Author + information
- Received August 12, 2014
- Revision received October 9, 2014
- Accepted October 21, 2014
- Published online February 10, 2015.
- ∗The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California
- †Division of Cardiology, Warren Alpert Medical School of Brown University, Providence, Rhode Island
- ↵∗Reprint requests and correspondence:
Dr. Sumeet S. Chugh, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Suite A3100, 127 South Vicente Boulevard, Los Angeles, California 90048.
The overwhelming majority of sports-related sudden deaths occur among those older than 35 years of age. Because increasing numbers of older people are participating in organized endurance and competitive sporting events, the incidence of sports-related sudden death in older adults is expected to rise. Older athletes will approach clinical cardiologists for advice regarding their fitness for participation. It is important to recognize both that strenuous exercise is associated with a transient elevation in risk of sudden cardiac death and that appropriate training substantially reduces this risk. The approach to pre-participation screening for risk of sudden death in the older athlete is a complex issue and at present is largely focused on identifying inducible ischemia due to significant coronary disease. In this brief review, we summarize the current state of knowledge in this area with respect to epidemiology, mechanisms, and approaches to risk stratification, as viewed from the perspective of the consulting clinical cardiologist.
The legend of the first marathon runner, Pheidippides, embodies the popular notion that endurance athletics increase the risk of death. An Athenian messenger approximately 40 years of age, he is fabled to have run from Marathon to Athens in 490 B.C., perishing on arrival after proclaiming the Greek victory over the Persians. The beneficial, health-promoting effects of habitual physical and sports activity are undeniable. However, a “sports paradox” exists: some people, most often those not habituated to exercise, experience sports activity–related cardiac arrests, usually associated with underlying heart disease. Middle-aged and older athletes are at significantly higher risk for sudden cardiac death (SCD) compared with younger athletes and are more vulnerable to misconceptions regarding the cardiovascular effects of sports. The burden of SCD during sports needs further evaluation but probably constitutes a small proportion (5% to 6%) of sudden deaths in the general population (1,2). However, from a societal perspective, sports-related SCD can have a disproportionate impact. People who engage in athletic activity are ostensibly healthier than most and therefore considered least likely to experience a cardiac arrest. The media attention on sports-related SCD tends to exaggerate the sports paradox and obscure the global health benefits of regular exercise. In addition to being cardiologists, both authors of this review are dedicated long-distance runners who seek to put the clinical risks and benefits of aerobic exercise in scientific balance.
A leisure athlete is “an individual, usually middle-aged or elderly (≥35 years), who participates in a variety of informal recreational sports, on either a regular or an inconsistent basis, which do not require systematic training or the pursuit of excellence” (3). For the purpose of this review, the term “older athlete” includes all athletes older than 35 years of age participating in sports at a competitive or masters level or as a leisure activity. Both clinical cardiologists and their patients will benefit from a balanced approach to education, risk stratification, and exercise prescription for the middle-aged and older athlete. The goal of this review is to put forth such an approach on the basis of a current and comprehensive assessment of previously published studies.
Current Burden and Future Projections
The overwhelming majority of sports-related sudden deaths occur among those 35 years of age or older (4) (Figure 1). Because many such deaths are unwitnessed, the magnitude of the problem is difficult to ascertain. Retrospective studies of athletes who participate in marathons yield estimates of 0.8 to 2 SCDs per 100,000 marathon runners (4–11). More comprehensively, a prospective 5-year study of sports-related SCD in the general population of France reported an annual incidence of 4.6 sports-related SCDs per 1 million residents of France (4). Most of these events occurred in older male athletes, with only 6% (50 of 820) of all cases of sports-related SCDs in young, competitive athletes. When placed in the context of the overall burden of SCD in the general population (600 to 900 per million), sports-related SCDs constitute a small subset. Some have reasoned that the absolute burden of sports-related SCD is small and therefore of modest clinical significance. For recreational joggers, however, the annual incidence of SCD is significantly higher: 13 SCDs per 100,000 joggers per year (8).
Several additional factors contribute to the clinical and public health importance of SCD in the older athlete. The number of older Americans is steadily increasing and is expected to double by 2035, reaching 70 million. By 2040, 21% of the U.S. population will be older than 65 years of age (currently 13.7%) (12). As the population ages, a burgeoning subgroup of older athletes is participating in leisure and organized sports. The popularity of endurance sports, especially running, is significantly on the rise in the United States. For example, there are approximately 20,000,000 participants in foot races in the United States annually. Of these, 54% are older than 35 years of age and 57% are male. The number of participants has been growing steadily for the past 15 years (13) (Figure 2). These trends are driven by the growing awareness of the health benefits of exercise activity but are matched by increasing levels of cardiovascular risk among aspiring older athletes. According to recently published studies, the overwhelming majority of sports-related SCDs have occurred in men, with a 9:1 ratio of men to women experiencing SCD during sports (11). Potential explanations include lower participation rates for women in marathons or similar events. Because women tend to develop atherosclerosis about 10 years later than men, the participation rate of women at risk may be even lower. As the demographics of endurance athletics change along with the population, we anticipate that increasing numbers of older women will pursue endurance athletics. However, women clearly enjoy the advantage of a lower likelihood of overall SCD, and the possibility remains that they have a special advantage during physical activity.
Evidence for Transient Elevation in Risk With Exercise, Countered by a Protective Effect of Regular Exercise
Several now-classic studies showed an increased risk of SCD and myocardial infarction (MI) during strenuous exercise. Siscovick et al. (7) interviewed the spouses of 133 men with SCD without known prior heart disease and reported a significant increase in relative risk with exercise, but this effect strongly depended on the habitual exercise level. Among sedentary people, the relative risk of SCD during exercise was increased 56-fold compared with other times. This contrasted strikingly with the lower relative risk during exercise of 5 for men with the highest level of habitual activity. Despite the residual 5-fold increased risk of SCD during vigorous activity, men with the highest habitual level of physical activity had a substantially lower relative risk (0.4) of global SCD compared with sedentary controls.
This “paradox of exercise” was confirmed by 2 other important epidemiological studies: one study of exercise-related MI, the most common substrate for SCD, and a second study of exercise-related SCD. Mittleman et al. (14) reported an overall increased relative risk of MI during exercise of 5.9. They also found an extraordinary 50-fold difference between sedentary patients (relative risk of MI associated with exertion of 107) and active patients (relative risk: 2.4). They showed a clear dose-response effect, and the greater the frequency of weekly exertion, the greater the reduction in relative risk of MI (Figure 3). Although SCD was not evaluated, the congruence of their findings with those of Siscovick et al. (7) for SCD is striking. A third prospective analysis, conducted by Albert et al. (10) from the Physicians Health Study, showed very similar findings. The overall relative risk of SCD within 30 min of vigorous exercise was 16.9. For those who exercised less than once per week, the relative risk was 74.1; for those who exercised ≥5 times per week, the relative risk was 10.9. These 3 seminal studies confirm both the increased risk of MI and SCD associated with exercise and the beneficial effect of regular exercise to reduce this risk.
The magnitudes of the risk reduction attributed to frequent exercise are impressive, in the range of 7- to 10-fold lowered risk for exercise-associated SCD and 50-fold reduction for exercise-associated MI. The global mortality benefits of exercise, we reiterate, far outweigh the increased risk (Table 1). Multiple studies confirm a dose-related beneficial impact of regular exercise on global cardiovascular risk, which is independent of sex, ethnicity, and probably of age. The magnitude of the risk reduction is comparable to or exceeds that of statin therapy and extends beyond cardiovascular risk to cancer. Moderate exercise (30 min of moderate activity 5 times per week) reduces cardiovascular risk by 20%, and high levels of exercise (30 min of vigorous activity 5 times per week) reduce cardiovascular risk by 30% to 40% (15). These benefits are enhanced by the observed additional impact of regular exercise on the risk of cancer. Over an 8-year period, regular high levels of exercise in healthy people were associated with a 70% reduction in age-adjusted all-cause mortality in men and an 80% reduction in women (16).
Potential Mechanisms of Exercise-Induced SCD
In older athletes, coronary artery disease (CAD) is the most common cause of sports-related SCD, identified in more than 80% of cases. The remaining sports-related cases of SCD are attributable to a number of other problems, such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular (RV) dysplasia, myocarditis, valvular heart disease, and a small but distinct subgroup of unexplained SCD (11,17–19). For the cases with significant associated CAD, the mechanism of sudden death is incompletely understood. Although ischemic ventricular arrhythmia is the final common pathway, the triggers have yet to be established. Hypothetical mechanisms include sympathetic activation, electrolyte and metabolic factors, activation of the hemostatic system, and hemodynamic effects on vulnerable coronary plaque. Exercise-related sympathetic activity may sensitize vulnerable myocardium to ischemia and arrhythmia. Prolonged exercise produces electrolyte abnormalities that may also contribute. It is striking that the overwhelming majority of sudden deaths occu in the final quartile of marathons and that marathons are associated with greater risk than half-marathons (9,11). Both findings support an electrolyte/metabolic contribution to risk of SCD. One recent retrospective study also raised the question of whether heat stroke is an underdiagnosed cause of death in long-distance races (20).
Postmortem studies strongly support roles for plaque rupture, hemostasis, and thrombosis. In a comparative pathological study of plaque morphology in men whose death was temporally linked to physical or emotional stress versus men who died at rest (21), acute plaque rupture was evident at autopsy in 68% of the stress-related deaths compared with 23% of the deaths at rest (p < 0.001). Similarly, hemorrhage into the plaque was found in 71% of stress-related SCDs compared with 41% of SCDs at rest (p = 0.007). Stress-related plaque rupture occurred in the central, thin-capped plaque, while plaque rupture that occurred at rest was found in the shoulders of plaque (Figure 4). Increased subjacent vasa vasorum was identified as a likely source of underlying hemorrhage in stress-related plaque rupture, whereas plaque rupture at rest was remote from the vasa vasorum. On this basis, the authors suggest that hemodynamic factors contribute to stress-related plaque rupture as the substrate for sports-related SCD. How habitual exercise confers protection against plaque rupture is not known, but both hemodynamic and tissue effects are potential contributors.
Potential Hazards at the High End of the Exercise Spectrum
Although high levels of habitual exercise clearly reduce all-cause mortality, the benefits at the highest levels of exercise may come at a price. Emerging evidence proposes 2 adverse cardiovascular consequences of exercise at the high end: 1) accumulation of coronary artery calcium (CAC) with myocardial fibrosis; and 2) RV fibrosis secondary to episodic volume/pressure overload. Mohlenkamp et al. (22) quantified CAC, as measured by computed tomography, and late gadolinium enhancement, as measured by magnetic resonance imaging, for myocardial fibrosis in 108 apparently healthy, experienced male marathon runners older than 50 years of age (22). Higher levels of accumulation of CAC were found in runners matched to controls on the basis of the Framingham risk score. However, accumulation of CAC was not significantly different from that of age-matched controls. Therefore, marathon runners had lower Framingham risk profiles, without lower CAC scores. Among 102 marathon runners, 12% had detectable late gadolinium enhancement in patterns consistent both with CAD scar and in a diffuse, patchy fashion; Breuckmann et al. (23) reported a similar prevalence. They also identified a statistically significant association between late gadolinium enhancement and CAC. The implications of these results are that endurance athletes may not be protected from accumulation of coronary calcium. It is important to recognize that this study did not support an adverse impact of endurance athletics on either CAC or cardiovascular events.
The acute effects of marathon running on RV size and function have also been evaluated. RV pressures and dimensions were consistently elevated at the conclusion of marathons compared with pre-race measurements. RV function also suffers transiently. In a study of 60 nonelite participants in the Boston Marathon (mean age of 41 years), Neilan et al. (24) found approximately 2-fold elevations of N-terminal pro–B-type natriuretic peptide and increased cardiac troponin T levels in 60%, with 40% exceeding the threshold usually used to diagnose MI. The increased levels of biomarkers correlated with impaired left ventricular diastolic function, increased pulmonary artery pressures, and RV dysfunction. One of the more remarkable findings in this study pertains to the role of training in relation to these markers of myocardial injury and dysfunction. Virtually all indexes of RV function and the pulmonary artery pressures were more severely affected in the least well-trained athletes compared with the best. La Gerche et al. (25) comparing marathon runners with ultraendurance athletes, confirmed the findings of transient RV dysfunction. They observed elevations of cardiac troponin T, B-type natriuretic peptide, and RV volumes with declines in RV function immediately after these endurance events. They also found that release of cardiac troponin T strongly correlated with a decline in RV ejection fraction, particularly in ultra-triathletes (r = 0.746; p = 0.003). Although the acute effects all reversed in the days after the events, they found late gadolinium enhancement in 12.8% of the athletes, which correlated with a modest reduction in resting RV ejection fraction (47.1 ± 5.9% vs. 51.1 ± 3.7%). The authors hypothesize that extreme endurance athletics is associated with repeated RV insult, injury, and fibrosis that can evolve late into a substrate for ventricular arrhythmia. It should be noted that this has not been documented as a cause of sports-related SCD on an epidemiological basis. From a public health perspective, we emphasize that although these findings raise some concerns about the benefits of endurance athletics at the high end, they do not undermine the substantial benefits of regular exercise on all-cause mortality in the vast majority of older athletes (Figure 5) (26).
Clinical Approach to Risk Stratification for SCD in Older Athletes: Greatest Utility in the Sport-Naïve Athlete
The growing popularity of endurance athletics in an aging population will result in a larger pool of older athletes. This is, of course, very good news, because regular exercise has enormous proven potential to reduce cardiovascular morbidity and mortality. Therefore, there is a growing need to provide practical, clinically relevant advice to minimize the associated risk. Among older athletes, the primary risk for sports-related SCD is CAD with acute plaque rupture. This risk is low for most endurance events, such as the marathon. Indeed, an epidemiological study has argued credibly that marathons reduce the death toll because the average number of race-associated SCDs is about one-half the number of deaths that would typically result from motor vehicle accidents if the race route were not closed to traffic (9). However, the risk associated with training is approximately 5-fold greater. Accordingly, we observe that cardiologists can intervene most effectively by advising noncompetitive or pre-competitive athletes. Because the most common substrate for risk is (by far) CAD, the main objective of pre-participation screening of the older athlete is ruling out significant occult CAD. We considered 3 published documents for pre-participation screening of the older athlete in developing recommendations for risk stratification of the older athlete: 1) recommendations from a working group of the American Heart Association and allied organizations (3); 2) the American College of Sports Medicine guidelines (27); and 3) the European Association for Cardiovascular Prevention and Rehabilitation guidelines (28).
Authors’ Recommendations for Risk Stratification in the Asymptomatic Patient
Because there is a significant amount of information common to the 3 guidelines and none of the approaches have been tested prospectively, we suggest a succinct, 3-step process (Central Illustration):
1. Assess risk using the American Heart Association pre-participation questionnaire (29) (Figure 6), which is a useful initial screening tool for completion by the patient that is designed to elicit evidence of known risk factors. If any are detected, evaluation by a physician is recommended. If the patient is in the cardiologist’s office, then one could move directly to step 2.
2. Perform a physician-led evaluation comprising a careful clinical history (including family history that can uncover familial conditions, such as long QT syndrome), physical examination, and estimation of the absolute 10-year risk of CAD using the Framingham risk score (30). Any criterion listed in Table 2 indicates a high-risk profile.
3. Use maximal exercise stress testing as a discriminator when the risk profile is high and the gap between habitual physical activity and intended level of activity is large (Figure 7). If maximal exercise electrocardiography is unsuitable for a given patient, we suggest single-photon emission computed tomography or stress echocardiography as appropriate alternatives. This applies to sedentary patients achieving <2 metabolic equivalents (MET)-h/week. For active patients already achieving >2 MET-h/week, low-intensity activity may be appropriate without this evaluation process. Routine use of stress testing in healthy, asymptomatic athletes is not recommended. Judicious use of resting 12-lead electrocardiogram and echocardiogram may be indicated and in some cases may result in diagnosis of previously unrecognized conditions, such as hypertrophic cardiomyopathy or arrhythmogenic RV dysplasia. Physical activity is important to manage, and potentially to restrict, in aspiring athletes, who may have conditions such as uncontrolled hypertension and active myocarditis.
Pre-participation Screening in the Older Athlete: Future Considerations
Stress testing is most likely to identify those with subocclusive CAD. However, plaque rupture, which is considered to be an important mechanism of SCD in the older athlete, can occur among coronary lesions that bring about mild to moderate coronary stenoses. Therefore, imaging of coronary plaque to identify lesions vulnerable to rupture has significant potential to enhance risk stratification. Although there is a conspicuous lack of studies that specifically evaluate SCD as an outcome, plaque characteristics clearly determine the risk of acute coronary syndrome and major adverse cardiovascular events (31). Increased coronary artery calcification, as measured by computed tomography, is a strong predictor of incident CAD beyond standard risk factors, with a 10-fold increased risk in those with coronary calcium scores >300 (32). However, any additions to the risk stratification armamentarium of the older athlete should require assessment of SCD as the outcome and careful consideration of cost versus benefit.
Strategies to Mitigate Risk in the Sport-Naïve Athlete: Authors’ Suggestions
We propose that gradually increasing the level of habitual activity has the greatest potential to render exercise safe while improving all-cause mortality. The increased risk associated with a sedentary lifestyle identifies this group as high risk, and graded training can in theory reduce the risk of sports-related SCD by a factor of 10 to 50 (7,10). Although specific, universally applicable recommendations for reducing risk through graded conditioning are difficult to provide, we propose a few principles. First, frequency of physical activity (rather than intensity) should be emphasized at the outset. Exercise intensity is usually defined by either METs or heart rate in relation to the maximum predicted heart rate and the number of sessions per week (Figure 8). An initial period of low-intensity exercise (<3 METs, or increase in heart rate to 50% to 70% of maximum predicted) performed 3 times a week attenuates the risk and may render moderate or higher intensity exercise safer (Figure 8). Each stage should ideally be covered in 6 to 8 weeks or longer, on the basis of the patient’s overall fitness and conditioning level. This graded approach obviates the risk of high-intensity exercise performed by poorly conditioned athletes.
In our opinion, the decision regarding cholesterol-lowering therapy, such as statins, should be driven by standard recommendations (33). For many, lifestyle alterations associated with sports activity may obviate the need for such drugs. Statins may, in theory, contribute to coronary plaque “stabilization,” but any modest beneficial effects could be offset by the statin-induced muscle fatigue or myopathy reported among 10% to 25% of patients in clinical practice (34), which is particularly relevant during exercise training adaptation (35). Low-dose aspirin (75–100 mg) may have a modest contribution to primary prevention of cardiovascular disease (36), but we propose that the overall mortality benefit is likely to exceed the risk in asymptomatic middle-aged and older athletes.
The increased risk of sports-related SCD in older athletes is real, but it is balanced by the benefits of fitness. However, as the population ages and endurance athletics gain in popularity, the population at risk is growing. Unlike in younger athletes, CAD is the predominant cause of SCD in older athletes. On a population basis, the risk associated with sporting events is much lower than the risk associated with training or leisure athletics. In multiple studies, low levels of habitual exercise are a very strong risk factor for sports-related SCD. Therefore, cardiologists should advise appropriately graded athletic training as the safest, most effective course. Both American and European societies recommend screening for occult CAD by questionnaire along with risk stratification on the basis of CAD risk profiles. Maximal stress testing for a high-risk subset may be beneficial in appropriate patients. However, a negative stress test may not identify all patients at risk for SCD. In the future, imaging of the coronary plaque may enhance pre-participation screening for occult CAD. It is important to remember that reductions in cardiovascular and all-cause mortality associated with moderate-intensity exercise performed ≥3 times per week are in the range of 40% to 60%. On balance, the health benefits of regular exercise heavily outweigh the risks of SCD in older athletes, especially in those who train appropriately.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- coronary artery calcium
- coronary artery disease
- metabolic equivalent
- myocardial infarction
- right ventricular
- sudden cardiac death
- Received August 12, 2014.
- Revision received October 9, 2014.
- Accepted October 21, 2014.
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- Current Burden and Future Projections
- Evidence for Transient Elevation in Risk With Exercise, Countered by a Protective Effect of Regular Exercise
- Potential Mechanisms of Exercise-Induced SCD
- Potential Hazards at the High End of the Exercise Spectrum
- Clinical Approach to Risk Stratification for SCD in Older Athletes: Greatest Utility in the Sport-Naïve Athlete
- Authors’ Recommendations for Risk Stratification in the Asymptomatic Patient
- Pre-participation Screening in the Older Athlete: Future Considerations
- Strategies to Mitigate Risk in the Sport-Naïve Athlete: Authors’ Suggestions