Physical activity and long-term prognosis in patients with stable coronary artery disease: How often, how intense, and how long?

The terms ‘physical activity’, ‘exercise’ and ‘physical fitness’ are often confused and sometimes used interchangeably. In 1985, Caspersen et al. clearly defined the terms as follows.1 Physical activity was defined as ‘any bodily movement produced by skeletal muscles that results in energy expenditure’. It can be measured in kilocalories. The amount of caloric expenditure is calculated by the total amount of bodily movements and the intensity, duration and frequency of muscular contractions. Physical activity can also be categorized as occupational, conditioning, household, sports or other activities in daily life.1 Although the amount of energy expenditure during sleep is small, sleep is also categorized as physical activity. ‘Exercise’ is commonly used interchangeably with ‘physical activity’; however, it is ‘a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermediate objective the improvement or maintenance of physical fitness’.1 Exercise is one of the important parts of physical activities because of the relatively high energy expenditure. In addition, sports and conditioning are able to improve and maintain physical fitness levels. Physical fitness is ‘a set of attributes that are either health- or skill-related’.1 There are five health-related components of physical fitness, as follows: cardiorespiratory endurance, muscular endurance, muscular strength, body composition, and flexibility.1 Each component can be measured and ranges from low to high using specific tests (Figure 1). Impact of physical activity, exercise and physical fitness on mortality in patients with coronary artery disease. Impact of physical activity, exercise and physical fitness on mortality in patients with coronary artery disease. Physical inactivity has been identified as an important risk factor for the development of coronary artery disease (CAD).2 In contrast, regular exercise and physical activity, including any leisure interests that involve increased energy expenditure, are associated with lower mortality in patients with stable CAD.3–5 The European Society of Cardiology guideline recommends moderate-to-vigorous-intensity aerobic exercise training ≥3 times a week and for 30 min per session in patients with stable CAD. In addition, sedentary patients with CAD are strongly encouraged to start light-intensity exercise programs after adequate exercise-related risk stratification.6 Numerous studies have suggested various beneficial effects of regular physical activity on coronary risk factors, circulating blood, heart and vasculature in patients with CAD.2,7 Exercise training ameliorates body composition, blood pressure, plasma lipid profiles, insulin sensitivity, glucose intolerance, platelet activation, number of progenitor cells, endothelial dysfunction, atherosclerotic development, collateral formation, resting heart rate, myocardial perfusion, pathological remodeling of left ventricle, wall compliance, contraction–relaxation velocity and cardiac output.2,7–9 We have previously reported an association between the percent changes in coronary plaque volume assessed using intravascular volumetric ultrasonography and physical activity in patients who participated in phase II cardiac rehabilitation after acute coronary syndrome (ACS).10 The percent change in the plaque volume was significantly and negatively correlated with daily physical activity evaluated using a pedometer.10 We have also reported the association between the changes in coronary plaque components assessed using serial integrated backscatter intravascular ultrasonography and physical activity in patients who participated in phase II cardiac rehabilitation after ACS.11 Percent change in the lipid volume was significantly lower in the active group (defined as ≥7000 steps/d) than in the inactive group (<7000 steps/d). In addition, these changes negatively and independently correlated with daily physical activity.11 In this issue of the European Journal of Preventive Cardiology, Biscaglia et al. have reported novel aspects of physical activity and long-term outcomes in 32,370 patients with stable CAD who were enrolled in CLARIFY (prospective observational longitudinal registry of patients with stable coronary artery disease).12 Study patients were enrolled from 45 countries in Africa, Asia, Australia, Europe, the Middle East, and North, Central and South America and followed for up to five years. At the baseline, physical activity was self-reported and categorized into the following four groups: no physical activity (sedentary), only light physical activity during most weeks (light), vigorous physical activity for ≥20 min once or twice a week (vigorous ≤2 × ), and vigorous physical activity for ≥20 min three or more times per week (vigorous >2×). Physical activity served as an independent predictor of the primary outcome, including cardiovascular death, non-fatal myocardial infarction, and stroke, on multivariate analyses. In comparison with those who performed light physical activity, sedentary patients had the highest risk of the primary outcome (hazard ratio, 1.31; 95% confidence interval (CI), 1.18–1.46) and those who did vigorous physical activity ≤2 × had the best outcomes (hazard ratio, 0.82; 95% CI, 0.71–0.93). Interestingly, more frequent exercise in the vigorous >2 × group was not associated with greater benefit (hazard ratio, 0.94; 95% CI, 0.82–1.07).12 This study presents important findings regarding the beneficial effects of physical activity in patients with stable CAD.12 The results suggest that (1) various levels of physical activity are associated with a favorable outcome in terms of all-cause mortality and cardiovascular mortality, (2) the determinants of physical activity levels were associated with sex, race/ethnicity, employment status, education level, smoking history, family history of CAD, dyslipidemia and various comorbidities, and (3) although vigorous activity ≤ 2 × is associated with outcomes superior to light activity and light activity is associated with better outcomes than sedentary, higher frequency of vigorous physical activity was not associated with greater clinical benefit. As discussed by the authors, this study has three major limitations. First, the physical activity levels were self-reported; therefore, they were not measured objectively using equipment, such as a pedometer or a specific device. Second, the information regarding cardiac rehabilitation participation is lacking. Third, the levels of physical activity were assessed only at baseline. Sustained physical activity confers the largest benefits against cardiovascular risks in patients with CAD.5 Further precise investigations are needed to clarify the findings of this study, especially in order to overcome the third limitation. We need to determine whether the subjects who performed vigorous physical activity for ≥20 min at least thrice per week (vigorous >2 × ) at baseline maintained the activity during the follow-up period or whether these subjects shifted from vigorous >2 × to vigorous ≤2 × or light or sedentary exercise. The frequency, intensity and duration of physical activity are important for reducing morbidity and mortality of cardiovascular events. Therefore, several confounding factors could have affected the results. In fact, the optimal amount, upper limit and the threshold of physical exercise required to reduce cardiovascular events remain controversial. Previous studies have shown a dose–response relationship between habitual exercise and mortality in patients with CAD.3,13 In contrast, Williams and Thompson reported increased cardiovascular disease mortality associated with excessive exercise among heart attack survivors, suggesting a U-shaped relationship between endurance exercise and mortality reduction.14 Similar trends which attenuated the benefits of exercise for reducing mortality risk in the most active subjects were observed in other studies.15,16 Very high and extreme levels of exercise may lead to cardiac fibrosis, remodeling and increased risk of serious ventricular arrhythmia and vulnerable plaque rupture.14,17 In addition, high levels of physical activity are associated with coronary calcification.18 Therefore, the evaluation of the changes in physical activity between at least two separate periods, as reported by Moholdt et al.,5 is necessary to assess the association between physical activity and mortality in patients with CAD. In conclusion, this large-scale study on the CLARIFY population clearly demonstrates that any level of physical activity is associated with reduced risk of all-cause mortality and cardiovascular mortality in patients with stable CAD. Currently, risk factor modification is largely insufficient, particularly in patients with CAD.19 It is important to increase the daily physical activity to address cardiovascular health and reduce mortality risk not only in primary preventive subjects, but also in secondary preventive patients with CAD. Nevertheless, the most efficient exercise type, frequency, intensity and duration remain unclear, especially in CAD patients. In the clinical setting, a tailored approach that is designed as per the specific health goals of each patient is essential.2,20 Further studies on this subject are also warranted. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: High Technology Research Center Grant, Strategic Research Foundation at Private Universities and KAKENHI (17K01470, 19K11374) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.