title: Extremes of an aromatase index predict increased 25-year risk of cardiovascular mortality in older women.
abstract: BACKGROUND
  Peripheral conversion of androgens to oestrogens via aromatase is the primary source of oestrogen in postmenopausal women and may play a role in cardiovascular health.
  
  
  METHODS
  Prospective. PARTICIPANTS, MEASUREMENTS: The association of an index of aromatase activity (AROM), the serum oestrone-to-androstenedione ratio, with 25-year cardiovascular disease (CVD) mortality was examined in 819 postmenopausal non-oestrogen using women (mean age at baseline = 72).
  
  
  RESULTS
  Overall, 247 deaths were attributed to CVD. The median AROM value was 60 (95% range 17-129). AROM was positively correlated with age (r = 0·28) and body mass index (BMI) (r = 0·22) (P < 0·001). The age-adjusted risk for CVD mortality was significantly elevated for women in the lowest (HR = 2·01, 95% CI 1·31-3·12) and highest (HR = 1·51, 95%CI 1·02-2·22) quintiles of AROM, compared with the middle quintile. This U-shaped association persisted after additional adjustment for BMI, waist-to-hip ratio, exercise, smoking, alcohol use and traditional CVD risk factor covariates. There was a significant interaction of AROM and BMI (P = 0·001), such that high AROM was associated with a 63% reduction in risk of CVD death for women with low BMI (<22 kg/m(2) ), but with 2·1- to 2·5-fold increased risk in women with mid-range (22-<25 kg/m(2) ) and high (≥25 kg/m(2) ) BMI. Oestradiol did not influence AROM associations and was not independently related to CVD death.
  
  
  CONCLUSIONS
  These results suggest that aromatase is a novel endocrine factor predictive of CVD mortality among postmenopausal women. If confirmed, additional studies are needed to determine whether extremes of aromatase reflect genetic influences or underlying disease processes.
authors: Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA 92093, USA. glaughlin@ucsd.edu
authors: Gail A
authors: GA
authors: Laughlin
authors: Joachim H
authors: JH
authors: Ix
authors: Kevin
authors: K
authors: Cummins
authors: Matthew A
authors: MA
authors: Allison
authors: Lori B
authors: LB
authors: Daniels
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000735:Androstenedione / Q000097:blood; D001141:Aromatase / Q000097:blood*; D002140:California / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000097:blood / Q000201:enzymology* / Q000401:mortality*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D004970:Estrone; D000735:Androstenedione; D001141:Aromatase