Sex Is Associated With the Presence of Atherosclerotic Plaque Hemorrhage and Modifies the Relation Between Plaque Hemorrhage and Cardiovascular Outcome

Background and Purpose Plaque hemorrhage (PH) may lead to accelerated progression of atherosclerotic disease. The presence of local PH in the carotid plaque predicts future cardiovascular events in any vascular territory. We investigated the prevalence of local PH and the predictive value of PH for the occurrence of cardiovascular events in men and women separately. Methods Atherosclerotic plaques from 1422 patients (969 men, 453 women) who underwent carotid endarterectomy were analyzed histologically for the presence of PH. Patients were monitored for 3 years for cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, vascular death, and vascular intervention). Results Plaques from men showed a significantly higher prevalence of PH compared with women (67% versus 54%; P<0.001). In 1353 patients with available follow-up data, with a median duration of 2.9 years, 270 events had occurred in men (29%) and 94 in women (22%). Stratified by presence of PH, the event rate was 32% in men with PH versus 23% in men without PH, and 23% in women with PH versus 21% in women without PH. A multivariable Cox proportional hazards model found a significant interaction between sex and PH. PH was significantly associated with events in men (adjusted hazard ratio, 1.9; 95% CI, 1.2-2.8) but not in women (adjusted hazard ratio, 1.0; 95% CI, 0.6-1.7). Conclusions Atherosclerotic carotid plaques obtained from men reveal a higher prevalence of PH compared with women. Local PH is strongly related to secondary manifestations of cardiovascular disease in men but not in women.