Extremes of an aromatase index predict increased 25-year risk of cardiovascular mortality in older women

Clin Endocrinol (Oxf). 2012 Sep;77(3):391-8. doi: 10.1111/j.1365-2265.2011.04287.x.

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.

Design: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenedione / blood
  • Aromatase / blood*
  • California / epidemiology
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / enzymology*
  • Cardiovascular Diseases / mortality*
  • Estrone / blood
  • Female
  • Humans
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Time Factors

Substances

  • Estrone
  • Androstenedione
  • Aromatase