European Heart Journal (2023) 00, 1 DISCUSSION FORUM

https://doi.org/10.1093/eurheartj/ehad641 Ischaemic heart disease

Pre-race aspirin to attenuate the risk

for marathon-related cardiac arrest:

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deconstructing the legacy of Pheidippides
1,2,3
Arthur J. Siegel *
1
Division of General Internal Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA ; 2Department of Internal Medicine, McLean Hospital, 115 Mill Street,
Belmont, MA 02478-1064, USA ; and 3Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA

This commentary refers to ‘Lifelong endurance exercise
and its relation with coronary atherosclerosis’, by
R. De Bosscher et al., https://doi.org/10.1093/eurheartj/
ehad152.
The association of incremental endurance exercise with progressive
coronary atherosclerosis demonstrated by De Bosscher et al., relates
robustly to evidence that male gender and the marathon were signifi-
cant and independent risk factors for cardiac arrest in a 10-year registry
of United States road races beginning in 2000.1,2 Most fatalities were in
middle-aged men due to atherosclerotic coronary heart disease.
Studies showing race-related activation of atherothrombosis due to in-
flammation following exertional rhabdomyolysis in same-aged asymp-
tomatic male Boston marathon physician-runners no doubt account
for this connection, showing a post-race haemostatic imbalance with
procoagulant effects and in vivo platelet activation.
Based in part on a 40% reduction in first acute myocardial infarctions
in middle-aged men in the Physicians Health Study, a randomized con-
trolled primary prevention trial,3 aspirin use has been recommended to
attenuate the transiently elevated risk for race-related acute cardiac
events.4 Coronary artery calcium (CAC) computed tomography scor-
ing can likely identify runners who might benefit the most from
enhanced primary prevention with aspirin (Table 1). Such use also pro-
vides at-risk runners with the benefit of having on board an agent with a
Class 1A recommendation from the American Heart Association for
pre-hospital administration for acute coronary syndromes, which
may occur during races.
In contrast to the incrementally cardioprotective benefit of mara-
thon training, running such races transiently increases the risk of cardiac
arrest and sudden death. It is prudent for runners with elevated CAC
scores to take pre-race aspirin, given that subclinical coronary athero-
sclerosis confers an eight-fold increased risk for major acute cardiac
events.5 Safe, inexpensive, and readily available worldwide, aspirin quali-
fies as evidence-based to mitigate the premature cardiac morbidity and
mortality, which continue to occur during marathon running in the
modern era since the index case of Pheidippides in 460 BC. Follow-up
registry data can prospectively assess the efficacy of this intervention
for reducing race-related cardiac arrests once accepted by the mara-
thon medical community.
Declarations
Disclosure of Interest
All authors declare no disclosure of interest for this contribution.

References
Table 1 Coronary artery calcium scores and the 1. De Bosscher R, Dausin C, Claus P, Bogaert J, Dymarkowski S, Goetschalclx K, et al.
anticipated benefit of enhanced primary prevention with Lifelong endurance exercise and its relation with coronary atherosclerosis. Eur Heart J
low-dose pre-race aspirin for reducing the risk of 2023;44:2388–2399. https://doi.org/10.1093/eurheartj/ehad152
2. Kim JH, Malhotra R, Chiampas G, d’Hemecourt P, Troyanos C, Cianca J, et al.
marathon-related cardiac arrest
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Coronary artery calcium Agatston Pre-race low-dose NEJMoa1106468
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.................................................................................... arrest: confronting Pheidippides’ legacy. Am J Med 2023;136:613–615. 10.1016/j.
0—no coronary plaque burden Not indicated amjmed.2023.02.007.
4. Steering Committee of the Physicians’ Health Study Research Group. Final report on the
1–99—mild disease Optional
aspirin component of the ongoing Physicians’ Health Study. N Engl J Med 1989;321:
100–399—moderate disease Recommended 129–135. https://doi.org/10.1056/NEJM198907203210301
5. Fuchs A, Kuhl JT, Sigvardsen PE, Afzal S, Knudsen AD, Sorgaard MH, et al. Subclinical cor-
≥400—severe disease Highly recommended onary atherosclerosis and risk for myocardial infarction in a Danish cohort. Ann Int Med
2023;176:489–495. https://doi.org/10.7326/M22-3027

* Corresponding author. Tel: +1 617 855 2358, Fax: +1 617 855 3731, Email: asiegel@mgh.harvard.edu
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