Causal and observational evidence on the role of early menopause in hypertension

Abstract Introduction Blood pressure has been suggested as potential factor contributing to the increased risk of cardiovascular disease observed in women experiencing early menopause (<45 years). However, whether the association between early menopause and hypertension is causal remains unclear (1,2). Purpose To evaluate the observational and causal association between age at natural menopause (ANM) and blood pressure (BP) traits in Caucasian women. Methods Cross-sectional and one-sample Mendelian randomization (MR) study was conducted in 4451 postmenopausal women from two different cohort studies. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg, and/or diastolic BP (DBP) ≥90 mmHg, and/or the use of antihypertensive medication. Multivariable linear and logistic regressions were implemented in the observational analysis. We calculated a weighted genetic risk score with 54 variants associated with ANM (GRS-ANM) (3). The genetic variants were previously identified in a genome wide association study (4), after that we implemented two-stage least squares in the one-sample MR. Estimates from all cohorts were pooled through meta-analysis Results The pooled analysis across cohorts showed early menopause, compared to menopause between 50–54 years, to be associated with lower DBP (β=−1.31 mmHg, 95% CI: −2.43; −0.18), while no association was found between other ANM categories and DBP. Similarly, the pooled analysis of both cohorts did not show an association of ANM with SBP, neither as a continuous variable nor by category. One year of later onset of menopause was associated with higher odds of developing hypertension (Odds ratio (OR): 1.02, 95% CI: 1:00; 1.04) while no association was found for the ANM categories and hypertension (Table 1). Results of the evaluation of MR assumption, supported their compliance, the GRS-ANM was associated with observed ANM and explained between 1.4% and 3.4% of the ANM variance in the included cohorts, F statistic values were among 11.15 and 40.63 (Figure 1). We found no association between GRS-ANM and SBP, DBP or hypertension (Table 1). Conclusion The present study does not support the hypothesis that early onset of menopause is associated with higher BP. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The CoLaus study was and is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 33CSCO-122661, 33CS30-139468 and 33CS30-148401).Zayne M. Roa-Díaz has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 801076, through the SSPH+ Global PhD Fellowship Programme in Public Health Sciences (GlobalP3HS) of the Swiss School of Public Health.