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

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

Impact of cyclooxygenase inhibitors in the Women's Health Initiative hormone trials: secondary analysis of a randomized trial.

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results

Maternal hypertension after a low-birth-weight delivery differs by race/ethnicity: Evidence from the National Health and Nutrition Examination Survey (NHANES) 1999-2006

Studies have suggested an increase in maternal morbidity and mortality due to cardiovascular diseases in women with a prior low-birth-weight (LBW, <2,500 grams) delivery. This study evaluated blood pressure and hypertension in women who reported a prior preterm or small-for-gestational-age (SGA) LBW delivery in the National Health and Nutrition Examination Survey 1999-2006 (n = 6,307). This study also aimed to explore if race/ethnicity, menopause status, and years since last pregnancy modified the above associations. A total of 3,239 white, 1,350 black, and 1,718 Hispanics were assessed. Linear regression models were used to evaluate blood pressure by birth characteristics (preterm-LBW, SGA-LBW, and birthweight ≥2,500). Logistic regression models estimated the odds ratios (OR) of hypertension among women who reported a preterm-LBW or SGA-LBW delivery compared with women who reported an infant with birthweight ≥2,500 at delivery. Overall, there was a positive association between a preterm-LBW delivery and hypertension (adjusted OR = 1.39, 95% confidence interval (CI) 1.02-1.90). Prior SGA-LBW also increased the odds of hypertension, but the estimate did not reach statistical significance (adjusted OR = 1.21, 95% CI 0.76-1.92). Race/ethnicity modified the above associations. Only black women had increased risk of hypertension following SGA-LBW delivery (adjusted OR = 2.09, 95% CI 1.12-3.90). Black women were at marginally increased risk of hypertension after delivery of a preterm-LBW (adjusted OR = 1.49, 95% CI 0.93-2.38). Whites and Hispanics had increased, but not statistically significant, risk of hypertension after a preterm-LBW (whites: adjusted OR = 1.39, 95% CI 0.92-2.10; Hispanics: adjusted OR = 1.22, 95% CI 0.62-2.38). Stratified analysis indicated that the associations were stronger among women who were premenopausal and whose last pregnancy were more recent. The current study suggests that in a representative United States population, women with a history of preterm- or SGA-LBW deliveries have increased odds of hypertension and this risk appears to be higher for black women and younger women. © 2014 Xu et al