Pheidippides Redux: Reducing Risk for Acute Cardiac Events During Marathon Running

doi:10.1016/j.amjmed.2011.11.008

The American Journal of Medicine

Volume 125, Issue 7, July 2012, Pages 630-635

https://doi.org/10.1016/j.amjmed.2011.11.008 Get rights and content

Abstract

Prolonged strenuous exercise such as marathon running transiently increases the absolute and relative risk for sudden cardiac death. A 17-fold increase in the latter over resting baseline in previously sedentary middle-aged men is reduced due to cardioprotection from training in experienced marathon runners. Exertional rhabdomyolysis as a common occurrence during the race is accompanied by neutrophilia and elevated biomarkers of inflammation, including interleukin-6 and C-reactive protein. A hemostatic imbalance with prothrombotic effects includes in vivo platelet activation during the race. Suggesting a pathogenic role for these findings, plaque rupture due to atherothrombosis triggers acute exertional cardiac events, including sudden death, in low-risk runners as in high-risk patients such as those with diabetes mellitus. Strategies including prophylactic aspirin are considered to decrease the risk for acute cardiac events.

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While proficient cardiac resuscitation has improved survival following cardiac arrest during road races in Japan, this accomplishment does not address coronary artery disease as the underlying cause of an increasing frequency of cardiac arrest in middle-aged men during marathons and ironman triathlons in the United States since the year 2000. Based on the high prevalence of subclinical coronary artery disease by cardiac computed tomography in endurance athletes with low conventional cardiac risk-factor profiles, we recommend coronary artery calcium scores as a more reliable and independent predictor of incident cardiac events, including death, as validated among adults aged 30-46 years. Scores of over 100 Agatston units indicate a 10-year cardiac risk of 7.5%, at which additional measures for primary prevention are recommended, including aspirin, as shown conclusively to reduce first myocardial infarctions in same-aged men in a prospective double-blind controlled trial. Targeted screening for subclinical coronary atherosclerosis with coronary artery calcium scores is prudent to guide appropriately dosed aspirin use to mitigate the increasing frequency of sports-related sudden cardiac death due to plaque rupture.
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Citation Excerpt :
Aspirin use has been proposed for decreasing short-term cardiac risk associated with systemic infections, as shown in patients with severe sepsis.47,48 Transposing this strategy to the marathon starting line, pre-race aspirin use has been proposed as a win-win strategy to provide antithrombotic protection during high, if transient, race-related cardiac risk.49 Usage pre-race use only in runners who are otherwise at low cardiovascular risk minimizes the chance for complications, such as the gastrointestinal bleeding associated with continuous prophylaxis.50
Cerebral edema due to exercise-associated hyponatremia and cardiac arrest due to atherosclerotic heart disease cause rare marathon-related fatalities in young female and middle-aged male runners, respectively. Studies in asymptomatic middle-aged male physician-runners during races identified inflammation due to skeletal muscle injury after glycogen depletion as the shared underlying cause. Nonosmotic secretion of arginine vasopressin as a neuroendocrine stress response to rhabdomyolysis mediates hyponatremia as a variant of the syndrome of inappropriate antidiuretic hormone secretion. Fatal hyponatremic encephalopathy in young female runners was curtailed using emergent infusion of intravenous hypertonic (3%) saline to reverse cerebral edema on the basis of this paradigm. This treatment was arrived at through a consensus process within the medical community. An increasing frequency of cardiac arrest and sudden death has been identified in middle-aged male runners in 2 studies since the year 2000. Same-aged asymptomatic male physician-runners showed post-race elevations in interleukin-6 and C-reactive protein, biomarkers that predict acute cardiac events in healthy persons. Hypercoagulability with in vivo platelet activation and release of cardiac troponin and N-terminal pro-brain natriuretic peptide were also observed post-race in these same subjects. High short-term risk for atherothrombosis during races as shown by stratification of biomarkers in asymptomatic men may render nonobstructive coronary atherosclerotic plaques vulnerable to rupture. Pre-race aspirin use in this high-risk subgroup is prudent according to conclusive evidence for preventing first acute myocardial infarctions in same-aged healthy male physicians. On the basis of validated clinical paradigms, taking a low-dose aspirin before a marathon and drinking to thirst during the race may avert preventable deaths in susceptible runners.

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: Conflict of Interest: None.

: Authorship: The author is solely responsible for writing this manuscript.

: Disclosure: The views herein are solely those of the author and do not imply agreement or endorsement by collaborators or associations for which he has volunteered.

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ReviewPheidippides Redux: Reducing Risk for Acute Cardiac Events During Marathon Running

Abstract

Atherosclerosis

Am Heart J

Ageing Res Rev

Am Heart J

Am J Cardiol

Am J Med

Am J Cardiol

Lancet

Lancet

Am J Cardiol

Am J Med

Am J Clin Nutr

The effects of violent and prolonged muscular exercise upon the heart

Phila Med J

A history of medical reports on the Boston Marathon: 112 years and still running

Med Sci Sports Exerc

Half a century of runningClinical, physiologic and autopsy findings in the case of Clarence DeMar (‘Mr. Marathon')

N Engl J Med

Marathon running and immunity to atherosclerosis

Ann NY Acad Sci

Acute coronary thrombosis in Boston marathon runners

N Engl J Med

Cardiac arrest during long-distance running

N Engl J Med

Dose response between physical activity and risk for coronary heart disease; a meta-analysis

Circulation

Physical exertion, exercise, and sudden cardiac death in women

JAMA

Triggering of sudden death from cardiac causes by vigorous exertion

N Engl J Med

Heart HealthThe bottom line on exercise, marathons, and heart-attack deaths

Competing risks of mortality with marathons: retrospective analysis

BMJ

Marathon cardiac deaths

Sports Med

Mortality among marathon runners in the United States, 2000-2009

Am J Sports Med

Heart disease in marathon runners: a review

Med Sci Sports Exerc

Clinical and angiographic characteristics of exertion-related acute myocardial infarction

JAMA

Plaque rupture and sudden death related to exertion in men with coronary artery disease

JAMA

Fatal myocardial infarction in marathon racing

Ann Intern Med

Creatine kinase elevations in marathon runners: relationship to training and competition

Yale J Biol Med

Observations upon long-distance runners

Boston Med Surg J

Effect of marathon running on hematologic and biochemical laboratory parameters, including cardiac markers

Am J Clin Pathol

Hyponatremia in marathon runners due to inappropriate arginine vasopressin secretion

Am J Med

Measurement of a plasma stroke biomarker panel and cardiac troponin T in marathon runners before and after the 2005 Boston Marathon

Am J Clin Pathol

Effect of marathon running on inflammatory and hemostatic markers

Am J Cardiol

Effects of marathon running on platelet activation markersDirect evidence for in vivo platelet activation

Am J Clin Pathol

Review
Pheidippides Redux: Reducing Risk for Acute Cardiac Events During Marathon Running