Estrogen Therapy and Coronary-Artery Calcification

Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
New England Journal of Medicine (Impact Factor: 55.87). 07/2007; 356(25):2591-602. DOI: 10.1056/NEJMoa071513
Source: PubMed


BACKGROUND: Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.
METHODS: In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status.
RESULTS: The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P

12 Reads
  • Source
    • "If E2 protects the kidney from diabetic damage by interfering with TGF-β1 signaling, an obvious extension of these studies would be to administer E2 to diabetic patients, to prevent or ameliorate diabetic kidney damage. Since exogenous estrogen’s protection against the development and progression of cardiovascular disease has been questioned,91–94 a clear answer to the possible protective role of E2 on kidney function should come from large-scale, randomized trials (which are not planned, so far). There are several theoretical limitations within the concept that E2 might be directly responsible for the observed sex difference in diabetic nephropathy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes mellitus is the major cause of end stage renal disease (ESRD). We cannot predict which patient will be affected. ESRD patients suffer an extremely high mortality rate, due to a very high incidence of cardiovascular disease. Several randomized, prospective studies have been conducted to quantify the impact of strict glycemic control on morbidity and mortality, and have consistently demonstrated an association between strict glycemic control and a reduction in ESRD. Within the past 20 years, despite the implementation of treatments that were presumed to be renoprotective, diabetes mellitus has continued to rank as the leading cause of ESRD, which clearly indicates that we are still far from understanding the mechanisms involved in the initiation of ESRD. Progressive albuminuria has been considered as the sine qua non of diabetic nephropathy, but we know now that progression to diabetic nephropathy may well happen in the absence of initial microalbuminuria. The search for new biomarkers of early kidney damage has received increasing interest, since early identification of the pathways leading to kidney damage may allow us to adopt measures to prevent the development of ESRD. Most of these biomarkers are deeply influenced by environment, genetics, sex differences, and so on, making it extremely difficult to identify the ideal biomarker to target. At present, there are no new drugs that come close to providing the solutions we desire for our patients (ie, reducing complications). Even when used in combination with standard care, renal complications are, at best, only modestly reduced, at the considerable expense of additional pill burden and exposure to serious off-target effects. In this review, some of the hypothesized mechanisms of this heterogeneous disease will be considered, with particular attention to the tubule-interstitial compartment.
    Full-text · Article · Mar 2014 · International Journal of Nephrology and Renovascular Disease
    • "The menopausal transition is associated with CVD [13] and hormone replacement therapy (HRT) in form of estrogen and progesterone application increases the risk of CVD [14]. But HRT has been reported to have an initially protective effect on the calcification of the coronary arteries [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Reproductive events may affect the onset of chronic diseases. We examined the possible association between reproductive parameters and intima media thickness (IMT) or carotid plaques in the common carotid artery in a population-based sample. This cross-sectional study analysed data of 800 postmenopausal women aged 50 to 81 years of the population-based KORA F4 study, conducted between 2006 and 2008 in Southern Germany. Reproductive parameters were obtained by standardised interviews. Age at menarche below 12 years compared to 12-15 years was significantly associated with carotid plaques (age-adjusted OR 2.23, 95% CI 1.13-4.43, p-value 0.018, multivariable adjusted 2.11, 1.05-4.26, 0.037), but not with IMT. Ever use of hormone replacement therapy was inversely associated with carotid plaques (age-adjusted 0.60, 0.44-0.81, p = 0.001, multivariable-adjusted 0.62, 0.45-0.86, 0.003) and IMT in the age-adjusted model (mean 0.89, 95% CI 0.88-0.90, p = 0.033) but not in the multivariable-adjusted model (mean 0.89, 95% CI 0.88-0.90, p = 0.075). Parity, age at menopause, time since menopause, duration of fertile period, current use of hormone replacement therapy, ever use of oral contraceptives, hysterectomy, bilateral oophorectomy, hot flashes and depressive mood in relation to the menopausal transition were not associated with carotid plaques or IMT. Our study showed, that there may be an independent association between the reproductive parameters age at menarche and ever use of hormone replacement therapy with carotid plaques in the common carotid artery, but not with IMT. Further research, especially in studies with prospective population-based study design, is necessary to assess in detail what events in women's life lead to increased IMT or CP.
    No preview · Article · Jan 2014 · BMC Women's Health
  • Source
    • "Duration of lactation has been associated with lower prevalence of the metabolic syndrome in midlife, making the BAC-lactation relationship somewhat paradoxical [70]. A significant inverse association has been reported between menopausal hormonal therapy and BAC in 4 studies [55, 71–73]. These data underscore a resemblance between BAC and coronary atherosclerosis, since increased duration of hormonal therapy has been shown to be associated with lower prevalence of CAC [74]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mammographically-detected breast arterial calcifications (BAC) are considered to be an incidental finding without clinical importance since they are not associated with increased risk of breast cancer. The goal of this article is to review existing evidence that the presence of BAC on mammography correlates with several (but not all) traditional cardiovascular disease (CVD) risk factors and with prevalent and incident CVD. Thus, BAC detected during routine mammography is a noteworthy finding that could be valuable in identifying asymptomatic women at increased future CVD risk that may be candidates for more aggressive management. In addition, there are notable differences in measures of subclinical atherosclerosis burden in women (ie, coronary artery calcification) by race/ethnic background, and the same appears to be true for BAC, although data are very limited. Another noteworthy limitation of prior research on BAC is the reliance on absence vs presence of BAC; no study to date has determined gradation of BAC. Further research is thus required to elucidate the role of BAC gradation in the prediction of CVD outcomes and to determine whether adding BAC gradation to prediction models based on traditional risk factors improves classification of CVD risk.
    Preview · Article · Apr 2013 · Current Cardiovascular Risk Reports
Show more