Living Longer Through Physical Activity
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 benefit 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) Office 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, significant mortality benefit 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 effect of physical activity on mortality because lifetime follow-up is rarely feasible. However, significant 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 benefit 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 six-month 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 significantly 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 significant 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 benefits of exercise may have substantial long-term benefits. Moreover, other pathways, in addition to traditional cardiovascular risk factors, may also mediate the mortality benefit 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 Inflammation, 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 inflammatory markers, such as C-reactive 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 definitively shown whether exercise can decrease inflammatory markers and, more importantly, whether reducing inflammation can improve survival. Further research is needed to clarify the interplay between inflammation, 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 benefit seen with exercise.30,31
Although most of its mortality benefit comes from reducing cardiovascular mortality, physical activity decreases cancer-specific mortality as well. Specifically, 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 benefit.11 Notably, the benefits of exercise may be comparable to those of breast or colon cancer screening in reducing the risk of cancer, especially when combined with other modifiable lifestyle interventions.35-37
In summary, exercise significantly 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 benefits 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 significant long-term cardiovascular and cancer-related mortality benefits that are achieved even when there is little immediate reduction in cardiovascular risk factors. Even when the long-term benefits of exercise are appreciated, many patients find it difficult 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 benefits on mortality and should encourage patients to find physical activities that they find 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.
- Paffenbarger 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.
- Paffenbarger 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.
- 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.
- Leitzmann MF, Park Y, Blair A, et al. Physical activity recommendations and decreased risk of mortality. Arch Intern Med 2007;167:2453-60.
- 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 2015;175:959-67.
- 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 2014;64:472-81.
- Franco OH, de Laet C, Peeters A, Jonker J, Mackenbach J, Nusselder W. Effects 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. Efficacy of exercise-based cardiac rehabilitation post-myocardial infarction: a systematic review and meta-analysis 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 2015;314:1915-6.
- 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. Effects 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;339:12-20.
- 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.
- Blumenthal JA, Sherwood A, Gullettee EC, et al. Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning. Arch Intern Med 2000;160:1947-58.
- Church TS, Blair SN, Cocreham S, et al. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA 2010;304:2253-62.
- Signal RJ, Kenny GP, Boule NG, et al. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med 2007;147:357-69.
- Jarvie JL, Whooley MA, Regan MC, Sin NL, Cohen BE. Effect of physical activity level on biomarkers of inflammation 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.
- Hamer M, Sabia S, Batty GD, et al. Physical activity and inflammatory markers over 10 years: follow-up in men and women from the Whitehall II cohort study. Circulation 2012;126:928-33.
- Danesh J, Wheeler JG, Hirschfield GM, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 2004;350:1387-97.
- Pahkala K, Heinonen OJ, Simell O, et al. Association of physical activity with vascular endothelial function and intima-media thickness. Circulation 2011;124:1956-63.
- 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 1999;341:1351-7.
- 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.
- Thune I, Brenn T, Lund E, Gaard M. Physical activity and the risk of breast cancer. N Engl J Med 1997;336:1269-75.
- 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.
- Ford ES, Bergmann MM, Kroger J, Schienkiewitz A, Weikert C, Boeing H. Healthy living is the best revenge: findings from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study. Arch Intern Med 2009;169:1355-62.
- 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.
- 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 2009;151:727-37.
- 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.
- Hallal PC, Andersen LB, Bull FC, et al. Global physical activity levels: surveillance progress, pitfalls, and prospects. Lancet 2012;380:247-57.
Keywords: Adult, Biomarkers, Blood Pressure, Body Mass Index, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, LDL, Colonic Neoplasms, Diabetes Mellitus, Diet, Fat-Restricted, Disease Progression, Dyslipidemias, Early Detection of Cancer, Exercise Therapy, Health Promotion, Hyperglycemia, Hypertension, Inflammation, Life Style, Longevity, Obesity, Overweight, Prostate, Risk Factors, Smoking, Weight Loss
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