Abstract
The benefits of exercise in the prevention of cardiovascular disease are irrefutable. However, the optimum ‘dose’ of exercise in order to derive the maximum cardiovascular benefit is not certain. Current national and international guidelines advocate the benefits of moderate-intensity exercise. The relative benefits of vigorous versus moderate-intensity exercise have been studied in large epidemiological studies, addressing coronary heart disease and mortality, as well as smaller randomized clinical trials which assessed effects on cardiovascular risk factors. There is evidence that exercise intensity, rather than duration or frequency, is the most important variable in determining cardioprotection. Applying this evidence into practice must take into account the impact of baseline fitness, compliance and the independent risk associated with a sedentary lifestyle. This review aims to evaluate the role of exercise intensity in the reduction of cardiovascular risk, and answer the question: should you be advising your patients to walk or run?
Introduction
The evidence supporting the cardioprotective effects of exercise is vast, robust and consistent.1–7 This benefit is partly derived from improved cardiovascular risk factors. However, when the effects of the enhanced physiological parameters (e.g. improved lipid profiles, body mass index, blood pressure and insulin resistance) are accounted for, exercise still has an independent effect on reducing cardiovascular risk.1–7 This suggests that there is something inherently beneficial, although unexplained, with regard to the value of exercise for health.
In earlier times, physical activity achieved through occupation, leisure time and general living activities was sufficient to offer cardiovascular protection. Studies comparing cardiovascular morbidity between bus conductors and bus drivers, 8 or between postmen and postoffice workers, 9 consistently found the sedentary counterpart to have increased cardiovascular risk. Simply having an active job could decrease the risk of having a coronary event by as much as a half. 2 However, with increasing automation in industry, the opportunity for activity in the workplace is decreasing and consequently the importance of exercise, i.e. physical activity that is structured and performed for a specific reason, 10 is growing.
Exercise can vary in frequency, duration and intensity, and the impact of these variables on the relative cardioprotection derived from exercise is less well characterized. Consequently, the optimum ‘dose’ of exercise in order to derive the maximum cardiovascular benefit is not certain. There is evidence that exercise intensity, rather than duration or frequency, is the most crucial variable in determining cardioprotection.11–13 At present, World Health Organization (WHO) guidelines recommend that adults take a minimum of 150 minutes of moderate-intensity exercise, or 75 minutes of vigorous exercise, each week. 14 But is moderate-intensity exercise sufficient to reduce mortality, or is higher-intensity exercise more effective? This review aims to evaluate the role of exercise intensity in the reduction of cardiovascular risk, and answer the question: should you be advising your patients to walk or run?
Search strategy and selection criteria
Data for this review were identified by searches of MEDLINE using combinations of the terms ‘exercise’, ‘physical activity’, ‘intensity’ and ‘cardiovascular’. References sourced from relevant articles were also included. Only articles available in English were used.
Moderate- versus high-intensity exercise for cardioprotection
Epidemiological studies
Although observational in nature, epidemiological studies have the advantage of a large multicentred approach, with long-term follow-up allowing analysis of hard cardiovascular endpoints. In general, such studies agree that as total activity levels increase, cardiovascular risk decreases.5,7,15 However, there is less agreement as to whether the intensity of exercise needs to be of a particular level in order to obtain the benefits. At present, guidelines in the UK, 16 USA 17 and from the WHO 14 recommend regular moderate-intensity activity. Appropriately, there are several studies that support this counsel by confirming the benefits that can be derived from moderate-intensity exercise.1,3,5,7,18–21 For instance, the Nurses’ Health Study found that moderate activity, even as little as once a week, was sufficient to reduce mortality risk by 22%. 21 However, other trials have shown that while moderate activity offers some protection, higher-intensity exercise offers greater protection.4,,5,7,21–23 For instance, with respect to coronary heart disease, moderate- and high-intensity exercise produced a relative risk of 0.94 and 0.83, respectively, in comparison with low-intensity exercise, even when overall exercise volume was accounted for. 7 In contrast to current guidelines, a few studies have concluded that exercise intensity had to be vigorous in order to confer any cardioprotective effect.24–26 Thus, there remains some contention as to whether moderate-intensity exercise does indeed offer protection, while the benefits of higher-intensity exercise are being increasingly well defined.
As with exercise intensity, a dose–response relationship has been shown for exercise duration. 7 However, when the total energy expenditure was held constant, a longer duration of exercise offered no additional protection. 27 Moreover, Wisloff et al. showed in a 16-year study that a single weekly bout of high-intensity exercise reduced the risk of cardiovascular death by 39% in men and 51% in women. Notably, increasing the duration or frequency of the exercise sessions offered no additional benefit. 11
Studies have also shown that the benefits of exercise cannot be stored. In the Harvard Alumni Study, those who excelled at sport in their youth, but later became sedentary enjoyed no prevailing protection. In contrast, those who were sedentary at the start of the study but later increased their activity levels had lower risk than those who remained inactive. 5 Similar results from the Nurses’ Health Study confirm that it is never too late to start gaining the benefits of exercise. 21
Clinical trials
Randomized clinical trials have compared different intensities of exercise while controlling overall energy expenditure. However, most clinical trials of exercise intensity involve small sample sizes, short follow-up and examine surrogate endpoints. In Swain and Franklin's 13 2006 systematic review the authors compiled and summarized trials comparing the effect of moderate- versus high-intensity exercise on established cardiovascular risk factors including blood pressure, lipids, glucose control and body composition. The sample size, populations studied, protocols used and outcomes measured in the studies varied widely, with inconsistencies in the results, making it difficult to draw a clear conclusion. In the majority of the studies, exercise appeared to have a beneficial impact on the selected variables; however, an intensity-dependent effect was less apparent. Vigorous exercise was more effective at improving more than one risk factor, and so would decrease an individual's global cardiovascular risk, even if results from individual studies were inconsistent. It should be noted that, of the 19 studies they examined, only 1 28 found moderate-intensity exercise to be more effective than high-intensity exercise at decreasing a risk factor.
By controlling total energy expenditure the studies address the simple question: does working twice as hard in half the time have greater or lesser cardioprotective effects? However, capping the total energy expenditure, which itself has been shown to be inversely related to cardiovascular risk, 5 limits the population inferences that can be drawn from the studies, since different types of exercise may offer greater potential to expend more energy. For instance, many people may be able to run on a treadmill for only ten minutes (approximately 200 calories) but could happily walk briskly for two hours (approximately 600 calories) and therefore may actually get more benefit from doing the lower intensity for longer. For a fit active person, where time is the limiting factor for their exercise, the converse may be true. 29 These examples illustrate the difficulty in transferring results from exercise studies into advice for patients.
There are possible mechanisms by which higher-intensity exercise may be more beneficial than lowerintensity exercise of the same overall energy expenditure. Swain and Franklin 13 suggested that it could be due to greater adaptations in autonomic control from higher-intensity exertion. Tjonna et al. 30 explained the increased ability of higher-intensity exercise to improve aerobic fitness in terms of improved stroke volume. Wisloff et al. 31 examined rat models and highlighted different responses in cardiomyocyte contractility, calcium handling and hypertrophy between high- and moderate-intensity exercise to explain the physiological difference in training responses.
Exercise intensity, physical fitness and the secondary prevention of cardiovascular disease
Aerobic capacity (measured by maximal oxygen consumption [VO2 max]) is a widely accepted measure of physical fitness. VO2 max has been shown to be a better predictor of cardiovascular mortality than any other established risk factor in patients attending for cardiac rehabilitation.32–35 VO2 max is also the best predictor of success in competitive endurance athletes. Consequently, it has been studied extensively in the field of sports medicine. In athletes it was found that higher-intensity (predominately interval style) training was more effective at increasing VO2 max than moderate-intensity exercise matched for total energy expenditure.36–39 This raised the question as to whether higher-intensity exercise is more effective at increasing VO2 max in patient populations, and as such could be more effective in the secondary prevention of cardiovascular disease? Trials in patient populations have since shown high-intensity exercise to be more effective at increasing VO2 max in patients with obesity, 40 metabolic syndrome, 30 coronary artery disease,22,41 intermittent claudication 42 and heart failure. 23
Risks of exercise
Vigorous exercise carries a transient increase in sudden cardiac death. 43 This risk is greatest in people who do not habitually perform vigorous exercise. 44 In a healthy 50-year-old man the risk of having an acute myocardial infarction in any given one-hour period has been estimated to be 1 in 1,000,000. 44 If this individual was to perform vigorous exercise his risk would be increased 100 times during and for one hour post-exercise. 45 However, if this individual regularly performed vigorous exercise, such as running for one or more hours a week, he would not only have a 42% lower baseline risk of having an event, but his exercise-associated increased risk of myocardial infarcation (MI) would also be lower.7,44,45 The evidence that the benefits of exercise outweigh the potential risks in healthy individuals is unequivocal. 16 In patients, while no adverse events have been reported in studies of high-intensity intervention, there is still concern over the safety of using such protocols in patient populations. Larger multicentre studies will be required to determine the safety of high-intensity protocols before they could be recommended for wide-scale patient use.
Applying the evidence
A difficulty in applying the evidence with regard to cardioprotective effects of exercise are the differences in the populations which have been studied. Athletes and patients are at extreme ends of a spectrum, but are the groups in which the effects of exercise have been most studied. This has led to increasing emphasis on tailoring the advice to suit the population. Baseline fitness appears fundamental with regard to deriving benefits from exercise. Walking has been shown to be sufficient to reduce risk in elderly men.3,24 However, when a younger group was specifically examined, it did not confer the same protection. 24 This is likely to be due to the fact that relative, rather than absolute, exertion is important. 6 While walking may be sufficient to produce a suitably high percentage of an elderly man's maximum heart rate to constitute exercise, it is less likely to do so in a younger person.
Within the patient population compliance is a major issue. No matter which type or intensity of exercise that the evidence deems the most effective, it will have no benefit unless the individual actually does it. Equally, any activity is likely to be better than no activity. So while it is vital to be able to advise our patients on the specifics of exercise that are most effective, it is arguably as important to be aware of the prescription of exercise that is likely to be most adhered to. One study suggests that high-frequency (>three times per week) moderate-intensity is the most effective exercise prescription in terms of compliance. 46 Similarly, the National Institute for Clinical Excellence (NICE) advocate moderate-intensity exercise in their review of the most effective public health interventions for promoting physical activity. 47 Higher-intensity exercises may not be better if people are less willing to do it.
An additional factor to be considered is the role of inactivity. Recent studies have shown that the number of hours spent in sedentary activities each day is an independent risk factor for cardiovascular mortality, regardless of exercise levels. Individuals who spent three quarters of their day sitting had a 47% greater risk of cardiovascular mortality, compared with those who spent no time sitting. 48 Watching television for more than four hours per day increased cardiovascular mortality by 80% when compared with individuals who watched television for less than two hours per day, independent of leisure time physical activity. 49 In light of this evidence, there are calls for guidelines to include targets for inactivity as well as activity. However, as occupations are increasingly driven deskbound by computers, in practical terms, it may be easier for an individual to increase their exercise than decrease their inactivity.
Conclusion
Physical activity is a vital factor in the prevention of cardiovascular disease. The relative risk of inactivity has been estimated to be comparable to smoking one packet of cigarettes a day. 45 Given that in the UK, only 21% of the population smoke 50 but 64% are not meeting the current physical activity targets, 51 it is alarming the extent to which exercise is underutilized as a prevention strategy. Doctors are good at prescribing drugs for cholesterol, hypertension, diabetes but are not so good at promoting exercise. This may reflect the questions that remain about the benefits of exercise. What is the least amount of exercise that can confer cardioprotective effects? Is this level of exercise the same for providing protection against other diseases, e.g. cancer, osteoporosis? Is there an upper limit whereby doing more exercise will not further decrease mortality? Despite these uncertainties, it appears that even moderate-intensity exercise is sufficient to reduce cardiovascular risk, particularly in elderly populations and those with chronic disease. However, it is also apparent that higher-intensity exercise offers greater cardioprotection and therefore should be encouraged in all patients where appropriate. In a society where activity levels are low and an adult is more likely to be overweight than ‘normal’ weight, 51 any physical activity is better than none, moderate intensity is better than low intensity and high-intensity exercise may be better still. Accordingly, advocating regular walking, before gradually advising the additional benefits of running or other higher-intensity exercise, would be an appropriate approach for most patients.