title: Gender and the extent of coronary atherosclerosis, plaque composition, and clinical outcomes in acute coronary syndromes.
abstract: OBJECTIVE
  This study sought to assess the extent and composition of atherosclerosis contributing to acute coronary syndrome events in women compared with men.
  
  
  BACKGROUND
  Pathological studies suggest that plaque composition and burden may differ by sex. It is unclear whether sex impacts the extent, characteristics, and potential vulnerability of coronary plaques.
  
  
  METHODS
  A total of 697 patients (24% women) with acute coronary syndromes were enrolled in the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Three-vessel multimodality intracoronary imaging (quantitative coronary angiography, grayscale, and radiofrequency intravascular ultrasound [IVUS]) was performed after treatment of the culprit lesion(s). Events during a median 3.4-year follow-up were ascribed to recurrent culprit versus untreated nonculprit lesions. The authors performed a post hoc, sex-based subgroup analysis.
  
  
  RESULTS
  Women were older and had more comorbid disease than men. By angiography, women had a similar number of angiographic culprit (p = 0.53) but fewer nonculprit (p = 0.05) lesions, and fewer vessels with nonculprit lesions (p = 0.048) compared with men even after multivariable adjustment (p = 0.002). By IVUS, women had fewer nonculprit lesions (p = 0.002), but similar plaque burden (PB) per lesion (55.6% vs. 55.3%; p = 0.35), and female sex was not predictive of severe (> 70%) PB (p = 0.052). Plaque rupture was less common in women (6.6% vs. 16.3%; p = 0.002) even after adjusting for comorbidities (p = 0.004), as was the total necrotic core volume (p < 0.0001). The frequency of other plaque phenotypes was similar for men and women including pathological intimal thickening, thin-cap fibroatheromas (TCFA), and thick-cap fibroatheromas. Rates of major adverse cardiovascular events attributed to culprit and nonculprit lesions at 1-, 2-, and 3-year follow-up were not significantly different between men and women, although women were rehospitalized more frequently due to culprit lesion-related angina. For men, nonculprit lesion minimal lumen area ≤ 4.0 mm(2), PB ≥70%, and TCFA predicted nonculprit MACE at 3 years, whereas for women, only TCFA and PB were predictive.
  
  
  CONCLUSIONS
  The PROSPECT study validates that despite having more comorbid risk factors than men, women have less extensive coronary artery disease by both angiographic and IVUS measures, and that lesions in women compared with men have less plaque rupture, less necrotic core and calcium, similar plaque burden, and smaller lumens. TCFA may also be a stronger marker of plaque vulnerability in women than men.
authors.affiliation: Yale University Medical Center, Division of Cardiology, New Haven, Connecticut, USA. alexandra.lansky@yale.edu
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Lansky
authors.forename: Vivian G
authors.initials: VG
authors.lastname: Ng
authors.forename: Akiko
authors.initials: A
authors.lastname: Maehara
authors.forename: Giora
authors.initials: G
authors.lastname: Weisz
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Gary S
authors.initials: GS
authors.lastname: Mintz
authors.forename: Bernard
authors.initials: B
authors.lastname: De Bruyne
authors.forename: Naim
authors.initials: N
authors.lastname: Farhat
authors.forename: Gary
authors.initials: G
authors.lastname: Niess
authors.forename: Ivana
authors.initials: I
authors.lastname: Jankovic
authors.forename: Dana
authors.initials: D
authors.lastname: Lazar
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Martin
authors.initials: M
authors.lastname: Fahy
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D000368:Aged; D000789:Angina, Unstable / Q000401:mortality; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000401:mortality; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D023921:Coronary Stenosis / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D005060:Europe / Q000453:epidemiology; D005260:Female; D005355:Fibrosis; D006323:Heart Arrest / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000401:mortality; D009336:Necrosis; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D014481:United States / Q000453:epidemiology; D061205:Vascular Calcification / Q000175:diagnosis