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Division of General Internal Medicine, Massachusetts General Hospital, BostonDepartment of Internal Medicine, McLean Hospital, Belmont, MassHarvard Medical School, Boston, Mass
Exercise-related acute cardiovascular events and potential deleterious adaptations following long-term exercise training: placing the risks into perspective-an update: a scientific statement from the American Heart Association.
The paradox that vigorous exercise decreases one's lifetime risk for major acute cardiac events but may also trigger sudden death may represent a U-shaped benefit-risk curve.
A retrospective study of mortality during United States marathons, beginning in 2000, determined that atherosclerotic coronary heart disease in middle-aged males was the main cause of death.
A 10-year prospective registry of United States road races from 2000 identified male sex and the marathon as the only significant and independent risk factors for cardiac arrest.
Pre-race low-dose aspirin use has been proposed to mitigate this dilemma based on a 44% reduction in first heart attacks in middle-aged males in the final report on this agent in the Physicians Health Study, a randomized controlled prospective primary prevention trial.
The impact of including such assessments in decision-making may qualify runners for aspirin use who fall below the threshold in sub-specialty guidelines (Figure).
FigureImpact on therapeutic decision-making for pre-race aspirin use by including coronary artery calcium scores and inflammatory and cardiac biomarkers in risk calculations (red=no, yellow=consider, and green=yes). ASVD= Atherosclerotic Cardiovascular Disease; CAC= coronary artery calcium; hsCRP= high-sensitivity C-reactive protein.
This enhanced risk stratification is appropriate for diverse participants, including novices, as runners who are less trained are more likely to have elevated post-race cardiac biomarkers.
High coronary artery calcium scores occur more commonly in habitual marathon runners, as exercise volume and especially intensity promote progression of coronary atherosclerosis.
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 [e-pub ahead of print]. Circulation. doi:10.1161/CIRCULATIONAHA.122.061173. accessed March 15, 2023.
recent studies suggest that such findings may have prognostic significance for major acute cardiovascular events, as in patients with acute cardiac conditions.
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.
Health care providers are advised to consider expanded risk stratification for pre-race aspirin use with patients who choose to run marathons, especially those who undertake training to maximize cardiovascular health but may be unaware of the risk associated with races. Using aspirin in those identified at high risk by these ancillary screening measures is analogous to advising such use based on lipoprotein subtypes.
Post-race activation of atherothrombosis is a likely proximate cause of cardiac arrest in middle-aged male runners with atherosclerotic coronary heart disease, which has been demonstrated by a concurrent post-race hemostatic imbalance with prothrombotic effects including in vivo activation of platelets in asymptomatic Boston marathon runners.
The anti-inflammatory and anti-thrombotic effects of aspirin also provide at-risk runners with the advantage of having an agent on board with a class 1A recommendation for pre-hospital administration should chest pain develop during or after races.
The efficacy of pre-race aspirin for reducing marathon-related fatalities can be assessed by a follow-up registry, as a prospective study like the aspirin arm of the Physicians Health Study lacks feasibility due to the infrequency of index events. The marathon medical community may hopefully undertake this measure to address the increasing frequency of race-related cardiac arrests in middle-aged males, as was successfully accomplished in curtailing fatalities due to exercise-associated hyponatremia mainly in novice and younger females.
As inflammation due to exertional rhabdomyolysis is the root cause of these life-threatening conditions, the hypothesis that muscle injury may cause adverse effects on the heart is validated, as advanced in the first medical study on Boston marathon runners in 1899.
Aspirin is a prime candidate to attenuate the incongruous cardiovascular conundrum presented by marathon training and racing. This agent is readily available worldwide, inexpensive, and safe, as determined in the polypill trials, which also showed a 31% reduction in acute cardiac events in individuals at moderate baseline cardiovascular risk.
To quote Amby Burfoot, Runners World editor-emeritus and 1968 Boston marathon champion: “Just because the incidence of cardiac arrest is low doesn't mean it can't be lower” (personal communication).
In sum, pre-race low-dose aspirin use qualifies as evidence-based to mitigate the increasing frequency of marathon-related cardiac arrests due to atherosclerotic coronary heart disease in middle-aged males. Assessment of coronary artery calcium scores and post-race cardiac biomarkers can stratify risk to identify runners who may benefit the most from such enhanced primary prevention.
References
Lee DH
Rezende LFM
Joh HK
et al.
Long-term leisure-time physical activity intensity and all-cause and cause-specific mortality: a prospective cohort of US adults.
Exercise-related acute cardiovascular events and potential deleterious adaptations following long-term exercise training: placing the risks into perspective-an update: a scientific statement from the American Heart Association.
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 [e-pub ahead of print]. Circulation. doi:10.1161/CIRCULATIONAHA.122.061173. accessed March 15, 2023.
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.
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