Exercise and Acute Cardiovascular Events

Habitual physical activity reduces coronary heart disease events, but vigorous activity can also acutely and transiently increase the risk of sudden cardiac death and acute myocardial infarction in susceptible persons. This scientific statement discusses the potential cardiovascular complications of exercise, their pathological substrate, and their incidence and suggests strategies to reduce these complications. 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 both acute myocardial infarction and sudden death is greatest in the habitually least physically active individuals. No strategies have been adequately studied to evaluate their ability to reduce exercise-related acute cardiovascular events. Maintaining physical fitness through regular physical activity may help to reduce events because a disproportionate number of events occur in 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. Regular physical activity is widely advocated by the medical community in part because substantial epidemiological, clinical, and basic science evidence suggests that physical activity and exercise training delay the development of atherosclerosis and reduce the incidence of coronary heart disease (CHD) events (1-4). Nevertheless, vigorous physical activity can also acutely and transiently increase the risk of acute myocardial infarction (AMI) and sudden cardiac death (SCD) in susceptible individuals (5-7). This scientific statement presents the cardiovascular complications of vigorous exercise, their pathophysiological substrate, and their incidence in specific patient groups and evaluates strategies directed at reducing these complications. The goal is to provide healthcare professionals with the information they need to advise patients more accurately about the benefits and risks of physical activity. Most studies of exercise-related cardiovascular events have examined events associated with sports participation in young subjects and with vigorous exercise in adults. Vigorous exercise is usually defined as an absolute exercise work rate of at least 6 metabolic equivalents (METs), which is historically assumed to equal an oxygen uptake (V˙O2) of 21 mL·kg-1·min-1. Six METs approximates the energy requirements of activities such as jogging. Six METs is an arbitrary threshold and does not account for the fact that the myocardial oxygen demands of any physical activity are more closely related to the V˙O2 requirements relative to maximal exercise capacity than to the absolute work rate per se. Consequently, exercise work rates < 6 METs may still place considerable stress on the cardiovascular systems of unfit and older individuals. PATHOPHYSIOLOGICAL BASIS FOR EXERTION-RELATED CARDIOVASCULAR EVENTS Exercise-associated acute cardiac events generally occur in individuals with structural cardiac disease. Pathological Findings in Young Individuals Among young individuals, variously defined as < 30 or < 40 years of age, the most frequent pathological findings are hereditary or congenital cardiovascular abnormalities (8-10), including hypertrophic cardiomyopathy; coronary artery anomalies (eg, anomalous coronary artery origin, acute angle takeoff and ostial ridges, or intramyocardial course) (11,12); aortic stenosis; aortic dissection and rupture probably associated with connective tissue defects such as Marfan syndrome; mitral valve prolapse; arrhythmogenic right ventricular cardiomyopathy; and arrhythmias, including those resulting from accessory atrioventricular pathways and channelopathies such as the long-QT syndrome. Myocarditis also is associated with exercise-related deaths in young individuals. Ventricular arrhythmias are the immediate cause of death in these conditions, except for Marfan syndrome, in which aortic rupture is often the proximate cause (Table 1).TABLE 1: Cardiovascular causes of exercise-related SCD in young athletes.*Pathological Findings in Adults In contrast to young subjects, coronary artery disease (CAD) is the most frequent pathological finding among older individuals who die during exertion (13,14). Among previously asymptomatic adults, evidence of acute coronary artery plaque disruption, including plaque rupture or erosion, with acute thrombotic occlusion is common (14). The mechanism by which vigorous exercise provokes such events is not defined, but suggested triggering mechanisms (15,16) include increased wall stress from increases in heart rate and blood pressure, exercise-induced coronary artery spasm in diseased artery segments (17), and increased flexing of atherosclerotic epicardial coronary arteries (15), leading to plaque disruption and thrombotic occlusion. Vigorous exercise also could provoke acute coronary thrombosis by deepening existing coronary fissures, augmenting catecholamine-induced platelet aggregation, or both. Spontaneous coronary plaque fissures are common and have been reported in 9% of subjects dying in motor vehicle accidents or by suicide and in 17% of people dying of noncoronary atherosclerosis (18). This observation suggests that mildly fissured coronary plaques require some exacerbating event such as vigorous physical activity to induce coronary thrombosis. An increase in thrombogenicity also could contribute to coronary thrombosis after plaque rupture or erosion. Increased platelet activation has been reported in sedentary individuals who engage in unaccustomed high-intensity exercise but not in physically conditioned individuals (19,20). Because circulating catecholamine levels are related more closely to the relative intensity of exercise for the individual than to the absolute exercise intensity, it is likely that platelet activation also is related to the relative intensity of the exercise session (21). Among individuals with symptomatic CHD, pathophysiological processes may include plaque disruption as above or ischemia-induced ventricular fibrillation from peri-infarction, ischemic tissue, or scar (22). Vigorous physical exertion, which increases myocardial oxygen demand and simultaneously shortens diastole and coronary perfusion time, may induce myocardial ischemia and malignant cardiac arrhythmias. Reduced coronary perfusion can be exacerbated by a decrease in venous return secondary to abrupt cessation of activity, which possibly explains the clinical observation that collapse not infrequently occurs immediately after exercise. Ischemia can alter depolarization, repolarization, and conduction velocity and thereby trigger threatening ventricular arrhythmias (Fig. 1). In addition, myocardial ischemia (23), sodium-potassium shifts with exercise, increased catecholamine levels, and circulating free fatty acids may all increase the risks of ventricular arrhythmias (24).FIGURE 1: Physiological alterations accompanying acute exercise and recovery and their possible sequelae. HR indicates heart rate; SBP, systolic blood pressure; and MVO2, myocardial oxygen uptake. Reprinted from Franklin (70), with permission.THE IMPORTANCE OF AGE AND PATHOLOGICAL SUBSTRATE The present scientific statement addresses the risks of exercise in both young and adult individuals, but it is critically important to recognize that these age groups have markedly different causes of exercise-related deaths and therefore markedly different risk-to-benefit ratios for vigorous exercise. The causes of exercise-related events are not strictly separated by age, given that, for example, some young individuals with genetic defects in the low-density lipoprotein receptor may develop premature CAD, whereas some older individuals may present with structural congenital cardiac abnormalities. Nevertheless, the predominant pathological cause of exercise-related events in adults is occult CAD. Habitual vigorous physical activity appears to reduce the incidence of CHD events, and cardiac rehabilitation appears to reduce the risk of CHD death in patients with diagnosed disease, although neither conclusion has been proved by a randomized, controlled clinical trial. Thus, the benefits of physical activity in those with or at risk for CHD appear to outweigh the risks. This situation is markedly different in young individuals with diagnosed or occult heart disease. Such subjects rarely die of CHD during exercise, and the clinical course of the responsible conditions such as hypertrophic cardiomyopathy and anomalous coronary arteries is not improved by vigorous exercise. Consequently, in populations with these diagnosed or occult cardiac diseases, the health risks of vigorous physical activity almost certainly exceed the benefits. Moderate physical activity may be justified in such patients on the basis of social and self-image considerations, as well as the benefits of physical activity in preventing obesity, obesity-related health problems, and atherosclerosis, all of which would further exacerbate the individual's cardiac risk. INCIDENCE OF EXERCISE-RELATED ACUTE CARDIOVASCULAR EVENTS The absolute risk of an exercise-related cardiovascular event varies with the prevalence of diagnosed or occult cardiac disease in the study population but appears to be extremely low in ostensibly healthy subjects. Because of the rarity of exercise-related cardiovascular events, studies examining its incidence are limited by small sample sizes and large confidence intervals. In addition, small changes in the number of events can produce large changes in the calculated incidence. Given these caveats, estimates are available for various patient groups. Young Athletes Van Camp and colleagues (8) estimated an absolute rate of exercise-related death among high school and college athletes of only 1 per 133,000 men and 1 per 769,000 women. These estimates include all sports-related nontraumatic deaths and are not restricted to cardiovascular events. A prospective, population-based study from Italy reported an incidence of ≈1 sudden death per 33,000 young athletes per year (25). The rate may be higher because of the higher mean age (23 versus 16 years) of the Italian athletes, participation in sports with higher levels of exercise intensity in Italy, and the inclusion of all events, not just those directly associated with active physical exertion, in the Italian study. Healthy Adults Malinow and colleagues (26) reported only 1 acute cardiovascular event per 2,897,057 person-hours of physical activity among participants at YMCA sports centers. Vander and associates (27) reported only 1 nonfatal and 1 fatal event per 1 124,200 and 887,526 hours, respectively, of recreational physical activity. Gibbons and colleagues (28) reported only 1 nonfatal event during 187,399 hours of exercise, which corresponds to maximal risk estimates of 0.3 to 2.7 and 0.6 to 6.0 events per 10,000 person-hours for men and women, respectively. Thompson and collaborators (29) estimated only 1 death per 396,000 person-hours of jogging or 1 death per year for every 7620 joggers. Because half of the victims had known or readily diagnosed CHD, the estimated hourly and annual rates for previously healthy individuals were 1 death per 792,000 hours and 15,260 subjects, respectively. Siscovick and colleagues (5) estimated a similar annual rate of exercise-related cardiac arrest among previously healthy persons of 1 per 18,000 men. Both studies have wide confidence limits because the rates were calculated with only 10 (Thompson et al. (29)) and 9 (Siscovick et al. (5)) exercise-related deaths. All victims in both studies were men, and there are few estimates of event rates among women. The reasons for the rarity of exercise-related deaths among adult women are not clear but may relate to the delayed development of CHD in women and a lower rate of participation in vigorous exercise among older women. More recently, a database consisting of > 2.9 million members of a large commercial health/fitness facility chain reported 71 deaths (mean age, 52 ± 13 years; 61 men, 10 women) over a 2-year period, yielding 1 death per 82,000 members and a rate of 1 death per 2.57 million workouts (30). Nearly half of the exercise-related deaths were among members who exercised infrequently or than a Vigorous exercise can also but estimates of the absolute incidence are available for in the population. Among men to in the because of and low-density lipoprotein an or SCD related to exertion during a mean of years An men had acute events not related to exercise, but the activity of men at the of their event Nevertheless, these that the annual rate of exercise-related cardiovascular events among high-risk individuals may be with of men an exercise-related event The risk of exercise-related also may be substantial in the population. the estimated incidence of SCD among healthy subjects from (29) and the observation that exercise-related is more frequent than SCD the annual incidence of exercise-related could from 1 per to 1 per healthy men. Individuals with CHD The incidence of exercise-related cardiovascular complications among persons with CHD has been estimated by at least with from cardiac rehabilitation 30 cardiac rehabilitation in and reported 1 nonfatal and 1 fatal cardiovascular per and hours, respectively. The rate appears lower in cardiac rehabilitation (Table because an of estimates 1 cardiac arrest per 1 myocardial infarction per 1 per and 1 per of participation This low rate only to that are to because the death rate would be higher the of cardiac arrest patients are before which could decrease event as could the by rehabilitation Such the of cardiac rehabilitation for patients after acute cardiac of cardiac rehabilitation OF ACUTE CARDIOVASCULAR evidence indicates that vigorous physical activity acutely increases the risk of cardiovascular events among young individuals and adults with both occult and diagnosed heart disease Young Athletes and colleagues of among individuals to years of age over a in the of were and per year per athletes and respectively, or a higher risk among the athletes (25). The death rate higher among athletes the fact that all Italian athletes are by to cardiovascular screening before participation This not limited to SCD during the increased death rate among athletes be to exercise Healthy Adults in adults also that exercise acutely increases the risk of cardiovascular events, a in CHD with physical activity. Both the study of exercise-related deaths (29) and the study of exercise-related cardiac (5) a higher estimated hourly death rate during exertion than during more In the SCD rate the hourly death rate during sedentary activities In among previously asymptomatic individuals, the incidence of cardiac arrest during exercise higher than the incidence at or during activity. The relative risk greatest in the least with the most physically active men and among the least and most active men, is a similar of increased risk with low levels of activity for exercise-related Vigorous physical activity has been reported 1 of in to of patients This rate is et al. to et al. higher than the rate during sedentary with the relative risk varies with physical activity and is greatest in the least physically active individuals. patients with CHD, the relative risk of cardiac arrest during vigorous exercise is estimated as 6 to than exertion (22). these (Table that vigorous exertion transiently increases the risk of and among habitually sedentary persons with occult or known performing vigorous physical activity. In the estimated that the risk of during or after vigorous exertion higher for the least active than for the most active (Fig. stress as a trigger of acute cardiovascular events during vigorous risk of associated with vigorous exertion 6 to of vigorous The confidence The indicates risk of with vigorous from with from OF CARDIOVASCULAR EVENTS Vigorous exercise increases the risk of a cardiovascular event during or after exertion in both young subjects with cardiovascular disease and adults with occult or diagnosed Nevertheless, evidence suggests that the risks of physical activity outweigh the benefits for healthy subjects. the appears to be In the the relative risk of cardiac arrest during exercise than at for all levels of physical activity, but the incidence of cardiac both at and during exercise, with exercise levels the incidence from events per 1 million person-hours in the least active to only in the most active subjects. The risk of an exercise-related also with of physical activity controlled the that regular physical activity, including vigorous activity, reduces CHD events over In contrast to adults in vigorous exercise appears to reduce the risk of CHD, exercise in young subjects with occult cardiovascular disease may increase both and sudden SCD during exertion in a young from the the heart disease or and the acute trigger of exertion possible associated with exercise, including and myocardial training may increase the risk of sudden death in the young with heart disease by the This could occur by disease or by the risk of cardiac by structural or example, in patients with hypertrophic of exercise-induced myocardial ischemia during training could produce death and myocardial which in ventricular In patients with arrhythmogenic right ventricular regular and physical activity could provoke right ventricular and which in may In Marfan syndrome, the stress on the by increased blood and during activity could increase the rate of aortic thereby the risk of aortic Consequently, the risk-to-benefit of exercise young and older subjects with occult cardiovascular disease. The of and The rarity of exercise-related events the of and activities because of small sample and SCD in adults are more frequent in the This has as to vigorous exercise be restricted to hours in individuals at increased risk. Young In contrast to adults, sudden death and cardiac arrest among young athletes occur primarily in the and and are associated with training and sudden death among patients with hypertrophic cardiomyopathy is more frequent in the hours, CHD The for observation is not and the of cardiac events in young subjects with cardiac disease is not and colleagues cardiovascular events in of cardiac rehabilitation exercise in the events per and events during the of exercise events per This not but are limited by the number of subjects and available events. Franklin and collaborators reported that of had or on the rate of cardiovascular complications during cardiac Given the likely benefits of exercise in reducing cardiovascular events and the low rate of exercise-related events, it is probably more important that individuals exercise at a of than at a specific of studies have high-risk activities, because of the rarity of exercise-related cardiovascular events. In the risk of any vigorous physical activity is an of the exercise per and the individual's physical fitness because physical lower cardiac demands in physically subjects than in unfit persons. has been associated with increased cardiovascular events probably because it can higher than does exercise because it is often of by unfit individuals, and because some cardiac patients develop at lower a coronary during exercise in EXERCISE-RELATED CARDIOVASCULAR EVENTS No strategies have been adequately studied to evaluate their ability to reduce exercise-related acute cardiovascular events. not the risks of exercise because the benefits of physical activity outweigh the risks. studies it appears that of the most important exercise-related cardiovascular events in adults is to physical fitness regular physical activity because a disproportionate number of exercise events occur in the least physically active subjects performing unaccustomed vigorous physical activity strategies to reduce events appear prudent although These include the excluding high-risk patients from some activities, and evaluating prodromal symptoms, fitness personnel and for cardiovascular emergencies, and prudent exercise of these is Young The cardiovascular screening for high school and college athletes before participation and at to The include a and and a physical on conditions associated with exercise-related events The does not such as a The of is because the on of the of has that be on all athletes as part of a The is on an study in the of Italy Italy has the screening of athletes, including an The annual incidence of sudden death among athletes to years of age with from deaths to deaths per in deaths among which suggests that screening the These provide the evidence to in of the screening of athletes but have The study not directly the screening and of athletes but a study. Other changes in the of the athletes could have to the In addition, the study not directly screening with and an there could be small in the and populations because the athletes were at the for whereas the population of subjects from the Healthy from controlled are available to the of exercise in asymptomatic adults known or before an exercise training the groups from the of on and the of have important by different specific the of these is and Individuals who appear to be at risk of be for exercise before a vigorous V˙O2 exercise training V˙O2 intensity V˙O2 V˙O2 This is in that both groups exercise before exercise training for patients with In the that evidence to the benefits and of exercise stress before exercise and for exercise before exercise of exercise is that exercise require the of a coronary whereas most acute cardiac events in previously asymptomatic subjects are to plaque Consequently, an exercise stress with or can be the of coronary plaque that may This that health professionals evaluate the atherosclerotic risk in patients on the of a vigorous exercise of Cardiovascular screening a of excluding high-risk subjects from and vigorous exercise Both the and the exercise before vigorous exercise training in persons with known cardiovascular disease. for for among and adults have been in the on These but can be to or vigorous exercise in patients with diagnosed cardiac and that individuals with exercise-related cardiovascular events had prodromal that were by the victims or their young athletes with of during or immediately after exertion, cardiac in the death among adults, of of and of who during exercise had cardiac before death (Table Most reported these only to and few medical Consequently, it is prudent for adults to the of prodromal cardiac and the need for medical In addition, evaluate possible cardiac in physically active individuals. Both patients and may or not adequately evaluate in active individuals in the that high levels of fitness than only the risk of cardiac reported by subjects 1 of their and for Cardiovascular The death rate from exercise-related cardiovascular events be personnel and with exercise activities were to cardiac The has that and high school and college athletes be in The and that participants in fitness be for heart disease with a and that facility be in cardiovascular These also have fitness to have available for cardiac The and the have a screening for to individuals at risk from exercise Nevertheless, a of health in that of the to cardiac most had > to and only had an it is these findings are of the that a and it would be prudent for to to have to regular and to have available for immediate by personnel and to a to medical healthy adults known cardiac disease be to develop exercise Because the least individuals are at greatest risk for exercise-related events, increase fitness and reduce acute events risk. with known cardiac disease also be to include at least of and in their exercise training to reduce the of cardiac ischemia with physical and to avoid the decrease in blood that can occur with the abrupt cessation of physical activity. with cardiovascular disease who are in in sports be and in with the individuals and patients with known cardiovascular disease avoid unaccustomed exercise in both and Vigorous exercise in the such as has been associated with acute cardiovascular events and require an increased heart rate to the increased Increased reduces oxygen and the and to a given work thereby cardiac Individuals at of > the intensity of their exercise No controlled studies have the of exercise training to reducing events. Nevertheless, a of epidemiological, basic and clinical evidence suggests that physical activity the risk of fatal and nonfatal events and that the benefits of regular physical activity outweigh its risks. Consequently, physical activity be for most individuals in with the for and for 30 of physical activity such as on of the Vigorous exercise, transiently increases the risk of and in individuals, and strategies are to reduce professionals the pathological conditions associated with exercise-related events that physically active and adults can be evaluated. individuals the of cardiac prodromal and medical such school and college athletes screening by professionals Athletes with known cardiac conditions be for to that their are in cardiac emergencies, have a and have individuals their exercise in to in their exercise their activity and the these have not been and to reduce exercise-related cardiovascular events, they appear prudent given present of the risks and benefits of every to avoid any or potential of that may as a of an or a or of a of the all members of the are to and a all such that be as or potential of