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Allen P. Burke, MD; Andrew Farb, MD; Gray T. Malcom, PhD; You-hui Liang, MD; John E. Smialek, MD; Renu Virmani, MD

JAMA. 1999;281:921-926.

Context  Exertion has been reported to acutely increase the risk of sudden coronary death, but the underlying mechanisms are unclear.

Objective  To determine the frequency of plaque rupture in sudden deaths related to exertion compared with sudden deaths not related to exertion.

Design  Autopsy survey. Coronary arteries were perfusion fixed and segments with more than 50% luminal narrowing were examined histologically. Ruptured plaques were defined as intraplaque hemorrhage with disruption of the fibrous cap and luminal thrombus. Exertion before death was determined by the investigator of the death.

Setting  Medical examiner's office.

Patients  A total of 141 men with severe coronary artery disease who died suddenly, including 116 whose deaths occurred at rest (mean [SD] age, 51 [11] years) and 25 who died during strenuous activity or emotional stress (age, 49 [9] years).

Main Outcome Measures  The frequency and morphology of plaque rupture was compared in men dying at rest vs those dying during exertion. Independent association of risk factors (total cholesterol, high-density lipoprotein cholesterol, glycosylated hemoglobin, cigarette smoking) in addition to acute exertion with plaque rupture were determined.

Results  The mean (SD) number of vulnerable plaques in the coronary arteries of men in the exertional-death group was 1.6 (1.5) and in the at-rest group was 0.9 (1.2) (P=.03). The culprit plaque in men dying during exertion was plaque rupture in 17 (68%) of 25 vs 27 (23%) of 116 men dying at rest (P<.001). Hemorrhage into the plaque occurred in 18 (72%) of 25 men in the exertional-death group and 47 (41%) of 116 men in the rest group (P=.007). Histological evidence of acute myocardial infarction was present in 0 of 25 in the exertion group and in 15 (13%) of 116 in the rest group. Men dying during exertion had a significantly higher mean (SD) total cholesterol–high-density lipoprotein cholesterol ratio (8.2 [3.0]) than those dying at rest (6.2 [ 2.7]; P=.002), and the majority (21/25) were not conditioned. In multivariate analysis, both exertion (P=.002) and total cholesterol–high-density lipoprotein cholesterol ratio (P=.002) were associated with acute plaque rupture, independent of age and other cardiac risk factors.

Conclusion  In men with severe coronary artery disease, sudden death related to exertion was associated with acute plaque rupture.

Author Affiliations: Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC (Drs Burke, Farb, Liang, and Virmani); Louisiana State University, New Orleans (Dr Malcom); and the University of Maryland, Baltimore (Dr Smialek).

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