The World Health Organization (WHO) lists physical inactivity as the fourth leading cause of non-communicable disease, behind only high blood pressure, smoking, and hyperglycemia. Moreover, the worldwide prevalence of a sedentary lifestyle is also growing, and a lack of leisure time physical activity is pandemic.¹ In this scenario, it is not a novelty that physical activity promotes health. Perhaps this message was formally incorporated in the body of knowledge of medicine by the landmark study carried out in London workers by Morris and collaborators in the 1950s.² Following this study, several other relevant contributions have been made by using different cohorts,^3-11 unanimously identifying beneficial effects of regular physical activity on mortality risk and comprising the current state-of-the-art in exercise and physical activity epidemiology. Nevertheless, there are still several unanswered, or partially answered, questions in this important public health topic. Particularly, there are very relevant gaps regarding the ideal intensity and/or quantity of physical activity for health promotion and for the improvement of life expectancy, as well as for a better characterization of a dose-response relationship between amount of physical activity and mortality risk reduction and if an exaggeration pattern can be precisely defined.^12-19

A recent large multicenter study published in JAMA Internal Medicine²⁰ added significant information to that which was already known in the topic and contributes to fill some of the major gaps in the knowledge. Arem et al.²⁰ pooled data from six studies in the National Cancer Institute Cohort Consortium, collecting prospective data from almost 700,000 men and women (ages varying from 21 to 98 years old, with a median age of 62 years), with a median follow-up time of approximately 14 years. About 10% of the subjects died during the follow-up period. Subjects were recruited from several regions of the U.S. and Sweden. Their main objectives were as follows: 1) to quantify the dose-response relationship between leisure time physical activity and mortality (all-cause, cardiovascular, and cancer-related), and 2) to define the upper limit of benefit or harm associated with higher levels of regular physical activity. The 2008 Physical Activity Guidelines for Americans was utilized²¹ as reference for analyzing the level of physical activity. According to these guidelines, the minimum leisure time physical activity has been defined as 150 minutes/week of moderate exercise, 75 minutes/week of a vigorous-intensity activity, or some combination of both. This is roughly equivalent to 7.5 metabolic equivalent (MET) hours/week. A single application of questionnaires obtained the data regarding physical activity pattern. The study authors also estimated weekly energy expenditure in MET hours/week, using MET intensities from the Compendium of physical activities.²² Subjects varied considerably regarding level of leisure time physical activity, with 8% completely inactive and only 0.6% extremely active.

One of the most striking of several interesting results was a clear dose-response relationship between the amount of leisure time physical activity and mortality risk reduction, even when adjusted for several relevant potential confounders. The risk reduction started at low levels of regular physical activity and practically doubled until three to five times the minimum recommended weekly physical activity levels were reached, with minimal or no significant changes thenceforth. Importantly, regular physical activity reduced the risk of both cardiovascular and cancer deaths, although the dose-response relationship slope was slightly steeper for cardiovascular deaths than for cancer-related deaths. Another relevant finding was that the 4,077 extremely active subjects also showed a clear mortality risk reduction – only 212 deaths – as compared with sedentary subjects, although their results did not differ from those subjects that just met or surpassed the minimum recommended dose of weekly physical activity.

Nevertheless, there are some aspects or limitations that are amenable to comment. It is remarkable that a simple one-point questionnaire using self-report leisure time physical activity questionnaire was so nicely able to disclose the beneficial effects on mortality. Unfortunately, this is a very difficult limitation to overcome, especially for such a large sample, since direct measurements of activity or energy expenditure are very complex to obtain. Additionally, there are some issues related to the sample. Unlike most other exercise/physical activity epidemiological studies, the large sample of this study was predominantly composed of women (56%). It could also be thought that the overall sample was somewhat biased toward a more physically active pattern. Only 8% were considered physically inactive (0 MET hours/week), and the vast majority of the subjects clearly exceed the minimum recommended amount of weekly physical activity for adults of all ages, a surprising fact for a sample with a median age of 62 years. Another important aspect to consider is the demographic characteristics of the sample (ethnicity/race, socioeconomic, and education) and if these data could be extrapolated for other populations with more diverse demographic profiles.

From a clinical cardiologist's perspective, the results of this study corroborate the available body of knowledge indicating that even modest amounts of regular physical exercise are able to substantially decrease mortality risk in adults. In addition, optimal dose for mortality reduction was three to five times the current minimum recommended amount of leisure time physical activity, a very important public health issue.

In summary, this study presents a powerful incentive for cardiologists to clearly advise their sedentary patients, or those with modest physical activity, to become more involved in regular physical activity. In addition, while the individual motivation to participate in a marathon or similar events may far exceed the objective of improving or promoting health, at least from the point of view of mortality risk; in general, it should not be formally discouraged. Finally, a definitive goal for a well-informed cardiologist should be to have all of his or her patients as exercisers. Let's make a proposal: why not start by filling your next prescription with exercise, and then follow with the appropriate and needed medications?

References

1. Kohl HW 3rd, Craig CL, Lambert EV, et al. The pandemic of physical inactivity: global action for public health: Lancet Physical Activity Series Working Group. Lancet 2012;;380:294-305.
2. Morris JN, Heady JA, Raffle PA, Roberts CG, Parks JW. Coronary heart-disease and physical activity of work. Lancet 1953;265:1053-7.
3. Paffenbarger RS Jr, Hyde RT, Wing AL, Hsieh CC. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med 1986;314:605-13.
4. Berlin JA, Colditz GA. A meta-analysis of physical activity in the prevention of coronary heart disease. Am J Epidemiol 1990;132:612-28.
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9. Myers J, Kaykha A, George S, et al. Fitness versus physical activity patterns in predicting mortality in men. Am J Med 2004;117:912-8.
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11. Moore SC, Patel AV, Matthews CE, et al. Leisure time physical activity of moderate to vigorous intensity and mortality: a large pooled cohort analysis. PLoS Med 2012;9:e1001335.
12. DeFina LF, Haskell WL, et al. Physical activity versus cardiorespiratory fitness: two (partly) distinct components of cardiovascular health? Prog Cardiovasc Dis 2015;57:324-9.
13. Haskell WL. Physical activity and health: need to define the required stimulus. Am J Cardiol 1985;55:4D-9D.
14. Blair SN, Kohl HW, Gordon NF, Paffenbarger RS, Jr. How much physical activity is good for health? Annu Rev Public Health 1992;13:99-126.
15. Lee IM, Paffenbarger RS, Jr. How much physical activity is optimal for health? Methodological considerations. Res Q Exerc Sport 1996;67:206-8.
16. Lee IM, Skerrett PJ. Physical activity and all-cause mortality: what is the dose-response relation? Med Sci Sports Exerc 2001;33:S459-71; discussion S93-4. 17. Lee IM, Sesso HD, Oguma Y, Paffenbarger RS, Jr. Relative intensity of physical activity and risk of coronary heart disease. Circulation 2003;107:1110-6.
17. Blair SN, Haskell WL. Objectively measured physical activity and mortality in older adults. JAMA 2006;296:216-8.
18. Powell KE, Paluch AE, Blair SN. Physical activity for health: What kind? How much? How intense? On top of what? Annu Rev Public Health 2011;32:349-65.
19. 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.
20. Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee Report, 2008. 2008:. U.S. Department of Health and Human Services Washington, DC.
21. Ainsworth BE, Haskell WL, Whitt MC, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000;32:S498-504.

Keywords: Energy Metabolism, Epidemiologic Studies, Exercise, Follow-Up Studies, Goals, Health Promotion, Hyperglycemia, Hypertension, Leisure Activities, Life Expectancy, Metabolic Equivalent, Motivation, Neoplasms, Pandemics, Prevalence, Prospective Studies, Public Health, Risk, Risk Reduction Behavior, Sedentary Behavior, Athletes

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