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Objectives: We examined whether the association between hormone therapy (HT) use and coronary heart disease (CHD) risk differed between women with and without vasomotor symptoms (VMS)., Study Design: We used data from a Dutch (EPOS) and Swedish (WHILA) population-based sample of 8865 women, aged 46-64 years, and free of CHD, stroke, venous thrombosis/pulmonary embolism or cancer at baseline. Data on HT use, VMS and potential confounders were collected by questionnaires., Main Outcome Measures: CHD endpoints, obtained via registries., Results: 252 CHD cases occurred during 10.3 years of follow-up. Neither for women with nor for women without flushing or (night) sweats ever HT use was associated with CHD risk, compared with never HT use. Among women with intense VMS, ever HT use borderline significantly decreased CHD risk compared with never HT use (HR 0.48 [95% CI 0.20-1.03]). Among women without intense VMS, ever HT use was associated with a borderline significant increased CHD risk (HR 1.28 [95% CI 0.96-1.70]; P for interaction=0.02). However, after multivariate adjustment, as compared to never HT use, ever HT use was not associated with risk of CHD among women with or without intense VMS., Conclusions: In both groups of women with and without VMS, HT use does not seem to be associated with the risk of CHD. Hence, our findings do not support the view that HT use increases the CHD risk among women with an indication, i.e. VMS, but this needs to be confirmed in specifically designed studies., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Emerging evidence suggests that women with vasomotor menopausal symptoms (VMS) may have an adverse cardiovascular disease (CVD) risk profile. We investigated whether VMS are related to an increased risk of future coronary heart disease (CHD) and whether possible associations can be explained by CVD risk factors., Methods: Data used were from a Dutch and Swedish population-based sample of 10,787 women enrolled between 1995 and 2000, aged 46 to 64 years, and free of CVD at baseline. Data on VMS were collected by questionnaires. Body mass index and blood pressure were measured in all women, and total cholesterol levels were measured in a subgroup of the population. Multivariable Cox regression models were used to analyze the data., Results: After a mean ± SD follow-up period of 10.3 ± 2.1 years, 303 women were diagnosed with CHD. Symptoms of flushing were not associated with risk of CHD. However, the presence of night sweats was associated with a significantly modest increased risk of CHD, with a multivariable-adjusted hazard ratio of 1.33 (95% CI, 1.05-1.69). This association was attenuated but not eliminated after correction for body mass index, blood pressure, and total cholesterol (hazard ratio, 1.25; 95% CI, 0.99-1.58)., Conclusions: Women with menopausal symptoms of night sweats have a significantly moderately increased risk of CHD, which cannot be totally explained by the levels of CVD risk factors.

We conducted a genome-wide association study for age at natural menopause in 2,979 European women and identified six SNPs in three loci associated with age at natural menopause: chromosome 19q13.4 (rs1172822; -0.4 year per T allele (39%); P = 6.3 × 10(-11)), chromosome 20p12.3 (rs236114; +0.5 year per A allele (21%); P = 9.7 × 10(-11)) and chromosome 13q34 (rs7333181; +0.5 year per A allele (12%); P = 2.5 × 10(-8)). These common genetic variants regulate timing of ovarian aging, an important risk factor for breast cancer, osteoporosis and cardiovascular disease.

It has been hypothesized that women with vasomotor symptoms differ from those without with respect to cardiovascular risk factors or responses to exogenous hormone therapy. We studied whether the presence and extent of menopausal complaints are associated with cardiovascular risk profile. Data were used from a population-based sample of 5523 women, aged 46 to 57 years, enrolled between 1994 and 1995. Data on menopausal complaints and potential confounders were collected by questionnaires. Total cholesterol, systolic and diastolic blood pressures, and body mass index were measured. Linear and logistic regression analyses were used to analyze the data. Night sweats were reported by 38% and flushing by 39% of women. After multivariate adjustment, women with complaints of flushing had a 0.27-mmol/L (95% CI: 0.15 to 0.39) higher cholesterol level, a 0.60-kg/m(2) (95% CI: 0.35 to 0.84) higher BMI, a 1.59-mm Hg (95% CI: 0.52 to 2.67) higher systolic blood pressure, and a 1.09-mm Hg (95% CI: 0.48 to 1.69) higher diastolic blood pressure compared with asymptomatic women. Flushing was also associated with hypercholesterolemia (odds ratio: 1.52; 95% CI: 1.25 to 1.84) and hypertension (OR: 1.20; 95% CI: 1.07 to 1.34). Results were similar for complaints of night sweating. The findings support the view that menopausal complaints are associated with a less favorable cardiovascular risk profile. These findings substantiate the view that differences in the presence of menopausal symptoms as a reason for using hormone therapy could explain discrepant findings between observational research and trials.

During menopause, a sharp increase in cholesterol concentration occurs with an unexplained wide variation in change. Possibly, this is attributable to genetic variation. The authors prospectively studied the effect of the apolipoprotein E (APOE) genotype on the change in cholesterol level with menopause among 1116 Dutch women. Women with the APOE3E3 genotype were regarded as the reference category and changes were adjusted for age at baseline, years of follow-up, years since menopause, and body mass index. At baseline, the women were on average 50.4 years. After 5.9 years of follow-up, the women were on average 4.3 years (S.D. 1.5 years) postmenopausal. The mean increase in cholesterol with menopause in women with the APOE3E3 genotype was 0.67 mmol/L (95% CI, 0.61-0.72 mmol/L). In women with the APOE2E3 genotype the increase in cholesterol was 0.44 mmol/L (CI, 0.32-0.56 mmol/L). The increase in cholesterol in women with the APOE3E4 genotype did not differ from the increase in women with the APOE3E3 genotype. These results show that the increase in cholesterol level with menopause is 30% lower in women with the APOE2E3 genotype when compared with women with the APOE3E3 genotype, indicating that the APOE genotype contributes to the variation in cholesterol increase with menopause.

During menopause, a sharp increase in cholesterol concentration occurs with an unexplained wide variation in change. Possibly, this is attributable to genetic variation. The authors prospectively studied the effect of the apolipoprotein E (APOE) genotype on the change in cholesterol level with menopause among 1116 Dutch women. Women with the APOE3E3 genotype were regarded as the reference category and changes were adjusted for age at baseline, years of follow-up, years since menopause, and body mass index. At baseline, the women were on average 50.4 years. After 5.9 years of follow-up, the women were on average 4.3 years (S.D. 1.5 years) postmenopausal. The mean increase in cholesterol with menopause in women with the APOE3E3 genotype was 0.67 mmol/L (95% CI, 0.61–0.72 mmol/L). In women with the APOE2E3 genotype the increase in cholesterol was 0.44 mmol/L (CI, 0.32–0.56 mmol/L). The increase in cholesterol in women with the APOE3E4 genotype did not differ from the increase in women with the APOE3E3 genotype. These results show that the increase in cholesterol level with menopause is 30% lower in women with the APOE2E3 genotype when compared with women with the APOE3E3 genotype, indicating that the APOE genotype contributes to the variation in cholesterol increase with menopause. [Copyright &y& Elsevier]