title: High level of plasma estradiol as a new predictor of ischemic arterial disease in older postmenopausal women: the three-city cohort study.
abstract: BACKGROUND
  Despite evidence that estrogens may be involved in atherothrombosis, the role of endogenous sex steroid hormones in ischemic arterial disease among postmenopausal women remains uncertain.
  
  
  RESULTS
  In the Three-City prospective cohort study of subjects (n=9294) >65 years of age, we investigated the association of total 17β-estradiol, bioavailable 17β-estradiol, and total testosterone with the 4-year incidence of ischemic arterial disease among postmenopausal women who did not use any hormone therapy. We designed a case-cohort study including a random sample of 537 subjects and 106 incident cases of first cardiovascular events. Weighted Cox proportional-hazards models with age as the time scale were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for ischemic arterial disease by a 1-standard deviation increase in sex steroid hormones. In univariate analysis, HR of ischemic arterial disease was positively and significantly associated with both total and bioavailable estradiol levels. These associations remained significant after adjustment for traditional cardiovascular risk factors, including body mass index, diabetes, hypercholesterolemia, hypertension, and smoking status (HR: 1.42, 95% CI: 1.12-1.79, P<0.01; and HR: 1.42, 95% CI: 1.12-1.78, P<0.01, respectively). Separate analysis for coronary heart disease yielded similar results (adjusted HR: 1.49, 95% CI: 1.10-2.02, P=0.01; and adjusted HR: 1.50, 95% CI: 1.11-2.04, P<0.01, respectively), and a borderline significant trend was observed for ischemic stroke (HR: 1.34, 95% CI: 0.95-1.89, P=0.08; and HR: 1.32, 95% CI: 0.94-1.84, P=0.11, respectively). By contrast, no significant association was found between total testosterone and ischemic arterial disease in both univariate and adjusted analyses.
  
  
  CONCLUSIONS
  High plasma level of endogenous estradiol emerges as a new predictor of ischemic arterial disease in older postmenopausal women. (J Am Heart Assoc. 2012;1:e001388 doi: 10.1161/JAHA.112.001388.).
authors.affiliation: Centre for Research in Epidemiology and Population Health, Inserm Unit 1018, Hormones and Cardiovascular Disease,  Villejuif, France (V.S., M.C., G.P.-B., P.-Y.S.) ; Université Paris-Sud, UMR-S 1018,  Villejuif, France (V.S., M.C., P.D., P.-Y.S.).
authors.forename: Valérie
authors.initials: V
authors.lastname: Scarabin-Carré
authors.forename: Marianne
authors.initials: M
authors.lastname: Canonico
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brailly-Tabard
authors.forename: Séverine
authors.initials: S
authors.lastname: Trabado
authors.forename: Pierre
authors.initials: P
authors.lastname: Ducimetière
authors.forename: Maurice
authors.initials: M
authors.lastname: Giroud
authors.forename: Joanne
authors.initials: J
authors.lastname: Ryan
authors.forename: Catherine
authors.initials: C
authors.lastname: Helmer
authors.forename: Geneviève
authors.initials: G
authors.lastname: Plu-Bureau
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Scarabin
keywords: cardiovascular diseases; hormones; risk factors; women