Introduction

In the general population, the overall burden of sports-related sudden death is 4.6 events per million population per year and is approximately 10-fold more common in men than women.¹ A recent review reported that approximately 90% of these deaths occur in the context of recreation sports and the average age at the time of event was 46 years old. The incidence is expected to increase as the number of recreational athletes, particularly those over 40 years, also increases.² In those with occult or known coronary disease, vigorous exercise can acutely and transiently increase the risk of cardiovascular events. A recent meta-analysis reported a fivefold increased risk of sudden cardiac death (SCD) and 3.5-fold increased risk of acute myocardial infarction (AMI) during vigorous-intensity physical activity.³ Though present in both active and sedentary groups, this pattern was much more pronounced in those who do not exercise regularly.

Given these statistics, it has been advocated that prior to significantly increasing exercise training, both competitive athletes and leisure-sport enthusiasts at high risk for cardiac events should undergo pre-participation screening.⁴ Pre-participation screening commonly includes a detailed medical and family history, as well as a physical exam and 12-lead electrocardiogram (ECG). Where exercise stress testing falls within the recommendations remains controversial. It is worth noting that at least two professional sporting bodies, IOC (International Olympic Committee) and FIFA (Federation International Football Association) mandate ECG stress testing in those ≥35 years or echocardiography as part of their pre-participation screening protocols.⁵ In this review, we will explore the utility and limitations of exercise stress testing to identify those at highest risk for SCD associated with exercise. More specifically, we will focus on the arguments in support and against stress testing in those at highest risk, namely athletes over the age of 35.

In Support of Exercise Stress Testing

Regular physical activity reduces the risk of developing cardiovascular disease and lowers all-cause mortality.⁶ Daily exercise has been shown to effectively treat and prevent numerous chronic diseases including coronary artery disease (CAD), hypertension, obesity, diabetes mellitus, dementia and depression.⁷ There also appears to be a dose-dependent relationship with aerobic exercise. Regular exercise for as little as 15 minutes a day shows modest benefit and risk reduction. Unfortunately, both during and immediately following vigorous exercise there is a small but measureable risk of non-fatal cardiovascular events as well as SCD. This "risk paradox" was first described in 1990 by Friedewald and Spence who recommended proper risk assessment and gradual progression in exercise intensity.⁸

Athletes represent a heterogeneous group with unique risk factors and therefore must be treated individually. In younger athletes (≤35 years), SCD is mainly caused by congenital or heritable cardiovascular diseases involving conduction abnormalities or myocardial structure.⁹ On the other hand, in those over 35 years of age, the SCD is largely due to acute complications of atherosclerosis and coronary artery disease.¹⁰ More specifically, atherosclerosis has been associated with over 80% of exercise related SCD in those older than 35 years and over 95% of cases in those over 40 years.¹¹ In fact, in one of the most complete datasets of cardiac arrests in marathon runners, the RACER registry reported that most athletes who died were found to have high grade fixed lesions which would have likely been discovered though stress testing.¹²

In 2008, Mohlenkamp and colleagues performed coronary artery calcification (CAC) scores on 108 male marathon runners. Not surprisingly, they found that as compared to non-runner age matched controls, Framingham risk scores (FRS) were lower in runners. The CAC in marathon runners was similar to age-matched controls but surprisingly, CAC scores were actually higher in runners as compared to controls with similar FRS.¹³ Building upon this data, it was recently reported that there is a dose dependent relationship with CAC and exercise. Perhaps surprisingly, those who participated in the most physical activity each week showed higher prevalence of CAC and atherosclerotic plaques.¹⁴ A second study again confirmed high CAC score seen in male athletes compared to sedentary controls.¹⁵ It is important to note that in both of these cohorts the plaques in athletes demonstrated more benign composition, with fewer mixed plaques and more often only calcified plaques. These data suggest that the CAC score and cardiovascular risk relationship may be inherently different in the general population as compared to athletes. Athletes appear more likely to have high CAC scores composed of stable plaques. Stress testing may be useful in stratifying those athletes with higher CAC scores by determining the clinical significance of these plaques under stress in a clinical setting prior to competitive training.

Lastly, due to its non-invasive nature, exercise electrocardiography with or without echocardiography is a widely used screening tool to detect coronary artery disease. This testing modality is especially useful in symptomatic patients with intermediate pretest probability. Within the general population, in those with suspected coronary artery disease, normal exercise echocardiography testing showed a negative predictive value (NPV) for MI and cardiac death of 98.4% over the following 33 months.¹⁶ In an athlete over 35 years with fewer traditional risk factors for coronary artery disease, a negative stress test would virtually eliminate the risk for exercise induced cardiac arrest.

Against Exercise Stress Testing

Bayes' Theorem provides us with a background for evaluating the accuracy and usefulness of a diagnostic test for rare conditions. When prevalence of a disease is low, diagnostic accuracy is almost entirely dependent on test specificity. In cases of low specificity, the abnormal screening result is most likely consistent with a false positive.¹⁷ Consistent with Bayes' Theorem, the accuracy of exercise testing in a population of athletes would inherently decrease due to low pretest probability. Studies have demonstrated that patients who achieved ≥10 METS had an exceedingly low prevalence of significant ischemia (0.4%) and incidence of cardiovascular mortality (0.1%/year).^18,19 A threshold of 10 METs is useful to provide a goal for people looking to begin an exercise regimen but is less useful in competitive athletes who can easily perform ≥10 METS during an exercise stress test.

In fact, a recent systematic review of exercise electrocardiography in pre-participation screening in asymptomatic athletes reported a 0.6% (range 0-29%) prevalence of abnormal exercise stress tests with a mean of with a positive predictive value (PPV) of just 9% (range 0-55%). Left ventricular hypertrophy was noted in 57% of the athletes with an abnormal exercise stress test and in 24% of the athletes with a normal stress test.²⁰ As age increases, the prevalence of an abnormal exercise stress test increases (5.1% in athletes age 35-60) and 8.5% in those >60 years. This is in line with other studies demonstrating that false positive results in athletes are often associated with increased left ventricular mass.²¹ Unfortunately, no conclusions could be made regarding negative predictive value (NPV).²⁰

Despite the unique adaptation of the athlete's heart in response to training, risk of sudden cardiac death (SCA) in athletes is likely driven by traditional risk factors for coronary artery disease. It is worth noting that in the RACER data mentioned above, a large number of those that died had one or more traditional risk factors prior to marathon participation such as smoking, exertional symptoms, hypertension or prior known CAD.²² In these cases, it is likely that a detailed history and physical exam could have risk stratified these patients without the need for exercise stress testing.

Conclusion

Despite these limitations in testing accuracy, current guidelines from the American College of Sports Medicine (ACSM) and the American Heart Association (AHA) recommend that pre-participation exercise testing should be performed in those who are "moderate risk." More specifically, they recommend against stress testing in men less than 45 years and women less than 55 years unless one or more coronary risk factors (other than age or gender) are present.^23,24 Guidelines in Europe differ in that exercise electrocardiography is only recommended in athletes who have an abnormal initial evaluation based on history, resting ECG or physical examination.^25,26

From a public health perspective, the sensitivity of screening entire populations is too low to be cost-effective. Similarly, it would not be feasible to require testing prior to participation in large events, such as marathons in major cities. Instead, the authors of this review suggest that exercise testing would be appropriate to consider in the following circumstances: 1) in people >35 years with significant risk factors for coronary disease (diabetes, elevated cholesterol, hypertension, obesity) prior to initiating a new exercise regimen; 2) to attempt to reproduce symptoms associated with exercise in any patient; or 3) to test exercise capacity in anyone who has noted a change in performance without other clear causes.

In all cases maximal stress testing is preferred. It is worth emphasizing that in the most heavily trained athletes, a standard Bruce graded exercise protocol may not be sufficient and other more aggressive exercise studies may be needed.²⁷ More aggressive graded exercise protocols such as the Astrand and Astrand-Saltin are done at increased speed and incline to help accommodate the greater aerobic capacity of an athlete. Often times, however, graded protocols fail to push an athlete to exhaustion. In these cases, a non-graded sport specific protocol can be designed for the athlete using very high intensity intervals. It is important to emphasize testing athletes in a manner that most closely reproduces the demands of the sport, both training and competition (e.g., exercise rowers with an ergometer). These specially designed protocols should take into account the strains unique to each athlete's event. In more sedentary individuals, the standard Bruce protocol is often adequate.

In conclusion, although exercise decreases cardiovascular risk, even active people can have significant atherosclerosis or other risk factors predisposing them to cardiac disease and potential SCA in the setting of vigorous training. Cardiac risk, particularly in older athletes, is driven by traditional cardiovascular risk factors, whereas in the younger population, stress testing should be dictated by symptomology rather than used as a screening tool. Athletes, especially older ones, should be counseled to pay close attention to prodromal cardiac symptoms.

References

1. Marijon E, Tafflet M, Celermajer DS, et al. Sports-related sudden death in the general population. Circulation 2011;124:672-81.
2. Running USA Road Running Information Centre. Trend and demographics 2008. Road Running Information Centre; 2008.
3. Dahabreh IJ, Paulus JK. Association of episodic physical and sexual activity with triggering of acute cardiac events: systematic review and meta-analysis. JAMA 2011;305:1225-33.
4. Corrado D, Schmied C, Basso C, et al. Risk of sports: do we need a pre-participation screening for competitive and leisure athletes? Eur Heart J 2011;32:934-44.
5. Ljungqvist A, Jenoure P, Engebretsen L, et al. The International Olympic Committee (IOC) consensus statement on periodic health evaluation of elite athletes March 2009. Br J Sports Med 2009;43:631-43.
6. Nocon M, Hiemann T, Muller-Riemenschneider F, Thalau F, Roll S, Willich SN. Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis. Eur J Cardiovasc Prev Rehabil 2008;15:239-46.
7. Haskell WL, Lee IM, Pate RR, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation 2007;116:1081-93.
8. Friedewald VE, Spence DW. Sudden cardiac death associated with exercise: the risk-benefit issue. Am J Cardiol 1990;66:183-8.
9. Harmon KG, Asif IM, Maleszewski JJ, et al. Incidence, cause, and comparative frequency of sudden cardiac death in national collegiate athletic association athletes: a decade in review. Circulation 2015;132:10-9.
10. Maron BJ, Araujo CG, Thompson PD, et al. Recommendations for preparticipation screening and the assessment of cardiovascular disease in masters athletes: an advisory for healthcare professionals from the working groups of the World Heart Federation, the International Federation of Sports Medicine, and the American Heart Association Committee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation 2001;103:327-34.
11. Chevalier L, Hajjar M, Douard H, et al. Sports-related acute cardiovascular events in a general population: a French prospective study. Eur J Cardiovasc Prev Rehabil 2009;16:365-70.
12. Kim JH, Malhotra R, Chiampas G, et al. Cardiac arrest during long-distance running races. N Engl J Med 2012;366:130-40.
13. Mohlenkamp S, Lehmann N, Breuckmann F, et al. Running: the risk of coronary events: prevalence and prognostic relevance of coronary atherosclerosis in marathon runners. Eur Heart J 2008;29:1903-10.
14. Aengevaeren VL, Mosterd A, Braber TL, et al. Relationship between lifelong exercise volume and coronary atherosclerosis in athletes. Circulation 2017;136:138-48.
15. Merghani A, Maestrini V, Rosmini S, et al. Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile. Circulation 2017;136:126-37.
16. Metz LD, Beattie M, Hom R, Redberg RF, Grady D, Fleischmann KE. The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a meta-analysis. J Am Coll Cardiol 2007;49:227-37.
17. La Gerche A, Baggish AL, Knuuti J, et al. Cardiac imaging and stress testing asymptomatic athletes to identify those at risk of sudden cardiac death. JACC Cardiovasc Imaging 2013;6:993-1007.
18. Bourque JM, Holland BH, Watson DD, Beller Ga. Achieving an exercise workload of ≥10 METS predicts a very low risk of inducible ischemia: does myocardial perfusion imaging have a role? J Am Coll Cardiol 2009;54:538-45.
19. Bourque JM, Charlton GT, Holland BH, Belyea CM, Watson DD, Beller GA. Prognosis in patients achieving ≥10 METS on exercise stress testing: was SPECT imaging useful? J Nucl Cardiol 2011;18:230-7.
20. van de Sande DA, Breuer MA, Kemps HM. Utility of exercise electrocardiography in pre-participation screening in asymptomatic athletes: a systematic review. Sports Med 2016;46:1155-64.
21. van de Sande DA, Hoogeveen A, Hoogsteen J, Kemps HM. The diagnostic accuracy of exercise electrocardiography in asymptomatic recreational and competitive athletes. Scand J Med Sci Sports 2016;26:214-20.
22. Post-Hoc data presented by Jonathan Kim at the ACC Conference on Care of the Athletic Heart. Snowbird, Utah 2017.
23. ASCM. 2010. ASCM's resource manual for guidelines for exercise testing and prescription. ASCM's resource manual for guidelines for exercise testing prescription. American College of Sports Medicine. Lippincott Williams and Wikins. Philadelphia, PA., USA.
24. Maron BJ, Thompson PD, Ackerman MJ, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2007;115:1643-55.
25. Borjesson M, Urhausen A, Kouidi E, et al. Cardiovascular evaluation of middle-aged/senior individuals engaged in leisure-time sport activities: position stand from the section of exercise physiology and sports cardiology of the European Association of Cardiovascular Prevention and Rehabilitation. Eur J Cardiovasc Prev Rehabil 2011;18:446-58.
26. https://www.uspreventiveservicestaskforce.org/Page/Document/Update
    SummaryFinal/coronary-heart-disease-screening-with-electrocardiography. Accessed 9/29/2017.
27. Sarma S, Levine BD. Beyond the Bruce protocol: advanced exercise testing for the sports cardiologist. Cardiol Clin 2016;34:603-8.

Keywords: Exercise Test, Coronary Artery Disease, Athletes, Risk Factors, Hypertrophy, Left Ventricular, Cardiovascular Diseases, Plaque, Atherosclerotic, Bayes Theorem, Diagnostic Tests, Routine, Electrocardiography, Death, Sudden, Cardiac, Risk Assessment, Exercise, Echocardiography, Atherosclerosis, Hypertension, Risk Reduction Behavior, Myocardial Infarction, Registries, Heart Arrest, Induced, Diabetes Mellitus, Obesity, Sports

< Back to Listings