Relationships of coronary heart disease with 27-hydroxycholesterol, low-density lipoprotein cholesterol, and menopausal hormone therapy.
ABSTRACT 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: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
- SourceAvailable from: Anita Hardon[Show abstract] [Hide abstract]
ABSTRACT: There is increasing evidence that outcomes of health care differ by patient characteristics, such as gender and ethnicity. If evidence-based medicine is to improve quality of care for all patients, it is essential to take this diversity into account when designing clinical studies. So far, this notion has mainly been translated into recommendations for including minority populations in trials. We argue that a more comprehensive view of the production of diversity-sensitive clinical evidence is needed, one that takes heterogeneity as a starting point in research. We call for a mix of methodological approaches aimed at identifying diversity issues that matter and analysing the impact of these diversities on clinical outcomes. Institutional changes are necessary to support this methodological reform.Trials 06/2013; 14(1):177. · 2.12 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Menopausal hormone therapy (HT) continues to have a clinical role in symptom management, but identifying women for whom benefits will outweigh the risks remains a challenge. Although hormone therapy (HT) is the most effective strategy for ameliorating vasomotor and other symptoms, randomized clinical trials show an unfavorable balance of benefits and risks for many women. However, closer examination of data from these trials suggests that it may be possible to classify women as better or worse candidates for HT by using individual risk stratification. Data from 2 landmark trials-the Women's Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS)-suggest an important role for clinical characteristics, serum biomarkers, genomic markers, and gene-environment interactions in developing a personalized approach to the prediction of risk for cardiovascular disease (CVD) events for women while on HT. The available data suggest several characteristics of women who are optimal candidates for HT use: younger age (<60 years), recent onset of menopause (<10 years), favorable lipid profile (LDL cholesterol <130 mg/dL or LDL/HDL cholesterol ratio <2.5), absence of metabolic syndrome, and absence of factor V Leiden genotype. The identification of other characteristics is an area of active investigation. In addition, women at high risk for venous thromboembolism should avoid systemic HT or choose a transdermal rather than oral delivery route. Personalized medicine-i.e., the use of the specific biological profile of an individual to guide the choice of treatment-is highly relevant for clinical decision-making regarding HT and offers promise for improved treatment efficacy and safety.Clinical Chemistry 01/2014; 60(1):68-77. · 7.77 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: There is clear evidence of the effects of sex and age on the prevalence of cardiovascular disease. We investigated the interactions of dietary omega (n)-3 polyunsaturated fatty acids (PUFA), sex, and age on plasma lipids and lipoproteins in the offspring of C57BL/6 mice exposed to high, medium, or low n-3 PUFA at weaning and 16 weeks postweaning. There was an increase in plasma triglycerides from weaning to 16 weeks in male and female offspring; however, the high n-3 PUFA group showed a reduction in triglycerides in both sexes at 16 weeks. High n-3 PUFA caused an increase in plasma LDL-cholesterol from weaning to 16 weeks in male offspring; however, the LDL particle size was significantly larger in the high n-3 PUFA group. Plasma from male mice showed higher cholesterol efflux compared to females; high n-3 PUFA increased cholesterol efflux. Thus the effects of n-3 PUFA are age and sex dependent.Prostaglandins Leukotrienes and Essential Fatty Acids 06/2014; · 1.98 Impact Factor