Coronary Artery Calcification (CAC) and post-trial cardiovascular events and mortality within the Women's Health Initiative (WHI) estrogen-alone trial

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 ageadjusted 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.