Preventing Sudden Cardiac Death during Marathons with Pre-Race Aspirin


Objectives: Prevention of sudden cardiac death is the number one clinical priority in sports cardiology. While the overall cardiovascular risk of long distance running is acknowledged as low, the frequency of cardiac arrests and sudden death has increased in middle-aged males during marathons since the year 2000. An evidence-based strategy for protecting susceptible runners from these acute cardiac events during races is considered based on identification of the underlying cause. Method: Review of articles in Pub Med on adverse cardiac events during marathons. Findings: Recent epidemiological studies have identified an increasing frequency of cardiac arrest in middle-aged males during marathons since the year 2000 with atherosclerotic heart disease as the main cause of sudden cardiac death. Same-aged asymptomatic middle-aged male physician-runners showed a post-race polymorphonuclear leukocytosis with sequential increases in interleukin-6 and C-reactive protein as a likely consequence of rhabdomyolysis after “hitting the wall”. Increased fibrinogen, von Willebrand factor and D-dimer with in vivo platelet activation indicated a concurrent hemostatic imbalance with pro-coagulant effects. Cardiac troponins I and T and NT-pro-B-type natriuretic peptide were elevated after races as additionally predictive of acute cardiac events in asymptomatic persons. Conclusions: High short-term risk for acute cardiac events in asymptomatic middle-aged male runners is shown by stratification of validated biomarkers, which may render non-obstructive coronary atherosclerotic plaques vulnerable to rupture during marathons. Pre-race aspirin usage is prudent to reduce these events mediated by atherothrombosis based on conclusive evidence for prevention of first acute myocardial infarctions in same-aged healthy male physicians. Prospective studies are needed to determine the efficacy of pre-race low-dose aspirin for curtailing the increasing frequency of race-related cardiac arrest and sudden death in susceptible runners.

Share and Cite:

Siegel, A. (2015) Preventing Sudden Cardiac Death during Marathons with Pre-Race Aspirin. World Journal of Cardiovascular Diseases, 5, 211-217. doi: 10.4236/wjcd.2015.58024.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Lawless, C.E., Asplund, C., Asif, I.M., et al. (2014) Protecting the Heart of the American Athlete. Proceedings of the American College of Cardiology Sports and Exercise Think Tank, October 18, 2012, Washington, DC. Journal of the American College of Cardiology, 64, 2146-2171.
[2] Bassler, T.J. (1977) Marathon Running and Immunity to Atherosclerosis. In: Milvy, P., Ed., The Marathon; Physiological, Epidemiological and Psychological Studies. Annals of the New York Academy of Sciences, 301, 579-592.
[3] Kim, J.H., Malhotra, R., Chiampas, G., et al. for the RACER Study Group (2012) Cardiac Arrest during Long-Distance Running Races. New England Journal of Medicine, 36, 130-142.
[4] Nearman, S. (2012) Cardiac Deaths in Marathons Much Lower than Previously Thought: Good News for Marathon Runners. American Medical Athletic Association Journal, 7-8.
[5] Roberts, W.O., Roberts, D.M. and Lunos, S. (2013) Marathon Related Cardiac Arrest Differences in Men and Women. British Journal of Sports Medicine, 47, 168-171.
[6] Webner, D., Duprey, K.M., Dresner, J.A., et al. (2012) Sudden Cardiac Arrest and Death in United States Marathons. Medicine & Science in Sports & Exercise, 1843-1845.
[7] Mathews, S.C., Narotsky, D.L., Berbholt, D.L., et al. (2012) Mortality among Marathon Runners in the United States, 2000-2009. American Journal of Sports Medicine, 40, 1495-1500.
[8] Go, A.S., Mozaffarian, D., Roger, V.L., et al. (2013) Heart Disease and Stroke Statistics—2014 Update: A Report from the American Heart Association. Circulation.
[9] Siegel, A.J., Silverman, L.M. and Lopez, M.S. (1980) Creatine Kinase Elevations in Marathon Runners: Relationship to Training and Competition. Yale Journal of Biology and Medicine, 53, 275-279.
[10] Kratz, A., Lewandrowski, K.B., Siegel, A.J., et al. (2002) Effect of Marathon Running on Hematological and Biochemical Laboratory Parameters including Cardiac Markers. American Journal of Clinical Pathology, 118, 856-863.
[11] Siegel, A.J., Verbalis, J.G., Clement, S., Mendelson, J.H., Mello, N.K., Adner, M., et al. (2007) Hyponatremia in Marathon Runners Due to Inappropriate Arginine Vasopressin Secre-tion. The American Journal of Medicine, 120, 461.e11-461.e17.
[12] Siegel, A.J., Stec, J.J., Lipinska, I., Van Cott, E.M., Lewandrowski, K.B., Ridker, P.M., et al. (2001) Effect of Marathon Running on Inflammatory and Hemostatic Markers. The American Journal of Cardiology, 88, 918-920.
[13] Kratz, A., Wood, M.J., Siegel, A.J., Hiers, J.R. and Van Cott, E.M. (2006) Effects of Marathon Running on Platelet Activation Markers: Direct Evidence for in Vivo Platelet Activation. American Journal of Clinical Pathology, 125, 296-300.
[14] Saenz, A.J., Lee-Lewandrowsi, E., Wood, M.J., Neilan, T.G., Siegel, A.J., Januzzi, J.L., et al. (2006) Measurement of a Plasma Stroke Biomarker Panel and Cardiac Troponin T in Marathon Runners before and after the 2005 Boston Marathon. American Journal of Clinical Pathology, 126, 185-189.
[15] Neilan, T.G., Januzzi, J.L., Lee-Lewandrowski, E., Ton-Nu, T.-T., Yoerger, D.M., Jassal, D.S., et al. (2006) Myocardial Injury and Ventricular Dysfunction Related to Training Adequacy among Non-Competitive Participants in the Boston Marathon. Circulation, 114, 2325-2333.
[16] Siegel, A.J., Januzzi, J., Sluss, P., Lee-Lewandrowski, E., Wood, M., Shirey, T., et al. (2008) Cardiac Biomarkers, Electrolytes and Other Anylates in Collapsed Marathon Runnners: Implications for the Evaluation of Runners Following Competition. American Journal of Clinical Pathology, 129, 948-951.
[17] Libby, P. and Crea, F. (2010) Clinical Implications of Inflammation for Cardiovascular Primary Prevention. European Heart Journal, 31, 777-783.
[18] Mauri, L. (2013) Non-Culprit Lesions—Innocent or Guilty by Association. New England Journal of Medicine, 369, 1166-1167.
[19] Anderson, D.R., Poterucha, J.T., Mikuls, T.R., Duryee, M.J., Garvin, R.P., Klassen, L.W., et al. (2013) IL-6 and Its Receptors in Coronary Artery Disease and Acute Myocardial Infarction. Cytokine, 62, 395-400.
[20] Lee, T., Murai, T., Yonetsu, T., Suzuki, A., Hishikari, K., Kanaji, Y., et al. (2015) Relationship between Subclinical Cardiac Troponin I Elevations and Culrpit Lesion Characteristics Assessed by Optical Coherence Tomography in Patients Undergoing Elective Percutaneous Coronary Intervention. Circulation: Cardio-vascular Interventions, 8, e0011727.
[21] Everett, B.M., Zeller, T., Glynn, R.J., Ridker, P.M. and Blankenberg, S. (2015) High Sensitivity Cardiac Troponin I and B-Type Natriuretic Peptide as Predicators of Vascular Events in Primary Prevention. Circulation, 131, 1851-1860.
[22] Albano, A.J., Thompson, P.D. and Kapur, N.K. (2012) Acute Coronary Thrombosis in Boston Marathon Runners. New England Journal of Medicine, 366, 184-185.
[23] Thygesen, K., Alpert, J.S., Jaffe, A.S., Simoons, M.L., Chaitman, B.R., White, H.D., et al. (2012) Third Universal Definition of Myocardial Infarction. Circulation, 126, 2020-2035.
[24] Albert, C.M., Mittleman, M.A., Chae, C.U., Lee, I.-M., Hennekens, C.H. and Manson, J.E. (2000) Triggering of Sudden Death from Cardiac Causes by Vigorous Exertion. New England Journal of Medicine, 343, 1355-1366.
[25] Marijon, E., Uy-Evanado, A., Reiner, K., Teodorescu, C., Narayanan, K., Jouven, X., et al. (2015) Sudden Cardiac Arrest during Sports in Middle Age. Circulation, 131, 1384-1391.
[26] Kales, S.N., Soteriades, E.S., Christophi, C.A. and Christiani, D.C. (2007) Emergency Duties and Deaths from Heart Disease among Firefighters in the United States. New England Journal of Medicine, 356, 1207-1215.
[27] Varvarigou, V., Farioli, A., Korre, M., Sato, S., Dahabreh, I.J. and Kales, S.N. (2014) Law Enforcement Duties and Sudden Cardiac Death among Police Officers in the United States: Case Distribution Study. BMJ, 349, g6534.
[28] Dalager-Pedersen, M., Sogaard, M., Schonheyder, H.C., Nielsen, H. and Thomsen, R.W. (2014) Risk for Myocardial Infarction and Stroke after Community-Acquired Bacteremia: A 20-Year Population-Based Cohort Study. Circulation, 129, 1387-1396.
[29] Chung, W.S., Lin, C.L., Hsu, W.H. and Kao, C.-H. (2014) Scrub Typhus Increases the Risk of Developing Acute Coronary Syndrome: A Nationwide Cohort Study. Heart, 100, 1844-1850.
[30] Eisen, D.P., Reid, D. and McBryde, E.S. (2012) Acetyl Salicylic Acid Usage and Mortality in Critically Ill Patients with the Systemic Inflammatory Response Syndrome and Sepsis. Critical Care Medicine, 40, 1761-1767.
[31] Henderson, J.T., Whitlock, E.P., O’Conner, E., Senger, C.A., Thompson, J.H. and Rowland, M.G. (2014) Low-Dose Aspirin for Prevention of Morbidity and Mortality from Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Service Task the Force. Annals of Internal Medicine, 160, 695-703.
[32] Siegel, A.J. (2015) Pre-Race Aspirin Usage to Prevent Cardiac Arrest in Susceptible Runners during Marathons: Is Opportunity Knocking? Open Heart, 2, e000102.
[33] Siegel, A.J. (2012) Phei-dippides Redux: Reducing Acute Cardiac Risk during Marathon Running. The American Journal of Medicine, 125, 630-635.
[34] Siegel, A.J. (2013) Aspirin Usage Pre-Race to Prevent Cardiac Arrest in Marathon Runners during Races. The American Journal of Medicine, 126, e47.
[35] Walkey, A.J. (2014) Preventing Cardiovascular Complications of Acute Infection: A Missed Opportunity? Circulation, 129, 1375-1377.
[36] Grosser, T., Fries, S., Lawson, J.A., Kapoor, S.C., Grant, G.R. and FitzGerald, G.A. (2013) Drug Resistance and Pseu- do-Resistance: An Unintended Consequence of Enter-ic-Coated Aspirin. Circulation, 127, 377-385.
[37] Cohen, S.I. and Ellis, E.R. (2012) Death and Near Death from Cardiac Arrest during the Boston Marathon. Pacing and Clinical Electrophysiology, 35, 241-244.
[38] Ray, W.A., Murray, K.T., Hall, K., Arbogast, P.G. and Stein, C.M. (2012) Azithromycin and Risk of Cardiovascular Death. New England Journal of Medicine, 366, 1881-1890.
[39] Azithromycin Poses Fatal Cardiac Risk. FDA Warns.
[40] Maharam, L.G., Siegel, A.J., Siegel, S., Adams, B., Pujol, P. and de Menezes, P.A.L. (2010) IMMDA’s Health Recommendations for Runners & Walkers. Approved by the International Marathon Medical Directors Association (IMMDA), Barcelona, 20 March 2010.
[41] Lourega de Menezes, P.A. (2014) Official Handbook for Runners in the Rio de Janeiro Marathon. Marathon Publications, 12-13.
[42] Steering Committee of the Physicians’ Health Study Research Group (1989) Final Report on the Aspirin Component of the Ongoing Physicians’ Health Study. New England Journal of Medicine, 321, 129-135.
[43] Pignone, M., Alberts, M.J., Colwell, J.A., Cushman, M., Inzucchi, S.E., Mukherjee, D., et al. (2010) Aspirin for Primary Prevention of Cardiovascular Events in People with Diabetes. Journal of the American College of Cardiology, 55, 2878-2885.
[44] Halvorsen, S., Andreotti, F., Berg, J.M., Cattaneo, M., Coccheri, S., Marchioli, R., et al. (2014) Aspirin Therapy in Primary Cardiovascular Disease Prevention. A Position Paper of the European Society of Cardiology Working Group on Thrombosis. Journal of the American College of Cardiology, 64, 319-327.
[45] Zilinski, J.L., Contursi, M.E., Isaacs, S.K., Deluca, J.R., Lewis, G.D., Weiner, R.B., et al. (2015) Myocardial Adaptations to Recreational Marathon Training among Middle-Aged Men. Circulation: Cardiovascular Imaging, 8, e002487.
[46] Harmon, K.G., Drezner, J.A., Wilson, M.G. and Sharma, S. (2014) Incidence of Sudden Cardiac Death in Athletes: A State of the Art Review. British Journal of Sports Medicine, 48, 1185-1192.
[47] Maron, B.J., Haas, T.S., Murphy, C.J., Ahluwalia, A. and Rutten-Ramos, S. (2014) Incidence and Causes of Sudden Death in U.S. Athletes. Journal of the American College of Cardiology, 63, 1636-1643.
[48] Siegel, A.J. (2015) IMMDA Advisory, 2015: Pre-Race Aspirin to Prevent Heart Attack and/or Cardiac Arrest during Long Distance Running.
[49] Miedema, M.D., Duprez, D.A., Misialek, J.R., Blaha, M.J., Nasir, K., Silverman, M.G., et al. (2014) Use of Coronary Artery Calcium Testing to Guide Aspirin Utilization for Primary Prevention: Estimates from the Multi-Ethnic Study of Atherosclerosis. Circulation. Cardiovascular Quality and Outcomes, 7, 453-460.
[50] Mohlenkamp, S., Lehmann, N., Breuckmann, F., Brocker-Preuss, M., Nassenstein, K., Halle, M., et al. (2008) Running and the Risk of Cardiac Events: Prevalence and Prognostic Relevance of Coronary Atherosclerosis in Marathon Runners. European Heart Journal, 29, 1903-1910.
[51] Schwartz, R.S., Kraus, S.M., Schwartz, J.G., Wickstrom, K.K., Peichel, G., Garberich, R.F., et al. (2014) Increased Coronary Artery Plaque Volume among Male Marathon Runners. Missouri Medicine, 111, 85-90.
[52] Mohlenkamp, S., Leineweber, K., Lehmann, N., Braun, S., Roggenbuck, U., Perrey, M., et al. (2014) Coronary Atherosclerosis Burden, but Not Transient Troponin Elevation, Predicts Long-Term Outcome in Recreational Marathon Runners. Basic Research in Cardiology, 109, 391-395.
[53] Buckley, S. (2013) Dave McGillivray Fights Heart Disease. Boston Herald, 24 December 2013.
[54] Knox, L. and Estaban, C. (2014) In the Running, Marathon Demographics. Boston Globe. C 8-9, 18 April 2014.
[55] D’Hemecourt, P.A., Dyer, K.S. and Baggish, A.L. Cardiac Wellness. Boston Athletic Association. Accessed 19 April 2015.
[56] Siegel, A.J. (2015) Fatal Water Intoxication and Cardiac Arrest in Runners during Marathons: Prevention and Treatment Based on Validated Clinical Paradigms. The American Journal of Medicine. (in press)
[57] Hew-Butler, T., Rosner, M.H., Fowkes-Godek, S., Dugas, J.P., Hoffman, M.D., Lewis, D.P., et al. (2015) Statement of the 3rd International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015. Clinical Journal of Sport Medicine, 25, 303-320.
[58] Rosner, M.H. Preventing Deaths Due to Exercise-Associated Hyponatremia: The 2015 Consensus Guidelines. Clinical Journal of Sports Medicine, 25, 301-302.
[59] Yared, K. and Wood, M.J. (2009) Is Marathon Running Hazardous to Your Cardiovascular Health? The Jury Is Still Out. Radiology, 251, 3-5.
[60] Noakes, T. (2014) Time to Quit That Marathon Running? Not Quite Yet! Basic Research in Cardiology, 109, 395-396.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.