Aspirin guided by coronary artery calcium scoring for primary prevention in persons with subclinical coronary atherosclerosis
Main Article Content
Abstract
Coronary artery calcium scoring reliably identifies persons with subclinical coronary atherosclerosis who are at risk for major acute cardiac events. Aspirin guided by such enhanced risk stratification can be used to advance primary cardiovascular prevention. This approach has been recommended to prevent cardiac arrests in middle-aged men during marathons and sudden cardiac deaths during recreational sports activity in the elderly persons. These strategies are supported by demonstration of a 44% reduction in first heart attacks in healthy middle-aged men in the final report on aspirin in the Physicians’ Health Study and a 31% decrease in major acute cardiac events in persons at moderate risk with the addition of aspirin to the polypill in the TIPS-3, which are both randomized controlled primary prevention trials. Beyond preventing sports-related exertional cardiac events, aspirin use guided by coronary artery calcium scoring may reduce the risk for major acute cardiac events in patients with conditions in which inflammation promotes progressive coronary atherosclerosis, such as autoimmune illnesses and infection with human immunodeficiency virus. This strategy may furthermore be applicable in general medical practice to identify persons with subclinical coronary atherosclerosis for enhanced primary prevention with aspirin in the absence of contraindications.
Keywords:
aspirin, cardiac arrest, sports activity, primary cardiovascular prevention
Article Details
How to Cite
SIEGEL, Arthur J..
Aspirin guided by coronary artery calcium scoring for primary prevention in persons with subclinical coronary atherosclerosis.
Medical Research Archives, [S.l.], v. 13, n. 2, feb. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6297>. Date accessed: 16 mar. 2025.
doi: https://doi.org/10.18103/mra.v13i2.6297.
Section
Review 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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13. De Bosscher R, Dausin C, Claus P, et al. Lifelong endurance exercise and its relation with coronary atherosclerosis. Eur Heart J. 2023; httpsdl.d2Lu.gl.L0-U93.Leubeutjl.ghadJ52.
14. Karam N, Pechmajou L, Dumas F, et al. Comprehensive assessment of coronary artery disease in sports-related sudden cardiac arrest. Circulation 2018;138:429-431.
15. Albano AJ, Thompson PD, Kapur NK. Acute coronary thrombosis in Boston marathon runners. N Engl J Med. 2012;366(2):185-186.
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17. Mohlenkamp S, Lehmann N, Breuckmann F, et al. Running: The risk of coronary events. Eur Heart J 2008. 29; 1903–1910.
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19. Graziano F, Juhasz V, Brunetti G, et al. May strenuous endurance of sports activity damage to the cardiovascular system of healthy athletes question a narrative review. J Cardiovasc Dev Dis. 2022;9;347-369.
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25. Nurmohamed NS, Min JK, Antopolos R, et al. Atherosclerosis quantification and cardiovascular risk: the ISCHEMIA trial. Eur Heart J. 2024 00; 1-13. https//doi.org/10.1093/eurheartj/ehae471.
26. Razavi AC, Uddin SMI, Dardari ZA, et al. Coronary Artery Calcium for Risk Stratification of Sudden Cardiac Death: The Coronary Artery Calcium Consortium. JACC Cardiovasc Imaging. 2022;15 (7):1259-1270. doi:10.1016/j.jcmg.2022.02.011.
27. Fuchs A, Kuhl JT, Sigvardsen PE, et al. Subclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort: A Prospective Observational Cohort Study. Ann Intern Med. 2023;176(4):433-442. doi:10.7326/ M22-3027.
28. Fuster V, Garcia-Alvarez A, Mass V, et al. Influence of subclinical atherosclerosis burden and progression on mortality. J Am Coll Cardiol Img. 2024; 84(15):1391-1403.
29. Chandra N, Papadakis M, Sharma S, et al. Preparticipation screening of young competitive athletes for cardiovascular disorders. Phys Sports Med 2010.1(3):54-63.
30. Holst AG, Wikel BG, Theilade J, et al. Incidence and etiology of sports-related sudden cardiac death in Denmark: implications for preparticipation screening. Heart rhythm 2010; 7: 1365–1371.
31. Shirakawa T, Tanaka H, Kinoshi T, et al. Analysis of sudden cardiac arrest during marathon races in Japan. Internat J Clin Med.2017;8;472-480.
32. Nearman S. Cardiac deaths in the marathons much lower than previously thought. AMAA Journal. Winter 2012: 7–8.
33. FDA drug safety communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms. U.S. Food and Drug Administration (2019). https://USFDA.org. Accessed Dec 20, 2024.
34. Siegel AJ, Noakes TD. Can pre-race aspirin prevent sudden cardiac death during marathons? Br J Sports Med. 2017;51(22):1579-1582.
35. Siegel AJ. Pre-race aspirin to protect susceptible runners from cardiac arrest during marathons: Is opportunity knocking? Open Heart 2015.2.e00010 2. doi:10.1136/openhrt-2014000102.
36. Patrono C, Garcia-Rodriguez LA, Landolfi R, et al. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005;353:22-29.
37. Ridker P, Cushman M, Stampler MJ, Tracy RP, Hennekens CH. Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. N Eng J Med..1997; 336:973-979.
38. 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): 129-35. doi:10.1056/NEJM198907203210301.
39. Haq A, Veerati T, Walser-Kuntz T, et al. Coronary artery calcium and the risk of cardiovascular events and mortality in younger adults: a meta-analysis. Eur J Prev Cardiol 2023 Dec 19, 2023. https://doi.org/10.1093/eurjpc/zwad399.
40. Siegel A. Pre-race aspirin to attenuate the risk for marathon-related cardiac arrest: deconstructing the legacy of Pheidippides. Eur Heart J. 2023, ehad641. https://doi.org/10.1093/eurheartj/ehad641 25.
41. Siegel A. Rationale for pre- race aspirin to attenuate risk for marathon-related cardiac arrest: confounding the legacy of Pheidippides. Medical research archives (online) 11 (4). https://doi.org/10.18103/mra.v 1114.3741.
42. Arnett DK, Claas SA. 2019ACC/AHA Guideline for prevention of CVD. J Am Coll Cardiol 2019; 8(19):e01460.
43. Mogul A,Leppien EE, Laughlin E, Spinler SA. Aspirin for primary prevention of cardiovascular disease: a review of recent literature and updated guideline recommendations. d2021. Jan: 22(1);83-91. doi: 10.1080/14656566.2020.18173.
44. Ajulo E, Ayers CR, Vigen R, et al. Value of coronary artery calcium scanning in association with the net benefit of aspirin in primary prevention of atherosclerotic cardiovascular disease. JAMA Cardiol. 2021 Feb 1; 6(2):179-187. Doi: 10.1001/ jamacardio2020.4939.
45. Doshi A, Gandi H, Patel KN, et al. Aspirin for primary prevention in patients with elevated coronary artery calcium scores: A systematic review of current evidences. Am J Cardiol 2024; 2209-2215.
46. Kim JH, Martinez MW, Guseh JS, et al. A contemporary review of sudden cardiac arrest and death in competitive and recreational athletes. Lancet 2024.404;10468:220-2222.
47. Holmstrom L, Chugh HS, Uy-Evanado A, et al. Sports-related sudden cardiac arrest in older individuals JACC: Clinical Electrophysiol 2023;9(7P t1):893-903.
48. TIPS-3 investigators. Polypill plus aspirin reduces incidence of cardiovascular events by 31%: TIPS-3 Cardiovasc J Afr. 2021;32(1):32-40.
49. Siegel A. Aspirin guided by coronary artery calcium scoring for primary cardiovascular prevention in persons with subclinical coronary atherosclerosis. Am J Med 2025; in press.
50. Mujkanovic J, Warming PE, Kessing LV, et al. Nationwide burden of sudden cardiac death among patients with a psychiatric disorder. Heart 2024;110(23):1365-1371.
51. Redevand L, Rahman Z, Hindley GFL, et al. Characterizing the shared genetic underpinnings of schizophrenia and cardiovascular risk factors. Am J Psychiatry 2023.180;11:815-826.
52. Joynt Maddox KE, Elkind MSV, Aparicio HJ, et al. Forcasting the burden of cardiovascular disease and stroke in the United States through 2050 -- prevalence of risk factors and disease: a presidential advisory from the American Heart Association, Circulation 2024;150(4):e65-e88.
2. 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 2021;141(13):e705-e736.
3. Kim JH, Malhotra R, Chiampas G, et al. Cardiac arrest during long-distance running races. N Engl J Med. 2012;366(2):130-40. doi:10.1056/NEJMoa1106468.
4. Mathews SC, Narotsky DL, Bernholt DL, et al. Mortality among marathon runners in the United States, 2000-2009. Am J Sports Med. 2012;40(7): 1495-500. doi:10.1177/0363546512444555.
5. Siegel AJ, Silverman LM, Lopez MS. Creatine kinase elevations in marathon runners: relationship to training and competition. Yale J Biol Med.1980; 53:275-279.
6. Siegel AJ, Stec JJ, Lipinska I, et al. Effect of marathon running on inflammatory and hemostatic markers. Am J Cardiol. 2001;88(8):918-20, A9. doi: 10.1016/s0002-9149(01)01909-9.
7. 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.
8. Eberhardt N, Noval MG, Kaur R, et a. SARS-CoV-2 infection triggers pro-atherogenic inflammatory response in human coronary vessels. Nature Cardiovascular Research 2023;2:899-916.
9. Williams H, Arnold H. The effects of violent and prolonged exercise upon the heart. Phila Med J. 189:1233-1235.
10. Bassler TJ. Marathon running and atherosclerosis. B Med J. 1977.Jan 22;1(6055):229.
11. Aengevaeren VL, Mostard A, Sharma S, et al. Exercise and coronary atherosclerosis: observations, explanations, relevance and clinical management. Circulation.2020;133-1350.
12. Aengevaeren VL, Mostard A, Bakker EA, et al. Exercise volume versus intensity and the progression of coronary atherosclerosis in middle-aged men and older athletes: findings from the MARC-2 Study. Circulation. 2023.
13. De Bosscher R, Dausin C, Claus P, et al. Lifelong endurance exercise and its relation with coronary atherosclerosis. Eur Heart J. 2023; httpsdl.d2Lu.gl.L0-U93.Leubeutjl.ghadJ52.
14. Karam N, Pechmajou L, Dumas F, et al. Comprehensive assessment of coronary artery disease in sports-related sudden cardiac arrest. Circulation 2018;138:429-431.
15. Albano AJ, Thompson PD, Kapur NK. Acute coronary thrombosis in Boston marathon runners. N Engl J Med. 2012;366(2):185-186.
16. Karlstedt E, Chelvanathon A, Da Silva M, et al. The impact of repeated marathon running on cardiovascular function in the aging population. J Cardiovasc Magnetic Resonance 2012; 14:58-66.
17. Mohlenkamp S, Lehmann N, Breuckmann F, et al. Running: The risk of coronary events. Eur Heart J 2008. 29; 1903–1910.
18. Dores H, Goncalves PA, Cardim N, et al. Coronary artery disease in athletes: an adverse effect of intense exercise? Cardiologia 2017. https://doi.org/10.101/j.repc.2017.0.00
19. Graziano F, Juhasz V, Brunetti G, et al. May strenuous endurance of sports activity damage to the cardiovascular system of healthy athletes question a narrative review. J Cardiovasc Dev Dis. 2022;9;347-369.
20. Nielan TG, Januzzi JL, Lee-Lewandrowski E, et al. Myocardial injury and ventricular dysfunction related to training adequacy among non-competitive participants in the Boston Marathon. Circulation. 2006;114(22):2325-33.
21. Zilinski JL, Contursi ME, Isaacs SK, et al. Myocardial adaptations to recreational marathon training among middle-aged men. Circ Cardiovasc Imaging 2015;8:e00247. Doi 10.111/CIRCIMAGING.114.00
22. Baggish AL, Lavine BD. Coronary artery calcification among endurance athletes:”hearts of stone”. Circulation.2017;136:147-151.
23. Green D, Sewry N, Derman WF, et al. A high incidence of serious life-threatening cardiovascular medical encounters during a marathon (2014–2019) calls for prevention strategies: SAFER XL. Physician Sports Medicine 2024. Doi:10.1080/0091 3847.2024.2399495.
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. Nurmohamed NS, Min JK, Antopolos R, et al. Atherosclerosis quantification and cardiovascular risk: the ISCHEMIA trial. Eur Heart J. 2024 00; 1-13. https//doi.org/10.1093/eurheartj/ehae471.
26. Razavi AC, Uddin SMI, Dardari ZA, et al. Coronary Artery Calcium for Risk Stratification of Sudden Cardiac Death: The Coronary Artery Calcium Consortium. JACC Cardiovasc Imaging. 2022;15 (7):1259-1270. doi:10.1016/j.jcmg.2022.02.011.
27. Fuchs A, Kuhl JT, Sigvardsen PE, et al. Subclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort: A Prospective Observational Cohort Study. Ann Intern Med. 2023;176(4):433-442. doi:10.7326/ M22-3027.
28. Fuster V, Garcia-Alvarez A, Mass V, et al. Influence of subclinical atherosclerosis burden and progression on mortality. J Am Coll Cardiol Img. 2024; 84(15):1391-1403.
29. Chandra N, Papadakis M, Sharma S, et al. Preparticipation screening of young competitive athletes for cardiovascular disorders. Phys Sports Med 2010.1(3):54-63.
30. Holst AG, Wikel BG, Theilade J, et al. Incidence and etiology of sports-related sudden cardiac death in Denmark: implications for preparticipation screening. Heart rhythm 2010; 7: 1365–1371.
31. Shirakawa T, Tanaka H, Kinoshi T, et al. Analysis of sudden cardiac arrest during marathon races in Japan. Internat J Clin Med.2017;8;472-480.
32. Nearman S. Cardiac deaths in the marathons much lower than previously thought. AMAA Journal. Winter 2012: 7–8.
33. FDA drug safety communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms. U.S. Food and Drug Administration (2019). https://USFDA.org. Accessed Dec 20, 2024.
34. Siegel AJ, Noakes TD. Can pre-race aspirin prevent sudden cardiac death during marathons? Br J Sports Med. 2017;51(22):1579-1582.
35. Siegel AJ. Pre-race aspirin to protect susceptible runners from cardiac arrest during marathons: Is opportunity knocking? Open Heart 2015.2.e00010 2. doi:10.1136/openhrt-2014000102.
36. Patrono C, Garcia-Rodriguez LA, Landolfi R, et al. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005;353:22-29.
37. Ridker P, Cushman M, Stampler MJ, Tracy RP, Hennekens CH. Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. N Eng J Med..1997; 336:973-979.
38. 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): 129-35. doi:10.1056/NEJM198907203210301.
39. Haq A, Veerati T, Walser-Kuntz T, et al. Coronary artery calcium and the risk of cardiovascular events and mortality in younger adults: a meta-analysis. Eur J Prev Cardiol 2023 Dec 19, 2023. https://doi.org/10.1093/eurjpc/zwad399.
40. Siegel A. Pre-race aspirin to attenuate the risk for marathon-related cardiac arrest: deconstructing the legacy of Pheidippides. Eur Heart J. 2023, ehad641. https://doi.org/10.1093/eurheartj/ehad641 25.
41. Siegel A. Rationale for pre- race aspirin to attenuate risk for marathon-related cardiac arrest: confounding the legacy of Pheidippides. Medical research archives (online) 11 (4). https://doi.org/10.18103/mra.v 1114.3741.
42. Arnett DK, Claas SA. 2019ACC/AHA Guideline for prevention of CVD. J Am Coll Cardiol 2019; 8(19):e01460.
43. Mogul A,Leppien EE, Laughlin E, Spinler SA. Aspirin for primary prevention of cardiovascular disease: a review of recent literature and updated guideline recommendations. d2021. Jan: 22(1);83-91. doi: 10.1080/14656566.2020.18173.
44. Ajulo E, Ayers CR, Vigen R, et al. Value of coronary artery calcium scanning in association with the net benefit of aspirin in primary prevention of atherosclerotic cardiovascular disease. JAMA Cardiol. 2021 Feb 1; 6(2):179-187. Doi: 10.1001/ jamacardio2020.4939.
45. Doshi A, Gandi H, Patel KN, et al. Aspirin for primary prevention in patients with elevated coronary artery calcium scores: A systematic review of current evidences. Am J Cardiol 2024; 2209-2215.
46. Kim JH, Martinez MW, Guseh JS, et al. A contemporary review of sudden cardiac arrest and death in competitive and recreational athletes. Lancet 2024.404;10468:220-2222.
47. Holmstrom L, Chugh HS, Uy-Evanado A, et al. Sports-related sudden cardiac arrest in older individuals JACC: Clinical Electrophysiol 2023;9(7P t1):893-903.
48. TIPS-3 investigators. Polypill plus aspirin reduces incidence of cardiovascular events by 31%: TIPS-3 Cardiovasc J Afr. 2021;32(1):32-40.
49. Siegel A. Aspirin guided by coronary artery calcium scoring for primary cardiovascular prevention in persons with subclinical coronary atherosclerosis. Am J Med 2025; in press.
50. Mujkanovic J, Warming PE, Kessing LV, et al. Nationwide burden of sudden cardiac death among patients with a psychiatric disorder. Heart 2024;110(23):1365-1371.
51. Redevand L, Rahman Z, Hindley GFL, et al. Characterizing the shared genetic underpinnings of schizophrenia and cardiovascular risk factors. Am J Psychiatry 2023.180;11:815-826.
52. Joynt Maddox KE, Elkind MSV, Aparicio HJ, et al. Forcasting the burden of cardiovascular disease and stroke in the United States through 2050 -- prevalence of risk factors and disease: a presidential advisory from the American Heart Association, Circulation 2024;150(4):e65-e88.