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Jul 25, 2016 |Catherine Wong, MD; Mary Whooley, MD, FACC

There is no debate: physically active people live longer than their inactive
counterparts. This relationship has been demonstrated in a variety of populations,
including men and women, middle-aged and older adults, and patients with and
without cardiovascular disease (CVD).1-15 The magnitude of benet is enormous;
moderate exercise has been associated with up to a 40% relative risk reduction in
mortality and a 3-year increase in longevity.5,6 The most recent (2008) Oce of
Disease Prevention and Health Promotion Physical Activity Guidelines Report
recommends 150 minutes per week of moderate aerobic exercise (e.g., brisk
walking or tennis) or 75 minutes per week of vigorous aerobic exercise (e.g.,

jogging or swimming laps).16 However, signicant mortality benet is seen even at

very low levels of physical activity and rises in a dose-dependent manner up to
four times the guideline recommended amount.4-8,17,18 Understanding the
nuances of how physical activity relates to mortality can help clinicians better
translate physical activity recommendations into practice.
No randomized controlled trials have directly looked at the eect of physical
activity on mortality because lifetime follow-up is rarely feasible. However,

signicant evidence suggests that the relationship is causal.19 Numerous high

quality observational studies have demonstrated a strong and consistent

relationship between increased physical activity and decreased mortality.4-8,17,18

Furthermore, studies have demonstrated that the relationship is appropriately
sequenced, with physical inactivity preceding the development of cardiovascular
disease, and that the relationship is dose-dependent, with increasing amounts of
physical activity conferring increasing survival within a certain range. Finally, there
are several biologically plausible mechanisms that can explain the connection.
Thus by the same criteria used to declare a causal relationship between smoking
and cancer, a relationship also lacking the support of RCT data, it can be
concluded with near certainty that physical activity and decreased mortality are
causally related.
Some of the mortality benet seen with physical activity is achieved via a
reduction in traditional cardiovascular risk factors. RCTs have demonstrated that

exercise can reduce obesity, hypertension, dyslipidemia, hyperglycemia, and

smoking.20-26 Unfortunately, the short-term absolute reduction in these risk

factors is modest, even with substantial intervention. For example, after a sixmonth supervised exercise intervention of 90 to 120 minutes of vigorous exercise
per week, Blumenthal et al. demonstrated only a 4 mmHg reduction in systolic

and diastolic blood pressure.24 Stefanick et al. showed that exercise alone did not
signicantly reduce low-density lipoprotein cholesterol (LDL-C) levels, but when
combined with a low-fat diet, exercise led to a mean reduction of 20 mg/dL in
LDL-C.20 The impact of exercise on obesity has been similarly
underwhelming.21,22 In a study by Villareal et al., obese elderly adults who
exercised one to two times the guideline amount achieved no signicant weight
loss.22 A younger overweight cohort was able to achieve some weight loss, but
only after a considerable exercise regimen of running 19km (approximately 12

miles) per week for a year.21 Nonetheless, the modest short-term benets of
exercise may have substantial long-term benets. Moreover, other pathways, in
addition to traditional cardiovascular risk factors, may also mediate the mortality
benet conferred by exercise.
Accordingly, several large-scale observational studies have shown that the
association between physical activity and mortality persists, even after adjusting

for body mass index, smoking, cholesterol, hypertension, and diabetes.3-5

Inammation, currently a hotly debated topic in cardiology, could potentially
explain some of the remaining association. Physical activity has been shown to be
independently associated with lower levels of inammatory markers, such as Creactive protein.27,28 C-reactive protein has, in turn, been shown to be

independently associated with major cardiovascular events.29 Because of the

inherent limitations of observational data, it remains to be denitively shown
whether exercise can decrease inammatory markers and, more importantly,
whether reducing inammation can improve survival. Further research is needed
to clarify the interplay between inammation, exercise, and mortality. Other
subclinical measures of CVD, such as intimal medial thickness, vascular endothelial
function, and vagal tone, also have potential to explain some of the mortality
benet seen with exercise.30,31

Although most of its mortality benet comes from reducing cardiovascular

mortality, physical activity decreases cancer-specic mortality as well. Specically,
exercise has been shown to reduce the risk of developing breast, prostate, and
colon cancer,32-34 possibly via its modulation of sex and metabolic hormones.
Individuals who exercise at or above the guideline recommended amount are 10
to 15% less likely to die from cancer as compared to those who are inactive.4
Furthermore, even after a diagnosis of cancer, physical activity may continue to

slow disease progression and confer survival benet.11 Notably, the benets of
exercise may be comparable to those of breast or colon cancer screening in
reducing the risk of cancer, especially when combined with other modiable
lifestyle interventions.35-37

In summary, exercise signicantly reduces the risk of developing and dying from
CVD and cancer. Although clinicians and patients have long recognized the
importance of physical activity, its adoption remains shockingly low. In the US,
approximately one quarter of adults report no physical activity at all, and nearly

half fail to meet guideline recommended amounts.38,39 An incomplete

appreciation of how physical activity actually brings about health benets may
pose a barrier to the adoption of regular exercise. Clinicians and patients often
overemphasize the importance of surrogate endpoints, such as weight loss and
cholesterol reduction, and overlook the signicant long-term cardiovascular and
cancer-related mortality benets that are achieved even when there is little
immediate reduction in cardiovascular risk factors. Even when the long-term
benets of exercise are appreciated, many patients nd it dicult to sustain
behavioral changes without more proximal rewards and can be discouraged when
surrogate endpoints are slow to attain, as they often are. Instead, clinicians should
emphasize that exercise has substantial long-term benets on mortality and
should encourage patients to nd physical activities that they nd enjoyable. Even
without short-term improvement in traditional risk factors, routine physical activity
at any dose reduces the long-term risk of dying from cancer or CVD.
1. Paenbarger RS, Hyde RT, Wing AL, Hsieh CC. Physical activity, all-cause
mortality, and longevity of college alumni. N Engl J Med 1986;31:605-13.
2. Paenbarger RS, Hyde RT, Wing AL, Lee IM, Jung DL, Kampert JB. The
association of changes in physical-activity level and other lifestyle
characteristics with mortality among men. N Engl J Med 1993;328:538-45.
3. Kujala UM, Kaprio J, Sarna S, Koskenvuo M. Relationship of leisure-time
physical activity and mortality: the Finnish twin cohort. JAMA 1998;279:440-4.
4. Leitzmann MF, Park Y, Blair A, et al. Physical activity recommendations and
decreased risk of mortality. Arch Intern Med 2007;167:2453-60.
5. Arem H, Moore SC, Patel A, et al. Leisure time physical activity and mortality: a
detailed pooled analysis of the dose-response relationship. JAMA Intern Med
6. Lee DC, Pate RR, Lavie CJ, Sui X, Church TS, Blair SN. Leisure-time running
reduces all-cause and cardiovascular mortality risk. J Am Coll Cardiol
7. Franco OH, de Laet C, Peeters A, Jonker J, Mackenbach J, Nusselder W. Eects
of physical activity on life expectancy with cardiovascular disease. Arch Intern









Med 2005;165:2355-60.
Wen CP, Wai JP, Tsai MK, et al. Minimum amount of physical activity for
reduced mortality and extended life expectancy: a prospective cohort study.
Lancet 2011;378:1244-53.
Gregg EW, Cauley JA, Stone K, et al. Relationship of changes in physical activity
and mortality among older women. JAMA 2003;289:2379-86.
Andersen LB, Schnohr P, Schroll M, Hein HO. All-cause mortality associated
with physical activity during leisure time, work, sports, and cycling to work.
Arch Intern Med 2000;160:1621-8.
Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity
and survival after breast cancer diagnosis. JAMA 2005;293:2479-86.
Manini TM, Everhart JE, Patel KV, et al. Daily activity energy expenditure and
mortality among older adults. JAMA 2006;296:171-9.
Lawler PR, Filion KB, Eisenberg MJ. Ecacy of exercise-based cardiac
rehabilitation post-myocardial infarction: a systematic review and metaanalysis of randomized controlled trials. Am Heart J 2011;162:571-84.
Taylor RS, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients
with coronary heart disease: systematic review and meta-analysis of
randomized controlled trials. Am J Med 2004;116:682-92.
Fried LP, Kronmal RA, Newman AB, et al. Risk factors for 5-year mortality in
older adults: the Cardiovascular Health Study. JAMA 1998;279:585-92.
Committee, P.A.G.A., Physical Activity Guidelines Advisory Committee Report.
Washington, DC 2008.
Eijsvogels TM, Thompson PD. Exercise is medicine: at any dose? JAMA
Eijsvogels TM, Molossi S, Lee DC, Emery MS, Thompson PD. Exercise at the
extremes: the amount of exercise to reduce cardiovascular events. J Am Coll
Cardiol 2016;67:316-29.
Powell KE, Thompson PD, Caspersen CJ, Kendrick JS. Physical activity and the
incidence of coronary heart disease. Annu Rev Public Health 1987;8:253-87.
Stefanick ML, Mackey S, Sheehan M, Ellsworth N, Haskell WL, Wood PD. Eects
of diet and exercise in men and postmenopausal women with low levels of
HDL cholesterol and high levels of LDL cholesterol. N Engl J Med 1998;339:1220.
Wood PD, Stefanick ML, Dreon DM, et al. Changes in plasma lipids and
lipoproteins in overweight men during weight loss through dieting as
compared with exercise. N Engl J Med 1988;319:1173-9.
Villareal DT, Chode S, Parimi N, et al. Weight loss, exercise, or both and
physical function in obese older adults. N Engl J Med 2011;364:1218-29.
Ross R, Dagnone D, Jones PJ, et al. Reduction in obesity and related comorbid
conditions after diet-induced weight loss or exercise-induced weight loss in
men. A randomized, controlled trial. Ann Intern Med 2000;133:92-103.

24. Blumenthal JA, Sherwood A, Gullettee EC, et al. Exercise and weight loss reduce
blood pressure in men and women with mild hypertension: eects on
cardiovascular, metabolic, and hemodynamic functioning. Arch Intern Med
25. Church TS, Blair SN, Cocreham S, et al. Eects of aerobic and resistance
training on hemoglobin A1c levels in patients with type 2 diabetes: a
randomized controlled trial. JAMA 2010;304:2253-62.
26. Signal RJ, Kenny GP, Boule NG, et al. Eects of aerobic training, resistance
training, or both on glycemic control in type 2 diabetes: a randomized trial.
Ann Intern Med 2007;147:357-69.
27. Jarvie JL, Whooley MA, Regan MC, Sin NL, Cohen BE. Eect of physical activity
level on biomarkers of inammation and insulin resistance over 5 years in
outpatients with coronary heart disease (from the Heart and Soul Study). Am J
Cardiol 2014;114:1192-7.
28. Hamer M, Sabia S, Batty GD, et al. Physical activity and inammatory markers
over 10 years: follow-up in men and women from the Whitehall II cohort study.
Circulation 2012;126:928-33.
29. Danesh J, Wheeler JG, Hirscheld GM, et al. C-reactive protein and other
circulating markers of inammation in the prediction of coronary heart
disease. N Engl J Med 2004;350:1387-97.
30. Pahkala K, Heinonen OJ, Simell O, et al. Association of physical activity with
vascular endothelial function and intima-media thickness. Circulation
31. Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS. Heart-rate recovery
immediately after exercise as a predictor of mortality. N Engl J Med
32. Boyle T, Keegel T, Bull F, Heyworth J, Fritschi L. Physical activity and risks of
proximal and distal colon cancers: a systematic review and meta-analysis. J
Natl Cancer Inst 2012;104:1548-61.
33. Thune I, Brenn T, Lund E, Gaard M. Physical activity and the risk of breast
cancer. N Engl J Med 1997;336:1269-75.
34. Giovannucci EL, Liu Y, Leitzmann MF, Stampfer MJ, Willett WC. A prospective
study of physical activity and incident and fatal prostate cancer. Arch Intern
Med 2005;165:1005-10.
35. Ford ES, Bergmann MM, Kroger J, Schienkiewitz A, Weikert C, Boeing H. Healthy
living is the best revenge: ndings from the European Prospective Investigation
Into Cancer and Nutrition-Potsdam study. Arch Intern Med 2009;169:1355-62.
36. Hewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal
cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst
Rev 2007:CD001216.
37. Nelson HD, Cantor A, Humphrey L, et al. Screening for breast cancer: an
update for the U.S. Preventive Services Task Force. Ann Intern Med

38. Dwyer-Lindgren L, Freedman G, Engell RE, et al. Prevalence of physical activity
and obesity in US counties, 2001-2011: a road map for action. Popul Health
Metr 2013;11:7.
39. Hallal PC, Andersen LB, Bull FC, et al. Global physical activity levels: surveillance
progress, pitfalls, and prospects. Lancet 2012;380:247-57.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia,
Prevention, Lipid Metabolism, Nonstatins, Diet, Exercise, Hypertension,
Keywords: Adult, Biological Markers, Blood Pressure, Body Mass Index, C-Reactive Protein,
Cardiovascular Diseases, Cholesterol, LDL, Colonic Neoplasms, Diabetes Mellitus, Diet, FatRestricted, Disease Progression, Dyslipidemias, Early Detection of Cancer, Exercise Therapy,
Health Promotion, Hyperglycemia, Hypertension, Inammation, Life Style, Longevity, Obesity,
Overweight, Prostate, Risk Factors, Smoking, Weight Loss

2016 American College of Cardiology Foundation. All rights reserved.