The WHO recommends that adults participate in 150 min of moderate intensity exercise each week. Guidelines of the European Society of Cardiology  and the American Heart Association/American College of Cardiology  recommend the same level of regular exercise for most patients with cardiovascular disease. The aim of this study is to summarize more recent research regarding exercise, sedentary behaviour and mortality, which is relevant to these guidelines.
THE GRADED ASSOCIATION BETWEEN PHYSICAL FITNESS AND MORTALITY
Many prospective cohort studies have reported a graded association between increasing physical fitness and lower cardiovascular risk [3–9]. Two recent studies, which evaluated cohorts with a 50-year difference in age, indicate that this graded association is evident throughout adult life.
The association between physical fitness on routine treadmill exercise testing and all-cause mortality was assessed in 2153 US men with hypertension aged at least 70 years . Fitness was based on peak metabolic equivalents (METs) adjusted for age. During 9 years of follow-up, after multivariate adjustment, mortality decreased by 11% for every 1-MET increase in exercise capacity. When compared with the least fit group (≤4 METs), mortality was 18% lower for the low-fit (4.1–6.0 METs), 36% for the moderate-fit (6.1–8.0 METs) and 48% for the high-fit individuals (>8.0 METs) (P ≤ 0.01 for all).
In 743 498 Swedish men aged 18 years, aerobic fitness and muscle strength were measured at military conscription from 1969 to 1984 . During a median follow-up of 34 years, myocardial infarctions (n = 11 526) were tracked through national registers. After adjustment for potential confounders, a one standard deviation increase in the level of physical fitness was associated with an 18% lower risk of myocardial infarction [hazard ratio 0.82, 95% confidence interval (CI) 0.80–0.85], with a graded decrease in risk with increasing physical fitness.
Studies of elite athletes also suggest a favourable association between physical fitness and mortality over the life course. In a meta-analysis of 10 studies that included 42 807 athletes, compared with the general population, the all-cause pooled standard mortality ratio was 0.67 (95% CI 0.55–0.81; P < 0.001), with a reduction in mortality from both cardiovascular disease and cancer [12▪].
THE GRADED ASSOCIATION BETWEEN PHYSICAL ACTIVITY AND MORTALITY
Rather than evaluating physical fitness, most large prospective cohort studies have evaluated associations of mortality with physical activity assessed by questionnaire. A meta-analysis that pooled data from six studies in the National Cancer Institute Cohort Consortium reported a graded association between greater self-reported moderate–vigorous activity and mortality risk in 661 137 individuals [13▪▪]. Compared with individuals who did no moderate–vigorous activity, mortality was 31% lower (hazard ratio 0.69, 95% CI 0.78–0.82) for those who reported 7.5–12.5 MET.h/week; this is one to two times the level recommended in clinical practice guidelines. Further increases in physical activity were associated with relatively small further reductions in mortality risk. Of note, increasing exercise was not associated with a higher mortality, including at levels more than 75 MET.h/week, which is more than 10 times higher than the recommended level.
The 45 and Up study, a large prospective cohort study of 267 153 Australians, also reported a graded relationship between self-reported moderate–vigorous activity and mortality [14▪]. Moderate activity was described as gentle swimming, social tennis, vigorous gardening or work around the house. Vigorous activity was defined as exercise that made it harder to breathe or to puff and pant. Examples included jogging, cycling, aerobics and competitive tennis, but not household chores or gardening. The adjusted hazard ratio for all-cause mortality for those reporting moderate–vigorous activity for less than 150 min/week was 0.66 (95% CI 0.61–0.71), for 150 to less than 300 min/week it was 0.53 (95% CI 0.48–0.57), and for more than 300 min/week it was 0.46 (95% CI 0.43–0.49) compared with those who reported none. The proportion of vigorous exercise was also important. After adjustment for overall physical activity, mortality was 13% lower for individuals who reported exercising vigorously for more than 30% of exercise time compared with those taking no vigorous exercise.
BENEFITS FROM SMALL AMOUNTS OF EXERCISE
The association between modest levels of physical activity and mortality has been reported in several studies. A prospective cohort study of 416 175 individuals in Taiwan  assessed the amount of weekly exercise by self-administered questionnaire. Compared with inactive individuals, those reporting low-volume activity, which averaged nearly 15 min of exercise a day, had a 14% lower risk of all-cause mortality, and had a 3-year longer life expectancy. Each additional 15 min of daily exercise was associated with a further 4% (95% CI 2.5–7.0) decrease in all-cause mortality.
The association between self-reported leisure time physical activity and life expectancy was also evaluated in nearly 650 000 individuals aged 21–90 years from the six cohort studies in the National Cancer Cohort Consortium described above for moderate–vigorous activity . In this report, a physical activity level of 0.1–3.74 MET.h each week, equivalent to brisk walking for 12.5 min/day or less, was associated with an increase in estimated life expectancy of nearly 1.8 years. There was a graded increase in life expectancy with greater amounts of usual physical activity.
Prospective observational cohort studies [3,6–9,15,16] that have reported mortality for a small amount of physical activity compared with no exercise are summarized in Fig. 1. Consistent associations were observed across all studies, suggesting a benefit from substantially less exercise than recommended in current guidelines.
An analysis from the National Health and Nutrition Examination Survey (NHANES)  emphasizes the importance of considering sedentary behaviour assessed by accelerometer as well as physical activity. In 1677 women and men aged at least 50 years, being sedentary for more than 8.6 h/day was associated with doubling of all-cause mortality [relative risk (RR) 2.03; 95% CI 1.1–3.8]. Low physical activity (<median of 6.6 min/day) was also associated with increased mortality (RR 3.3; 95% CI 1.3–8.2). Individuals reporting both high sedentary time and low physical activity had substantially increased mortality (RR for mortality 7.8; 95% CI 2.3–26.8).
SITTING AND MORTALITY
The association between total daily sitting time and all-cause mortality has been assessed in a meta-analysis of six prospective cohort studies that included data from 595 086 predominantly female, middle-aged or older adults from high-income countries [18▪]. Associations between sitting time and all-cause mortality were not linear. Mortality increased for every additional hour of sitting longer than 7 h/day (hazard ratio 1.05, 95% CI 1.02–1.08), but not when sitting time was less than 7 h. Adults sitting 10 h each day had a nearly 34% increase in mortality after adjustment for physical activity. The proportion of all-cause mortality attributed to prolonged daily sitting was nearly 6%.
A second systematic review reported modest associations between greater sedentary time and an increased risk of cardiovascular disease, cancer, diabetes and all-cause mortality from 47 reports [19▪]. The hazard ratios for sedentary time and outcomes were generally larger at lower than higher levels of physical activity.
Standing rather than sitting may be beneficial to health. In the ‘45 and Up’ study [20▪], hazard ratios for all-cause mortality were also evaluated by self-reported standing time. Compared with standing for 2 or less hours each day, all-cause mortality was lower for persons standing from 2 to less than 5 h/day (hazard ratio 0.90, 95% CI 0.85–0.95), from 5 to less than 8 h/day (hazard ratio 0.85, 95% CI 0.80–0.95) and more than 8 h/day (hazard ratio 0.76, 95% CI 0.69–0.95) after adjustment for potential confounders.
RUNNING AND MORTALITY
Running or jogging, even for short periods and at slow speeds, has been associated with lower mortality. In the Aerobics Centre Longitudinal Study [21▪▪], a 15-year prospective, observational cohort study of 55 137 healthy Texans, runners had lower total and cardiovascular mortality than nonrunners. This association persisted after adjustment for multiple other risk predictors and was evident across multiple subgroups. Mortality was 29% lower for persistent runners than those who reported running on only one of the two assessments. This study also suggested benefits from relatively low levels of physical activity, from running for only 5–10 min/day and at slow speeds <6 miles/h (hazard ratio 0.59, 95% CI 0.40–0.86). There was no clear evidence for a further reduction in mortality with faster speeds or longer duration of running. Those who ran the most (>176 min each week) had a lower mortality than nonjoggers (hazard ratio 0.86, 95% CI 0.62–1.21), but a 10% higher risk than those who ran between 150 and 176 min each week.
The Copenhagen City Heart Study [22▪], which included 1098 joggers and 3950 nonjoggers, also evaluated associations between running and all-cause mortality. Compared with sedentary nonjoggers, mortality was lower for individuals who reported the lowest amount of running, less than 1 h each week or running once each week (hazard ratio 0.51; 95% CI 0.24–1.10). Those who jogged 1–2.4 h and two to three times per week (hazard ratio 0.38, 95% CI 0.22–0.66) had an even lower mortality risk. However, high levels of jogging were not clearly associated with a further mortality benefit. For individuals who jogged for longer than 2.5 h each week or more than three times each week at faster paces, survival was similar to sedentary nonjoggers (hazard ratio 0.94, 95% CI 0.40–2.18).
Results from three studies [21▪▪,22▪,23▪▪], which report mortality for low-intensity and duration of running, are displayed in Fig. 2. Each of these studies suggests that low speeds and durations of running are associated with lower mortality than no running.
PHYSICAL ACTIVITY AND MORTALITY IN POPULATIONS WITH CORONARY ARTERY DISEASE
Fewer studies have evaluated associations between physical activity and mortality in patients with coronary artery disease. In an analysis from the US National Runners Health Study and National Walkers Health study 2377 [23▪▪], persons who self-identified as heart attack survivors were followed for mortality from national death registries. Physical activity was estimated from the average time and intensity of running or walking each week in METS. One MET.h/day was estimated to be the energy equivalent of running 1 km/day. There was a graded increase in mortality for those running up to 5.4–7.2 MET.h/day (P < 0.001), which was 63% lower than those who exercised for less than 1.1 MET.h/day. However, individuals who exercised more than 7.2 MET.h/day had a relatively higher mortality (hazard ratio 2.63, P = 0.009) than the optimal exercise group, an increase in risk that occurred despite a more favourable cardiovascular risk factor profile.
The association between strenuous leisure time physical activity and mortality in individuals with known coronary artery disease was also evaluated in 1038 participants in cardiac rehabilitation programme followed for 10 years . A single question was used to assess exercise: ‘On average how often have you engaged in physically strenuous or sweat inducing activity during your leisure time in the past 12 months (cycling, speeding hiking, gardening, sport)?’ Overall physical activity levels decreased during follow-up. The risks of major cardiovascular events and mortality were highest in the least physically active group who exercised ‘rarely/never’ (hazard ratio 1.85, 95% CI 1.06–3.23) compared with the lowest mortality group, those who exercised two to four times per week. For individuals who took vigorous exercise five to six times a week or more, there was a trend for a higher mortality than those who exercised two to four times each week (hazard ratio 1.54, 95% CI 0.87–2.71).
POSSIBLE EXPLANATIONS FOR AN INCREASED RISK WITH EXTREME EXERCISE LEVELS
A ‘reverse J’ shaped association between exercise and mortality suggested by some studies is consistent with some hazard associated with very high levels of physical activity (Fig. 3). The risk of myocardial infarction and sudden death is known to be increased during and 1 h after vigorous exercise . The risk of exercise triggering a cardiac event is highest in normally inactive persons, and lower in those who take regular moderate exercise. Harm from prolonged vigorous exercise could be greater in individuals with coronary artery or other cardiovascular disease [23▪▪,24]. Prolonged regular physical activity has also been associated with atrial fibrillation, right ventricular dysfunction, interstitial fibrosis and ventricular arrhythmias [26,27]. However, the low long-term cardiovascular and all-cause mortality of elite athletes compared with the general population [12▪] suggests that these hazards are likely to be small and are outweighed by the benefits of exercise for most people.
CLINICAL TRIALS OF EXERCISE INTERVENTIONS
Trials of exercise-based interventions in patients with cardiovascular risk factors but without cardiovascular disease have been too small to evaluate morbidity and mortality. A recent Cochrane review identified only four studies with a total of 823 participants randomized to either an exercise intervention or control for 4–6 months , but none included assessment of mortality or major cardiovascular events.
The most recent Cochrane review of exercise-based cardiac rehabilitation included 47 randomized controlled trials with 10 794 patients with known coronary heart disease [29▪]. Most participants had a history of myocardial infarction or percutaneous coronary revascularization, and they were predominantly male (88%) with a mean age of 55 years. There was a trend for a reduction in total mortality both before (RR 0.82; 95% CI 0.67–1.01) and beyond 12 months (RR 0.87; 95% CI 0.75–0.99). Reductions in cardiovascular mortality during the first 12 months were not statistically significant (RR 0.93; 95% CI 0.71–1.21), but they were after 12 months (RR 0.74; 95% CI 0.63–0.87). There was no decrease in the risk of reinfarction or need for revascularization between the exercise and control groups.
The risk of death or a cardiac arrest while participating in a supervised cardiac rehabilitation programme is very low, and randomized trials are reassuring about the risks of increasing physical activity in patients with coronary artery disease. However, the management and outcomes of acute myocardial infarction and secondary prevention have changed dramatically over the last four to five decades, during which clinical trials of cardiac rehabilitation have been undertaken. There are also significant limitations in the reporting of these trials .
In most exercise programmes, a graded increase in exercise is recommended and very high levels of vigorous-intensity exercise are avoided. However, the exercise interventions varied considerably between trials in duration (range 1–30 months), frequency (one to seven sessions/week) and session length (20–90 min/session). These studies do not allow a reliable evaluation of the most effective type and amount of exercise intervention to reduce mortality risk. No clinical trials have compared major cardiovascular events with two different exercise interventions. The observation that benefits extend beyond 1 year suggests that changes in physical activity after completing the intervention are important, but the longer-term changes in exercise behaviour achieved in these studies are uncertain.
With modern treatment, most patients are able to return to usual activities soon after an acute coronary syndrome, and attendance at supervised exercise-based rehabilitation programmes is low. Novel approaches are needed that appropriately engage patients with coronary artery disease in order to sustain modest long-term increases in modest physical activity.
PROMOTING EXERCISE AND EVALUATING THE MOST EFFECTIVE WAY TO DO THIS
An approach emphasizing individualized exercise interventions is an attractive strategy . Several small studies with short-term outcomes suggest that personal monitoring devices, web-based programmes, remote monitoring and text to exercise can increase physical activity [32,33]. In patients with coronary artery disease, a text messaging intervention increased leisure time exercise and walking at 6 months, with behaviour changes mediated by increases in self-efficacy [34,35]. Larger and longer-term studies are needed to evaluate the most effective strategies to increase usual exercise and reduce sedentary time.
As with smoking and diet, population-wide strategies that reduce sedentary time and increase physical activity, even by a modest amount, are likely to improve population health. They can include urban designs that create and improve opportunities to walk and cycle, and increasing use of public transport, which usually includes some walking . The workplace accounts for about half of weekly sedentary time . Some innovative companies have incorporated fluid workspaces, standing desks, access to exercise facilities for workers, walking meetings and flexible scheduling to allow time for exercise and to reduce prolonged sitting .
IMPLICATIONS FOR GUIDELINES ON PHYSICAL ACTIVITY
About one-third of adults are inactive worldwide . Inactivity is also common in patients with stable coronary artery disease and is associated with socioeconomic, cultural and geographic factors . Consistent associations between both prolonged sedentary time and low exercise levels and mortality suggest that physical activity guidelines could emphasize more modest targets, to sit less and move more, for inactive persons. Because the cardiovascular risks of reducing sedentary time and of modest intensity physical activity are low, supervised exercise programmes may not be needed to achieve these goals.
A graded association between greater physical activity and lower mortality has been consistently reported in many general population studies. More recent research suggests that there are substantial mortality benefits from relatively low levels of exercise, and also from decreasing the time spent sitting. The incremental benefits of increasing physical activity above those recommended in guidelines are more modest. These benefits of low levels of physical activity and of reducing sitting time are also likely to apply to patients with cardiovascular disease, but data are more limited.
We thank Michelle D'Souza for assistance with the preparation of this manuscript.
Financial support and sponsorship
Dr Ralph Stewart was supported by a Clinical Practitioner Fellowship from the Health Research Council of New Zealand.
Conflicts of interest
There are no conflicts of interest.
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