As if reprising the index case of Pheidippides in 490 BC, the sudden cardiac death of a 32-year-old modern-day warrior at mile 20 in the 2016 London marathon mandates an expedited search to prevent such tragic events based on novel insights into the underlying cause (figure 1).1 2 Although the cardiac findings in this case have not been released, an acute coronary event is most likely as the most common cause of sudden cardiac death in men over the age of 30 years including among experienced runners in that event.3–5

While the overall incidence of sudden cardiac death during marathons is low, cardiac arrests occur in roughly 1 in 50 000 finishers.6 Based on 59 cases with a mean age of 42 years in a 10-year prospective registry of American road races since 2000, male sex and the marathon were the only significant risk factors for cardiac arrest.7 Atherosclerotic heart disease was the predominant underlying cause in same-aged runners in a concurrent Parisian registry.8 Marathon running thereby illustrates the triggering of acute myocardial infarction by strenuous exercise in middle-aged males with underlying non-obstructive coronary atherosclerosis.9

Rationale for targeted prevention

Supported by a 44% reduction in first acute myocardial infarctions in healthy middle-aged men in the Physicians Health Study, a randomised controlled primary prevention trial,10 the International Marathon Medical Directors Association (IMMDA) has recommended prerace aspirin for males over the age of 40 years with approval by their physicians after considering risks such as gastrointestinal bleeding or allergy.11 This strategy is concordant with clinical guidelines endorsing aspirin for primary prevention in persons at high cardiovascular risk, which includes middle-aged males at increased short-term risk for acute myocardial ischaemia.12 13

IMMDA’s advisory is analogous to that proposed for firefighters, who are at increased risk for sudden cardiac death during emergency duties in part related to procoagulant effects as shown in athletes after strenuous physical exercise.14–16 Attenuation of training-induced prothrombotic effects by aspirin in firefighters would apply as well to runners based on atherothrombosis as the shared pathogenic paradigm.17 In contrast to continuous prophylaxis to cover unpredictable risk in firefighters, prerace use may suffice for marathoners who are at otherwise low cardiovascular risk as assessed by 10-year Framingham measures.

Assessment of coronary artery calcification, which independently predicts incident coronary heart disease and death in males aged 32 to 46 years,18 may be useful for stratifying the utility of aspirin for marathoners with such evidence for atherosclerosis.19 This strategy may be especially relevant for habitual marathoners whose paradoxically higher scores correlate inversely with event-free survival.20 This finding indicates short-term risk for acute cardiac events associated with atherosclerotic plaque burden, confounding the benefit of enhanced longevity with this lifestyle.21–23