Rationale for Pre-Race Aspirin to Attenuate Risk for Marathon-Related Cardiac Arrest: Confounding the Legacy of Pheidippides
Main Article Content
Abstract
While increasing levels of recreational sports participation are incrementally cardioprotective, strenuous physical exertion transiently increases the risk for acute cardiac events including sudden death. The frequency of marathon-related cardiac arrests has been increasing since the year 2000 mainly in middle-aged men due to atherosclerotic coronary artery disease. Coronary artery calcium scores and post-race cardiac biomarkers are recommended to identify runners who might benefit the most from pre-race aspirin for enhanced primary prevention.
Keywords:
marathon, cardiac arrest, aspirin, primary cardiovascular prevention
Article Details
How to Cite
SIEGEL, Arthur J..
Rationale for Pre-Race Aspirin to Attenuate Risk for Marathon-Related Cardiac Arrest: Confounding the Legacy of Pheidippides.
Medical Research Archives, [S.l.], v. 11, n. 4, apr. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3741>. Date accessed: 26 dec. 2024.
doi: https://doi.org/10.18103/mra.v11i4.3741.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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4. Albano AJ, Thompson PD, Kapur NK. Acute coronary thrombosis in Boston marathon runners. New Engl J Med 2012;66:184-185.
5. Burke AP, Farb A, Malcom GT, Virmani R. Plaque rupture and sudden death related to exertion in men with coronary artery disease. J Am Med Assoc 1999; doi: 10.1001/jama.281.10.921.
6. Holmstrom L, Chugh HS, Uy-Evando A, et al. Sudden cardiac arrest during sports activity in older adults. J Am Coll Cardiol EP. Jan 18; EPublished DOI:10.1016/j.jacep.2022.10.033.
7. Thompson PD, Eijsvogels TMH, Kim JH. Can the heart get an overuse sports injury?
New Engl J Med. 2022;2(1):
8. Farahmand B, Hallmarker U, Brobert GP, Ahlboma,A. Acute mortality during long-distance ski races (Vasaloppet). Scand J Med Sci Sports 2007;17:356-361.
9. Schnohr P, O’Keefe JH, Lavie C, et al. U-shaped association between duration of sports activities and mortality: Copenhagen City Heart Study. Mayo Clin Proceedings. 2021;
10. Merghani A, Malhotra A, Sharma S. The U-shaped relationship between exercise and cardiac morbidity. Trends Cardiovasc Med 2016;26(3):232-240.
11. Matthews SC, Narotsky DL, Berbholt DV, et al. Mortality among marathon runners in the United States, 2000-2009. Am J Sports Med 2012; May 4:
12. Kim JH, Malhotra R, Chiampas G, et al. Race-Associated Cardiac Arrest Event Registry (RACER) Study Group: cardiac arrest during long-distance running races. N Engl J Med 2012;366 (2):130-140.
13. Shirakawa T, Tanaka H, Kinoshi T, Tanaka S, Takyu H. Analysis of sudden cardiac arrest during marathon races in Japan. Internat J Clin Med. 2017, 8, 472–480.
14. Harris KM, Creswell LL, Haas TS, Thomas T, Tung M, Isaacson BS, et al. Death and cardiac arrest in U.S. triathlon participants, 1980 to 2016: a case series. Ann Int Med 2017: [E pub a head of print]
15. Ridker P, Cushman M, Stamper MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973–979.
16. Siegel AJ. Pheidippides Redux: reducing risk for acute cardiac events during marathon running. Am J Med 2012;125:630-635.
17. Siegel AJ. Pre-race aspirin to protect susceptible runners from cardiac arrest during marathons: is opportunity knocking? Open Heart 2015.2(1): e000102. Doi. 10.1136/openhrt-2014-000102.
18. Siegel AJ, Noakes TD. Can prerace aspirin prevent sudden cardiac death during marathons? Br Sports Med 2017;51(22): 1579-1582.
19. Siegel AJ. Aspirin is used to mitigate the increasing frequency of marathon-related cardiac arrests. J Cardiovasc Med Cardiol 2022. 9(4):077-078.
20. Siegel AJ. Pre-race aspirin for enhanced primary prevention of marathon-related cardiac arrests: confronting Pheidippides’ legacy. Am J Med 2023; in press.
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22. Joseph P, Pais P, Dans AL, et al. The international polycap-3 (TIPS-3): design, baseline characteristics and challenges in conduct. Am Heart J 2018;206:72-79.
23. TIPS-3 investigators. Polypill plus aspirin reduces incidence of cardiovascular events by 31%: TIPS-3 Cardiovasc J Afr 2021;32(1):32-40.
24. Siegel AJ, Noakes TD. Aspirin to prevent sudden cardiac death in athletes with high coronary artery calcium scores. Am J Med 2019.132:138-141.
25. Siegel AJ. Aspirin to reduce risk for sudden cardiac death in athletes with elevated C-reactive protein level. Am J Med 2020. 133(9):1014-1016.
26. Kahn SS, Pencina MJ. Cardiovascular disease risk prediction in young adults: the next frontier. JAMA Cardiol 2023;8(2):137-138.
27. Fahey TD, Swanson GD. A model for defining the optimal amount of exercise contributing to health and avoiding sudden cardiac death. Med Sport 2008; 12(4):124-128.
28. Marston NA, Pirruccello JP, Melloni GEM, et. al. Predictive utility of a coronary artery disease polygenic risk score in primary prevention. JAMA Cardiol 2023;8(2):130-137.
29. Lacaze P, Bakshi A, Riaz M, et al. Aspirin for primary prevention of cardiovascular events in relation to lipoprotein(a) genotypes. J Am Coll Cardiol 2022, 80(14):1287-1298
30. Aengevaeren VL, Mostard A, Bakker EA, et.al. Exercise volume versus intensity and the progression of coronary atherosclerosis in middle-aged and older athletes: findings from the MARC-2 Study. Circulation 2023.0. https://doi.org/10.1161/CIRCULATIONAHA.122.061173.
31. Freeman AM, Raman SV, Aggarwal M, et al. Integrating coronary atherosclerotic burden and progression with coronary artery disease risk factors to guide therapeutic decision making, Amer J Med 2022.136(4);260-269.E7.
32. Razavi AC, Iftekar Uddin SM, Dardari ZA, et al. Coronary artery calcium for risk stratification of sudden cardiac death: the Coronary Artery Calcium Consortium. J Am Col Cardiol Img 2022. Jul.15(7):1259-1270.
33. Neilan TG, Januzzi JL, Lee-Lewandrowski E, et al. Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon. Circulation 2006.114:2325-2333.
34. Sahlen A, Gustafsson TF, Sc LM, et al. Predisposing factors and consequences of elevated biomarker levels in long-distance runners aged > 55 years. Am J Cardiol 2009;104:1434-1440.
35. Skadberg O, Kleiven O, Bjorkavoll-Bergseth M , et al. Highly increased troponin I levels following high-intensity endurance cycling may detect subclinical coronary artery disease in presumably healthy leisure sports cyclists: the North Sea Race Endurance Exercise Study (NEEDED) 2013. Eur J Prev Cardiol 2017;24(8):885-894.
36. Aengevaeren VL, Hopman MTE, Thompson PD. et al. Exercise-induced cardiac troponin-I increase and incident mortality and cardiovascular events. Circulation 2019;140(10):804-814.
37. Zelnicker TA, Wiviott SD, Mosenzon O. et al. Association of cardiac biomarkers with major adverse cardiovascular events in high-risk patients with diabetes. JAMA Cardiol published online March 1, 2023. doi:10.1001/jamacardio.2023.0019.
38. Sagris M, Antonopolos AA, Antoniadis A, Tousoulis DT. High-sensitivity troponin (hs-cTn) for cardiovascular risk prognostication: a systemic review and meta-analysis. Eur Heart J 2022.doi:10.1093/eurheartj/ehac544.2287.
39. Brzezinski RY, Melloul A, Berliner S. Early detection of inflammation-prone STEMI patients using the CRP troponin test (CTT). European Heart J Oct 2022. 43(Supplement_2).
40. Ferencik M, Mayrhofer T, Lu MT., et al. Coronary atherosclerosis, cardiac troponin and interleukin-6 in patients with chest pain: the Promise Trial results. JACC 2022;15(8):1427-1438.
41. O’Hanlon R, Wilson M, Wage R, et al. Troponin release following endurance exercise: is inflammation the cause? A cardiovascular magnetic resonance study. J Cardiovasc Magnetic Resonance 2019.201012: published online.com/content/12/1/38
42. Artico J, Shiwani H, Moon JC, et al. Myocardial involvement after hospitalization for COVID-19 complicated by troponin elevation: a prospective, multi-center observational study. Circulation 2023;147(5):364-374.
43. Siegel AJ, Stec JJ, Lipinska I, Van Cott EM, Lewandrowski KB, Ridker PM, Tofler GH. Effect of marathon running on inflammatory and hemostatic markers. Am J Cardiol 2001.88:35-37.
44. Kratz A, Wood MJ, Siegel AJ, Hiers JR, VanCott EM. Effects of marathon running on platelet activation markers. direct evidence for in vivo platelet activation. Am J Clin Pathol 2006.125:296-300.
45. Fahey TD, Swanson GD. A model for defining the optimal amount of exercise contributing to health and avoiding sudden cardiac death. Med Sport 2008. 12 (4); 124-128.
46. Currens JH, White PD. Half a century of running – clinical, physiologic and autopsy findings in the case of Clarence de Mar (Mr. Marathon). N Engl J Med 1961;265;988-993.
47. Burt B. Marathon McGillivray: race director reflects on highlights in advance of 50th consecutive Boston Marathon. bburt@eagletribune,com Apr 14, 2022. Accessed on Feb 4, 2023.
48. Mohlenkamp S, Schmermund A, Kroger K, et al. Coronary atherosclerosis and cardiovascular risk in Masters male marathon runners. Hertz 2006; 31 (6):
49. Siegel AJ. Fatal water intoxication and cardiac arrest in runners during marathons: prevention and treatment based on validated clinical paradigms. Am J Med 2015 Apr 22. pii: S0002-9343(15)00353-8. doi:10.1016/j.amjmed.2015.03.031.
50. Williams H, Arnold H. The effects of violence and prolonged muscular exercise upon the heart. Philadelphia Med J 1899; 1233–1235.
51. Cristantiello R. 26-year-old Brown graduate, Forbes 30 under 30 member, dies after completing marathon in Arizona. BOSTON.com. February 14, 2023.
52. Paratz ED, Rowe SJ, Stub D, et al. A systemic review of global autopsy rates in all-causw mortality and young sudden death. HeartRhythm 2023; DOI:https://doi.org/10.1016/j.hrthm.2023.01.008 2023.
2. Ahmadi MN, Clare PJ, Katzmarzyk PT, et al. Vigorous physical activity, incident heart disease and cancer: how little is enough? European Heart J 2022;00:1-14.
3. Franklin BA, Thompson PD, Al-Zaiti SS, et al. on behalf of the American Heart Association Physical Activity Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Stroke Council. Exercise-related acute cardiovascular events and potential deleterious adaptations following long-term exercise. Downloaded from http://ahajournals.org by on March 3, 2020. Exercise-Related Acute Cardiovascular Events Circulation 2020;141:00–00. DOI: 10.1161/CIR.0000000000000749
4. Albano AJ, Thompson PD, Kapur NK. Acute coronary thrombosis in Boston marathon runners. New Engl J Med 2012;66:184-185.
5. Burke AP, Farb A, Malcom GT, Virmani R. Plaque rupture and sudden death related to exertion in men with coronary artery disease. J Am Med Assoc 1999; doi: 10.1001/jama.281.10.921.
6. Holmstrom L, Chugh HS, Uy-Evando A, et al. Sudden cardiac arrest during sports activity in older adults. J Am Coll Cardiol EP. Jan 18; EPublished DOI:10.1016/j.jacep.2022.10.033.
7. Thompson PD, Eijsvogels TMH, Kim JH. Can the heart get an overuse sports injury?
New Engl J Med. 2022;2(1):
8. Farahmand B, Hallmarker U, Brobert GP, Ahlboma,A. Acute mortality during long-distance ski races (Vasaloppet). Scand J Med Sci Sports 2007;17:356-361.
9. Schnohr P, O’Keefe JH, Lavie C, et al. U-shaped association between duration of sports activities and mortality: Copenhagen City Heart Study. Mayo Clin Proceedings. 2021;
10. Merghani A, Malhotra A, Sharma S. The U-shaped relationship between exercise and cardiac morbidity. Trends Cardiovasc Med 2016;26(3):232-240.
11. Matthews SC, Narotsky DL, Berbholt DV, et al. Mortality among marathon runners in the United States, 2000-2009. Am J Sports Med 2012; May 4:
12. Kim JH, Malhotra R, Chiampas G, et al. Race-Associated Cardiac Arrest Event Registry (RACER) Study Group: cardiac arrest during long-distance running races. N Engl J Med 2012;366 (2):130-140.
13. Shirakawa T, Tanaka H, Kinoshi T, Tanaka S, Takyu H. Analysis of sudden cardiac arrest during marathon races in Japan. Internat J Clin Med. 2017, 8, 472–480.
14. Harris KM, Creswell LL, Haas TS, Thomas T, Tung M, Isaacson BS, et al. Death and cardiac arrest in U.S. triathlon participants, 1980 to 2016: a case series. Ann Int Med 2017: [E pub a head of print]
15. Ridker P, Cushman M, Stamper MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973–979.
16. Siegel AJ. Pheidippides Redux: reducing risk for acute cardiac events during marathon running. Am J Med 2012;125:630-635.
17. Siegel AJ. Pre-race aspirin to protect susceptible runners from cardiac arrest during marathons: is opportunity knocking? Open Heart 2015.2(1): e000102. Doi. 10.1136/openhrt-2014-000102.
18. Siegel AJ, Noakes TD. Can prerace aspirin prevent sudden cardiac death during marathons? Br Sports Med 2017;51(22): 1579-1582.
19. Siegel AJ. Aspirin is used to mitigate the increasing frequency of marathon-related cardiac arrests. J Cardiovasc Med Cardiol 2022. 9(4):077-078.
20. Siegel AJ. Pre-race aspirin for enhanced primary prevention of marathon-related cardiac arrests: confronting Pheidippides’ legacy. Am J Med 2023; in press.
21. Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med 1989; 321 (3): 129-135.
22. Joseph P, Pais P, Dans AL, et al. The international polycap-3 (TIPS-3): design, baseline characteristics and challenges in conduct. Am Heart J 2018;206:72-79.
23. TIPS-3 investigators. Polypill plus aspirin reduces incidence of cardiovascular events by 31%: TIPS-3 Cardiovasc J Afr 2021;32(1):32-40.
24. Siegel AJ, Noakes TD. Aspirin to prevent sudden cardiac death in athletes with high coronary artery calcium scores. Am J Med 2019.132:138-141.
25. Siegel AJ. Aspirin to reduce risk for sudden cardiac death in athletes with elevated C-reactive protein level. Am J Med 2020. 133(9):1014-1016.
26. Kahn SS, Pencina MJ. Cardiovascular disease risk prediction in young adults: the next frontier. JAMA Cardiol 2023;8(2):137-138.
27. Fahey TD, Swanson GD. A model for defining the optimal amount of exercise contributing to health and avoiding sudden cardiac death. Med Sport 2008; 12(4):124-128.
28. Marston NA, Pirruccello JP, Melloni GEM, et. al. Predictive utility of a coronary artery disease polygenic risk score in primary prevention. JAMA Cardiol 2023;8(2):130-137.
29. Lacaze P, Bakshi A, Riaz M, et al. Aspirin for primary prevention of cardiovascular events in relation to lipoprotein(a) genotypes. J Am Coll Cardiol 2022, 80(14):1287-1298
30. Aengevaeren VL, Mostard A, Bakker EA, et.al. Exercise volume versus intensity and the progression of coronary atherosclerosis in middle-aged and older athletes: findings from the MARC-2 Study. Circulation 2023.0. https://doi.org/10.1161/CIRCULATIONAHA.122.061173.
31. Freeman AM, Raman SV, Aggarwal M, et al. Integrating coronary atherosclerotic burden and progression with coronary artery disease risk factors to guide therapeutic decision making, Amer J Med 2022.136(4);260-269.E7.
32. Razavi AC, Iftekar Uddin SM, Dardari ZA, et al. Coronary artery calcium for risk stratification of sudden cardiac death: the Coronary Artery Calcium Consortium. J Am Col Cardiol Img 2022. Jul.15(7):1259-1270.
33. Neilan TG, Januzzi JL, Lee-Lewandrowski E, et al. Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon. Circulation 2006.114:2325-2333.
34. Sahlen A, Gustafsson TF, Sc LM, et al. Predisposing factors and consequences of elevated biomarker levels in long-distance runners aged > 55 years. Am J Cardiol 2009;104:1434-1440.
35. Skadberg O, Kleiven O, Bjorkavoll-Bergseth M , et al. Highly increased troponin I levels following high-intensity endurance cycling may detect subclinical coronary artery disease in presumably healthy leisure sports cyclists: the North Sea Race Endurance Exercise Study (NEEDED) 2013. Eur J Prev Cardiol 2017;24(8):885-894.
36. Aengevaeren VL, Hopman MTE, Thompson PD. et al. Exercise-induced cardiac troponin-I increase and incident mortality and cardiovascular events. Circulation 2019;140(10):804-814.
37. Zelnicker TA, Wiviott SD, Mosenzon O. et al. Association of cardiac biomarkers with major adverse cardiovascular events in high-risk patients with diabetes. JAMA Cardiol published online March 1, 2023. doi:10.1001/jamacardio.2023.0019.
38. Sagris M, Antonopolos AA, Antoniadis A, Tousoulis DT. High-sensitivity troponin (hs-cTn) for cardiovascular risk prognostication: a systemic review and meta-analysis. Eur Heart J 2022.doi:10.1093/eurheartj/ehac544.2287.
39. Brzezinski RY, Melloul A, Berliner S. Early detection of inflammation-prone STEMI patients using the CRP troponin test (CTT). European Heart J Oct 2022. 43(Supplement_2).
40. Ferencik M, Mayrhofer T, Lu MT., et al. Coronary atherosclerosis, cardiac troponin and interleukin-6 in patients with chest pain: the Promise Trial results. JACC 2022;15(8):1427-1438.
41. O’Hanlon R, Wilson M, Wage R, et al. Troponin release following endurance exercise: is inflammation the cause? A cardiovascular magnetic resonance study. J Cardiovasc Magnetic Resonance 2019.201012: published online.com/content/12/1/38
42. Artico J, Shiwani H, Moon JC, et al. Myocardial involvement after hospitalization for COVID-19 complicated by troponin elevation: a prospective, multi-center observational study. Circulation 2023;147(5):364-374.
43. Siegel AJ, Stec JJ, Lipinska I, Van Cott EM, Lewandrowski KB, Ridker PM, Tofler GH. Effect of marathon running on inflammatory and hemostatic markers. Am J Cardiol 2001.88:35-37.
44. Kratz A, Wood MJ, Siegel AJ, Hiers JR, VanCott EM. Effects of marathon running on platelet activation markers. direct evidence for in vivo platelet activation. Am J Clin Pathol 2006.125:296-300.
45. Fahey TD, Swanson GD. A model for defining the optimal amount of exercise contributing to health and avoiding sudden cardiac death. Med Sport 2008. 12 (4); 124-128.
46. Currens JH, White PD. Half a century of running – clinical, physiologic and autopsy findings in the case of Clarence de Mar (Mr. Marathon). N Engl J Med 1961;265;988-993.
47. Burt B. Marathon McGillivray: race director reflects on highlights in advance of 50th consecutive Boston Marathon. bburt@eagletribune,com Apr 14, 2022. Accessed on Feb 4, 2023.
48. Mohlenkamp S, Schmermund A, Kroger K, et al. Coronary atherosclerosis and cardiovascular risk in Masters male marathon runners. Hertz 2006; 31 (6):
49. Siegel AJ. Fatal water intoxication and cardiac arrest in runners during marathons: prevention and treatment based on validated clinical paradigms. Am J Med 2015 Apr 22. pii: S0002-9343(15)00353-8. doi:10.1016/j.amjmed.2015.03.031.
50. Williams H, Arnold H. The effects of violence and prolonged muscular exercise upon the heart. Philadelphia Med J 1899; 1233–1235.
51. Cristantiello R. 26-year-old Brown graduate, Forbes 30 under 30 member, dies after completing marathon in Arizona. BOSTON.com. February 14, 2023.
52. Paratz ED, Rowe SJ, Stub D, et al. A systemic review of global autopsy rates in all-causw mortality and young sudden death. HeartRhythm 2023; DOI:https://doi.org/10.1016/j.hrthm.2023.01.008 2023.