Epidemiologic Reviews Copyright © 1992 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved

Vol. 14,1992 Printed in U.S.A.

Physical Activity, Physical Fitness, and Sudden Cardiac Death

H. W. Kohl III,1

2

K. E. Powell,3 N. F. Gordon,4 S. N. Blair,' and R. S. Paffenbarger, Jr.5

delivering his important message, presumably because he overexerted himself. One version of the tale holds that this messenger had run 100 miles on his penultimate day. Although sudden cardiac death is not a specifically coded cause of death, it is estimated that it accounts for approximately 50 percent of deaths attributed to coronary artery disease (1, 2). Therefore, sudden unexpected cardiac death may be a close second behind other forms of heart disease and malignant neoplasms as a leading cause of death in the United States. The proportion of sudden cardiac deaths that are, or may be, associated with or "caused by" various intensities of physical activity and exertion is unknown. Do the acute risks of sudden cardiac death associated with physical activity outweigh the benefits of an habitually physically active lifestyle? The purpose of this paper is to explore the pertinent literature concerning the apparent paradox that an acute bout of strenuous physical activity is associated with increased rates of sudden cardiac death while habitual physical activity is associated with decreased rates of coronary artery disease death (3). Our focus is mainly on the former half of the apparent contradiction, namely, the increased rates of sudden cardiac death during activity. We consider the latter half, the reduced risk of developing and/or dying of coronary artery disease among those who are regularly active, to be established (3). First, we will review both the acute and longterm cardiovascular responses to physical activity. Second, the pathophysiology of sudden cardiac death as it relates to physical activity will be reviewed in the context of several potential predisposing factors. Third, we will examine the relevant scientific liter-

The idea of sudden death during physical activity elicits an image of a presumably healthy person dying unexpectedly while participating in a physically strenuous task. Regular physical activity is associated with a lower risk of heart disease, but history has ingrained images of elite athletes, presumably in top physical condition, who succumb to sudden cardiac death. The deaths of Jim Fixx, John Kelly, Pete Maravich, Flo Hyman, and Hank Gathers are wellpublicized examples of such events. Less promulgated, but familiar to most, are stories of sudden death while shoveling snow, digging in the garden, or jogging. More remotely, legend has it that in 492 B.C., Phidipides ran from the plains of Marathon to Athens, a distance of about 20 miles, to bring the news that the Athenians had defeated the Persians on land and that the city should redouble its efforts to defend itself from the sea. The Athenians apparently did so, and, as they say, the rest is history. The legend also says that Phidipides died suddenly after

Received for publication April 8, 1991, and in final form November 13, 1991. 1 Division of Epidemiology, Institute for Aerobics Research, Dallas, Texas. 2 School of Public Health, University of Texas, Houston, Texas. 3 Division of Injury Control, Centers for Disease Control, Atlanta, Georgia. 4 Division of Exercise Physiology, Institute for Aerobics Research, Dallas, Texas. 5 Division of Epidemiology, Stanford University, Stanford, California. Reprint requests to Dr. H. W. Kohl III, Division of Epidemiology, Institute for Aerobics Research, 12330 Preston Road, Dallas, TX 75230. This work was supported in part by grants AG06945, AR39715, HL34174, and 8CA44854 from the National Institutes of Health. The authors thank Christopher B. Scott for comments on an early version of this paper.

37

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Kohl et al.

ature on sudden death related to physical activity, with an emphasis on populationbased studies. Finally, we will recommend further work in light of the data presented. CARDIOVASCULAR RESPONSE TO EXERCISE Responses to an acute bout of exercise

During an acute bout of dynamic exercise (an alternate contraction and relaxation of skeletal muscle causing partial or complete movement through a joint's range of motion), energy metabolism in the active skeletal musculature increases in proportion to the intensity of exertion. The resultant increase in energy expenditure can be sustained only if the working skeletal muscles are supplied with appropriate metabolic substrates, such as oxygen, glucose, and free fatty acids, and are adequately cleared of metabolic products, such as carbon dioxide, lactic acid, and heat. The final common denominator of cardiovascular function during exercise is to ensure that the provision of essential metabolic substrates and clearance of metabolic products in fact take place at rates that appropriately match their rates of utilization and production, respectively (4, 5). Cardiac output. Cardiac output increases rapidly at the onset of constant intensity dynamic exercise and then gradually levels off within minutes as a steady state of oxygen uptake is attained. With subsequent increases in exercise intensity, cardiac output responds in a similar fashion, increasing linearly as a function of oxygen uptake until a maximal value is achieved immediately prior to the attainment of maximal oxygen uptake. Indeed, when rearranging the Fick equation (which states that cardiac output equals oxygen uptake divided by arteriovenous oxygen difference), it is evident that the maximal cardiac output that can be achieved is a key determinant of the maximal oxygen uptake and, thus, capacity to perform dynamic exercise (6). Cardiac output, in turn, is determined by the product of heart rate and stroke volume. Like cardiac output, heart rate increases lin-

early as a function of oxygen uptake and reaches a maximal value just before the attainment of maximal oxygen uptake (4, 5). However, in contrast to cardiac output and heart rate, stroke volume increases progressively only until the attainment of 40 to 50 percent of maximal oxygen uptake during graded dynamic exercise. This early leveling of stroke volume results from the progressive reduction in diastolic filling time as heart rate increases (4, 5). Myocardial oxygen demand and supply. The myocardial oxygen requirement during exercise is determined by a variety of factors, the most important of which are reflected by the product of heart rate and systolic blood pressure (which is indicative of the force generated by the heart during left ventricular contraction), the so-called ratepressure product (7). Because the ratepressure product increases linearly during graded exercise, so does the myocardial oxygen demand. However, unlike skeletal muscle oxygen requirements which are directly determined by the absolute exercise intensity (or power output), the rate-pressure product and, consequently, myocardial oxygen requirements are linearly proportional to the relative exercise intensity (or percent of maximal power output). Thus, identical exercise tasks usually produce similar skeletal muscle oxygen uptakes in individuals with differing maximal exercise capacities but markedly different myocardial oxygen uptakes (8). Since the resting myocardium already extracts some 70 to 80 percent of the oxygen available in the coronary arterial blood, the increased myocardial oxygen demand evoked by exercise must be met primarily by increased coronary arterial blood flow (7, 9). Fortunately, under normal circumstances, coronary blood flow and myocardial perfusion do increase, almost in proportion to the metabolic consumption of oxygen by the heart. Static exercise. In contrast to dynamic exercise, static exercise is the contraction of a skeletal muscle or group of muscles without movement of a joint. The acute cardiovascular response to static exercise differs

Exercise, Fitness, and Sudden Death

from that of dynamic exercise in a variety of ways. Many of these differences relate to the fact that sustained muscle contractions above about 15 percent of the maximal voluntary contraction occlude arterial blood flow and impede oxygen delivery to the active skeletal musculature (4). The resultant metabolic events elicit cardiovascular responses which are commonly referred to as the pressor response. Briefly, the pressor response involves only moderate increases in heart rate, stroke volume (this may not change at all), and cardiac output relative to dynamic exercise, but a marked increase in the diastolic blood pressure (which is indicative of the total peripheral resistance). The magnitude of this pressor response is primarily dependent on the percentage of the maximal voluntary contraction and the size of the muscle mass involved (5). From a myocardial oxygenation standpoint, it should be noted that the increase in rate-pressure product is accompanied by an increase in diastolic blood pressure which serves to enhance myocardial perfusion. This mechanism also is thought to explain the lower prevalence of ischemic abnormalities during combined static and dynamic exercise than exists during dynamic exercise alone, despite a higher rate-pressure product (10). Adaptations to habitual physical activity

Dynamic endurance conditioning. When dynamic exercise is performed regularly at an appropriate intensity and duration, there is an increase in the maximal cardiac output that can be achieved. Because the maximal heart rate usually remains unchanged or may even decrease slightly in normal persons after a period of training, higher maximal cardiac outputs in the endurance trained state are exclusively attributable to a greater maximal stroke volume. In contrast to maximal exercise, the heart rate is substantially decreased at rest and at any given level of submaximal exercise with endurance training. Such reductions are accompanied by an increased stroke volume and, thus, an insignificantly changed cardiac output (4, 5).

39

Data on the effect of endurance training on myocardial oxygen supply, especially regarding coronary collateralization, are equivocal at the present time (11). However, exercise training almost universally increases maximal exercise capacity. In so doing, the same submaximal exercise task represents a lower percentage of the maximal exercise capacity after training and, therefore, elicits a lower rate-pressure product. Consequently, myocardial oxygen requirements are lessened, and the balance between myocardial oxygen supply and demand is shifted in a favorable direction (8). Static exercise conditioning. In contrast to dynamic exercise training, which produces eccentric hypertrophy (that is, an increase in left ventricular chamber size with a lesser increase in left ventricular wall thickness) as an adaptive response to volume overloading of the left ventricle, static exercise training may result in concentric hypertrophy (that is, an increase in left ventricular wall thickness without a corresponding increase in chamber size) as an adaptive response to pressure overloading (12). However, while the eccentric hypertrophy that often results from endurance exercise training is physiologically more desirable than the concentric hypertrophy that may result from static exercise training, neither form of exercise-induced hypertrophy appears to produce any untoward changes in left ventricular function (12). Indeed, it is now postulated that both types of exercise-induced hypertrophy are associated with an increase in myocyte vascularity that is commensurate with the degree of hypertrophy of the myocytes themselves, and may thereby improve myocardial function and help assure myocyte health (13).

PATHOPHYSIOLOGY OF EXERTIONRELATED SUDDEN CARDIAC DEATH By definition, the event immediately preceding all cases of sudden cardiac death is an abrupt disturbance of cardiac function that is incompatible with the maintenance of cerebral blood flow and, thus, consciousness. Such perturbations of cardiac function

40

Kohl et al.

may result either from cardiac arrhythmias or from mechanical abnormalities. However, the vast majority, in fact, are arrhythmic in origin (14). The most common arrhythmia that precipitates an acute, fatal loss of effective circulation is ventricular fibrillation; less common arrhythmias include bradyarrhythmias, asystole, and sustained ventricular tachycardia (15). These potentially lethal arrhythmias are believed to result from the combination of a triggering event, usually a premature ventricular contraction, and a susceptible myocardium (15). In the absence of a triggering event the presence of a susceptible myocardium may be innocuous. Likewise, without a susceptible myocardium a premature ventricular contraction or other potential triggering event is unlikely to evoke a fatal arrhythmia. Triggering events and myocardial susceptibility are both endpoints of a cascade of pathophysiologic abnormalities that are initiated by complex interactions among a variety of factors. In the case of exertionrelated sudden cardiac death, such postulated factors include an excessive elevation in myocardial oxygen demand, alterations in sympathetic and parasympathetic tone, release of coronary vasoconstrictor substances such as thromboxane A2, an increase in blood coagulability, lactic acidosis, electrolyte derangements, elevated circulating free fatty acid levels, a sudden precipitous fall in cardiac output consequent to abrupt cessation of exercise, and an excessive rise in body temperature (16-19). While the precise mechanisms by which they act are still to be determined fully, multiple combinations of such exercise-related factors are likely to be responsible. Moreover, it is evident from existing studies that, in almost all instances of sudden cardiac death, the various relevant exercise-related factors combine with preexisting cardiac disease to culminate in the genesis of a susceptible myocardium and lethal triggering event. The healthy heart, even when subjected to strenuous exertion, appears to be protected from lethal arrhythmias except in unusual cir-

cumstances such as profound electrolyte disturbances, heat stroke, or drug abuse. Thus, although rare cases of exertion-related sudden cardiac death have been reported to occur in association with physical activity in apparently healthy persons (20), it is the combination of exercise and underlying heart disease, rather than exercise alone, that usually leads to the final common pathway of lethal arrhythmia. The specific cardiac diseases that have been linked to sudden cardiac death during physical activity are listed in table 1. Of these, coronary artery disease has been found most frequently upon autopsy in persons over 35 years of age, and the cardiomyopathies have been found most fre quently in persons under 35 years of age (figure 1). In view of this, in the section that follows we focus on the pathophysiology of coronary artery disease- and cardiomyopathyrelated sudden cardiac death.

TABLE 1. Pathologic conditions possibly associated with sudden cardiac death during exercise* Conditions resulting in myocardial ischemia Atherosclerotic coronary artery disease Coronary artery spasm De novo coronary artery thrombus Myocardial bridging Hypoplastic coronary artery Anomalous coronary arteries Structural abnormalities Hypertrophic cardiomyopathy Idiopathic concentric left ventricular hypertrophy Right ventricular cardiomyopathy Mitral valve prolapse Other valvular heart disease Marfan's syndrome Congenital cardiac defects Conduction abnormalities Wolfe-Parkinson-White syndrome Lown-Ganong-Levine syndrome QT interval prolongation syndrome Miscellaneous Heat stroke Myocarditis Sarcoidosis • Adapted from Sadaniantz and Thompson (31).

Exercise, Fitness, and Sudden Death

CAD

HCM 48%

41

80%

Unexplained 3% Idiopathic LVH 18% Unexplained 5% MVP Acquired 5% Valve Disease 5% FIGURE 1. Autopsy results of victims of exertion-related sudden cardiac death by age group of decedent: left, subjects aged < 35 years; right, subjects aged > 35 years. HCM, hypertrophic cardiomyopathies; LVH, left ventricular hypertrophy; CAD, coronary artery disease; MVP, mitral valve prolapse. Adapted from Maron et al. (21). Coronary Artery Anomalies 14%

CAD 10%

Coronary artery disease

Mechanisms for sudden cardiac death. Atherosclerosis of the coronary arteries is the most common pathologic abnormality in victims of exertion-related sudden cardiac death. Indeed, coronary artery disease is found at autopsy in more than 80 percent of persons over the age of 35 years who die suddenly during or shortly after exercise (21). It is estimated that of these persons, as many as 43 percent are reported to have been previously asymptomatic and unaware of their underlying cardiac disorder (22). These clinical findings add possible insight to the problem but at the same time say nothing about how these frequencies compare with the underlying rate in the general population. In the majority of persons with coronary artery disease who succumb to exertionrelated sudden cardiac death, myocardial ischemia is believed to create the setting in which a trigger event, such as a premature ventricular contraction, and a susceptible myocardium combine to evoke a potentially lethal arrhythmia. The onset of myocardial ischemia is accompanied by dramatic cellular electrophysiologic changes in the affected area. These immediate cellular consequences of ischemia, which include loss of cell membrane integrity, potassium ion efflux, calcium ion influx, acidosis, reduction

in transmembrane resting potential, and enhanced automaticity, are followed by another dramatic series of deleterious perturbations during the restoration of blood flow to the previously ischemic region. Both the immediate consequences of myocardial ischemia as well as the delayed consequences of reperfusion are capable of producing electrophysiologic irritability (15). Studies have demonstrated further that these adverse consequences of acute myocardial ischemia and reperfusion may be more arrhythmogenic in the presence of a recent or healed myocardial infarction (15). The specific mechanisms by which fatal myocardial ischemia develops in persons with coronary artery disease who perform an acute bout of exercise are not fully understood at the present time. Three major possibilities exist. First, exertion-related fissuring of a fragile atherosclerotic plaque with resultant thrombus formation may transform a previously nonocclusive plaque into a total or near total occlusion (23). This would lead to myocardial ischemia, particularly in the absence of adequate coronary collaterals. While this mechanism is likely to account for some cases of exertion-related sudden cardiac death, it must be noted that less than one-third of resuscitated patients are reported to subsequently develop new Q waves or show enzymatic evidence of myocardial infarction (24). Indeed, of 25 life-

42

Kohl et al.

threatening arrhythmias that necessitated resuscitation during cardiac rehabilitation exercise training in one study (24), none was associated with acute myocardial infarction. While these observations argue against total or near total coronary artery occlusion as being the major mechanism for exertionrelated sudden cardiac death, factors such as spontaneous lysis of blood clots confound the situation. Nonetheless, it does appear that the ischemia which precedes lifethreatening arrhythmias is transient in nature. Second, in the absence of near total occlusion, an atherosclerotic plaque with or without a superimposed acute thrombosis, may prevent the myocardial oxygen supply from meeting the increased myocardial oxygen demand imposed by exercise (figure 2). Such a scenario would result in transient myocardial ischemia and is thought by some to be the most common cause of exertion-related sudden cardiac death in persons with coronary artery disease (15). Although the role of plaque fissuring and thrombus formation in this mechanism are unclear, it is of interest that most asymptomatic persons who subsequently die suddenly of cardiac causes have normal exercise tests (23). This may be partly related to their having a false-negative exercise test (due to a deficiency in the ability of this procedure to detect a clinically significant coronary artery stenosis), but could also be indicative of the rapid progression of a clinically unimportant coronary artery stenosis to a flow-limiting lesion via plaque fissuring and thrombus formation (23). Finally, myocardial ischemia may occur secondary to exercise-induced coronary artery spasm. Vasospasm of the coronary arteries may directly (by producing a flowlimiting narrowing of a coronary artery) or indirectly (as a trigger responsible for plaque rupture during exercise (25)) result in myocardial ischemia. While there are scarce objective data in support of either mechanism, coronary spasm cannot be excluded as an important contributory factor at the present time. The mechanism for exercise-induced coronary artery spasm in persons with coronary artery disease is postulated to be re-

Normal Heart

Intensity ol Physical Activity

Coronary Artory Disease

Intensity of Physical Activity

FIGURE 2. Relation between myocardial oxygen supply and demand during physical activity for a normal heart and a heart with coronary artery disease.

lated to unopposed a-adrenergic stimulation by circulating catecholamines as a result of segmental endothelial dysfunction (25). Similarly, there are a variety of mechanisms by which reperfusion of areas of the myocardium that have been rendered ischemic by exercise may occur. These include spontaneous thrombolysis of flow-limiting blood clots, a reduction in exercise intensity and, hence, myocardial oxygen demand, reversal of coronary artery spasm, and collateral blood flow to the ischemic region. Recently, it has been suggested that cardiac arrhythmias resulting from reperfusion of previously ischemic areas of myocardium may be responsible for the frequent occurrence of sudden death after the cessation of physical activity (25). Protection against sudden cardiac death. Mechanisms by which exercise participation

Exercise, Fitness, and Sudden Death

could be expected to reduce the risk for exertion-related sudden cardiac death in persons with coronary artery disease include an increased resistance to ventricular fibrillation during myocardial ischemia, reduced platelet aggregability, enhanced fibrinolytic activity, and favorable alterations in myocardial oxygen supply and/or demand (26). Of these potential protective mechanisms, a favorable alteration in myocardial oxygen demand has been best documented in humans. As already discussed, the relative intensity at which exercise is performed is a major determinant of the rate-pressure product and, thus, myocardial oxygen demand. In persons with a fixed atherosclerotic coronary artery stenosis, significant myocardial ischemia generally only occurs during exercise once a threshold relative intensity has been exceeded. Because the resistance to coronary artery blood flow is partly dependent on the degree of coronary stenosis, the precise threshold of relative exercise intensity above which there is a substantial increase in the risk for myocardial ischemia and, consequently, sudden cardiac death will vary from person to person (figure 3). By

co a>

Q

43

increasing the maximal exercise capacity, exercise training can be expected to increase the absolute exercise intensity needed to achieve the critical relative exercise intensity at which significant ischemia occurs in a person with a given fixed atherosclerotic stenosis (8). In so doing, exercise training is likely to increase the absolute exercise intensity that is needed to evoke sudden cardiac death during exercise.

Cardiomyopathy-related sudden cardiac death

Hypertrophic cardiomyopathy. The cardiomyopathies constitute a group of diseases, often of undetermined etiology, in which the dominant feature is myocardial involvement (27). Hypertrophic cardiomyopathy is usually genetically transmitted as an autosomal dominant trait and is characterized by inappropriate myocardial hypertrophy of a nondilated left ventricle. The ventricular wall thickening is usually asymmetric, with the septum disproportionately thicker than the left ventricular free wall. Histologically,

90% occlusion

o as co O c CD

T3

CO

if Intensity of Effort (% VO2(max)) FIGURE 3. Theoretical relation of the intensity of physical activity to risk of sudden cardiac death. Dotted lines represent thresholds for "increased" risk; VO2(max) refers to maximal oxygen uptake, and in this context is used as an indication of relative exercise intensity.

44

Kohl et al.

there is bizarre cellular architecture and an increased number of abnormal intramural coronary arteries with narrowed lumens. Clinically, it is occasionally difficult to distinguish pathologic hypertrophic cardiomyopathy from the physiologic left ventricular hypertrophy that accompanies exercise training in normal persons (28). In persons under the age of 35 years, hypertrophic cardiomyopathy is the most common pathologic condition associated with exertion-related sudden cardiac death (figure 1). As is the case with coronary artery disease, the precise mechanism by which sudden death occurs during or shortly after an acute bout of exercise in persons with hypertrophic cardiomyopathy is unclear. It is generally presumed, but not established, that most of these deaths are due to ventricular arrhythmias that result from the interaction between exercise and structural and functional abnormalities accompanying hypertrophic cardiomyopathy (21, 29). Interestingly, angina pectoris is found in about three-quarters of symptomatic patients and exertion-induced myocardial ischemia is a potential precipitating factor of such lethal arrhythmias (27). Myocardial ischemia could be expected to occur during exercise in persons with hypertrophic cardiomyopathy as a result of a variety of factors, including an imbalance between oxygen supply and demand consequent to the markedly increased myocardial mass, narrowing of intramural coronary arteries, and prolonged maintenance of left ventricular wall tension with a concomitant slower-than-normal reduction in the impedance to coronary artery blood flow during diastole (27). An alternate possibility is that exertionrelated sudden cardiac death in persons with hypertrophic cardiomyopathy may be precipitated by an abrupt fall in stroke volume that is not secondary to ventricular or other arrhythmias. Whether the fall in stroke volume in such circumstances is primarily the result of impaired ventricular filling, due to increased left ventricular wall stiffness, or impaired ventricular emptying, due to left ventricular outflow tract obstruction, or some other mechanism, is uncertain.

Right ventricular cardiomyopathy. Recent research has identified right ventricular cardiomyopathy, sometimes referred to as right ventricular dysplasia, as a relatively frequent cause of sudden death in young athletes (30, 31). Indeed, in one study this condition was found in nearly 30 percent of young athletes who succumbed to sudden death (30). The localized fibrolipomatous transformation of the free wall of the right ventricle which is characteristic of right ventricular cardiomyopathy is hypothesized to produce electrical instability and, thereby, predispose to lethal ventricular arrhythmias. PUBLISHED WORK ON SUDDEN CARDIAC DEATH RELATED TO PHYSICAL ACTIVITY Clinical studies

The bulk of scientific literature on physical activity and sudden cardiac death is based on clinical reports, patient case series, and even anecdotal information (17, 22, 30, 32-58). Although such reports provide useful clinical information, rates and risks cannot be estimated from the results of such studies. None of these will be reviewed in detail here since much of the information provided in the previous section has been derived from such reports. Population-based studies

Unsupervised physical activity: incidence estimates. A summary of population-based studies providing estimates of the incidence of sudden death during unsupervised physical activity is presented in table 2. Column 3 of the table shows the types of populations investigated: general, likely competitive athletes, or military personnel. To qualify for inclusion in this table, published data needed to be available to estimate not only the number of sudden cardiac deaths in a defined population but also the period of exposure, so that an event rate in the population in question could be calculated. Eight of 10 studies provided enough information to estimate risk per hour of exposure, and the remaining two allowed risk estimates per person-year of observation. In 1980, Gibbons et al. (59) reported the cardiac event experience of 2,935 men and

E 2. Summary of population-based studies providing estimates of incidence of sudden cardiac death during unsupervised physical activity, 1975-1988

Study (reference no.)

Definition of sudden death Exposure (estimated)

Population/activity

Time between collapse and death

Temporal relation between exertion and collapse

Gibbons et al. (59)

374,798 person-hours

2,935 Dallas, Texas, health club members—general exercise

No deaths

No deaths

Vander et al. (60)

33,726,000 person-hours

YMCA* and JCC* members in the United States in 5 years—general exercise

During or immediately post exercise

Thompson et al. (61)

3,970,000 man-hours

12,728 (est.) male joggers aged 3064 years in Rhode Island—jogging

Marti et al. (62)

351,000 person-hours

Marti et al. (62)

Deaths

Rate/100,000 hours

0

0.00

Not reported

33

0.10

While running

While running

10

0.25

279,905 Swiss male foot race participants aged 20 years and older—road racing

During or within minutes of races

Within 24 hours

3

0.85

906,500 person-hours

906,400 Swiss male foot race participants aged 20 years and older—road racing

During or within minutes of races

Within 24 hours

7

0.77

Opie (63)

100,000 man-hours

2,100 South African rubgy players—rugby

0-1 hour after exercise

Within 1 hour

2

2.00

Vuori et al. (64)

6,695,000 man-hours

1,030,000 Finnish cross-country ski performances in 16 years

0-24 hours

Within 24 hours

8

0.12

Phillips et al. (65)

48,200,000 person-hours

1,606,167 United States Air Force recruits—military training

With exercise

Within 1 hour

17

0.03

Koskenvuo (66)

660,000 man-years

Finnish conscripts—near maximum physical effort

During exercise

Within 24 hours

12

1.82f

Lynch (67)

1,600,000 man-years

Male British soldiers—sporting deaths

During exercise

Within 24 hours

40

2.50t

Siscovick et al. (68)

23,800,000 man-hours

Married men, aged 25-75 years with no clinical heart disease

During high intensity leisure time activity

Not applicable

MCA, Young Men's Christian Association; JCC, Jewish Community Center, ates based on person-year denominator rather than person-hour exposure, ot all cases died; definition was "a sudden pulseless condition and the absence of a noncardiac cause of primary cardiac arrest."

9*

0.04

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Kohl et al.

women members of a Dallas, Texas, health club during nearly a 5.5-year period. These persons recorded their activity and exercise participation in a computer-based tracking program, logging 374,798 person-hours of physical activity. Most activity was recreational walking and running. No sudden cardiac deaths were reported in this study. One participant collapsed while running but was resuscitated and another had a myocardial infarction during a postexercise shower. The dependence of the exposure estimate on selfreport likely underestimated the amount of person-hours of exercise in this study population. Vander et al. (60) conducted a 5-year survey of community recreation centers to determine cardiovascular complication rates "during or immediately after physical activity." A total of 155 Young Men's Christian Associations (YMCA) and Jewish Community Centers throughout the United States were surveyed. A 50 percent response rate was obtained, but unusable questionnaires reduced the effective response rate to 31 percent. Based on these self-report data of fatal cardiovascular complications occurring during or immediately after exercise, a death rate of 0.10 per 100,000 person-hours of exercise was reported. Exposure was estimated using business-hour descriptions and assumptions of attendance and an average time per exercise period (1 hour). Thompson et al. (61) estimated the incidence of sudden cardiac death among men during jogging in Rhode Island for 1975 through 1980. Events were defined as death occurring during running or jogging. Exposure was estimated by estimating the number of men, aged 30-64 years, residing in Rhode Island who, in 1978, reported jogging at least twice per week. Using several assumptions, 3,970,000 man-hours of jogging were estimated to have taken place during the 6-year period. Ten deaths were cardiacrelated. Of the 10 persons who died, six were autopsied and found to have coronary artery disease, two had previously documented myocardial infarctions, and two had "complained of anginal chest pain." A sudden cardiac death rate of 0.25 per 100,000 man-

hours of jogging was estimated from these data. This value was further estimated to be nearly seven times the underlying rate of sudden cardiac death during rest. Two studies of sudden cardiac death during vigorous exercise were published by Marti et al. (62) in 1989. Cases were taken from male participants 20 years of age and older of all organized foot runs in Switzerland between 1984 and 1987 (906,400 estimated hours at risk) or in the nine largest runs between 1978 and 1987 (351,285 estimated hours at risk). Events were defined as runners who collapsed and died during or within a few minutes after finishing the race and who died within 24 hours (75 percent died within 1 hour). Among the five cases with autopsies, two had evidence of coronary artery disease (ages 46 and 50 years), one had evidence of hypertrophic cardiomyopathy (aged 31 years), and two had no obvious abnormalities identified (both aged 21 years). For the two studies, estimates of 0.85 and 0.77 per 100,000 person-hours at risk are calculated. Because the distance of the events was known, estimates of the person-hours at risk are likely to be more accurate than estimates made in other studies. In a review of the experience of approximately 2,100 rugby players in one season (March to October 1973), Opie (63) estimated the risk of sudden death during the matches to be approximately two per 100,000 man-hours. Assumptions about the period of exposure are somewhat imprecise, however, and it is unclear if the sudden deaths (possibly trauma related) that were counted were actually cardiac in nature. Thus, this rate may also not be directly comparable with others listed in table 3. Eight deaths during 16 years in Finland (approximately 1,030,000 ski hikes) were evaluated by Vuori et al. (64). By using 024 hours as the risk period, and assuming 6.5 hours per ski performance, an estimate of 0.12 sudden cardiac deaths per 100,000 man-hours of exercise participation is estimated from these data. The sudden cardiac death experience of 1.6 million United States Air Force recruits

Exercise, Fitness, and Sudden Death

between 1965 and 1985 was reported by Phillips et al. (65). In this young (ages 1728 years), mostly male (90 percent), and apparently healthy population, sudden cardiac deaths were enumerated for the 42-day basic military training period and risk was estimated on the basis of 30 of these 42 days, each of which included a minimum of 60 minutes of physical activity. The 17 deaths associated "with exercise" and attributed to cardiac origin represented a rate of 0.03 per 100,000 person-hours of exercise. It is noteworthy that the definition of sudden cardiac death used in this study was an event occurring within an hour of onset of symptoms and not limited necessarily to events occurring during physical activity per se. Two other studies of military populations provide for an interesting contrast of the data from Phillips et al. (65). Koskenvuo (66) reported the sudden death experience of Finnish men conscripted between 1948 and 1972. Although person-hours of exercise were not used for exposure in this study (person-years was the denominator provided) each death was classified by the type of activity being performed at the onset of symptoms. The 12 sudden cardiac deaths were events occurring up to 24 hours after the onset of symptoms. Although a rate of 1.82 per 100,000 person-years is possible to calculate, it is not directly comparable to others because of the different units involved in exposure calculation. In 1980, Lynch (67) reported on sudden death occurring specifically after "sport" in male British soldiers between 1968 and 1977. Forty deaths due to ischemic heart disease or congenital cardiac abnormalities, occurring within 24 hours of exertion, were enumerated over the 10 year period in this group of predominantly young men. As was done in the study by Koskenvuo (66), manyears, rather than hours, served as the basis for event rate calculation in this study. An estimated rate of sudden cardiac death in this population is 2.5 per 100,000 manyears. Unsupervised physical activity: risk factor studies. One study which provides useful data on the risk of sudden cardiac death

47

during physical activity, as balanced by possible benefits, was contributed by Siscovick et al. (68). These authors conducted a casecomparison study involving 133 men in King County, Washington, without known prior heart disease or other chronic illnesses, who suffered primary cardiac arrest. Survivors and nonsurvivors were studied, and nine of these men had their primary cardiac arrest during exercise. An estimated rate of sudden cardiac death based on these data is 0.04 per 100,000 man-hours of exercise. On the basis of interview data given by wives of these cases, and from 133 wives of randomly selected community comparison subjects, the risk of primary cardiac arrest during physical activity and while at rest was calculated. Further, this study design also allowed stratification of risk by level of usual habitual physical activity. This study, therefore, allows for a simultaneous evaluation of the benefits of habitual physical activity as well as the risks of sudden cardiac death. The data in figure 4 are adapted from those of by Siscovick et al. (68) and graphically display the rate of primary cardiac arrest in the population. The rate of sudden cardiac death is considerably lower among those men who engage in more frequent habitual physical activity. These data correspond to an approximate risk of primary cardiac arrest in those with no high-intensity physical activity, relative to those who took more than 140 minutes of physical activity per week, of 3.6. The data from Siscovick et al. (68) also suggest an increased risk of primary cardiac arrest during physical activity (figure 5). The striking finding, however, is an exaggerated risk during physical activity among those men who less-frequently engaged in highintensity physical activity in their leisure time. The risk of primary cardiac arrest during physical activity among those men who participated in high-intensity physical activity 1-19 minutes per week, relative to the incidence at other times of the day, was reported to be 56 (95 percent confidence interval 23-131). While the risk during vigorous physical activity was increased even among those who were habitually active (rel-

48

Kohl et al.

I

Incidence/100,000,000 man hours 20 -f

15 -

5-

M 1-19 20-139 High-Intensity Activity (min/wk)

>140

FIGURE 4. Overall incidence of primary cardiac arrest (during and not during physical activity) by habitual vigorous physical activity level, King County, Washington, 1980. Numbers above the bars are the actual numbers of deaths in each group. Adapted from Siscovick et al. (68).

Relative Risk of Primary Cardiac Arrest 70-] (23-131)

60 5040-

(5-32) /'

'

(2-14)

10

1-19

20-139 High-Intensity Activity (min/wk)

>140

FIGURE 5. Risk of primary cardiac arrest during vigorous physical activity relative to other times of day, King County, Washington, 1980. The numbers corresponding to the top of the bars are relative risks, and the numbers within the parentheses are 95 percent confidence intervals around the risk estimates. Adapted from Siscovick et al. (68).

Exercise, Fitness, and Sudden Death

ative risk = 5,95 percent confidence interval 2-14), it was significantly less than the risk in those who were inactive. These risk estimates are based on two and four deaths occurring during activity, respectively. An estimate of the risk during physical activity among those who reported no vigorous physical activity could not be calculated. Supervised physical activity. A summary of population-based studies providing estimates of the incidence of sudden death during supervised physical activity is presented in table 3. The data are subset within this table by studies reporting sudden cardiac death during exercise testing and those reporting events as part of cardiac rehabilitation programs. The reasons for this separation will be addressed in the following paragraphs. Exercise testing. Exercise testing protocols are designed to stress the cardiovascular system in such a way that subclinical abnormalities in heart structure and/or function may be detected. As a group, persons submitting to an exercise test are not likely to be as healthy as other populations reviewed above. This carefully structured and monitored evaluation of cardiac function during exertion allows another model with which to examine the risk of sudden cardiac death as a result of physical activity. At least eight published reports which allow estimates of rates of sudden cardiac death during exercise testing exist. Perhaps the seminal work on the safety of exercise testing was published by Rochmis and Blackburn in 1971 (69). In this survey of 73 medical centers, 170,000 exercise tests using a variety of testing protocols reported a total of 12 sudden cardiac deaths within 24 hours of the exercise test. Eight of these deaths occurred within 1 hour of the test, and four additional events occurred between 1 hour and up to 4 days after the test. These four tests are not included in the rate calculations in table 3 because it is unclear if they were precipitated by the exercise test. With a 55 percent response rate to the survey, the 12 sudden cardiac deaths represented an overall rate of 7.00 per 100,000 exercise tests. Most

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testing facilities employed submaximal effort protocols, meaning that tests were not usually terminated because of symptom limitation, but rather because of the person attained some predetermined physiologic submaximal endpoint. Three other surveys of exercise testing facilities have been reported. Atterhog et al. (70) reported results from a prospective study of departments of clinical physiology in Sweden. Twenty departments participated in an 18-month study of exercise testing complications. During this period, two fatalities were reported doing "about 50,000" tests, most of which were discontinued at a submaximal workload. The two deaths translate into an approximate rate of 4 per 100,000 tests. In 1980, Stuart and Ellestad (71) reported the results of a survey of the characteristics of 6,000 exercise testing facilities in the United States, Canada, and Puerto Rico. Seventy percent of the 1,375 responding facilities employed a physiologic maximal exercise test protocol. In the 12 months before the survey, 518,448 tests and 26 deaths were recorded, although the time between occurrence of these deaths and the exercise bout was not. Thus, it is likely that at least some fatalities occurred outside the 24-hour definition limits for sudden cardiac death. If this were true, it would be expected that the actual rate of sudden cardiac death would be somewhat lower than the reported 5 per 100,000 tests. Finally, Scherer and Kaltenbach (72) reported a European experience with the safety of exercise testing in two types of populations in Germany: sports persons and coronary patients. No fatalities were reported during the 353,638 tests in athletes, and 17 occurred during the 712,285 tests conducted on coronary patients (2.4 per 100,000 tests). No information was available regarding the time frame for definition of sudden cardiac death. The first report of the safety of exercise testing to involve use of a standardized protocol of intense exercise was provided by Sheffield et al. (73) on data collected during

LE 3.

Summary of studies providing estimates of incidence of sudden cardiac death during supervised physical activity, 1971-1989 Definition of sudden death

Study (reference no.)

Exposure

Population

Temporal relation between exertion and collapse

Time between collapse and death

Rate/100,000 hours*

Deaths

Rate/100,000 tests

8 4 12

4.7 2.3 7.0

16.5

Exercise testing Time from test to death