Role of Increased Physical Activity in Primary Prevention of Cardiovascular Disease

The cardiovascular health benefits of regular exercise are well established. According to the U.S. Department of Health and Human Services, strong evidence demonstrates that compared with less active persons, more active men and women have lower rates of all-cause mortality, coronary heart disease, hypertension, stroke, type 2 diabetes, metabolic syndrome, colon cancer, breast cancer, and depression. The risk of dying prematurely declines as people become physically active, as evidenced by data shown in Table 33-1 .

Strong evidence also supports the conclusion that compared with less active people, physically active adults and older adults exhibit a higher level of cardiorespiratory and muscular fitness, have a healthier body mass and composition, and have a metabolic profile that is more favorable for prevention of cardiovascular disease and type 2 diabetes. Modest evidence indicates that physically active adults and older adults have better quality sleep, health-related quality of life, and enhanced bone health.

A recent meta-analysis of 26 studies, incorporating 513,472 individuals (20,666 coronary heart disease events) followed up for 4 to 25 years, showed that individuals who reported performing a high level of leisure-time physical activity had significant protection against coronary heart disease (relative risk, 0.73; P <0.00001), whereas those individuals who practiced a moderate level of physical activity also had a reduced risk of coronary heart disease (relative risk, 0.88; P <0.0001). Data from the Physicians’ Health Study showed that adherence to healthy lifestyle factors (normal body weight, never smoking, regular exercise, moderate alcohol intake, and consumption of breakfast cereal and fruits and vegetables) is independently associated with an 11% lifetime risk of heart failure with exercising ≥5 times per week versus a 14% risk for exercising <5 times per week. Thus, there is substantial protection against the occurrence of cardiovascular disease from moderate to high levels of physical activity, thereby strengthening the recommendations of guidelines.

Increased levels of physical activity and exercise are also associated with increased longevity and a decrease in cardiovascular disease risk factors, metabolic syndrome, and diabetes. In 2009, the American College of Sports Medicine’s position statement “Exercise and Physical Activity for Older Adults” reported that although no amount of physical activity can stop the biologic aging process, there is evidence that regular exercise can minimize the physiologic effects of an otherwise sedentary lifestyle and increase active life expectancy by limiting the development and progression of chronic disease and disabling conditions. There is also emerging evidence for significant psychological and cognitive benefits accruing from regular exercise participation by older adults.

Ideally, exercise prescriptions for older adults should include aerobic exercise, muscle strengthening exercises, and flexibility exercises. Although this chapter focuses on cardiovascular disease, adults with chronic conditions such as type 2 diabetes, cancer, osteoarthritis, cognitive disorders, and renal disease are also likely to derive significant therapeutic benefit from prescribed exercise and increased physical activity. In many cases, persons with cardiovascular disease also suffer from these comorbidities, thereby enhancing the importance of exercise training as part of their overall treatment plan.

Despite numerous epidemiologic and experimental studies supporting the beneficial effects of being physically active, this scientific knowledge has not resulted in a more active population. According to the Centers for Disease Control and Prevention, the prevalence of leisure-time physical inactivity throughout the United States ranged from 16% to 49%, whereas the prevalence of adults who engaged in at least moderate physical activity ranged from 33% to 62%, and the prevalence of vigorous physical activity ranged from 15% to 42%. Among adults aged 60 years or older, more than half reported no leisure-time physical activity at all. Thus, a substantial number of adults do not engage in levels of activity sufficient to produce health benefits.

People with chronic disease are more likely to report a sedentary lifestyle, as are minorities and individuals in lower socioeconomic classes. Unfortunately, less than 30% of individuals at high risk for cardiovascular disease receive physical activity counseling during ambulatory care visits. By adding a sedentary lifestyle to its list of controllable risk factors for coronary artery disease, the American Heart Association has made regular exercise a major focus for preventive medicine.

The physical activity goal in the Healthy People 2010 report by the Centers for Disease Control and Prevention is to increase the proportion of adults who engage in regular exercise and moderate activity for at least 30 minutes each day. This goal matches the Surgeon General’s recommendation that all Americans should accumulate at least 30 minutes of activity throughout the day on most days of the week. These guidelines establish the minimal effort needed to derive health benefits from physical activity, although individuals exceeding these recommendations in terms of frequency or intensity are likely to derive additional health and fitness benefits.

Several studies have established an inverse dose-response relationship between the amount of physical activity performed and health risk. Thus, the most fit and active individuals generally have the best risk profiles and reduced levels of early mortality and morbidity from a variety of diseases, including cardiovascular disease. For example, men and women who were generally healthy but less fit by exercise testing had a higher risk of all-cause mortality during an 8-year follow-up compared with those who were moderately or highly fit. Data from the Nurses’ Health Study found that physical activity of less than 3.5 hours per week and excess body weight (defined as a body mass index of 25 or higher) accounted for 31% of all premature deaths, 59% of cardiovascular deaths, and 21% of cancer deaths.

In another study, Puerto Rican men in the middle of the physical activity distribution had a 32% to 37% reduction in risk for all-cause mortality. Moreover, compared with the most sedentary quartile of participants, the next most active quartile had an accumulated survival that was approximately 3 years longer. We previously showed that exercise-induced reductions in total and abdominal obesity after 6 months of training were associated with favorable changes in risk factors for cardiovascular disease, including those that constitute metabolic syndrome.

Exercise Training Effect

The underlying principles for enhanced cardiovascular and musculoskeletal function are similar for those with and without cardiovascular disease and also apply to most other chronic health conditions, such as type 2 diabetes. A brief summary of these principles is provided.

The body adapts to the kind and amount of physical demands placed on it. The response is specific , with the most change generally occurring in those parts of the body on which demands are placed. For exercise to improve fitness, it must overload the muscles or organ system involved in the exercise. In this context, overload is defined as performing exercise at a greater intensity than the intensity to which one is accustomed. Because the effects of exercise are specific to the type of activity engaged, an optimal exercise program should include a variety of activities designed to improve each of the major components of fitness. These are cardiovascular endurance, muscle strength, muscle endurance, and flexibility.

Cardiovascular endurance depends on the ability of the muscles to use oxygen during exercise; hence, it is also known as aerobic endurance. Cardiovascular endurance is dependent on cardiac output providing sufficient oxygen-carrying blood, distribution of the blood to the working muscles, and capacity of the muscles to extract oxygen from a given blood flow.

The principal hemodynamic adaptation to aerobic exercise in individuals with and without heart disease takes place in the peripheral vascular and muscular systems. With regular exercise, the skeletal muscles can extract more oxygen from a given blood flow, and there is a better distribution of the cardiac output. Heart rate and blood pressure are also lower at rest and at a given submaximal workload. As a result, the individual can do more work with less cardiac effort. This adaptation is especially beneficial to cardiac patients who may have limited coronary artery blood supply or poor left ventricular function. Angina may occur at the same threshold, that is, the same double product (heart rate × systolic blood pressure), but this threshold is reached at a higher level of body work.

Risks of Increased Physical Activity

Although habitual physical activity reduces coronary heart disease events, vigorous activity can also acutely and transiently increase the risk of sudden cardiac death and acute myocardial infarction in susceptible persons, as discussed in detail in an American Heart Association Scientific Statement. Exercise-associated acute cardiac events generally occur in individuals with structural cardiac disease. Hereditary or congenital cardiovascular abnormalities are predominantly responsible for cardiac events among young individuals, whereas atherosclerotic disease is primarily responsible for these events in adults.

The absolute rate of exercise-related sudden cardiac death varies with the prevalence of disease in the study population. The incidence of acute myocardial infarction and sudden death is greatest in the habitually least physically active individuals. Although no specific strategies have been widely studied to reduce exercise-related acute cardiovascular events, maintaining regular physical activity may help reduce events because a disproportionate number of events occur in the least physically active subjects performing unaccustomed physical activity. Other strategies, such as screening patients before participation in exercise, excluding high-risk patients from certain activities, promptly evaluating possible prodromal symptoms, training fitness personnel for emergencies, and encouraging patients to avoid high-risk activities, appear prudent but have not been systematically evaluated.

Cardiac Rehabilitation

Cardiac rehabilitation and secondary prevention programs are recognized as integral to the comprehensive care of patients with cardiovascular disease and as such are recommended as useful and effective (Class I) by the American Heart Association and the American College of Cardiology in the treatment of patients with coronary artery disease and chronic heart failure. In 2009, an estimated 785,000 Americans had a new coronary event, and about 470,000 had a recurrent event. It is estimated that an additional 195,000 silent first myocardial infarctions occur each year. At the same time, the death rate from cardiovascular disease declined by 26% from 1995 to 2005. Thus, the burden of chronic cardiovascular disease remains high, and a growing number of patients will be candidates for cardiac rehabilitation.

In 2007, the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation recommended that cardiac rehabilitation programs provide several important core components consisting of baseline patient assessment, nutritional counseling, risk factor management (lipids, hypertension, weight, diabetes, and smoking), psychosocial management, physical activity counseling, and exercise training. The American Heart Association also recommends these cardiac rehabilitation components for the elderly. Whereas secondary prevention therapies, such as pharmacologic management of atherosclerosis risk factors and depression, are provided by clinicians in their offices, cardiac rehabilitation is often the most advantageous setting for bringing many of these core components together in a comprehensive approach to provide exercise training, patient education, behavioral counseling, and psychosocial support.

Studies of efficacy and effectiveness of cardiac rehabilitation document reductions in mortality and improvements in clinical and behavioral outcomes beyond the improvements in morbidity and mortality already available through revascularization and optimal pharmacotherapy. Yet cardiac rehabilitation, like many preventive measures, is underused.

Unfortunately, it is estimated that only 10% to 40% of eligible patients participate in cardiac rehabilitation programs. These rates of participation are even less for older patients, a group with the highest prevalence of cardiovascular disease. Although Medicare provides payment for cardiac rehabilitation for the diagnoses of myocardial infarction, coronary artery bypass surgery, stable angina, and, more recently, percutaneous revascularization, heart transplantation, and heart valve surgery, there is no such payment for patients who have heart failure or peripheral arterial disease. Insurance coverage by other third-party payers varies considerably throughout the United States.

There are also numerous disparities in cardiac rehabilitation program participation; women with lower incomes are less likely to be referred and less likely to enroll in cardiac rehabilitation, and there is a strong trend for African American women to be less likely to be referred and to enroll. Among 1933 cardiac patients who met the selection criteria of the American College of Cardiology guidelines of eligibility for cardiac rehabilitation, whites were more likely to be referred for cardiac rehabilitation than were blacks. Because almost all patients who have had an acute coronary event, with or without revascularization procedures, will benefit from cardiac rehabilitation, automatic referral systems should be considered to increase use and to reduce disparities.

To compound the problem of access to cardiac rehabilitation based on race, blacks are more likely to have a greater number of adverse risk factors compared with whites. Although both groups gained secondary prevention benefits, the degree of improvement was less for blacks than for whites, and this was especially evident among black women.

A review of all components of cardiac rehabilitation and secondary prevention (such as smoking cessation, behavioral counseling, and pharmacotherapy) is beyond the scope of this chapter. To some extent, the scope is also limited by the nature of the studies on cardiac rehabilitation, which used supervised exercise training as the primary treatment modality. Although not fully evaluated in large-scale trials, a comprehensive approach to cardiac rehabilitation would be more than just exercise training and presumably would produce greater improvements in health and functional status for patients than is evident in the literature. Nevertheless, there is considerable evidence that exercise training by itself produces substantial physiologic benefits, improves risk factors, reduces mortality, and increases aerobic capacity, muscle strength, and functional performance.

Regular exercise training, with the goal of attaining a training effect , is beneficial for almost all patients after myocardial infarction. Contemporary cardiac rehabilitation programs are also experienced in addressing the educational deficiencies of patients, including the special needs of those with cardiac pacemakers and implanted defibrillators, chronic heart failure, diabetes, peripheral arterial disease, and other comorbidities.

In recent years, there is also increased recognition of the importance of resistance training for individuals with and without cardiovascular disease. The American Heart Association recently updated its Scientific Advisory “Resistance Exercise in Individuals With and Without Cardiovascular Disease.” It notes that after appropriate screening, resistance training is an effective method to improve muscle strength and endurance, to prevent and manage a variety of chronic medical conditions, to modify cardiac risk factors, and to enhance psychosocial well-being. Although weight machines are most commonly used in formal cardiac rehabilitation programs, alternative modes of resistance training are calisthenics, isometrics, and use of elastic stretch bands.

Most activities requiring lifting and straining, such as weight training, have a large static component. In such activities, there is increased peripheral vascular resistance, with an expected increase in blood pressure but much less of an increase in heart rate or cardiac output compared with aerobic exercise. Nevertheless, brief periods of moderate resistive exercise appear safe and may pose less of a cardiac burden than aerobic exercises of similar effort. In fact, studies show that cardiac patients who were required to carry or lift weights or to perform isometric exercise after a myocardial infarction had fewer ischemic electrocardiographic changes and arrhythmias during resistance exercise than during aerobic exercises. Gradual involvement in resistance training may therefore be beneficial and desirable, especially for patients whose jobs or recreational activities require static efforts.

Key Benefits of Exercise Training in Patients with Cardiovascular Disease

Cardiac Rehabilitation in the Elderly

Increasing evidence has accumulated during the past 3 decades that elderly individuals with coronary heart disease can benefit greatly from exercise training and other aspects of cardiac rehabilitation and secondary prevention programs. This is especially important given that those ≥65 years of age represent the greatest number of individuals with heart disease. Traditionally, components of secondary prevention programming (exercise; smoking cessation; management of dyslipidemia, hypertension, diabetes, and weight; and interventions directed at return to work and psychosocial issues) are provided by the clinician through the office setting or through cardiac rehabilitation programs. Cardiac rehabilitation programs are particularly well suited to the provision of secondary prevention services, but unfortunately, many older patients who would derive benefit from these interventions do not participate because of lack of referral or a variety of societal and other barriers.

A structured exercise program may be novel to older individuals or, in some instances, an activity in which they have not participated for many years. Furthermore, for older persons with coronary heart disease, the clinical manifestations represent the effects of the disease superimposed on the physiologic effects of age, which too often lead to decreases in exercise capacity and overall physical activity.

Whereas exertional angina pectoris remains common in this age group, an increased percentage of older patients have atypical manifestations of myocardial ischemia, including dyspnea on exertion and poor functional capacity, often exacerbated by comorbidities such as chronic lung disease, peripheral arterial disease, arthritis, and neuromuscular disorders that may limit ambulation. Thus, the absence of exercise-related anginal symptoms in older patients with suspected coronary heart disease may merely reflect the lack of physical activity.

As a means of increasing physical activity and fitness for older persons with heart disease, the prescription of exercise is an essential component of secondary prevention. The basis for the exercise intervention in these patients includes improved functional capacity with reduced activity-related abnormal signs or symptoms, including fatigue. Expected outcomes are similar to those for younger patients, although absolute levels of functional capacity in the elderly are less, and results may require longer program participation in this age group. As with younger patients, a multidisciplinary approach to secondary prevention that includes exercise may have a positive impact on other heart disease risk factors.

Whether exercise as a part of secondary prevention is associated with a reduction in morbidity or mortality as in younger patients has yet to be established. However, studies of older patients with and without heart disease have suggested a positive impact of physical activity on mortality. Findings have suggested that light to moderate activity is associated with a significantly lower risk of all-cause mortality in persons with established coronary heart disease and an inverse association between physical activity and all-cause mortality in both older men and women.

Role of Exercise Training in Patients with Peripheral Arterial Disease

Exercise training plays a critical role as a primary treatment of patients with peripheral arterial disease (PAD), with the goal of improving quality of life and functional capacity. According to the practice guidelines of the American College of Cardiology and the American Heart Association (ACC/AHA) for the management of PAD, supervised exercise training is rated as Class I, Level of Evidence A, for the initial treatment of claudication. The first randomized controlled trial was published in 1966; a marked improvement in walking ability was seen in patients with claudication assigned to daily exercise.

Several prospective randomized trials have demonstrated that exercise training improves claudication symptoms. Studies differ in terms of the magnitude of the reported response to exercise, a finding likely explained by variability both in the exercise intervention itself (duration, frequency, and intensity) and in outcome measures. A meta-analysis of 21 nonrandomized and randomized studies reported a 179% increase in pain-free walking distance and a 122% increase in maximum walking distance. A more recent Cochrane review of 22 randomized controlled trials for claudication reported an overall improvement in walking ability of approximately 50% to 200%.

Overall, patients can expect approximately a doubling of their pain-free and maximum walking distances with exercise training, with the best results occurring in supervised programs compared with unsupervised home-based training. Another Cochrane review of eight small trials including a total of 319 subjects found a significant improvement in maximum treadmill walking distance in supervised compared with unsupervised programs, with a difference of approximately 150 meters. The magnitude and durability of the benefits of home-based exercise for treatment of claudication, however, remain controversial.

Surprisingly, only a small number of studies have compared exercise training with lower extremity revascularization for the treatment of claudication. One such prospective randomized trial compared supervised exercise with angioplasty and found that mean maximum walking distances progressively increased in the supervised exercise group at 6, 9, and 12 months but did not increase in the angioplasty group even though the ankle-brachial indices improved with angioplasty. Subsequently, the same group reported that after a median follow-up of 70 months, the functional outcome was the same between the exercise and angioplasty groups. Among 62 patients randomized to angioplasty or medical treatment, there were no significant group differences at 2 years in treadmill walking distances or quality of life; the medical group was not in a supervised program but was given “exercise advice” to walk at home.

A trial from the Netherlands randomized 151 patients with claudication to either endovascular revascularization (angioplasty with conditional stenting) or 24 weeks of twice-weekly 30-minute hospital-based treadmill exercise sessions. Endovascular revascularization provided more immediate clinical success, but after 6 and 12 months, the treatment groups were equivalent in terms of functional capacity and quality of life scores. The CLEVER (Claudication: Exercise Versus Endoluminal Revascularization) trial is a similar ongoing National Institutes of Health/National Heart, Lung, and Blood Institute–funded multicenter randomized clinical trial comparing supervised exercise with endovascular revascularization for the treatment of claudication due to aortoiliac disease. The results of the CLEVER trial are hoped to provide more definitive data on the optimal approach to treatment of aortoiliac disease.

The exact mechanism to explain why exercise training improves claudication symptoms is not known but is likely multifactorial. Initial theories proposed that exercise increases collateral vessels through angiogenesis or leads to increased blood flow, but subsequent data on these hypotheses are inconsistent. More likely, mechanisms for the benefit of exercise training include metabolic adaptations with improved oxygen extraction by the muscle, better walking efficiency from a biomechanical standpoint, and enhanced endothelial function. Calf skeletal muscle may increase its oxidative capacity; improvements in exercise have correlated with changes in carnitine metabolism.

In addition, the benefits of exercise may not be fully explained by local effects on the lower extremities, as evidenced by a randomized trial in which 104 patients with PAD were assigned to upper limb aerobic exercise, lower limb aerobic exercise, or no exercise for 24 weeks. Similar improvements in claudication distance and maximum walking distance were observed in both exercise groups but not in the control group, suggesting a systemic benefit of exercise; an increase in exercise pain tolerance was also noted in the exercise groups.

Exercise may attenuate the inflammatory response in the long term and has well-established beneficial effects on cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and obesity. Further rigorous prospective investigation is needed to ascertain whether this global improvement in vascular health may translate into reduced morbidity or mortality in patients with PAD. A retrospective cohort study from Japan showed that completion of a 12-week supervised exercise training program reduced both cardiovascular morbidity and mortality in patients with PAD. The long-term impact of supervised exercise training on outcomes in PAD patients remains unknown.

Whereas the efficacy of exercise training for the treatment of symptomatic PAD has been well established, recent evidence now suggests that exercise training may also play an important role in the treatment of asymptomatic PAD. McDermott and coworkers found that supervised treadmill training improved walking and quality of life outcomes in patients with PAD with and without claudication. Lower extremity resistance training was also beneficial for improving functional performance but not to the same degree as supervised treadmill training. Given that the large majority of patients with PAD are either asymptomatic or have atypical symptoms, these findings are particularly important and may herald a significant change in the clinical approach to treatment of PAD; further research in this area is warranted.

In spite of the numerous studies demonstrating the efficacy of exercise training, several barriers prevent its widespread use. Perhaps most notably, supervised exercise is not generally a covered benefit under most health insurance plans including Medicare, although PAD rehabilitation has had a Current Procedural Terminology code (CPT 93668) since 2001. Other barriers to participation include a time commitment and lack of broad availability of PAD rehabilitation centers.

Barriers also exist at the provider level, as many clinicians may hesitate to refer a high-risk patient with multiple comorbidities to an exercise program. However, that same patient may in fact derive the greatest benefit from exercise. Because of the systemic nature of obstructive atherosclerotic vascular disease and the high prevalence of coronary artery disease in this population, patients with PAD in many cases may qualify for cardiac rehabilitation from an insurance standpoint by meeting one of the other criteria as noted elsewhere in this chapter (e.g., recent myocardial infarction, coronary revascularization, or angina). The decision to enroll a patient with PAD in an exercise training program should be individualized and may be affected by medical comorbidities that limit walking ability, such as pulmonary or degenerative joint disease. Treadmill exercise is not recommended in patients with foot ulcers or critical limb ischemia.

A meta-analysis found that the best results were seen with walking programs lasting more than 30 minutes per session, at least three times per week, for at least 6 months. Studies suggest that the benefits of the supervised program may extend beyond the duration of the program. For example, among patients who attended supervised training twice weekly for 10 weeks, the improvements in claudication distance and maximum walking distance were sustained at 3 years ; there was no difference between the results at 3 months and at 1, 2, or 3 years.