Relationships of Coronary Heart Disease with 27-Hydroxycholesterol, Low Density Lipoprotein Cholesterol, and Menopausal Hormone Therapy
Background—Menopausal hormone therapy (MHT) increases 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 beneficial effects of estrogen on the cardiovascular system.
Methods and Results—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 (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. Using log scales the MHT effect on CHD increased linearly with increasing level of baseline LDLC, with a transition from no risk to increased risk at approximately 3.36 mmol/L (130 mg/dl).
Conclusions—27OHC does not independently increase risk of CHD, does not modify the increased risk of CHD due to 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.
Clinical Trial Registration Information—clinicaltrials.gov; Identifier: NCT00000611.
- acute coronary syndrome
- low-density lipoprotein (LDL)-cholesterol
- Received March 1, 2012.
- Accepted August 15, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited