Coronary Artery Calcification (CAC) and Post-Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen-Alone Trial

J Am Heart Assoc. 2017 Oct 27;6(11):e006887. doi: 10.1161/JAHA.117.006887.

Abstract

Background: Among women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen-Alone (E-Alone) trial, randomization to conjugated equine estrogen-alone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI-CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post-trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors.

Methods and results: WHI-CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age-adjusted rates/1000 person-years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2-fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen-alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality.

Conclusions: Among a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E-Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen-alone versus placebo or CVD risk factors.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Keywords: cardiovascular disease; coronary artery calcification; hormonal therapy; mortality; women.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Chi-Square Distribution
  • Computed Tomography Angiography
  • Coronary Angiography / methods
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / epidemiology*
  • Coronary Artery Disease / mortality
  • Estrogen Replacement Therapy / adverse effects
  • Estrogen Replacement Therapy / methods*
  • Estrogen Replacement Therapy / mortality
  • Estrogens, Conjugated (USP) / administration & dosage*
  • Estrogens, Conjugated (USP) / adverse effects
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Multivariate Analysis
  • Postmenopause
  • Proportional Hazards Models
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / epidemiology*
  • Vascular Calcification / mortality
  • Women's Health*

Substances

  • Estrogens, Conjugated (USP)

Associated data

  • ClinicalTrials.gov/NCT00000611