Relationships of Coronary Heart Disease With 27-Hydroxycholesterol, Low-Density Lipoprotein Cholesterol, and Menopausal Hormone Therapy

National Heart, Lung, and Blood Institute, Rockledge 2 Bldg, Room 9192, Bethesda, MD 20892. .
Circulation (Impact Factor: 14.43). 08/2012; 126(13):1577-86. DOI: 10.1161/CIRCULATIONAHA.112.103218
Source: PubMed


Menopausal hormone therapy (MHT) increases the risk of coronary heart disease (CHD) in older women with elevated low-density lipoprotein (LDLC) levels. The endogenous estrogen receptor antagonist 27-hydroxycholesterol (27OHC) is correlated with LDLC levels and may block the beneficial effects of estrogen on the cardiovascular system.
We conducted a nested case-control study in the Women's Health Initiative trials of 350 CHD cases and 813 matched controls to explore potential mediation by 27OHC of the dependence of the CHD risk elevation with MHT on LDLC. Baseline levels of 27OHC were not associated with CHD risk when LDLC was included in the multivariable models. The odds ratio for CHD associated with increased LDLC was 1.15 (95% confidence interval, 1.08-1.23) and was unchanged at 1.14 (95% confidence interval, 1.07-1.22) when 27OHC was added to the model. Baseline 27OHC did not interact with MHT on CHD risk (P=0.81). In contrast, LDLC levels modified the effect of MHT on CHD risk (P for interaction=0.02), and adding 27OHC did not affect this result. With the use of log scales, the effect of MHT on CHD increased linearly with increasing level of baseline LDLC, with a transition from no risk to increased risk at ≈3.36 mmol/L (130 mg/dL).
This study found that 27OHC does not independently increase the risk of CHD, does not modify the increased risk of CHD resulting from MHT, and does not mediate the interaction of LDLC with MHT. Measuring blood lipids may aid in counseling individual women about initiating MHT and cardiovascular risk mitigation.
URL: Unique identifier: NCT00000611.

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Available from: Charles Eaton, Nov 22, 2015
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    • "If the effect of the intervention under study is hypothesized to differ between subgroups, such as the hypothesis that the preventive effect of aspirin differs between men and women, there are two options. First, new RCTs can be designed that specifically test treatment effects in relevant subgroups, as was done in the Women’s Health Initiative, which critically examined the existing evidence on the preventive effects of hormone replacement therapy on cardiovascular disease [20]. A second option is to enlarge the original trial with sufficient members from each subgroup, so that the potential differential effect - called effect modification in epidemiological terms - can be studied. "
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