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.


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Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Diet, Exercise, Hypertension, Smoking

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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