, 1324 Graduated driver licensing (GDL) systems, 1309 Grant, Anthony, 301 Gratitude, 290– 291 GRDs, see  Generalized resistance deficits (GRDs) “ Green Prescription”  program, 158 Greenville Health System, 151, 157 Grocery Manufacturers Association, 95 Gross National Happiness Index, 1207 Group Exercise Instructors (GEI), 148 Growth hormone (GH), 1130– 1131 GRRs, see  Generalized resistance resources (GRRs) Guidelines Advisory Committee, 178 Guidelines for Nutrition and Physical Activity for Cancer Prevention, 434 Guidelines for Pediatric and Adult Nutrition, 10 Guidelines for Physical Activity 2008, 32 Gut microbiota, 565 GWA, see  Genome-wide association (GWA)

H Habitual physical activity vs.  systematic training, 874– 875 HACE, see  High-altitude cerebral edema (HACE) Halberg, Franz, 401 HAPA, see  Health action process approach (HAPA) HAPE, see  High altitude pulmonary edema (HAPE) HAPO, see  Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Harris, Nadine Burke, 1202, 1203 Harrison Narcotics Tax Act (1914), 1053 Harvard Alumni Health Study, 39

Harvard Nurses’  Health Study, 717 Harvard School of Public Health, 231, 1075, 1191 HBM, see  Health Belief Model (HBM) HBV, see  Hepatitis B Virus (HBV) HCA, see  Heterocyclic amines (HCA) HCPs, see  Healthcare providers (HCPs) HCUP, see  Healthcare Cost and Utilization Project (HCUP) HDL, see  High-density lipoprotein (HDL) Health action process approach (HAPA), 244, 245 Health and lifestyle, 1191– 1196 approach to prevention and control strategies, 1195 country-specific programs, 1195 mental health, 1193 obesity, 1194 overview, 1191– 1192 physical activity, 1194– 1195 primary care capacity, 1192 risk assessment, 1192– 1193 factors measured globally, 1193 technology, 1195– 1196 tobacco, 1193– 1194, 1197 United States vs.  developed countries, 1195 WHO voluntary global noncommunicable disease targets: 2020, 1192 Health and Well-being Assessment (HWA), 1184 Health and wellness coaching (HWC), 299– 309 assimilation of coaches, 308 client and patient populations and care settings, 304– 305 client/patient privacy, 308 evaluation and research, 306– 307 as field and profession, 300– 304 vs.  health education and case management, 302 standardizing, 302– 303 theoretical platform and historical underpinnings, 300– 301 vs.  therapy, 301– 302 training and education, 303– 304 future of health care, 308 hiring coaches, 307– 308 overview, 299– 300 payment models, 305– 306 physician referrals, 307 professional coaches, 307 visit structures and delivery methods, 305 Health Behavior and Health Education: Theory, Research, and Practice,  194 Health Belief Model (HBM), 194, 198, 203 Healthcare Cost and Utilization Project (HCUP), 1187 Healthcare Effectiveness Data and Information Set (HEDIS), 1178, 1362 “ Healthcare Providers’  Action Guide,”  155, 158 Healthcare providers (HCPs), 492, 498



1418  Index Healthcare Quality, 914 Healthcare reform, 1357– 1362 Health Care Reform Act, 20 Health coaching, 783 “ Health-enhancing”  PA, 433– 435 guidelines adherence, 435 guidelines for cancer populations, 434– 435 guidelines for healthy populations, 434 Health Impact in 5 Years (HI-5) initiative, 1203 Health Information Technology for Economic and Clinical Health (HITECH) Act, 1361 Health information technology (HIT), 1361 HealthKit, 316 Health Professional Follow-up Study, 13 Health promotion, 1169– 1170 history, 1171– 1174 accelerating health improvement, 1174 emerging trends and technologies, 1172– 1174 integrated models of population health, 1171– 1172 overview, 1171 ROI and VOI, 1172 from wellness to well-being, health and productivity, 1172 and role of physician, 1219– 1223 behavior change, 1221 definitions, 1220– 1221 future, 1221 overview, 1219 positive individual health, 1221 settings approach, 1219– 1220 sustainable change, 1222 tools, 1222 total health, 1220 Health Risk Appraisal (HRA), 1192– 1193 Health Risk Factors Exercise Training and Genetics (HERITAGE), 43, 68 Health Risk Intervention (HRI), 224 Healthy eating, 1375– 1381, 1383 access to nutritious foods, 1376 acceptability and accommodation, 1376 accessibility, 1376 affordability, 1376 availability, 1376 behaviors, 1376– 1377 disparities/inequities, 1376– 1377 challenges, 1388– 1389 advocacy, 1388 lead community change, 1389 neighborhood environments, 1388– 1389 supporting partnerships, 1389 Charleston, West Virginia, 1385– 1386 Cuba, New Mexico, 1386– 1388 Chicago, Illinois, 1387 group process, 1388 physicians in strategic alliances, 1387 Portland, Oregon, 1386– 1387 environmental factors, 1377 full-service grocery stores, 1377 overview, 1375 partnerships in action, 1385

policies, 1377– 1380 behavioral economics, 1378– 1379 food labels, 1377– 1378 food vending, 1379 full-service grocery stores, 1377 MyPlate, 1380 recommendations, 1379– 1380 restaurant menus, 1378 strategic alliances, 1384– 1385 Healthy Eating Index (HEI), 89, 90, 92, 105 Healthy-eating patterns, 104, 105– 106 Healthy Food Financing Initiative (HFFI), 1377 Healthy Kids, Healthy Communities grant, 1386 Healthy People 2010, 9– 10, 1392, 1396 Healthy People 2020, 9– 10, 24, 184, 673 Healthy People: The Surgeon General’ s Report on Health Promotion and Disease Prevention,  154 Healthy places, 1201– 1208 co-producing change, 1205– 1208 organizations and individuals, 1202– 1203 overview, 1201– 1202 theoretical framework, 1203– 1205 Healthy Study Group, 874 Healthy US-Style Eating Pattern, 104, 105– 106, 112, 113 Healthy Vegetarian Eating Pattern, 104 Heart-Check Food Certification Nutrition Requirements, 95 Heart Check program, 95 Heart disease and obesity, 1394 Heart failure (HF), 41 Heart rate recovery (HRR), 565 Heart rate variability (HRV), 565 HEDIS, see  Healthcare Effectiveness Data and Information Set (HEDIS) HeFH, see  Heterozygous familial hypercholesterolemia (HeFH) HEI, see  Healthy eating index (HEI) Helping relationships, 223 Hemoptysis, 583– 584 definition and physiology, 583 etiology, 583– 584 Hemostatic factors, 12 Henry Ford Exercise Testing Project, 774 Hepatitis A virus, 698, 702 Hepatitis B virus (HBV), 698, 702 Hepatitis C virus, 702– 703 Herbal remedies, 1080 HERITAGE, see  Health Risk Factors Exercise Training and Genetics (HERITAGE) Herpes simplex virus (HSV), 703– 704 Heterocyclic amines (HCA), 413, 718 Heterozygous familial hypercholesterolemia (HeFH), 924– 925 HF, see  Heart failure (HF) HFFI, see  Healthy Food Financing Initiative (HFFI) HGH, see  Human Growth Hormone (HGH) HHS, see  Department of Health and Human Services (HHS) HI-5, see  Health Impact in 5 Years (HI-5) initiative

High-altitude cerebral edema (HACE), 617 High-altitude illnesses (HAI), 616– 617 High altitude pulmonary edema (HAPE), 617 acetazolamide, 617 controlled ascent, 617 High-density lipoprotein (HDL), 7, 54, 812 High intensity training (HIT), in cardiac rehabilitation, 787– 797 atrial fibrillation, 794– 795 cardioprotective medications prior to strenuous exercise, 796 cardiorespiratory fitness in secondary prevention, 789 exercise-related cardiovascular events, 789 extreme exercise and immunity, 792– 794 Bassler hypothesis, 793 high-volume and high-intensity endurance training, 793 marathon running and triathlon participation, 793– 794 moderate, continuous vs.,  792 overview, 787– 789 preparticipation screening and participation, 794 prophylactic strategies, 790– 791 reverse J-shaped association, 791 High sensitivity C-reactive protein (Hs-CRP), 12 HIT, see  Health information technology (HIT); High intensity training (HIT) HITECH, see  Health Information Technology for Economic and Clinical Health (HITECH) Act HMG-CoA, see  Hydroxymethylglutarylcoenzyme A (HMG-CoA) H1N1, 633 Holmes, T. H., 1006 HOMA-IR, see  Homeostasis model assessment-estimated insulin resistance (HOMA-IR) Homeostasis model assessmentestimated insulin resistance (HOMA-IR), 373 Home showerheads and dishwashers, 645– 646 Homocysteine, 12 Homocysteine Trialists Collaboration, 812 Hookah, see  Water pipe smoking Hormone replacement therapy (HRT), 348, 716, 720 Hospital Anxiety and Depression Scale, 1012 HPA, see  Hypothalamus-Pituitary-Adreno Axes (HPA) HPV, see  Human papillomavirus (HPV) HRA, see  Health Risk Appraisal (HRA) HRI, see  Health Risk Intervention (HRI) HRR, see  Heart rate recovery (HRR) HRT, see  Hormone replacement therapy (HRT) HRV, see  Heart rate variability (HRV) Hs-CRP, see  High sensitivity C-reactive protein (Hs-CRP) HSV, see  Herpes simplex virus (HSV)

Index  1419 HTN, see  Hypertension (HTN) Human Development Index, 1207 Human Growth Hormone (HGH), 1133 Human immunodeficiency virus (HIV), 555– 561, 703 blood lipids, 559 body composition, 559 cardiorespiratory fitness, 559 epidemic, 556 and exercise as medicine, 558– 559 psychological improvements, 560 recommendations, 560 immune system, 559 overview, 555 symptomatology, 556– 558 antiretroviral therapy, 557 physical consequences, 557 psychological consequences, 556– 557 toxic side effects, 557– 558 treatment, 558 virology and infection, 556 asymptomatic, 556 primary, 556 symptomatic, 556 Human Milk Banking Association of North America, 682 Human papillomavirus (HPV), 698, 704, 726– 727 Humoral immunity and PA, 566– 567 cross-sectional studies, 566– 567 prospective training studies, 567 Humphreys, Keith, 1079 Huss, Magnus, 1052 HWA, see  Health and Well-being Assessment (HWA) HWC, see  Health and wellness coaching (HWC) Hydrodensiometry/underwater weighing, 171– 173 Hydrodensitometry, 456 Hydroxymethylglutaryl-coenzyme A (HMG-CoA), 7, 929– 930 Hypercholesterolemia and hyperlipidemia, 7 therapy for pure, 926– 931 adjunctive dietary therapies, 926 bile acid sequestrants, 930 CHILD-1, 926 CHILD-2-LDL, 926 cholesterol absorption inhibitors, 930– 931 clinical case 1 follow-up, 931 dietary and lifestyle intervention, 926 goals, 928 hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, 929– 930 pharmacological intervention, 926 statin medication, 926– 928 Hyperglycemia and Adverse Pregnancy Outcomes (HAPO), 867 Hypersensitivity pneumonitis, 618 clinical presentation and diagnosis, 618 epidemiology, 618 treatment and prevention, 618 Hypertension (HTN), 7– 8, 26– 28, 40– 41, 130, 894– 896 in children and adolescents, 937– 948

ambulatory blood pressure monitoring (ABPM), 940 associated comorbidities, 941 attention deficit hyperactivity disorder (ADHD) and cognition, 942 chronic kidney disease (CKD), 941 coarctation and congenital abnormalities, 942 diabetes mellitus (DM), 941 diagnosis, 938– 940 emergency and urgency, 941 endocrine-related causes, 942 essential, 942 masked hypertension (MH), 941 medications and environment, 942 monogenic hypertensionogenic, 942 neonates and infants, 940 obstructive sleep apnea (OSA), 941 overview, 937– 938 prevalence, 938 sleep disordered breathing (SDB), 941 target-organ damage (TOD) and, 942– 943 treatment of systemic, 943– 948 white coat hypertension (WCH), 940– 941 definitions, 894 dietary patterns, 895 lifestyle management, 26– 28 prevention, 65– 71 dietary modifications, 68– 69 etiology and relationship to CVD, 66– 67 measurement, 66 overview, 65– 66 pharmacological management of hypertension, 71 physical activity and exercise, 67– 68 weight management, 69– 70 resistance exercise training and blood pressure, 41 sodium, 895– 896 weight management and, 894– 895 Hypertensive retinopathy, 943 Hypertriglyceridemia, 7, 932– 933 clinical case 2 follow-up, 933 dietary goals, 932 fibric acid derivatives, 933 goals, 933 long-chain omega-3 fatty acids, 933 pharmacologic, 932– 933 Hypothalamus-Pituitary-Adreno Axes (HPA), 282, 1232, 1285 Hypovitaminosis D, 1136

I IACR, see  International Agency for Cancer Research (IACR) IASO, see  International Association for the Study of Obesity (IASO) IBCLCs, see  International Board Certified Lactation Consultants (IBCLCs) IBG, see  Intention-behavior gap (IBG) IBIS, see  International Breast Cancer Intervention Study (IBIS) IBM, see  Integrated Behavior Model (IBM)

ICD, see  International Classification of Disease (ICD) ICF, see  International Coach Federation (ICF) ICHWC, see  International Consortium for Health and Wellness Coaching (ICHWC) ICR, see  Intensive Cardiac Rehabilitation (ICR) IDC, see  Individual drug counseling (IDC) IDL, see  Intermediate-density lipoprotein (IDL) IDPP, see  Indian Diabetes Prevention Program (IDPP) IDSA, see  Infectious Diseases Society of America (IDSA) IEN, see  Immune-enhancing nutrition (IEN) IER, see  Intermittent energy restriction (IER) IF, see  Intermittent fasting (IF) IFG, see  Impaired fasting glucose (IFG) IGF-1, see  Insulin-like growth factor-1 (IGF-1) Ignition interlocks, 1307 IGT, see  Impaired glucose tolerance (IGT) IHD, see  Ischemic heart disease (IHD) IIA, see  Irritant-Induced Asthma (IIA) Illness-Wellness continuum, 301 ILMP, see  Intensive lifestyle modification program (ILMP) ILSI NA, see  International Life Sciences Institute of North America (ILSI NA) Immune-enhancing nutrition (IEN), 444 Immune function, 130 Impaired fasting glucose (IFG), 367, 368, 371, 372– 373 Impaired glucose tolerance (IGT), 367, 368, 371, 372– 373 Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), 768 Inactive lifestyle, 9– 10 Indian Diabetes Prevention Program (IDPP), 372, 374 Indirect costs, 464– 466 disability and premature mortality, 465– 466 presenteeism and absenteeism, 464– 465 Individual drug counseling (IDC), 1115 Indoor air quality, 639– 646 animal dander, 643 carbon monoxide, 641– 642 cockroaches, 644 dust mites, 643 electronic cigarettes, 645 home showerheads, dishwashers, and CPAP devices, 645– 646 indoor mold, 642– 643 mice, 644 overview, 639 radon, 641 secondhand smoke exposure in children, 641 overview, 639– 614 smart devices technology, 646 water pipe smoking, 644– 645



1420  Index Indoor allergens, 594 Indoor mold, 642– 643 Infancy, 867 Infant benefits of breast-feeding, 676– 678 atopic disease and asthma, 677 diabetes, 677 gastrointestinal effects, 676– 677 infectious processes, 677 leukemia, 677 neurodevelopment, 677– 678 obesity, 677 Infectious Diseases Society of America (IDSA), 557 Inflammaging and PA, 563– 564 Inflammatory markers, 479 Influenza, 631– 637 antiviral therapy, 636– 637 clinical illness, 633– 634 avian, 634 seasonal, 633– 634 definition, 631 economic impact, 633 epidemiology, 632– 633 genetic variation, 632 history, 631 laboratory diagnosis, 634– 635 overview, 631 pathophysiology, 633 prevention, 635– 636 chemoprophylaxis, 635– 636 vaccination, 635 virology, 631– 632 Injuries, 1293– 1300 and accident, 1296– 1297 axioms in prevention, 1297– 1298 burden, 1294– 1295 community impact, 1295 costs, 1294 global impact, 1295 causes, 1297 control, 1297 and disabled persons, 1349– 1353 burdens and barriers, 1352 call to action, 1352– 1353 invisibility of people, 1350– 1351 overview, 1349 public safety, 1351– 1352 risk, 1350 youth with disabilities, 1350 disproportionate impact, 1296 lifestyle medicine practitioners, 1298 overview, 1293– 1294 as public health problem, 1294 trends and variations, 1295– 1296 Inner Game approach, 301 Institute for Credentialing Excellence, 148 Institute of Lifestyle Medicine, 971 Institute of Medicine (IOM), 113, 125, 401, 663, 938, 1113, 1195 Insulin and blood glucose monitoring, 385 Insulin-like growth factor-1 (IGF-1), 420, 432, 1130– 1131, 1133, 1145 Integrated Behavior Model (IBM), 198– 200 Integrated Cardiovascular Risk Reduction Guidelines, 926 Integrative medicine, 965 Intel-GE Validation Institute, 1187

Intensive cardiac rehabilitation (ICR), 825, 825– 831, 826 considerations, 829– 830 efficacy and preliminary outcomes, 827– 829 blood lipid profile, 827– 828 functional capacity and physical activity, 828 heart disease and cardiovascular risk, 829 psychosocial function and quality of life, 828– 829 systolic and diastolic blood pressure, 827 weight management, 828 evolution, 826– 827 overview, 825 Intensive lifestyle modification program (ILMP), 827– 829 Intensive therapeutic lifestyle change (ITLC), 32, 1019– 1032 Intention– behavior gap (IBG), 241– 250 action and coping planning, 244– 245 overview, 244– 245 practical application, 245 capacity, 246– 248 overview, 246– 247 practical application, 247– 248 definition, 242 emotional response, 248– 249 overview, 248– 249 practical application, 249 intention definition, 243 in practice, 243 response, 243– 244 stability, 243 overview, 241– 242 self-efficacy, 245– 246 overview, 245– 246 practical application, 246 Interdepartmental Task Force on Childhood Obesity, 1387 INTERHEART case-control study, 771, 775– 776 Intermediate-density lipoprotein (IDL), 55 Intermittent energy restriction (IER), 448 Intermittent fasting (IF), 448 Intermountain Healthcare System, 157 International Agency for Cancer Research (IACR), 334, 413, 414, 420, 640, 717, 718, 1394– 1395 International Association for the Study of Obesity (IASO), 43, 44 International Board Certified Lactation Consultants (IBCLCs), 681 International Breast Cancer Intervention Study (IBIS), 332 International Classification of Disease (ICD), 45, 1271 International Coach Federation (ICF), 301 International Consortium for Health and Wellness Coaching (ICHWC), 149, 303, 304, 307 International Food Information Council Foundation, 1380 International Journal of Clinical Practice,  962

International Ketogenic Diet Study Group, 449 International Lactation Consultant Association, 681 International Life Sciences Institute of North America (ILSI NA), 82 International Obesity Task Force (IOTF), 457 International Opium Convention, 1053 Internet and American Life Project, 315 Intrauterine contraception (IUDs), 692– 693, 698, 726 clinical considerations, 693 options and mechanisms of action, 692– 693 An Introduction to Lifestyle Medicine,  961 IOM, see  Institute of Medicine (IOM) Ionamin, see  Phentermine IOTF, see  International Obesity Task Force (IOTF) Iowa Women’ s Health Study, 726 Irritant-Induced Asthma (IIA), 611 Ischemic heart disease (IHD), 40 ITLC, see  Intensive therapeutic lifestyle change (ITLC) IUDs, see  Intrauterine contraception (IUDs)

J Jackson, Richard, 1202 Jacobs, Jane, 1202 JAMA Oncology,  717 Japanese diet, 114 Jarisch-Herxheimer reaction, 702 Jeffrey, Jamie, 1385 JNC, see  Joint National Committee on Prevention, Evaluation and Treatment of High Blood Pressure (JNC) JOEM, see Journal of Occupational and Environmental Medicine  (JOEM) Johns Hopkins Global mHealth Initiative, 315 Johnson, Mark, 962, 970 Joint National Committee on Prevention, Evaluation and Treatment of High Blood Pressure (JNC), 7– 8, 21, 26– 27, 40, 119 Jones, Jannah, 531 Journal of Addiction,  1052 Journal of Occupational and Environmental Medicine  (JOEM), 1185 Journal of the American Dietetic Association,  194 Journal of the American Medical Association, 970, 1020

K Kaiser Permanente, 157, 1196, 1202 Kanawha Coalition for Community Health Improvement, 1385 Katz, David, 962, 963, 975, 1211 Ketogenic diet, 449 KEYS 4 Healthy Kids (K4HK), 1385 K4HK, see  KEYS 4 Healthy Kids (K4HK) Koob, George F., 1071 Koop, Everett, 1182

Index  1421 Koplan, Jeffrey, 763 Korsakoff, Sergei, 1052 Kozoll, Richard, 1386

L LABA, see  Long-acting beta-2 agonist (LABA) LABS, see  Longitudinal Assessment of Bariatric Surgery (LABS) LADA, see  Latent Autoimmune Diabetes of Adults (LADA) LAGB, see  Laparoscopic Adjustable Gastric Banding (LAGB) La Leche League, International (LLLI), 681 Lancet,  1020 Laparoscopic Adjustable Gastric Banding (LAGB), 506 Laparoscopic sleeve gastrectomy (LSG), 506 LAP-BANDTM , 506 LARC, see  Long-acting reversible contraception (LARC) Large neutral amino acids (LNAA), 1011 L-arginine, 816 Latent Autoimmune Diabetes of Adults (LADA), 384 LBM, see  Lean body mass (LBM) L-carnitine, 816 LCAT, see  Cholesterol acyltransferase (LCAT) LDL, see  Low-density lipoprotein (LDL) Lean body mass (LBM), 172– 173 Left ventricular hypertrophy (LVH), 942– 943 Legatum Institute, 1207 Leisure-time physical activity (LTPA), 1238 Leonard, Thomas, 301 Lesbians, gay, bisexual, and transgender (LGBT), 699– 700 “ L et’ s Move”  campaign, 1396 Leukocyte number and function, 547 Leukotriene receptor blockers and synthesis inhibitors, 595 LGBT, see  Lesbians, gay, bisexual, and transgender (LGBT) LGIT, see  Low Glycemic Index Treatment (LGIT) LHT, see  Lifestyle Heart Trial (LHT) Lianov, Liana, 970, 971 Life course approach and chronic disease, 861– 867 childhood and adolescence, 867 early exposures, 865– 866 postnatal nutrition, 865 shared environment, 865– 866 endocrine disrupting chemicals (EDCS), 864– 865 infancy, 867 overnutrition, 863– 864 overview, 861– 862 physical activity, 864 pre-conception, 866 pregnancy, 866– 867 smoking, 864 undernutrition, 862– 863 Lifestyle Heart Trial (LHT), 1020 Lifestyle medicine, 961– 967; see also individual entries 

categories, 965– 966 compare and contrast, 966 constructs, 964 defining, 961– 962 dimensions, 962– 964 health provider core competencies in, 969– 976 certification, 971, 973– 974 evolution, 974– 975 national consensus panel, 970 overview, 969 refining, 970 training, 970– 971 overview, 961 role within allopathic medicine, 966– 967 Lifestyle medicine clinical processes, 977– 992 anthropometric measurement and body composition, 985 blood pressure, 985 cardiorespiratory fitness testing, 985– 986 chronic care model, 987– 990 components, 988– 989 sample effective programs, 989– 990 community and digital connection, 990 diabetes risk assessment, 984– 985 history, 978 USPSTF preventive services, 978 information systems, 990 laboratory testing, 987 mental health, 983– 984 depression screening, 983 and emotional wellbeing, 983– 984 generalized anxiety disorder, 983 metabolic syndrome assessment, 984 muscular fitness testing, 986– 987 nutrition assessment, 981, 983 overview, 977– 978 overweight and obesity identification, 985 physical activity assessment, 978, 981 prediabetes evaluation, 987 quality improvement, 990– 992 plan– do– study– act, 991– 992 process mapping, 990– 991 root cause analysis, 992 risk factor assessment tools, 984 rockport fitness walking test, 986 shared medical appointments, 990 six-minute walk test, 986 step tests, 986 submaximal talk test, 986 team-based approach, 987 Lifestyle Medicine Education Collaborative (LMEd), 156 The Lifestyle Medicine Standards,  962 Lifestyle Medicine Standards Task Force, 970 Lifestyle Modification Program Demonstration (LMPD), 1021 Lifestyle-related dyslipidemia, 931 clinical case 2, 931 combined dyslipidemia of obesity (CDO), 931 Linder vs. the United States,  1053 Lipid, 44– 45, 479

classification and treatment targets, 55– 57 management in secondary prevention, 767– 770 dietary therapy, 767– 768 overview, 767 PCSK9 inhibitors, 769– 770 statin-associated muscle complaints, 768– 769 statin treatment, 768 treatment goals, 767 metabolism, 358 Lipid Research Clinics Study, 478 Lipoprotein (a), 12 Lipoprotein lipase (LPL), 54, 882 Lipton, Bruce, 333 Liraglutide, 497– 498 LIVESTRONG, 149 LLLI, see  La Leche League, International (LLLI) LMed, 971 LMEd, see  Lifestyle Medicine Education Collaborative (LMEd) LMPD, see  Lifestyle Modification Program Demonstration (LMPD) LNAA, see  Large neutral amino acids (LNAA) Loeppke, Ron, 1169 Lomaira, see  Phentermine Long-acting beta-2 agonist (LABA), 596 Long-acting muscarinic antagonists, 596 Long-acting reversible contraception (LARC), 688, 692– 693 intrauterine contraception (IUDs), 692– 693 clinical considerations, 693 options and mechanisms of action, 692– 693 Nexplanon implant, 692 clinical considerations, 692 efficacy, 692 mechanism of action, 692 postpartum, 694 Long-chain omega-3 fatty acids, 933 Longitudinal Assessment of Bariatric Surgery (LABS), 511, 511, 513 Longjohn, Matt, 1387 Look AHEAD Trial, 30, 478, 855, 1028 Loomis, Evarts, 301 Lorcaserin, 494– 495s Loucks, Anne, 344 Loving Kindness Meditation, 289 Low-carbohydrate diets, 113 Low-density lipoprotein (LDL), 7, 12, 53– 54, 767, 812, 890, 926– 927 Lower-fat diets, 113 Low Glycemic Index Treatment (LGIT), 449 LPL, see  Lipoprotein lipase (LPL) LSG, see  Laparoscopic sleeve gastrectomy (LSG) LTPA, see  Leisure-time physical activity (LTPA) Lumsden, D. P., 1006 Lung volume testing, 575 LVH, see  Left ventricular hypertrophy (LVH) Lynch/HNPCC syndrome, 722– 726 Lyon Diet Heart Study, 1022



1422  Index M MacArthur Foundation, 1152 Machine learning (ML), 321 Magnetic-resonance imaging (MRI), 1228– 1229, 1253 Maintenance, 220– 221 Major Depressive Disorder (MDD), 1228, 1231, 1281, 1282– 1286 Making Health Communication Programs Work, 315 Malignant pleural mesothelioma (MPM), 614 Malmö  Diet and Cancer Study (MDCS), 13 Malnutrition, 80 Malnutrition Screening Tool (MST), 443 Malnutrition Universal Screening Tool (MUST), 443 Man’ s Search for Meaning,  230 MAO, see  Metabolically abnormal obesity (MAO) Marlatt, G. A., 782 MARS, see  Mobile App Rating Scale (MARS) MAs, see  Medical assistants (MAs) Masked hypertension (MH), 941 Maslow, Abraham, 230 Massachusetts General Hospital, 150, 275 Mastitis, 680 Maternal benefits of breast-feeding, 675– 676 Maternal cytomegalovirus (CMV), 680 MBMI, see  Benson-Henry Mind Body Medical Institute (MBMI) MBTs, see  Mind-body therapies (MBTs) MCAT, see  Medical College Admission Test (MCAT) MCI, see  Mild cognitive impairment (MCI) MD Anderson Cancer Center, 723 MDCS, see  Malmö  Diet and Cancer Study (MDCS) MDD, see  Major Depressive Disorder (MDD) MDI, see  Multiple daily subcutaneous injections (MDI) MDP, see  Multidimensional dyspnea profile (MDP) Meat, 116 Mechanistic target of rapamycin complex 1 (mTORC1), 400 MedEdPORTAL, 156 Medical assistants (MAs), 157 Medical College Admission Test (MCAT), 193 Medical Expenditure Panel Survey, 1351 Medical marijuana laws (MMLs), 1098, 1099 Medical nutrition therapy (MNT), 383– 384, 385, 387– 388, 390– 391, 443, 487 Medicare, 159, 1183 Medication-induced asthma, 604– 605 Medications and lactation, 681 Meditation, 286– 289 Body Scan, 286, 288 breath awareness, 286 contemplation and prayer, 289 guided imagery, 288

Loving Kindness, 289 Mediterranean diets, 113– 114, 361– 362, 519, 1144 Mediterranean-Style Eating Pattern, 104 MEND, see  Mind, exercise, nutrition… do it! (MEND) Menstrual disorders, 707– 712 lifestyle-related, 707 and menopause management, 709– 712 overview, 708– 709 overview, 707 treatment, 708 Mental health, 983– 984 depression screening, 983 and emotional wellbeing, 983– 984 generalized anxiety disorder, 983 Mental Health Parity and Addiction Equity Act (MHPAEA), 1054 Mentally ill smokers, 1063 Menu Labeling Rule, 1378 Mepolizumab, 597 MET, see  Metabolic equivalent of task (MET); Motivational enhancement therapy (MET) Metabolically abnormal obesity (MAO), 802 Metabolically healthy obesity (MHO), 802, 802– 803 Metabolic components of dysglycemia, 356– 361 advanced glycated end products, 360 antioxidants, 358– 359 artificial sweeteners, 361 carbohydrate metabolism, 356– 357 endocrine disruptors, 361 fructose, 357– 358 lipid metabolism, 358 omega-3 fatty acids, 358 plant polyphenols, 359– 360 starch, fiber and sugar, 357 systemic inflammation, 360– 361 Metabolic dietary therapies, 448 Metabolic equivalent of task (MET), 165, 166, 169, 181, 789, 1238 Metabolic syndrome (MetS), 356, 802, 879 cardiorespiratory fitness and, 47 definitions, 45 muscular strength and, 47 and obesity, 1395 prevalence, 45 and T2DM, 41– 42 Metabolic therapy vs.  dietary approaches, 447, 448 Methadone maintenance treatment (MMT), 1086– 1087 advantages, 1086 disadvantages, 1086– 1087 Methylenetetrahydrolate reductase (MTHFR), 411 MetS, see  Metabolic syndrome (MetS) MH, see  Masked hypertension (MH) MHO, see  Metabolically healthy obesity (MHO) MHPAEA, see  Mental Health Parity and Addiction Equity Act (MHPAEA) MI, see  Motivational interviewing (MI)

Mice, 644 MICT, see  Moderate-intensity continuous exercise training (MICT) Mifflin-St. Jeor Equation (MSJE), 484 Mild cognitive impairment (MCI), 1142, 1254 Mild traumatic brain injury (MTBI) in children, 1319– 1325 clinical presentation, 1320 dissemination and implementation, 1324 educational tools, 1324 outreach efforts, 1324 improving care, 1321, 1324 management, 1321 neurological function, 1320– 1321 overview, 1319– 1320 Miller, W. R., 193, 210, 213 Miller, William, 301, 782 Million Women Study, 728 Mind, exercise, nutrition… do it! (MEND), 913– 914 Mind/body interactions in exercise, 1227– 1234 impact of stress, 1231– 1234 overview, 1227 thinking and feeling mind, 1227– 1231 Mind body medicine, 965 Mind-body therapies (MBTs), 281, 284, 284– 293, 294 adaptive coping strategies, 291– 292 teaching patients to change mind, 291– 292 building positive perspective, 291 gratitude, 290– 291 practicing, 291 meditation, 286– 289 Body Scan, 286, 288 breath awareness, 286 contemplation and prayer, 289 guided imagery, 288 Loving Kindness, 289 movement, 289– 290 Tai Chi, 289– 290 yoga, 289 nutrition and stress, 292– 293 mindful eating, 292– 293 sleep and stress, 293 teaching patients, 293 Mindful eating, 292– 293 Mindfulness and mental health, 316 and stress, 317 Mindfulness meditation (MM), 1000 MIND-IT, see  Myocardial Infarction and Depression-Intervention (MIND-IT) Trial Mind the Hype: A Critical Evaluation and Prescriptive Agenda for Research on Mindfulness and Meditation,  1008 Minimum legal drinking age (MLDA) laws, 1306 Minnesota Model, 1053 Minority and disadvantaged smokers, 1063 Mitochondrial synthesis, 1258 ML, see  Machine learning (ML) MLDA, see  Minimum legal drinking age (MLDA) laws

Index  1423 MM, see  Mindfulness meditation (MM); Recovery and Moderation Management (MM) MMLs, see  Medical marijuana laws (MMLs) MMRC, see  Modified Medical Research Council (MMRC) MMT, see  Methadone maintenance treatment (MMT) MNT, see  Medical nutrition therapy (MNT) Mobile App Rating Scale (MARS), 235, 316 Moderate-intensity continuous exercise training (MICT), 792, 806 Moderate-to-vigorous physical activity (MVPA), 259, 261, 342, 789, 874, 903, 1368– 1369 Modified Medical Research Council (MMRC), 613 Molluscum contagiosum, 704 Monocytes and tissue macrophages, 547– 548 Monogenic hypertensionogenic hypertension, 942 Monounsaturated fatty acids (MUFAs), 58 Mortality fitness and, 478 and positive psychology factors, 232 MOs, see  Motivating operations (MOs) Motivating operations (MOs), 854– 855 Motivation, 1211– 1216 autonomous, 1212 complexities of lifestyle, 1212 controlled, 1212– 1213 definition, 1212 extrinsic to intrinsic, 1213 healing power, 1214 helping patients, 1213– 1214 holding compassion, 1214 interviewing, 1215– 1216 listening, 1215 nature of willpower, 1213 need-supportive guidance, 1213 overview, 1211 patients’  fundamental human needs, 1213 personal goals, purpose, and meaning, 1215 self-determination theory, 1212 Motivational enhancement therapy (MET), 1091, 1098, 1115 Motivational interviewing (MI), 207– 216, 486, 856, 914, 1098, 1115, 1215– 1216 definition, 208– 210 research and evidence, 209– 210 efficacy based on science, 782– 783 four processes, 210– 216 engaging, 210– 212 evoking, 213– 215 focusing, 213 planning, 215– 216 overview, 207– 208 Motivation and Personality,  230 Motivation Interviewing,  274 Motorcycle helmets, 1309 Move to Improve trial, 1368 MPM, see  Malignant pleural mesothelioma (MPM)

MRFIT, see  Multiple Risk Factor Intervention Trial (MRFIT) MRI, see  Magnetic-resonance imaging (MRI) MSD, see  Mediterranean-style diets (MSD) MSJE, see  Mifflin-St. Jeor Equation (MSJE) MST, see  Malnutrition Screening Tool (MST) MTHFR, see  Methylenetetrahydrolate reductase (MTHFR) mTORC1, see  Mechanistic target of rapamycin complex 1 (mTORC1) MUFAs, see  Monounsaturated fatty acids (MUFAs) Multidimensional dyspnea profile (MDP), 574 Multi-Ethnic Study of Atherosclerosis, 56 Multiomics, 320 Multiple daily subcutaneous injections (MDI), 385 Multiple Risk Factor Intervention Trial (MRFIT), 7 Multivitamins (MVIs), 811– 812 Muraven, Mark, 1213 Murthy, Vivek, 645 Muscular endurance, 171 Muscular fitness, 170, 986– 987 Muscular strength, 170– 171 MUST, see  Malnutrition Universal Screening Tool (MUST) Mutual Aid Groups, 1052 Mutual help groups, 1079– 1080 MVIs, see  Multivitamins (MVIs) MVPA, see  Moderate-to-vigorous physical activity (MVPA) MyFitnessPal, 345 Myocardial Infarction and DepressionIntervention (MIND-IT) Trial, 754 Myocardial infarction and stroke, 689 MyPlate, 108 MyPlate Food Guide,  127 MyPlate for Older Adults,  126

N NA, see  Neuraminidase (NA) NAATs, see  Nucleic Acid Amplification Testing (NAATs) NAEB, see  Nonasthmatic eosinophilic bronchitis (NAEB) NAEPP, see  National Asthma Education and Prevention Program (NAEPP) NAEPP Asthma Guidelines 2007, 605 Naltrexone, 1078 Naltrexone and XR-naltrexone, 1087– 1090 advantages, 1090 disadvantages, 1090 Naltrexone ER-bupropion SR, 496– 497 Narcotic Addict Treatment Act (1974), 1054 NASM, see  National Academy of Sports Medicine (NASM) Nathan Pritikin’ s Center, 393 National Academy of Sciences, 95 National Academy of Sports Medicine (NASM), 148 National Asthma Education and Prevention Program (NAEPP), 591, 593, 594, 595

National Blue Ribbon Panel, 970 National Board Certification for Health & Wellness Coaches, 149 National Board of Medical Examiners (NBME), 149, 303, 304, 307 National Cancer Institute (NCI), 81, 315, 334 National Center for Complementary and Integrative Health, 446 National Center for Health Statistics, 1083 National Center for Injury Prevention and Control (NCIPC), 1321, 1338 National Cholesterol Education Program Adult Treatment Panel III, 44 National Cholesterol Education Program (NCEP), 7, 21, 24– 25, 45, 55 National Cholesterol Program, 116 National Commission of Certifying Agencies (NCCA), 148 National Committee for Quality Assurance (NCQA), 1184, 1362 National Comprehensive Cancer Network, 434 National Consortium for Credentialing Health and Wellness Coaching (NCCHWC), 302, 303, 307 National Diabetes Prevention Program, 348 National Electronic Injury Surveillance System (NEISS), 1344 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III), 1069 National Fire Protection Association, 1351 National Food and Nutrient Analysis Program (NFNAP), 82 National Health and Nutrition Examination Survey (NHANES), 7, 40, 42, 44, 81, 84, 93, 259, 359, 400, 459, 474, 491, 521, 529, 773, 887, 1136, 1328, 1392 National Health Care Workforce Commission, 1359 National Health Interview Survey (NHIS), 435, 447, 1350 National Heart, Lung, and Blood Institute (NHLBI), 12, 173, 926, 938, 984, 1392 National High Blood Pressure Education Program (NHBPEP), 938 National Highway Traffic Safety Administration, 1304 National Initiative for Children, 914 National Institute for Health and Clinical Excellence, 316 National Institute of Allergy and Infectious Diseases, 541 National Institute of Occupational Safety and Health (NIOSH), 1172 National Institute on Alcohol Abuse and Alcoholism (NIAAA), 1054, 1073, 1074, 1116 National Institute on Drug Abuse (NIDA), 1054 National Institutes of Health (NIH), 83, 193, 446, 1054, 1396 National Lipid Association, 767 National Nutrient Database for Standard Reference, 82



1424  Index National Park Rx Initiative, 150– 151, 150– 151 National Research Council, 639 National Sleep Foundation, 901, 915 National Strategic Plan for Tobacco Control, 24 National Strength and Conditioning Association (NSCA), 148 National Tobacco Cessation Collaborative, 1108 National Toxicology Program, 640 National Violent Death Reporting System (NVDRS), 1344 National Walkers’  and Runners’  Health Studies, 791 National Weight Control Registry (NWCR), 44, 316, 510 National Youth Physical Activity and Nutrition Study (NYPANS), 1379 National Youth Tobacco Survey, 1062 Natural killer cells (NK-cells), 548 NBME, see  National Board of Medical Examiners (NBME) NCCA, see  National Commission of Certifying Agencies (NCCA) NCCHWC, see  National Consortium for Credentialing Health and Wellness Coaching (NCCHWC) NCDs, see  Non-communicable diseases (NCDs) NCI, see  National Cancer Institute (NCI) NCIPC, see  National Center for Injury Prevention and Control (NCIPC) NCQA, see  National Committee for Quality Assurance (NCQA) NEAT, see  Non-exercise activity thermogenesis (NEAT) Nedley Hypothesis, 1012, 1013 Neighborhood Walkability Scale, 263 NEISS, see  National Electronic Injury Surveillance System (NEISS) NESARC-III, see  National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III) Neuraminidase (NA), 636 Neurogenesis, 1257 Neutrophils, 548 New England Journal of Medicine,  657 New Nordic Diet (NND), 362, 519 Newton, Isaac, 1006 New York State Inebriate Asylum, 1052 New Zealand Guidelines Committee, 21 New Zealand Guidelines Group, 14 Nexplanon implant, 692 clinical considerations, 692 efficacy, 692 mechanism of action, 692 NFNAP, see  National Food and Nutrient Analysis Program (NFNAP) NHANES, see  National Health and Nutrition Examination Survey (NHANES) NHBPEP, see  National High Blood Pressure Education Program (NHBPEP) NHIS, see  National Health Interview Survey (NHIS) NHL, see  Non-Hodgkin lymphoma (NHL) NHLBI, see  National Heart, Lung, and Blood Institute (NHLBI)

NIAAA, see  National Institute on Alcohol Abuse and Alcoholism (NIAAA) Niacin, 812– 813 Nicotine replacement therapies (NTRs), 1058 NIDA, see  National Institute on Drug Abuse (NIDA) Niemann-Pick C1 like 1 (NPC1L1), 54 NIH, see  National Institutes of Health (NIH) NIH-AARP Diet and Study Health Cohort, 720 NK-cells, see  Natural killer cells (NK-cells) NLEA, see  Nutrition Labeling and Education Act (1990) (NLEA) NND, see  New Nordic Diet (NND) NOAEL, see  No observed adverse effects (NOAEL) No Child Left Behind law, 342 Nonasthmatic eosinophilic bronchitis (NAEB), 582 Non-communicable diseases (NCDs), 154, 1157– 1158, 1191– 1192, 1195 Non-exercise activity thermogenesis (NEAT), 475, 981 Non-HDL, see  Non-high-density lipoprotein (non-HDL) cholesterol Non-high-density lipoprotein (non-HDL) cholesterol, 55– 56, 58, 887, 890 Non-Hodgkin lymphoma (NHL), 414 No observed adverse effects (NOAEL), 88 Novo Nordisk, 532 NPC1L1, see  Niemann-Pick C1 like 1 (NPC1L1) NRF, see  Nutrient Rich Foods (NRF) Index NSCA, see  National Strength and Conditioning Association (NSCA) NTRs, see  Nicotine replacement therapies (NTRs) Nucleic Acid Amplification Testing (NAATs), 701 Nurses’  Health Study, 7, 9, 39, 675– 676 Nurses Health Trial, 6, 13 Nutrient Rich Foods (NRF) Index, 92 Nutritional biomarkers, 83– 84 Nutritional counseling, 31 Nutritional status, 77– 97 concept, 78– 79 bioactive food components, 78– 79 nutrient requirements, 78 special nutrient requirements, 78 guidelines for dietary intakes, 89– 90 Choose My Plate graphic, 90 Dietary Guidelines for Americans, 90 food groups vs.  nutrients, 89 healthy eating index, 90 patterns, 89– 90 USDA food group patterns, 90 guidelines for energy and nutrient intakes, 85– 89 challenges of updating DRI, 88– 89 criteria for setting recommendations, 86– 87 dietary reference intakes (DRI), 85– 86 dietary risk assessment, 88 DRI framework for chronic disease risk, 87– 88

limitations of DRI, 88 measurement, 79– 85 acute/very short-term intakes, 82 biomarkers, 83– 84 dietary assessment methods, 81 dietary data validity, 83 error in dietary assessment, 82– 83 evaluating diet, 80– 81 food and supplement databases, 82 issues in interpreting biomarkers, 85 malnutrition, 80 overview, 79 total dietary intakes, 82 usual diets and total intakes, 81– 82 nutrient information on food labels, 92– 95 Facts Up Front, 95 health claims, 94 Heart Check, 95 label claims, 94 nutrient claims, 94 Nutrition Facts label, 93– 94 Smart Choices program, 95 structure/function claims, 94 supermarket scoring systems and icons, 95 voluntary and Front of Package (FOP) labeling, 94– 95 overview, 77– 78 personalized nutrition, 96– 97 availability, 96– 97 definition, 96 potential, 96 terms in describing diets and foods, 90– 92 determining nutrient quality, 91– 92 energy density and nutrient density, 91 Nutrient Rich Foods Index, 92 Nutrition and CVD, 111– 120 AHA diet and lifestyle recommendations, 118– 120 avoiding tobacco products, 119 consuming overall healthy diet, 118 desirable lipid profile, 119 healthy body weight, 118– 119 normal blood pressure, 119 physical activity, 119 specific, 119– 120 dietary patterns, 112– 114 food items, 114– 118 alcohol, 117 chocolate, 118 coffee and caffeine, 117 dairy products, 116– 117 eggs, 117 fish, 116 fruits and vegetables, 116 garlic, 117– 118 meat, 116 nuts, 116 soy, 117 sugar sweetened beverages (SSBs), 117 tea, 117 whole grains and dietary fiber, 116 heart healthy nutrition plans, 120 overview, 111– 112

Index  1425 salt and sodium, 118 vitamin D, 118 vitamins E and C, 118 Nutrition and stress, 292– 293 mindful eating, 292– 293 Nutrition Care Process, 443 Nutrition Cholesterol Education Program, 7 Nutrition Evidence Library, 89 Nutrition Facts label, 93– 94 Nutrition guidance for older adults, 125– 131 nutrients of concern, 127– 128 added sugar, 128 calcium, 127 fiber, 127 potassium, 127 saturated fat, 128 sodium, 127– 128 vitamin D, 127 overview, 125 physiological changes, 130– 131 cancer, 130– 131 cardiovascular disease, 130 dentition and associated senses, 130 glucose intolerance and type 2 diabetes, 130 hypertension, 130 immune function, 130 osteoporosis, 130 recommendations, 125– 127 special dietary considerations, 128– 129 organ systems, 128 social factors, 129 taste and smell, 129 vision, dexterity, and mobility, 129 Nutrition Labeling and Education Act (1990) (NLEA), 92, 94 Nutrition prescription and behavioral approaches, 269– 279 basics, 270– 271 counseling techniques, 273– 274 cultural sensitivity, 272– 273 education in group medical visit model, 274– 276 nutrients for wellness, 272 overview, 269– 270 portion control, 271– 272 practical culinary skills, 276– 279 whole foods, 271 Nutrition therapy for cancer patient, 441– 449 complementary and restorative therapeutic treatment, 446– 4 49 fasting diet, 448– 4 49 ketogenic diet, 449 metabolic dietary therapies, 448 metabolic therapy vs.  dietary approaches, 447, 448 malnutrition and cancer cachexia, 441–  4 42 metabolic alterations, 442– 4 43 altered carbohydrate metabolism, 442 altered fat metabolism, 442– 4 43 overview, 441 screening, 443–  4 44 nutrient needs, 444 treatment and side effect management, 444 chemotherapy and radiation therapy, 444

lifestyle strategies, 444 Nuts, 116 NuvaRing, 690 NVDRS, see  National Violent Death Reporting System (NVDRS) NWCR, see  National Weight Control Registry (NWCR) NYPANS, see  National Youth Physical Activity and Nutrition Study (NYPANS) Nyswander, Marie, 1054

O OARS, see  Open-ended questions, Affirmations, Reflective listening, and Summaries (OARS) Obama, Barack, 529 Obama, Michelle, 95, 1396 Obesity, 9, 42– 43, 455– 466, 1194, 1391– 1400 and adiposity, 455 measurement, 455– 458 and arthritis, 1395 asthma and, 604 and breast cancer, 334– 338 clean eating, 335 CoQ10, 337 exercise and recreational activity, 336 folate, 337 lifestyle evaluation and modifications, 336 nutrition, 336 prevention, 338 retinol and β - carotene, 337 selenium, 338 sleep, 335– 336 stress reduction, 336– 337 vitamin D, 337 vitamin E and vitamin C, 337 vitamins, antioxidants, and minerals, 337 zinc, 338 and cancer, 419– 427, 1394– 1395 body surface area (BSA), 427 lifestyle modifications for primary cancer prevention, 423– 425 mechanisms, 420– 422 overview, 419– 420 secondary prevention in survivors, 425– 426 strategies to disrupt, 422 type 2 diabetes mellitus, 426– 427 coronary patients and, 801– 807 epidemiology, 802 measuring, 802 MHO, 802– 803 modifying lifestyle, 805– 807 overview, 801– 802 paradox, 803– 805 physiologic effects, 805 and diabetes, 1394 economic impact, 1395– 1396 and heart disease, 1394 and medical conditions, 1395 and metabolic syndrome, 1395 need for healthcare professional involvement, 1399– 1400 overview, 455, 1391– 1392

overweight and, 171, 483– 488, 1392– 1394 adults, 1394 children and adolescents, 1394– 1396 dietary assessment, 484– 485 dietary intervention, 486– 487 eating environment and readiness for intervention, 485– 486 intensity of intervention, 487 medical assessment, 483– 484 nutrition assessment, 484 overview, 483 and PA, 348, 473– 479 cardiovascular activity, 474 combined with energy intake, 476 fitness and health outcomes, 478–  lifestyle activity, 475 overview, 473 physical activity bouts, 475– 476 prevention of weight gain, 473– 474 resistance exercise, 474 sedentary behavior, 475 surgically induced weight loss, 476– 477 weight loss variability, 477– 478 yoga, 474– 475 pharmacological management of patient, 491– 501 concurrent pharmacotherapy, 498 FDA-approved drugs, 492– 498 FDA indications and state law, 499– 500 optimizing weight management, 500– 501 overview, 491 pharmacotherapy for adults, 498– 499 serious condition, 491– 492 treatment, 492 weight loss drug, 500 prevalence, 458– 461 economic costs in U.S, 463– 466 direct, 464 indirect, 464– 466 global trends, 460– 461 health consequences, 463 potential causes, 461– 463 cranial radiotherapy, 463 endocrine disruptors, 463 energy imbalance, 461– 462 genetics and epigenetics, 462 gut microbiota, 463 infections, 462– 463 pharmaceutical agents, 463 sleep, 463 smoking, 463 U.S. trends, 459– 460 prevention and management, 28– 29 public health implications, 1396 public policy and environmental strategies, 1397– 1399 closing energy gap, 1399 food environment, 1397– 1398 genetics, 1399 physical activity, 1399 searching for solutions, 1397 small steps approach, 1399 role of adipocytes, 1394 surgery for, 505– 513 alcohol misuse, 511



1426  Index bariatric surgical procedures, 505 behavioral/psychological care, 511 comprehensive lifestyle interventions, 512– 513 dietary changes, 508 dietary patterns and eating behaviors, 508 disordered eating, 511 importance of lifestyle intervention, 505 mood disorders, 511 overview, 505 physical activity, 510 postoperative care, 508 preparing patient, 507 prevention of micronutrient deficiencies, 508– 509 psychological counseling and peer support, 512 weight loss outcomes and improvement, 507– 508 weight regain, 513 and weight management, 529– 533 overview, 529 public health strategies, 531– 532 removing barriers, 530– 531 research priorities, 532– 533 Obesity-hypoventilation syndrome (OHS), 585 Obstructive sleep apnea (OSA), 521, 585, 646, 941 OBT, see  Buprenorphine office-based treatment (OBT) Occupational and environmental lung diseases, 611– 618 acute mountain sickness (AMS), 617 asbestos-related lung disease, 613– 614 clinical presentation and diagnosis, 614 epidemiology, 614 berylliosis, 615– 616 clinical presentation and diagnosis, 615– 616 epidemiology, 615 treatment and prevention, 616 chronic obstructive pulmonary disease (COPD), 612– 613 clinical presentation and diagnosis, 612– 613 epidemiology, 612 non-pharmacologic therapy, 613 pharmacologic therapy, 613 prevention and treatment, 613 coal mine dust lung disease (CMDLD), 616 clinical presentation and diagnosis, 616 epidemiology, 616 prevention and treatment, 616 high altitude cerebral edema (HACE), 617 high-altitude illnesses, 616– 617 high altitude pulmonary edema (HAPE), 617 acetazolamide, 617 controlled ascent, 617 hypersensitivity pneumonitis, 618 clinical presentation and diagnosis, 618

epidemiology, 618 treatment and prevention, 618 overview, 611 silicosis, 614– 615 clinical presentation and diagnosis, 614– 615 epidemiology, 614 prevention and treatment, 615 work-related asthma, 611– 612 clinical presentation and diagnosis, 612 epidemiology, 611– 612 prevention and treatment, 612 Occupational asthma, 603– 604 Occupational Safety and Health Administration (OSHA), 615 OD, see  Ornish diet (OD) OECD, see  Organisation for Economic Co-operation and Development (OECD) Office of Disease Prevention and Health Promotion, 109 OHS, see  Obesity-hypoventilation syndrome (OHS) Older adult falls, 1327– 1333 epidemiology, 1327– 1328 evidenced-based strategies, 1330– 1331 overview, 1327 prevention activities, 1331– 1332 risk factors, 1328, 1330 and PA, 185 Olevsky, Jerrold, 394 Omalizumab, 596– 597 Omega-3 polyunsaturated fatty acids, 57, 69, 358 OMT, see  Optimal medical therapy (OMT) Oncology Nursing Society, 434 Online social networks, 258 Open circuit spirometry, 164 Open-ended questions, 210 Open-ended questions, Affirmations, Reflective listening, and Summaries (OARS), 1115 Operant psychology, 853 Opioids for chronic pain, 1315– 1317 determination, 1316– 1317 guideline development, 1315– 1316 overview, 1315 Opioid Treatment Program (OTP), 1054, 1086 Opioid use disorders, 1083– 1091 buprenorphine office-based treatment (OBT), 1087 advantages, 1087 disadvantages, 1087 diagnosis, 1084– 1086 integration of psychosocial support, 1090– 1091 methadone maintenance treatment (MMT), 1086– 1087 advantages, 1086 disadvantages, 1086– 1087 naltrexone and XR-naltrexone, 1087– 1090 advantages, 1090 disadvantages, 1090 overview, 1083

psychosocial treatment modalities and adjuncts, 1091 risk factors, 1083– 1084 treatment, 1086 Optimal medical therapy (OMT), 772 Oral contraceptive pills (OCPs), 723, 726 Oregon Department of Education, 1387 Organisation for Economic Co-operation and Development (OECD), 1193, 1195, 1207, 1351 Organ systems, 128 Orlistat, 494 ORN, see  Dr. Dean Ornish Program for Reversing Heart Disease (ORN) Ornish, Dean, 394, 826, 961 Ornish diet (OD), 362, 519 Ortho Evra patch, 689 OSA, see  Obstructive sleep apnea (OSA) Oseltamivir, 636 OSHA, see  Occupational Safety and Health Administration (OSHA) Osler, William, 1006 Osteoporosis, 130 in children and adolescents, 951– 956 bone accrual, 951– 952, 956 cannabis use, 955 genetics, 952 lifestyle factors, 956 nutrition, 953– 954, 956 overview, 951 physical activity, 952– 953, 955 sleep, 955 tobacco use, 954– 955 Ostrom, Elinor, 1204, 1206 OTC, see  Over-the-counter (OTC) products OTP, see  Opioid Treatment Program (OTP) Ottawa Charter, 1219 Outdoor allergens, 594– 595 OutdoorsRx, 150– 151, 150– 151 Ovarian cancer, 719– 723 epidemiology/risk factors, 719– 720 intervention/prevention, 723 lifestyle, 722– 723 screening, 720– 722 Overnutrition, 863– 864 Over-the-counter (OTC) products, 494, 817, 819, 1058 Overweight and obesity, 171, 483– 488, 1392– 1394 adults, 1392 children and adolescents, 1392– 1394 dietary assessment, 484– 485 energy expenditure, 484– 485 energy intake, 485 intervention, 485 dietary intervention, 486– 487 eating environment and readiness for intervention, 485– 486 intensity of intervention, 487 medical assessment, 483– 484 nutrition assessment, 484 overview, 483

P PA, see  Physical activity (PA) PAGA, see Physical Activity Guidelines for Americans  (PAGA)

Index  1427 PAH, see  Polycyclic aromatic hydrocarbons (PAH) Palmer, S. 783 Paradoxical vocal cord dysfunction (PVD), 584 Parkinson, Michael, 1169 Parkinson, Mike, 970 Paroxysmal nocturnal dyspnea (PND), 579 Partnership, 209 “ Partnership for Healthy America,”  1396 PATH Mobile Messaging Toolkit, 315 Patient-centered medical home (PCMH), 1182, 1188– 1189, 1221 Patient-Centered Outcomes Research Institute (PCORI), 1359 Patient Generated-Subjective Global Assessment (PG-SGA), 443 Patient Health Questionnaire (PHQ), 983, 1012 Patient Protection and Affordable Care Act, see  Affordable Care Act (ACA) PAVS, see  Physical Activity Vital Sign (PAVS) PCMH, see  Patient-centered medical home (PCMH) PCORI, see  Patient-Centered Outcomes Research Institute (PCORI) PCOS, see  Polycystic ovarian syndrome (PCOS) PCP, see  Primary care provider (PCP) PCR, see  Polymerase chain reaction (PCR) PCSK9, see  Proprotein convertase subtilisin kexin type 9 (PCSK9) PCSSMAT, see  Provider’ s Clinical Support System for Medication-Assisted Treatment (PCSSMAT) PDMP, see  Prescription drug monitoring program (PDMP) PDSA, see  Plan-Do-Study-Act (PDSA) PE, see  Pulmonary embolism (PE) PEAK, see  Physical Education for All Kids (PEAK) Peak expiratory flow rate (PEFR), 592 Pediatric CVD risk factors and diet, 887– 896 dyslipidemia, 890– 893 hypertension, 894– 896 obesity, 888– 890 overview, 887– 888 and PA, 873– 882 habitual physical activity vs.  systematic training, 874– 875 mechanisms, 881– 882 non-invasive estimation, 879– 881 overview, 873– 874 physical fitness and health, 876– 879 sedentary behaviors and CMRF, 875– 876 Pediatric lifestyle medicine, 851– 858 behavior and in children, 855 family-based treatment, 855– 856 models, 852– 853 principles, 853– 855 economics, 857– 858 disease predictors and response to treatment, 857 motivational interviewing, 856

skill vs.  motivation deficits, 856– 857 overview, 851– 852 Pediatric obstructive sleep apnea, 903 Pediatric Sleep Council, 905 Pediculosis pubis, 705 Pedometers, 257 Peer recovery coach (PRC), 1116 Peer support, 1116 PEFR, see  Peak expiratory flow rate (PEFR) Pelvic inflammatory disease (PID), 700, 720 Penchansky, R., 1376 PEP, see  Prevention Education Program (PEP) Peramivir, 636 Perceived control, 200 PERMA, see  Positive Emotions Engagement Relationships Meaning Accomplishments (PERMA) model Peroxisome activated receptor gamma coactivator-1-α  (PGC-α ), 1133 Personalized nutrition, 96– 97 availability, 96– 97 definition, 96 potential, 96 Personal trainer, 148 Peterson, Christopher, 230 Pew Research Center, 257, 315, 744 PFTs, see  Pulmonary function tests (PFTs) PGC-α , see  Peroxisome activated receptor gamma coactivator-1-α  (PGC-α ) PGP, see  Physician Group Practice (PGP) PG-SGA, see  Patient Generated-Subjective Global Assessment (PG-SGA) Pharmaceutical measures for cardiac protection, 28 Pharmacological management of hypertension, 71 Pharmacologic therapy of asthma, 595– 598 benralizumab, 597 biologic therapies, 596 bronchial thermoplasty, 597 long-acting beta-2 agonist (LABA), 596 long-acting muscarinic antagonists, 596 mepolizumab, 597 omalizumab, 596– 597 quick-relief medications, 598 reslizumab, 597 Phendimetrazine, 493– 494 Phentermine, 492– 493 Phentermine-topiramate ER, 495– 496 PHI, see  Primary HIV infection (PHI) PHM, see  Population Health Management (PHM) PHP, see  Physician Health Program (PHP) PHQ, see  Patient Health Questionnaire (PHQ) Physical Activity and Health,  178 Physical Activity Compendium, 345 Physical Activity Guidelines for Americans  (PAGA), 4, 6, 10, 30, 31, 38, 157, 178, 180, 182, 184, 185, 341, 342, 347, 915, 974, 1399 Physical activity (PA), 316, 317, 864, 1194– 1195 and active living, 1365– 1371 community-based approaches, 1365– 1367

community organizations, 1369 costs/benefits and funding, 1370– 1371 overview, 1365 promoting use of trails, 1370 public recreation facilities and built environment, 1369 schools, 1367– 1368 worksites, 1368– 1369 and aging, 563– 567, 1145 adipose tissue modulation, 564 cholinergic anti-inflammatory pathway, 564– 565 gut microbiota, 565 humoral immunity, 566– 567 “ inflammaging,”  563– 564 overview, 563 T cell-mediated immunity, 565– 566 and anxiety, 1271– 1277 anxiolytic effect in healthy, 1275 definitions and diagnoses, 1271– 1272 endurance training, 1275– 1276 mechanisms of anxiolytic activity, 1276– 1277 meta-analytical findings, 1276 one-time, 1275 overview, 1271 prevalence and incidence, 1274– 1275 treatment, 1272– 1274 and bariatric surgery barriers, 510 benefits in postoperative, 510 levels, 510 recommendations, 510 and brain aging, 1251– 1265 angiogenesis, 1257– 1258 APOE-Ɛ 4 carriers, 1262 APOE genotype, 1262– 1263 attenuation of glucocorticoids, 1258– 1259 benefits in children and young adults, 1263– 1264 brain connectivity, 1261 brain-derived neurotrophic factor (BDNF), 1261– 1262 challenges, 1265 counteracting, 1259– 1260 epidemiological evidence, 1260– 1261 genetic influence, 1261 genetics, aging, and Alzheimer’ s disease, 1262 history, 1252– 1253 intensity and modality vs.  skillful movement, 1264– 1265 mitochondrial synthesis, 1258 neurobiological benefits, 1255 neurogenesis, 1257 neurotransmitters, 1255– 1256 neurotrophic factors, 1256– 1256 normal vs.  pathologic, 1253– 1255 overview, 1251– 1252 synaptogenesis, 1257 and cancer, 431– 437 behavior change, 435– 436 defining “ health-enhancing,”  433– 435 growing burden, 431



1428  Index limitations, 437 overview, 431 prevention, 431– 433 strategies for interventions, 436– 437 cognitive and behavioral approaches to enhance, 253– 265 assessing and targeting sedentary behavior (SB), 259– 261 community-wide interventions, 262 computer and web-based interventions, 257– 258 environmental factors, 262– 263 intervention dissemination, 263– 265 mobile phones and devices, 258– 259 monitoring, 256– 257 overview, 253– 256 racial/ethnic underserved samples, 261– 262 in CVD prevention, 37– 47 central adiposity and inflammation, 43– 4 4 diabetes, 41– 42 heart failure, 41 hypertension, 40– 41 lipids, 44– 45 metabolic syndrome, 45– 47 obesity, 42– 43 overview, 37– 38 physical fitness vs.,  38 recommendations for different age groups, 38– 39 stroke, 40 women and CHD, 39– 40 and depression, 1281– 1287 cross-sectional and longitudinal studies, 1282 mechanisms of antidepressant action, 1285– 1286 overview, 1281 predictors of antidepressant action, 1286 prescription, 1283– 1284 randomized controlled trials, 1282– 1283 symptoms in diseased populations, 1284– 1285 and diet behavior change, 374– 376 and dysglycemia-based chronic disease, 362– 363 and gestational diabetes, 391 and HIV as medicine, 558– 559 psychological improvements, 560 recommendations, 560 and hypertension, 67– 68 inflammation and respiratory infection, 539– 543 chronic anti-inflammatory influence, 539 enhanced immunosurveillance, 543 fitness and chronic, 540 overview, 539 potential mechanisms, 540– 541 upper respiratory tract infections (URTI) risk, 541– 543 and obesity, 473– 479 cardiovascular activity, 474 combined with energy intake, 476

fitness and health outcomes, 478–  lifestyle activity, 475 overview, 473 physical activity bouts, 475– 476 prevention of weight gain, 473– 474 resistance exercise, 474 sedentary behavior, 475 surgically induced weight loss, 476– 477 weight loss variability, 477– 478 yoga, 474– 475 of older adults, 1157– 1165 benefits, 1158– 1159 communication, 1161– 1162 frequently asked questions, 1162– 1165 motivation, 1160– 1161 overview, 1157– 1158 recommendations and guidelines, 1159– 1160 and pediatric CVD risk factors, 873– 882 habitual physical activity vs.  systematic training, 874– 875 mechanisms, 881– 882 non-invasive estimation, 879– 881 overview, 873– 874 physical fitness and health, 876– 879 sedentary behaviors and CMRF, 875– 876 pregnancy and, 658– 670 benefits, 666 contraindications, 668– 669 duration/frequency, 669– 670 fetal distress, 667 glycemic control, 664– 665 improvement in musculoskeletal pain, 666 low birth weight, 667– 668 maternal injury, 668 overview, 663 prescription, 669 preterm delivery, 668 principles, 670 psychological benefits, 665– 666 rates of intervention, 666 recommendations, 669 risk reduction of hypertensive disorders, 665 risks of exercise, 666 spontaneous abortion, 666– 667 types of exercise, 670 weight management, 663– 664 and primary cancer prevention, 424 promotion, 153– 160 barriers to implementation, 156 being role model, 159 call to action, 154 chronic disease pandemic, 153– 154 continuing education to fill knowledge gaps, 156– 157 guiding principles, 158 national plans, 154 overview, 153 Physical Activity Guidelines for Americans (PAGA), 157 Physical Activity Vital Sign (PAVS), 157

professional organizations, 154– 156 providing prescription, 157– 158 refer to experts, 158– 159 role of physician, 156 and sarcopenia beneficial effects, 1132 prevention and management, 1132 and sports for women and girls, 341– 349 ACL injuries, 343– 344 bone health, 348 breast cancer prevention and management, 348– 349 competitive sports, 343 contraceptive use, 346– 347 diabetes prevention and management, 348 early sport specialization and risk of injury, 343 eating disorders and disordered eating, 344 epidemiology, 342 exercise during pregnancy and postpartum, 347 female athlete triad, 344– 345 health benefits, 343 high blood pressure prevention and management, 348 hormone replacement therapy, 348 overview, 341– 342 physical literacy, 343 preventing overweight and obesity, 348 prevention of dementia, 349 recommendations, 342 school-based, 342– 343 social and emotional benefits, 343 and type 1 diabetes, 385, 387 and type 2 diabetes, 388– 389 Physical Activity Vital Sign (PAVS), 157 Physical Education for All Kids (PEAK), 1387 Physical fitness evaluation, 163– 174 aerobic and anaerobic, 163– 164 body composition, 171– 173 hydrodensiometry/underwater weighing, 171– 173 other methods, 173 overweight and obesity, 171 cardiorespiratory fitness (CRF) non-exercise test estimates, 170 walk tests for, 169– 170 cycle ergometer protocols, 168 definition, 163 determining aerobic fitness using indirect methods, 164– 166 muscular endurance, 171 muscular fitness, 170 muscular strength, 170– 171 open circuit spirometry, 164 overview, 163 protocols, 166 ramp testing, 168– 169 skinfold assessment, 174 submaximal testing, 169 tests of anaerobic power, 171 waist circumference, 173– 174 Physical inactivity, 30– 31

Index  1429 Physical therapist (PT), 149 Physician Group Practice (PGP), 1360 Physician health practices, 1033– 1043 contemporary mortality rates, 1033– 1034 Canadian physicians’  health, 1034 male physicians’  health in United States, 1033– 1034 women physicians’  health in United States, 1034 counseling patients, 1035, 1039 exercise vanquishes stress, 1036, 1038 multi-tasking exercise, 1036 exercise and healthy patients, 1034 healthier habits, 1038 Healthy Doctor = Healthy Patient project, 1039– 1043 case study, 1041– 1043 Colombian medical students, 1041 medical students and personal– clinical relationships, 1040 HMO, 1038 intervention, 1043 North American, 1043 overview, 1033 personal habits and patient health, 1034– 1035 Physician Health Program (PHP), 1075 Physician’ s Health Study, 412 Phytochemicals, 410 Phytosterols, 926 PID, see  Pelvic inflammatory disease (PID) Pitts, Jennifer S., 1169 Plan-Do-Study-Act (PDSA), 973, 991– 992 Plan4Health, 1202 Planned interventions, 220 Plant-based diets, 114 Plant polyphenols, 359– 360 Platypnea, 580 PMF, see  Progressive massive fibrosis (PMF) PMR, see  Progressive muscle relaxation (PMR) PND, see  Paroxysmal nocturnal dyspnea (PND) Poké mon Go, 320 Polycyclic aromatic hydrocarbons (PAH), 413 Polycystic ovarian syndrome (PCOS), 355– 356, 370, 653– 654, 707, 720 Polymerase chain reaction (PCR), 634– 635 Polyunsaturated fatty acids (PUFA), 358, 678, 892 Population Health Management (PHM), 1181, 1182, 1183, 1184, 1187, 1188 Position Stand on Exercise and Physical Activity for Older Adults, 1158 Positive Emotions Engagement Relationships Meaning Accomplishments (PERMA) model, 230– 231 Positive psychology, 229– 237 incorporating into lifestyle medicine practice, 235– 237 health coaches in primary care practices, 236– 237

modeling principles, 235 positive health conversations with patients, 235– 236 prescribing PPIs, 236 overview, 229– 231 PERMA model, 230– 231 and positive health, 231– 233 cardiovascular disease, 231– 232 chronic illness, 233 diabetes, 232 mortality, 232 PPIs, 233– 235 and moderating factors, 234 technological devices, 234– 235 Positive psychology interventions (PPIs), 229, 233, 233– 235, 234 and moderating factors, 234 prescribing, 236 technological devices, 234– 235 Post menopausal estrogen therapy, 31 Postnatal nutrition, 865 Postpartum, 694– 695 combined contraception methods, 694 LARCs, 694 sterilization, 694– 695 Post-traumatic stress disorder (PTSD), 1099 Potassium, 127 Potassium intake, 69 PPIs, see  Positive psychology interventions (PPIs) PPS, see  Project for Public Spaces (PPS) A Practitioner’ s Guide of Themed Follow-up Visits to Help Patients Achieve a Healthy Weight,  914 Pravaz, Charles-Gabriel, 1052 PRC, see  Peer recovery coach (PRC) Pre-conception, 866 Precontemplation, 219– 220 Prediabetes, 367– 377 diagnosis, 367– 369 lifestyle factors in development, 369– 371 lifestyle interventions programs, 373– 376 insulin secretion and action, 374 modality, 373 physical activity and diet behavior change, 374– 376 weight loss, 373– 374 managing, 376– 377 overview, 367 prevention and treatment, 371– 373 Pre-diabetes Risk Education and Physical Activity Recommendation and Encouragement (PREPARE), 374 PREDIMED-Reus Nutrition intervention randomized trial, 375 Preeclampsia, 655– 656 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 302, 783 Pregnancy, 866– 867 and asthma, 605– 606 and PA, 658– 670 benefits, 666 contraindications, 668– 669 duration/frequency, 669– 670 fetal distress, 667 glycemic control, 664– 665

improvement in musculoskeletal pain, 666 low birth weight, 667– 668 maternal injury, 668 overview, 663 prescription, 669 preterm delivery, 668 principles, 670 psychological benefits, 665– 666 rates of intervention, 666 recommendations, 669 risk reduction of hypertensive disorders, 665 risks of exercise, 666 spontaneous abortion, 666– 667 types of exercise, 670 weight management, 663– 664 and postpartum, 185– 186 and STIs, 699 Pregnant smokers, 1063 Prelu-2, see  Phendimetrazine Preparation and action, 220 PREPARE, see  Pre-diabetes Risk Education and Physical Activity Recommendation and Encouragement (PREPARE) Prescription drug monitoring program (PDMP), 1316– 1317 Prevent All Cigarette Trafficking Act, 24 Prevention Education Program (PEP), 845 Preventive Cardiovascular Nurses Association, 31 Preventive medicine, 966 The Preventive Plan®  , 1184 The Preventive Plan Population Health Management Program, 1184 PRI, see  Pritikin Program (PRI) Primary cancer prevention, 423– 425 healthy eating patterns, 423– 424 high-calorie foods and sugary drinks, 423 lean weight across life span, 423 overweight/obese, 424– 425 physical activity and, 424, 432– 433 screening guidelines, 425 sleep hygiene, 424 Primary care provider (PCP), 272, 1060 Primary HIV infection (PHI), 556 Primordial prevention and “ ideal”  cardiovascular health, 5– 6 PRISMA, see  Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) Pritikin Program (PRI), 825, 1026– 1027 PROBIT, see  Promotion of Breastfeeding Intervention Trial (PROBIT) Problem-solving, 1004 Process mapping, 990– 991 Prochaska, James, 193, 782 Pro-Children Act (1994), 641 Progesterone-only pills, 690 Progressive massive fibrosis (PMF), 616 Progressive muscle relaxation (PMR), 1009 Prohibition Party, 1053 Project for Public Spaces (PPS), 1202, 1207 Project Play, 343 Promotion of Breastfeeding Intervention Trial (PROBIT), 677, 678, 865



1430  Index Proprotein convertase subtilisin kexin type 9 (PCSK9), 53– 54, 767, 769– 770 Prosperity Index, 1207 Protein glycation, 1130 Provider’ s Clinical Support System for Medication-Assisted Treatment (PCSSMAT), 1054 Prudent diet, 114 Psychological risk factors and counseling, 31 Psychological theories, 197– 204 Health Belief Model, 198 healthy lifestyle intervention in research and practice, 202– 203 Integrated Behavior Model (IBM), 198– 200 overview, 197 Social Cognitive Theory, 200– 201 Socioecological Model, 201– 202 Theory of Planned Behavior (TPB), 198– 200 Theory of Reasoned Action (TRA), 198– 200 Transtheoretical Model, 200 PT, see  Physical therapist (PT) PTSD, see  Post-traumatic stress disorder (PTSD) Public Health Agency of Canada, 1350 Public safety, 1351– 1352 PUFA, see  Polyunsaturated fatty acids (PUFA) Pulmonary embolism (PE), 626– 627 isolated subsegmental, 627 massive, 626– 627 Pulmonary function tests (PFTs), 574– 575 diffusion limitation of carbon monoxide, 575 lung volume testing, 575 pulse oximetry, 575 spirometry, 574– 575 Pulse oximetry, 575 Pulse wave velocity (PWV), 1143 Punishment, 854 PVD, see  Paradoxical vocal cord dysfunction (PVD) PWV, see  Pulse wave velocity (PWV)

Q Qsymia, see  Phentermine-topiramate ER

R Radon, 641 Rahe, R. H., 1006 Ramp testing, 168– 169 RAND Health Workplace Wellness Programs Study, 1172 Randomized controlled trials (RCT), 963– 964 Rating of perceived exertion (RPE), 137– 138, 138– 139 Rational Recovery (RR), 1091 RCEP, see  Registered clinical exercise physiologist (RCEP) RCT, see  Randomized controlled trials (RCT) RDA, see  Recommended dietary allowance (RDA)

RDN, see  Registered Dietitian Nutritionist (RDN) Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, 263– 264 RE-AIM, see  Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework REALIZETM , 506 Rear Seating Position, 1308 Reaven, Gerald, 45, 394 Recommended dietary allowance (RDA), 85– 86, 90, 113, 125, 401 Recovery and Moderation Management (MM), 1091 Red yeast rice (RYR), 816 REE, see  Resting energy expenditure (REE) Registered clinical exercise physiologist (RCEP), 149, 158– 159 Registered Dietitian Nutritionist (RDN), 483, 484, 487 Reinforcement, 853 management, 223 Relapse prevention, 782 Relaxation response, 1008 Renal cell cancer, 414 Report on Nutrition and Health, 764 Report on Physical Activity and Health, 4, 10, 30, 38 ResearchKit, 316 Research on BecomeAnEx.org, 319 ResearchStack, 316 Resilience, 282, 284 Resistance exercise, 474 Resistance training, 182– 183 frequency, 183 rate of progression, 183 repetitions and sets, 183 type, 182– 183 and weight loss, 44 Reslizumab, 597 Respiratory symptoms, 573– 587 assessment, 574– 575 dyspnea scales, 574 pulmonary function tests, 574– 575 cough, 580– 583 acute, 581 chronic cough with abnormal chest X-ray, 582– 583 clinical causes, 581 definition and physiology, 580 subacute and chronic, 581– 582 dyspnea, 576– 580 acute vs.  chronic, 578– 579 definition, 576 night vs.  day, 579 palliative management, 580 physiology, 576– 577 position, 579– 580 qualities, 577 hemoptysis, 583– 584 definition and physiology, 583 etiology, 583– 584 overview, 573– 574 snoring and apnea, 585– 587 definition and physiology, 585 essentials of history, 586– 587

etiology, 585– 586 wheezing, 584– 585 definition and physiology, 584 etiology, 584– 585 Respiratory syncytial virus (RSV), 677 Resting energy expenditure (REE), 442, 484 Resting metabolic rate (RMR), 477, 484 Retinol and β - carotene, 337 Return on investment (ROI), 1172, 1178 Reye’ s syndrome, 634 Reynolds Risk Score, 14, 21, 56 Richmond, Julius, 154 Rippe, James, 961 Risk of Ovarian Cancer Algorithm (ROCA), 721 RMR, see  Resting metabolic rate (RMR) Roadblock-type communication skills, 212 Roberto, Christina, 531 Roberts, William, 762 Robert Wood Johnson Foundation (RWJF), 1171, 1202, 1386 ROCA, see  Risk of Ovarian Cancer Algorithm (ROCA) Rockport fitness walking test, 986 Rockport One-mile Fitness Walking Test, 169 ROI, see  Return on investment (ROI) Rollnick, S., 193, 210, 213 Rooke, Jennifer, 970 Root cause analysis, 992 Rossner, S., 961 Rous, Payton, 448 Roux-en-Y gastric bypass (RYGB), 505 Rowe, John, 1148 RPE, see  Rating of perceived exertion (RPE) RR, see  Rational Recovery (RR) RSV, see  Respiratory syncytial virus (RSV) Rush, Benjamin, 1051 RWJF, see  Robert Wood Johnson Foundation (RWJF) Ryan, Richard, 230, 1212 RYGB, see  Roux-en-Y gastric bypass (RYGB) Rynd, Francis, 1052 RYR, see  Red yeast rice (RYR)

S SA, see  Successful aging (SA) SAD, see  Sagitta abdominal diameter (SAD) SADHART, see  Sertraline and Depression Heart Attack Randomized Trial (SADHART) Safe Routes to School program, 1368 Sagitta abdominal diameter (SAD), 458 St. James Women Take Heart Project, 40 Sallis, Robert, 157 Salt and sodium, 118 SAM, see  Sympatho-Adreno-Medullary Axis (SAM) SAMHSA, see  Substance Abuse and Mental Health Services Administration (SAMHSA) Sanger, M., 962 Sarcopenia, 1127– 1137 aging-related muscle decline, 1128 anabolic hormone activity, 1130– 1131 insulin resistance, 1131

Index  1431 anatomic changes, 1128 anti-inflammation effects, 1133 apoptosis, 1129– 1130, 1132 biological mechanisms, 1128 blood supply, 1131– 1132 damaged muscle proteins, 1130 food-derived antioxidants, 1136– 1137 food energy intake, 1134– 1135 inflammation, 1130 insulin-glucose dynamics, 1133 molecular and biochemics contributors, 1129 muscle blood supply, 1134 muscle fiber change, 1128– 1129 muscle protein and mitochondria, 1133 neuromuscular adaptations, 1134 nutritional strategies, 1134 overview, 1127 oxidative stress, 1132 protein glycation, 1130 protein intake, 1135 public health impact, 1128 role of exercise beneficial effects, 1132 prevention and management, 1132 skeletal muscle function, 1127– 1128 hypertrophy, 1133– 1134 vitamin D blood levels, 1135– 1136 Satcher, David, 529 Satisfaction with Life Scale (SWLS), 983 Saturated fat, 128 Saturated fatty acids (SFAs), 57 Saxenda, see  Liraglutide SB, see  Sedentary behavior (SB) SBIRT, see  Screening, Brief Intervention and Referral to Treatment (SBIRT) model Scharmer, Otto, 1215 Schroeder, Connie, 1351 Schuckit, Marc A., 1070 Schultz, Alyssa, 1170 Scientific Report of the  2015  Dietary Guidelines Advisory Committee,  102– 103 SCORE, see  Systematic Coronary Risk Evaluation Project (SCORE) Scottish Intercollegiate Guidelines Network (SIGN) system, 256 Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R), 1084 Screening, Brief Intervention and Referral to Treatment (SBIRT) model, 1097 SCT, see  Social Cognitive Theory (SCT) SDB, see  Sleep disordered breathing (SDB) SDV, see  Self-directed violence (SDV) Seasonal influenza, 633– 634 Seat belts, 1308 Secondary cancer prevention, 425– 426 avoiding weight gain, 425 cancer survival odds, 425 dietary changes for weight loss, 425– 426 obesity, 425 physical activity and, 433 sleep hygiene, 426 Secondary prevention and CVD, 751– 757 addressing depression, 753– 756

antidepressant medication, 754 cardiac rehabilitation, 755 heart failure, 755– 756 psychotherapy, 754– 755 screening, 753 treating, 754 anger/hostility, 753 anxiety, 753 complementary and alternative medicine approaches, 757 depression, 753 effects of antidepressants, 757 overview, 751 patient, 751– 752 psychosocial factors, 752– 753 risk, 756 treatments for, 756– 757 social support, 753 Secondary prevention of myocardial infarction (MI), 735– 738 medication non-adherence, 736– 737 factors contributing to, 737– 738 optimal medical management, 735– 736 overview, 735 potential explanations, 736 strategies improving adherence, 738 Second Diabetes Surgery Summit (DSS-II), 508 Secondhand smoke exposure in children, 641 overview, 639– 614 Secular Organization for Sobriety (SOS), 1091 Sedentary behavior (SB), 253, 255, 259– 261, 475 Selective Optimization with Compensation (SOC) model, 1148 Selective serotonin norepinephrine reuptake inhibitors (SSNRIs), 1273 Selective serotonin reuptake inhibitors (SSRIs), 1273, 1283, 1285 Selenium, 338, 816– 817 Self-determination theory, 1212 Self-directed violence (SDV), 1338 Self-efficacy, 223, 225, 245– 246 concept, 197, 198, 200– 201 overview, 245– 246 practical application, 246 Self-esteem, 1004 Self-liberation, 222– 223 Self-Management and Recovery Training (SMART), 195, 196, 215, 1053– 1054, 1091 Self-management support, 988 Self-reevaluation, 222 Self-regulation, 243 Self-worth, 1004 Seligman, Martin, 230, 1005 Selye, H., 1006 SEM, see  Socioecological Model (SEM) Senior Odyssey, 1151 Sense of coherence (SOC), 1204 Sensitizer-Induced Asthma (SIA), 611– 612 Serine/threonine-regulated kinase (S6K)-1, 400 Sertraline and Depression Heart Attack Randomized Trial (SADHART), 752, 754

Sertü rner, Friedrich, 1052 Server intervention and training programs, 1307 Sex hormone binding globulin (SHBG), 653– 654, 707 Sexually transmitted infections (STIs), 697– 705 diagnosis and treatment, 700– 705 chancroid, 705 chlamydia, 700– 701 gonorrhea, 701 hepatitis A virus, 702 hepatitis B virus, 702 hepatitis C virus, 702– 703 herpes simplex virus (HSV), 703– 704 human immunodeficiency virus (HIV), 703 human papilloma virus (HPV), 704 information, 700 molluscum contagiosum, 704 pediculosis pubis, 705 pelvic inflammatory disease (PID), 700 syphilis, 701– 702 Trichomonas vaginalis,  704 overview, 697 prevention, 697– 698 contraceptive counseling, 698 education, 697– 698 epidemiology, 697 male circumcision, 698 vaccines, 698 screening, 699– 700 adolescents, 699 lesbians, gay, bisexual, and transgender (LGBT), 699– 700 pregnancy, 699 risk factors, 699 sexual history, 699 SFAs, see  Saturated fatty acids (SFAs) SHBG, see  Sex hormone binding globulin (SHBG) Short-acting beta-2 agonist therapy, 598 Short Message Service (SMS), 1106, 1108 SHS, see  Subjective Happiness Scale (SHS) Shurney, Dexter, 1169 SIA, see  Sensitizer-Induced Asthma (SIA) SIDS, see  Sudden infant death syndrome (SIDS) SIGN, see  Scottish Intercollegiate Guidelines Network (SIGN) system Silicosis, 614– 615 clinical presentation and diagnosis, 614– 615 epidemiology, 614 prevention and treatment, 615 SilverSneakers, 150 Simple reflection, 211 Six-minute walk test, 986 S6K-1, see  Serine/threonine-regulated kinase (S6K)-1 Skinfolds, 174, 458 Sleep and obesity prevention in children and adolescents, 901– 905 assessment, 903 diet, 902 epidemic, 901



1432  Index influence on health behavior patterns, 903 overview, 901 pediatric obstructive sleep apnea, 903 physical activity and screen time, 903 poor sleep health, 901– 902 treatment of disorders, 904– 905 Sleep and stress, 293 Sleep as medicine, 995– 1001 assessment, 997– 998 chronic disease, 995– 996 cancer, 996 cardiovascular diseases, 996 excessive BMI and metabolic disorders, 995– 996 inflammatory disorders, 996 mood disorders, 996 circadian biology, 996– 997 light, 997 thermoregulation, 997 and health, 995 lifestyle prescriptions for optimal, 999– 1000 dietary habits for enhancement, 999– 1000 light exposure interventions, 999 mindfulness and cognitive behavioral therapy interventions, 1000 thermal regulation interventions, 1000 overview, 995 Sleep disordered breathing (SDB), 941 Sleep hygiene, 520– 521 Sleep restriction (SR), 902, 904 SMART, see  Self-Management and Recovery Training (SMART); Specific, measurable, actionoriented, realistic, and timesensitive (SMART) Smart Choices program, 95 Smartphone-based technologies, in addiction treatment, 1105– 1109 alcohol use disorder (AUD), 1107 healthcare, 1105– 1106 limitations, 1109 mental health, 1106 overview, 1105 pathological gambling treatment, 1108 smoking cessation treatment, 1107– 1108 substance use disorders, 1106– 1107 Smartphones and tablet, 315– 316 Smith, Bob, 1053 Smoking, 6, 864, 1057– 1064 abrupt quitting and gradual reduction, 1064 community-based approaches, 1061– 1062 mass media campaigns, 1061 worksite programs, 1061– 1062 counseling and therapy-based approaches, 1059 group, 1059 individual, 1059 motivational interviewing, 1059 telephone counseling, 1059 electronic cigarettes, 1064 exercise, 1063– 1064 health consequences, 1057– 1058

overview, 1057 prevalence and epidemiology, 1058 technology-driven approaches, 1062 internet-based interventions, 1062 mobile phone interventions, 1062 Smoking cessation, 6, 21– 24 behavioral strategies, 1058– 1059 in medical settings, 1060– 1061 inpatient hospitalization, 1061 primary care visits, 1060– 1061 mentally ill smokers, 1063 minority and disadvantaged smokers, 1063 pharmacological, 1058 pregnant smokers, 1063 rates, 1058 smartphone-based intervention in treatment, 1107– 1108 young adult and adolescent smokers, 1062 Smoking Opium Exclusion Act (1909), 1053 SMS, see  Short Message Service (SMS) Snoring and apnea, 585– 587 definition and physiology, 585 essentials of history, 586– 587 etiology, 585– 586 SOAPP-R, see  Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) Sobriety checkpoints, 1306 SOC, see  Selective Optimization with Compensation (SOC) model; Sense of coherence (SOC) Social Cognitive Theory (SCT), 194, 195, 200– 201, 203 Social learning theory, 781– 782 Social liberation, 223 Social media, 318– 319 Social Progress Imperative, 1207 Social Progress Index, 1207 Society of Gynecologic Oncologists Education Committee, 721, 724 Socioecological Model (SEM), 106, 194, 195, 201– 202, 852 Sodium, 69, 127– 128 SOS, see  Secular Organization for Sobriety (SOS); Swedish Obese Subjects (SOS) SOWS, see  Subjective Opiate Withdrawal Scale (SOWS) Soy, 117 “ Spanish Flu,”  633 Special nutrient requirements, 78 Special Turku Risk Intervention Program (STRIP), 842, 891– 892 Specific, measurable, action-oriented, realistic, and time-sensitive (SMART), 270, 274 Spirometry, 574– 575 SPRINT, see  Systolic Blood Pressure Intervention Trial (SPRINT) SR, see  Sleep restriction (SR) SSBs, see  Sugar sweetened beverages (SSBs) SSNRIs, see  Selective serotonin norepinephrine reuptake inhibitors (SSNRIs) SSRIs, see  Selective serotonin reuptake inhibitors (SSRIs)

Stanford University, 316 Starch and fiber, 357 State Physician Health Program, 1075 STEADI, see  Stopping Elderly Accidents, Deaths and Injuries (STEADI) Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS), 749 Step into Cuba Alliance, 1386 Step tests, 986 Sternberg, Esther, 1202 Stimulus control, 223, 854, 904 STIs, see  Sexually transmitted infections (STIs) Stopping Elderly Accidents, Deaths and Injuries (STEADI), 1327, 1331 Stress asthma and, 604 reduction, 521 response, 1006 tools for managing, 1007– 1012 alcohol, 1011 caffeine, 1010– 1011 calming mind and body, 1008– 1009 deep/diaphragmatic breathing, 1009 diet, 1011 exercise, 1010 hydrotherapy, 1010 improving mood, 1009– 1010 music therapy, 1009 progressive muscle relaxation (PMR), 1009 rest, 1010 spirituality aids, 1011– 1012 and type A personality, 13 unhealthy lifestyles, 1006 Stress management, 281– 294 building resilience, 282, 284 mind-body therapies, 284– 293 adaptive coping strategies, 291– 292 building positive perspective, 291 gratitude, 290– 291 meditation, 286– 289 movement, 289– 290 nutrition, 292– 293 sleep, 293 overview, 281 and relaxation, 281– 282 biochemical, 282 physiological, 281 technology in, 293– 294 STRIP, see  Special Turku Risk Intervention Program (STRIP) Stroke, 40 Study of Women’ s Health Across the Nation (SWAN), 709 Subjective Happiness Scale (SHS), 983 Subjective Opiate Withdrawal Scale (SOWS), 1088 Submaximal talk test, 169, 986 Substance Abuse and Mental Health Services Administration (SAMHSA), 1054, 1116 Substance use disorder (SUD), 1047– 1048, 1094– 1095, 1113– 1118 12-step facilitation (TSF), 1116 ASAM’ s levels of care, 1116

Index  1433 behavioral couples therapy (BCT), 1113– 1114 brief interventions, 1115– 1116 cognitive behavioral coping skills therapy (CBT), 1114– 1115 community reinforcement approach (CRA), 1115 contingency management (CM), 1115 family therapy, 1114 individual drug counseling (IDC), 1115 motivational interviewing (MI), 1115 overview, 1113 peer support, 1116 Successful aging (SA), 1147– 1154 adverse effects, 1152 cognitive training and stimulation, 1150– 1151 defining, 1147– 1148 determinants, 1149 dietary influences, 1151 exercise/physical activity, 1149– 1150 life-course approach, 1148– 1149 models, 1148 overview, 1147 role of health care practitioners, 1152– 1153 social engagement and volunteerism, 1151– 1152 SUD, see  Substance use disorder (SUD) Sudden infant death syndrome (SIDS), 641 Sugar, 357 Sugar sweetened beverages (SSBs), 117 Suicidal behavior, 1337– 1345 epidemiology, 1338– 1340 overview, 1337– 1338 prevention strategies, 1341– 1343 protective factors, 1341 risk factors, 1340– 1341 adolescents and young adults, 1340 children/pre-adolescents, 1340 middle-aged adults, 1340 older adults, 1340– 1341 role of lifestyle medicine practitioners, 1343– 1344 Supermarket scoring systems and icons, 95 SuperTracker, 981 Supplement Facts label, 93 Surgeon General, 4, 10, 30, 38, 178, 334, 639, 764 The 1989 Surgeon General’ s Report, 24 Sustain talk, 213, 215 Sutton, Thomas, 1052 SWAN, see  Study of Women’ s Health Across the Nation (SWAN) Swedish Obese Subjects (SOS), 508, 511 SWLS, see  Satisfaction with Life Scale (SWLS) Sympatho-Adreno-Medullary Axis (SAM), 282, 1232 Synaptogenesis, 1257 Syndenham, Thomas, 1052 Syphilis, 701– 702 Systematic Coronary Risk Evaluation Project (SCORE), 21 Systemic hypertension, treatment of, 943– 948 2004 Fourth Report vs.  2017 Clinical Practice Guideline, 944

2017 Clinical Practice Guidelines, 943– 944 cases, 944– 948 non-pharmacologic, 943 pharmacologic, 943 Systolic and diastolic blood pressure, 827 Systolic Blood Pressure Intervention Trial (SPRINT), 27, 65

T Tai Chi, 289– 290 Take Our Trail Campaign, 1370 T and B lymphocytes, 549 Target-organ damage (TOD), and hypertension, 942– 943 left ventricular hypertrophy (LVH), 942– 943 ophthalmologic examination and hypertensive retinopathy, 943 Taste and smell, 129 Taylor, Roy, 396 TBI, see  Traumatic brain injury (TBI) T cell-mediated immunity, 565– 566 T2DM, see  Type 2 diabetes mellitus (T2DM) Tea, 117 Technical Expert Collaborative on the Study of Dietary Patterns, 89 TED MED Talk, 1203 TEE, see  Total energy expenditures (TEE) Teen-LABS, see  Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS), 916 Telemedicine, 1195 Template for Intervention Description and Replication (TIDieR), 256 Temporal Self-Regulation Theory (TST), 1229 Tenuate, see  Diethylpropion Termination, 221 Tertiary cancer prevention and PA, 433 Text4Health Task Force, 315 Text messaging, 313– 315 Text Messaging in Healthcare Research Toolkit, 315 TFAs, see  Trans fatty acids (TFAs) TG, see  Triglycerides (TG) THC, see  Delta-9-tetrahydrocannabinal (THC) Theophylline, 596 Theory of Planned Behavior (TPB), 198– 200, 203 Theory of Reasoned Action (TRA), 198– 200 Thirdhand smoke, 640 Thomas, J. A., 1376 Th1/Th2 balance, 549– 550 TIAs, see  Transient ischemic attacks (TIAs) TIDieR, see  Template for Intervention Description and Replication (TIDieR) Tiotropium, 596 TLR4, see  Toll-Like Receptor (TLR4) TMS, see  Transcranial magnetic stimulation (TMS)

Tobacco, 6– 7, 1193– 1194 TOD, see  Target-organ damage (TOD) Tolerable Upper Intake Level (UL), 86 Toll-Like Receptor (TLR4), 548, 551 Total energy expenditures (TEE), 86 TPB, see  Theory of Planned Behavior (TPB) TRA, see  Theory of Reasoned Action (TRA) Tracey, Kevin, 564 Traffic injury prevention, 1303– 1311 cell phone use while driving, 1310 changing age distribution of US population, 1310 designated driver programs, 1310 drug-impaired driving, 1310– 1311 effective interventions, 1306– 1310 alcohol-impaired driving, 1306– 1308 bicycle helmets, 1309 graduated driver licensing systems, 1309 motorcycle helmets, 1309 occupant protection, 1308 parental monitoring of young drivers, 1309 speed and red light cameras, 1309– 1310 epidemiology, 1304– 1305 and lifestyle, 1303– 1304 overview, 1303 primary care practice, 1311 Traffic light diet, 914 Transcranial magnetic stimulation (TMS), 1080 Transculturization, 524 Transcutaneous electrical acupuncture stimulation, 1080 Transdermal contraceptive patch, 689– 690 contraceptive vaginal ring, 690 mechanism of action and clinical considerations, 689– 690 Trans fatty acids (TFAs), 58 Transient ischemic attacks (TIAs), 40 Transtheoretical Model (TTM), 193, 194, 196, 200, 219– 227, 301 critical assumptions, 224 multiple behavior change programs, 224–  225 multiple domains of well-being, 225–  226 overview, 219 principles and processes of change, 221–  223 stages of change, 219– 221 studies challenging, 225 Transvaginal ultrasound, 721 Traumatic brain injury (TBI), 1143 Travis, John, 301 Triad, see  Female athlete triad (Triad) Tri-axial accelerometer sensors, 317 Trichomonas vaginalis,  704 Triglycerides (TG), 54– 55 Tryptophan, 1011 TSF, see  12-step facilitation (TSF) TST, see  Temporal Self-Regulation Theory (TST) TTM, see  Transtheoretical Model (TTM) Tü bingen Lifestyle Intervention Program (TULIP), 371



1434  Index Type 1 diabetes, 384– 387 education/counseling and support, 387 insulin and blood glucose monitoring, 385 medical nutrition therapy (MNT), 385 physical activity/exercise, 385, 387 psychosocial care, 387 Type 2 diabetes mellitus (T2DM), 41– 42, 348, 355– 356, 368, 376, 387– 389, 393– 403, 1284, 1394 education/counseling and support, 389 glucose intolerance and, 130 lifestyle programs for, 396– 402 100% plant-based eating patterns, 396, 399 grain intake, 399– 400 high fiber diet, 400 hydration and sodium intake, 401 increased fruit, 399 increased vegetable intake, 399 low fat eating patterns, 396 low protein diet, 400– 401 meal timing and intermittent fasting, 401– 402 medical nutrition therapy (MNT), 387– 388 overview, 393– 394 physical activity, 388– 389 primary prevention, 394– 395 psychosocial care, 389 secondary and tertiary prevention, 395– 396

U UACS, see  Upper airway cough syndrome (UACS) UK Million Women Study, 232 UL, see  Tolerable Upper Intake Level (UL) Ultrasound and CVD, 880 Ultrasound technique (UT), 458 Undernutrition, 862– 863 Underwater weighing (UWW), see  Hydrodensitometry UN-Habitat, 1207 UnitedHealth Group, 150 United Kingdom Prospective Diabetes Study, 56 United Nations’  Sustainable Development Goals, 1205 United States Civil War, 1052 United States vs. Behrman,  1053 University of Colorado, 315 University of Kentucky, 721 University of Rochester, 337 Upper airway cough syndrome (UACS), 581 Upper-respiratory symptoms (URS), 550– 551 Upper respiratory tract infections (URTI), and PA, 541– 543, 550– 551 Urban Land Institute, 1202 URS, see  Upper-respiratory symptoms (URS) URTI, see  Upper respiratory tract infections (URTI) US Breast-feeding Committee, 681 US Department of Agriculture (USDA), 82, 90, 92, 102, 108, 335, 890, 981, 1375, 1376

Choose My Plate graphic, 90 dietary guidelines, 890 Food Patterns, 90 MyPlate, 890 US Department of Transportation (DOT), 1368, 1370 US Department of Veterans Affairs (VA), 275 US Male Professional Health Trial, 6, 7, 9 US National Activity Plan, 154 US Nurses’  Health Study, 723 USPM, see  U.S. Preventive Medicine (USPM) USPM Preventive Plan Diabetes Care Management, 1185, 1187 US Preventative Screening Task Force, 1073 US Preventive Medicine (USPM), 1184, 1184– 1187, 1187, 1189 US Preventive Services Task Force (USPSTF), 20, 24, 28, 31, 264, 269, 371, 699, 716, 811, 978, 1097, 1172, 1220, 1221, 1344 US Public Health Service, 24, 640, 1053, 1108 UT, see  Ultrasound technique (UT) UWW, see  Hydrodensitometry

V VA, see  US Department of Veterans Affairs (VA) VaD, see  Vascular-induced dementia (VaD) Valproic acid, 1076 Value of health, 1181– 1189 how, 1183 overview, 1181 shared accountability, 1183– 1184 USPM program outcomes, 1184– 1187 client case study results, 1185, 1187 Intel-GE Validation Institute, 1187 what, 1184 why, 1181– 1183 Value of investment (VOI), 1172 Varenicline, 1058 Variable airflow obstruction, 590 Vascular endothelial growth factor (VEGF), 1257 Vascular-induced dementia (VaD), 1143 Vegetarian diets, 114 VEGF, see  Vascular endothelial growth factor (VEGF) Venous thromboembolism (VTE), 621– 627, 689 distal DVT, 627 embolization to pulmonary vasculature, 622 epidemiology, 621– 622 isolated subsegmental PE, 627 malignancy-associated, 627 overview, 621 pathophysiology, 622 risk factors, 623– 627 diagnosis, 625– 626 immobility, 623 massive PE, 626– 627 obesity, 623– 624 smoking, 624– 625 treatment, 626

Ventilatory threshold (VT), 1230 Very low-calorie diet (VLCD), 914, 1028, 1029 Very low-density lipoprotein (VLDL), 54, 891, 933 Very-low-energy diet (VLED), 494 Veterans Exercise Testing Study, 478 Veterans Specific Activity Questionnaire (VSAQ), 170 Virtual reality (VR), 320– 321 Vision and dexterity, 129 Vitamin C, 118, 337, 813 Vitamin D, 118, 127, 337, 813– 814, 954, 1144– 1145, 1330– 1331 Vitamin E, 118, 337– 338, 814 VIVA Connects, 1386 VLCD, see  Very low-calorie diet (VLCD) VLDL, see  Very low-density lipoprotein (VLDL) VLED, see  Very-low-energy diet (VLED) VOI, see  Value of investment (VOI) Volkow, N. D., 1071 Voluntary exercise behavior, 1237– 1247 definitions, 1237– 1238 family studies, 1246– 1247 gene-finding studies, 1247 overview, 1237 prevalence, 1238, 1239 twin studies, 1239– 1244, 1246 Voluntary labeling, 94– 95 VR, see  Virtual reality (VR) VSAQ, see  Veterans Specific Activity Questionnaire (VSAQ) VT, see  Ventilatory threshold (VT) VTE, see  Venous thromboembolism (VTE)

W Waist circumference (WC), 173– 174, 457 Waist-stature ratio (WSR), 457– 458 Waist-to-height ratio (WHtR), 457– 458 Waist-to-hip ratio (WHR), 457 Warburg effect, 448 Warm-up and cool-down, 184 Washington, George, 1051 Washingtonian Movement, 1052 WAT, see  White adipose tissue (WAT) Water balance, 135– 136 Water pipe smoking, 644– 645 Water requirements and active lifestyle, 135– 141 drinking strategies, 139 hydration as part of healthy lifestyle, 139– 141 for recreational activity, 138– 139 status and performance, 137– 138 overview, 135 sweating and body water turnover, 136– 137 water balance, 135– 136 WATI, see  Web-Assisted Tobacco Intervention (WATI) Watson, Bill, 1053 Ways of Coping  measure, 1004 WC, see  Waist circumference (WC) WCH, see  White coat hypertension (WCH) WCRF, see  World Cancer Research Fund (WCRF)

Index  1435 WEA, see  Work-exacerbated asthma (WEA) Weaning, 682 “ Wear Red”  program, 11 Web-Assisted Tobacco Intervention (WATI), 1108 Weight loss interventions (WLI), 388 Weight loss variability and PA, 477– 478 biological factors, 477 components of energy expenditure, 477 energy intake, 477 factors influencing adherence, 477– 478 Weight management, 69, 315– 316, 317 complementary therapies, 70 dyslipidemias and, 59– 60 Weight management and obesity, 529– 533 overview, 529 public health strategies, 531– 532 accounting for complex systems, 531– 532 focus on food policy, 531 removing barriers, 530– 531 bias and stigma, 530 inadequate resources for care, 530 payment systems, 530– 531 research priorities, 532– 533 attention to long-term outcomes, 533 pharmacotherapy, 532 precision medicine, 532– 533 translation science, 533 Weight Watchers©  , 1361 Wellbeing Index, 1207 Wellness Inventor, The,  301 Wernicke, Carl, 1052 WGHS, see  Women’ s Genome Health Study (WGHS) Wheezing, 584– 585 definition and physiology, 584 etiology, 584– 585 WHEL, see  Women’ s Healthy Eating and Living (WHEL) WHI, see  Women’ s Health Initiative (WHI) White, William, 1052, 1202

White adipose tissue (WAT), 443 White coat hypertension (WCH), 940– 941 White House BRAIN Initiative, 1141 WHO, see  World Health Organization (WHO) WHO European Ministerial Conference, 1193 Whole grains and dietary fiber, 116 WHR, see  Waist-to-hip ratio (WHR) WHtR, see  Waist-to-height ratio (WHtR) Wilder, R. M., 449 William J. Clinton Foundation, 1396 WINS, see  Women’ s Initiative in Nutrition Study (WINS) WLI, see  Weight loss interventions (WLI) Wolff’ s Law, 348 Women and coronary heart disease, 39– 40 Women Physicians'  Health Study,  1035 Women’ s cancers, 715– 728 breast, 715– 719 epidemiology/risk factors, 715– 716 intervention/prevention, 719 lifestyle, 717– 719 screening, 716– 717 cervical, 726– 728 epidemiology/risk factors, 726– 727 intervention/prevention, 728 lifestyle, 727– 728 screening, 727 endometrial, 723– 726 epidemiology/risk factors, 723– 724 intervention/prevention, 726 lifestyle, 725– 726 screening, 724– 725 ovarian, 719– 723 epidemiology/risk factors, 719– 720 intervention/prevention, 723 lifestyle, 722– 723 screening, 720– 722 overview, 715 Women’ s Christian Temperance Union, 1053

Women’ s Genome Health Study (WGHS), 13 Women’ s Health Initiative (WHI), 6, 31, 333, 675, 710, 722, 814 Women’ s Healthy Eating and Living (WHEL), 425– 426 Women’ s Initiative in Nutrition Study (WINS), 426 Wood, Alexander, 1052 Work-exacerbated asthma (WEA), 611 Work-related asthma (WRA), 611– 612 clinical presentation and diagnosis, 612 epidemiology, 611– 612 prevention and treatment, 612 World Cancer Research Fund (WCRF), 409, 410– 411, 412, 413, 432, 715 World Economic Forum, 1191 World Health Organization (WHO), 85, 153, 173, 231, 315, 367, 456– 457, 491, 524, 632, 673, 688, 736, 771, 802, 853, 865, 888, 951, 1004, 1011, 1048, 1128, 1158, 1159, 1193, 1195, 1219, 1220– 1221, 1271, 1277, 1337, 1351 WRA, see  Work-related asthma (WRA) Wright, C. R., 1052 WSR, see  Waist-stature ratio (WSR) Wynder, Ernst, 961

X XenicalTM , see  Orlistat Xulan, see  Ortho Evra patch

Y Yoga, 289, 474– 475 Young adult and adolescent smokers, 1062

Z Zero tolerance laws, 1306 Zinc, 338