title: Sex is associated with the presence of atherosclerotic plaque hemorrhage and modifies the relation between plaque hemorrhage and cardiovascular outcome.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Experimental Cardiology Laboratory (J.E.P.V., H.M.D.R., D.P.V.d.K., S.M.V.d.W., G.P.), Julius Center of Health Sciences and Primary Care (H.M.D.R., M.L.B.), and Departments of Vascular Surgery (J.E.P.V., G.J.D.B., F.L.M.) and Pathology (A.V.), University Medical Center, Utrecht, the Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands (J.E.P.V., D.P.V.d.K.); Department of Surgery and Cardiovascular Research Institute, National University (NU) & National University Hospital (NUH), Singapore (D.P.V.d.K.); and Department of Vascular Surgery, St Antonius Hospital, Nieuwegein, the Netherlands (J.-P.P.M.D.V.).
authors.forename: Joyce E P
authors.initials: JE
authors.lastname: Vrijenhoek
authors.forename: Hester M
authors.initials: HM
authors.lastname: Den Ruijter
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: De Borst
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Jean-Paul P M
authors.initials: JP
authors.lastname: De Vries
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.forename: Sander M
authors.initials: SM
authors.lastname: Van de Weg
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000453:epidemiology* / Q000473:pathology / Q000601:surgery; D016893:Carotid Stenosis / Q000453:epidemiology* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D016894:Endarterectomy, Carotid; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000453:epidemiology* / Q000473:pathology / Q000601:surgery; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D012737:Sex Factors
keywords: atherosclerosis; carotid artery plaque; endarterectomy, carotid; epidemiology; prognosis; sex