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

Abstract

BackgroundAmong 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 ResultsWHI‐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.ConclusionsAmong 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 RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Racial Differences in the Effects of Hormone Therapy on Incident Open-Angle Glaucoma in a Randomized Trial

“…18 Similarly, breast cancer, cardiovascular disease, Alzheimer disease, and other WHI outcomes differed by CEE vs CEE þ MPA, with more favorable outcomes with CEE alone. 45 Consistent with other studies in the WHI and the claims database, the present study demonstrated the protective effect of CEE alone (oral CEE, 0.625 mg/day) in hysterectomized women, but not CEE þ MPA in women with a uterus. Whether the benefits of CEE alone generalize to women with a uterus is therefore unknown.…”

Blood Pressure Patterns and Subsequent Coronary Artery Calcification in Women Who Delivered Preterm Births

“…Recent evidence indicates that presence of any CAC, including those with low scores as we include here, is linked to coronary heart disease events and death. 31,32 Indeed, some have called for the inclusion of CAC screening to stratify women and men for treatment. 33 Our results raise important questions about how pregnancy history may help inform CVD screening and treatment guidelines for women.…”

<p>Resveratrol attenuates hydrogen peroxide-induced aging through upregulation of autophagy in human umbilical vein endothelial cells</p>

“…More recently, we reported that estrogen can resist oxidative stress, protect endothelial function, and delay cellular aging 10. Several studies have also suggested the cardioprotective effects of estrogen, and its potential for the treatment of coronary heart disease 11,12. However, the long-term use of estrogen might pose serious health risks, including increasing the risk of cancer or thromboembolic disease,13,14 thereby limiting its clinical application.…”