Background

Guidelines on physical activity from the American Heart Association and American College of Cardiology¹ recommend that most patients with cardiovascular disease take 150 minutes of moderate or vigorous intensity exercise each week. This amount of exercise is the same as that recommended by the World Health Organisation for all adults. However, about a quarter of the world's population are sedentary, and many patients decrease habitual physical activity after the diagnosis of coronary heart disease (CHD).² Patients, and sometimes physicians, may be cautious about the risks of more vigorous exercise, particularly if there are exertional symptoms or indicators of increased cardiovascular risk. It is therefore relevant to consider whether more modest increases in physical activity below the recommended guidelines could benefit sedentary patients and to evaluate evidence of possible risks of more vigorous exercise in patients with stable CHD.

Habitual Exercise and Mortality in General Populations

A graded association between increasing amounts of physical activity and both cardiovascular and non-cardiovascular mortality has been observed in epidemiological studies in diverse populations.^3,4 Benefits related to leisure time physical activity, which is relatively more important in rich countries, and exercise related to work and daily activities, which is relatively more important in lower and middle income countries, are both associated with lower mortality and fewer major cardiovascular events.^5,6

Epidemiological studies also suggest that excessive sedentary time, for example prolonged sitting, increases mortality,⁷ and more time spent standing is associated with lower mortality.⁸ The association between increasing physical activity and mortality is not linear, being relatively greater in more sedentary people and more modest between people who take regular moderate or vigorous exercise.^3,6 In many studies, people who take any vigorous physical activity have a lower mortality risk compared with those who do not, but the incremental benefits of increasing volumes of vigorous physical activity are also more modest. In the Copenhagen City Heart Study,⁹ mortality was about halved in joggers who ran once or <1 hour each week and lower again for those who jogged 1-2.4 hours or 2-3 times per week compared with sedentary non-joggers. However, higher jogging volumes were not associated with a further mortality benefit. In the Aerobics Centre Longitudinal Study,¹⁰ a 15-year prospective study of 55,137 healthy Texans, runners (including those who ran for short periods and at slow speeds) had lower total and cardiovascular mortality compared with non-runners. Persistent runners also had lower mortality than intermittent runners, suggesting that maintenance of vigorous physical activity over the longer term is important.

That vigorous physical activity over the life course has a favourable effect on mortality is supported by a meta-analysis of 10 studies that included 42,807 athletes.¹¹ Compared with the general population, the all-cause pooled standard mortality ratio was 0.67 (95% confidence interval [CI], 0.55-0.81), with reduction in mortality from both cardiovascular disease and cancer. Also, large general population studies report graded decreases in mortality, including in persons who report the highest volumes and intensities of physical activity.^3,4

Benefits of Modest Physical Activity in Patients With Stable CHD

The importance of modest amounts of physical activity was evaluated in patients enrolled in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, which enrolled 15,828 high-risk patients with stable CHD from 39 countries and assessed outcomes over 3.7 years.¹² In this study, as in most epidemiological studies, usual physical activity was assessed by questionnaire. Questions from the International Physical Activity Questionnaire were used to estimate the hours each week taking mild, moderate, and vigorous physical activity. Despite imprecision in estimates of habitual exercise, there was a clear graded decrease in mortality with increasing volume of self-reported physical activity (Figure 1). As observed in general population studies, this risk reduction was steeper at lower levels of usual activity and more modest when above the level of moderate or vigorous activity recommended in current guidelines.

Figure 1: Association Between Self-Reported Physical Activity and Cardiovascular and Non-Cardiovascular Mortality in Patients With Stable CHD Who Participated in the STABILITY Trial

In the STABILITY trial, the association between doubling of physical activity volume and lower all-cause mortality was present both before (Hazard ratio [HR] 0.82; 95% CI, 0.79-0.85) and after adjusting for covariates (HR 0.90; 95% CI, 0.87-0.93). Reduced risk was observed for both cardiovascular and non-cardiovascular mortality, but associations were weaker for risk of myocardial infarction and not significant for stroke. Separate analyses confirmed that both exercise duration and average exercise intensity were important. The associations with mortality may be partly explained by other cardiovascular risk factors, by co-morbidity (which can reduce exercise capacity), and by socioeconomic factors related to geography and education. These potential confounders make it more difficult to quantify the true benefits of exercise. However, associations are consistent with those observed in many large epidemiological studies and with meta-analyses of randomised trials of exercise-based cardiac rehabilitation in which interventions that increase physical activity are associated with a lower cardiovascular death rate.¹³

Impact of Increased Cardiovascular Risk and Symptoms

In the STABILITY study, reduction in mortality associated with increase in physical activity volume was greater in participants who reported taking less than the 10 MET.hours of moderate or vigorous exercise per week recommended in guidelines compared with participants taking more than the recommended MET.hours. It was also greater in participants who reported limitation of exercise by dyspnea and those at higher risk of adverse cardiovascular events estimated from the STABILITY CHD risk score,¹⁴ which is calculated from age, troponin T, N-terminal pro-B-type natriuretic peptide, low-density lipoprotein cholesterol, peripheral vascular disease, diabetes, and smoking. Reduction in risk with greater habitual exercise was similar in patients limited and not limited by exertional chest discomfort. Left ventricular function was not assessed in the STABILITY trial, and risk factors related to exercise such as myocardial ischemia and arrhythmia were also not evaluated. With these caveats, the observations suggest that the majority of patients with stable CHD at high cardiovascular risk are likely to benefit at least as much or more from increasing physical activity as low-risk patients.

Vigorous Physical Activity in Patients With Stable CHD

It is possible that vigorous exercise may increase risk in some people with heart disease. The risk of myocardial infarction and sudden death increases during and 1 hour after vigorous exercise. This temporal increase in risk is highest in normally inactive persons and much lower in those who take regular moderate exercise.^15,16 The risk of death or a cardiac arrest while participating in a supervised cardiac rehabilitation programme is very low, and randomised trials are reassuring about increasing exercise intensity in patients with stable CHD.¹³

In self-identified heart attack survivors from the US National Runners Health Study and National Walkers Health study,¹⁷ those running up to 5.4-7.2 MET.hours per day had 63% lower mortality than non-runners. However, individuals who exercised more than 7.2 MET.hours per day had a relatively higher mortality, despite a more favourable cardiovascular risk factor profile. A similar "J-shaped" association has been reported in 1,038 participants in a cardiac rehabilitation programme followed for 10 years.¹⁸ The risks of major cardiovascular events and mortality over 10 years was nearly twice as high in the least-physically active group who exercised "rarely/never" compared with the lowest mortality group who exercised 2-4 times per week. However, for individuals who took vigorous exercise 5-6 times a week or more, there was a trend for a higher mortality. In contrast, in the STABILITY trial,¹² increasing durations of vigorous physical activity above those recommended in guidelines had a neutral association with outcomes. In that study, the number of persons reporting very high levels of vigorous exercise was relatively small, and a modest hazard cannot be excluded.

Implications for Guidelines on Physical Activity

Large cohort studies in both general and stable CHD populations therefore support current recommendations to take 150 minutes of moderate or vigorous physical activity each week. In addition, there is good evidence that engaging in more modest levels of exercise and avoiding prolonged sedentary time are likely to benefit sedentary patients with stable CHD, including those limited by exertional angina or dyspnea.

One challenge is to communicate the clinical importance of the non-linear association between physical activity and mortality. In the STABILITY analysis, the risk reduction associated with each doubling of habitual exercise volume was reported. This approach allows an estimate of potential benefits from increasing habitual exercise intensity and/or exercise duration, relative to current activity levels. Individuals who take little exercise would have an important benefit from modest increases in usual activity; for persons who regularly exercise at a higher level, the potential for benefit is smaller and may be harder to achieve.

Given the range of habitual exercise taken by patients with stable CHD and the large number who are sedentary, these observations may assist with more individualised advice. This can be guided by the current level of physical activity, with goals thought likely to be achieved and maintained over the short and medium term. Because the cardiovascular risks of reducing sedentary time and of moderate-intensity physical activity are low, modest increases in physical activity can generally be achieved without a supervised exercise programme.

References

1. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2960-84.
2. Stewart R, Held C, Brown R, et al. Physical activity in patients with stable coronary heart disease: an international perspective. Eur Heart J 2013;34:3286-93.
3. 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.
4. 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.
5. Bennett DA, Du H, Clarke R, et al. Association of Physical Activity With Risk of Major Cardiovascular Diseases in Chinese Men and Women. JAMA Cardiol 2017;2:1349-58.
6. Lear SA, Hu W, Rangarajan S, et al. The effect of physical activity on mortality and cardiovascular disease in 130,000 people from 17 high-income, middle-income, and low-income countries: the PURE study. Lancet 2017;390:2643-54.
7. Biswas A, Oh PI, Faulkner GE, et al. Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis. Ann Intern Med 2015;162:123-32.
8. van der Ploeg HP, Chey T, Ding D, Chau JY, Stamatakis E, Bauman AE. Standing time and all-cause mortality in a large cohort of Australian adults. Prev Med 2014;69:187-91, .
9. Schnohr P, O'Keefe JH, Marott JL, Lange P, Jensen GB. Dose of jogging and long-term mortality: the Copenhagen City Heart Study. J Am Coll Cardiol 2015;65:411-9.
10. 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.
11. Garatachea N, Santos-Lozano A, Sanchis-Gomar F, et al. Elite athletes live longer than the general population: a meta-analysis. Mayo Clin Proc 2014;89:1195-200.
12. Stewart RAH, Held C, Hadziosmanovic N, et al. Physical Activity and Mortality in Patients With Stable Coronary Heart Disease. J Am Coll Cardiol 2017;70:1689-700.
13. Anderson L, Oldridge N, Thompson DR, et al. Exercise-Based Cardiac Rehabilitation for Coronary Heart Disease: Cochrane Systematic Review and Meta-Analysis. J Am Coll Cardiol 2016;67:1-12.
14. Lindholm D, Lindbäck J, Armstrong PW, et al. Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease. J Am Coll Cardiol 2017;70:813-26.
15. Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators. N Engl J Med 1993;329:1677-83.
16. Albert CM, Mittleman MA, Chae CU, Lee IM, Hennekens CH, Manson JE. Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med 2000;343:1355-61.
17. Williams PT, Thompson PD. Increased cardiovascular disease mortality associated with excessive exercise in heart attack survivors. Mayo Clin Proc 2014;89:1187-94.
18. Mons U, Hahmann H, Brenner H. A reverse J-shaped association of leisure time physical activity with prognosis in patients with stable coronary heart disease: evidence from a large cohort with repeated measurements. Heart 2014;100:1043-9.

Keywords: American Heart Association, Arrhythmias, Cardiac, Athletes, Benzaldehydes, Cardiac Rehabilitation, Cardiovascular Diseases, Cholesterol, LDL, Cohort Studies, Confidence Intervals, Coronary Artery Disease, Coronary Disease, Death, Sudden, Death, Sudden, Cardiac, Diabetes Mellitus, Dyspnea, Epidemiologic Studies, Exercise, Exercise Therapy, Heart Arrest, Jogging, Longitudinal Studies, Myocardial Infarction, Natriuretic Peptide, Brain, Neoplasms, Oximes, Peptide Fragments, Peripheral Vascular Diseases, Plaque, Atherosclerotic, Prospective Studies, Risk Factors, Risk Reduction Behavior, Running, Sedentary Behavior, Socioeconomic Factors, Stroke, Survivors, Troponin T, Ventricular Function, Left, Angina, Stable

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