Premenopausal cardiovascular disease and age at natural menopause: a pooled analysis of over 170,000 women

The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the city of Rotterdam, The Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. The study focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1700 research articles and reports. This article provides an update on the rationale and design of the study. It also presents a summary of the major findings from the preceding 3 years and outlines developments for the coming period.

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“…For additional EJE references please see [142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157][158][159][160].…”

Section: Main Results In the Last 3 Yearsunclassified

Objectives, design and main findings until 2020 from the Rotterdam Study

et al. 2020

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“…In addition to confounding, reverse causation can also play a role in explaining the contradictory findings. Conditions such as hypertension, coronary heart diseases, and stroke can be related to menopause onset [ 10 ]. A physiological explanation for the effect of hypertension is the possible decline in ovarian blood flow, which could lead to follicle loss and substantial decrease in ovarian reserve with the acceleration of the onset of menopause [ 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the results of the association between age at menopause and BP traits are not consistent across studies [ 6 , 8 , 9 ], and causal association of age at menopause with BP has not been clarified [ 6 ]. Further, the association between early menopause and cardiovascular disease is independent of BP, suggesting other pathways (e.g., reverse causation) could explain the association [ 5 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study

Roa‐Díaz

Asllanaj

Amin

et al. 2021

JCM

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Observational studies suggest that early onset of menopause is associated with increased risk of hypertension. Whether this association is causal or due to residual confounding and/or reverse causation remains undetermined. We aimed to evaluate the observational and causal association between age at natural menopause (ANM) and blood pressure traits in Caucasian women. A cross-sectional and one-sample Mendelian randomization (MR) study was conducted in 4451 postmenopausal women from the CoLaus and Rotterdam studies. Regression models were built with observational data to study the associations of ANM with systolic and diastolic blood pressure (SBP/DBP) and hypertension. One-sample MR analysis was performed by calculating a genetic risk score of 54 ANM-related variants, previously identified in a genome-wide association study (GWAS) on ANM. In the two-sample MR analysis we used the estimates from the ANM-GWAS and association estimates from 168,575 women of the UK Biobank to evaluate ANM-related variants and their causal association with SBP and DBP. Pooled analysis from both cohorts showed that a one-year delay in menopause onset was associated with 2% (95% CI 0; 4) increased odds of having hypertension, and that early menopause was associated with lower DBP (β = −1.31, 95% CI −2.43; −0.18). While one-sample MR did not show a causal association between ANM and blood pressure traits, the two-sample MR showed a positive causal association of ANM with SBP; the last was driven by genes related to DNA damage repair. The present study does not support the hypothesis that early onset of menopause is associated with higher blood pressure. Our results suggest different ANM-related genetic pathways could differently impact blood pressure.

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“… 10 That is, women with a CVD event before age 35 are more likely to have an ANM less than 45 years. 10 It is also possible that women who undergo surgical menopause may have other concurrent CVD risk factors including hypertension, diabetes, high cholesterol, and obesity. 3 , 11 , 12 The objective of our study is to estimate the 10-year CVD risk Framingham Risk Score according to menopausal type, natural versus surgical, and natural menopausal timing in women without prior known CVD from the Canadian Longitudinal Study on Aging.…”

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confidence: 99%

Early and surgical menopause associated with higher Framingham Risk Scores for cardiovascular disease in the Canadian Longitudinal Study on Aging

et al. 2021

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Objective: In women, the risk of cardiovascular disease (CVD) is higher in the postmenopausal period. The effect that menopausal type, natural versus surgical, or the age at natural menopause has on CVD needs further investigation. To this end, we assessed the association between menopausal type and timing and the 10-year office-based Framingham Risk Score (FRS) in women from the Canadian Longitudinal Study on Aging. Methods: We included women aged 45 to 85 years from the Canadian Longitudinal Study on Aging Comprehensive cohort of seven Canadian provinces who were menopausal at the time of recruitment and had no prior CVD. Poisson regressions were used to evaluate the association between menopausal characteristics and the FRS. Natural menopause was defined as the cessation of menstrual periods for at least 1 year in women with no history of hysterectomy. Surgical menopause was defined as hysterectomy with or without oophorectomy prior to natural menopause. As main covariates, we examined age, education, province of residency, and hormone therapy. Results: A total of 10,090 women (8,200 natural menopausal and 1,890 surgical menopausal) were eligible for the study. In the multivariable model, surgical menopause was associated with a higher mean FRS compared with natural menopause (CVD risk 12.4% vs 10.8%, P < 0.001). Compared with women with age at natural menopause from 50 to 54 years (CVD risk 10.2%), natural menopause before age 40, 40 to 44, or 45 to 49 had a higher CVD risk (12.2%, 11.4%, and 10.6%, respectively, P < 0.001). Conclusions: Our study supports an association between menopausal type and timing on CVD risk prediction and highlights the need to be judicious about surgical menopause. Preventative interventions for CVD should be considered in surgical menopausal women and women with an age at natural menopause less than 45 years. Video Summary: .

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Premenopausal cardiovascular disease and age at natural menopause: a pooled analysis of over 170,000 women

Cited by 54 publications

References 48 publications

Objectives, design and main findings until 2020 from the Rotterdam Study

Objectives, design and main findings until 2020 from the Rotterdam Study

Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study

Early and surgical menopause associated with higher Framingham Risk Scores for cardiovascular disease in the Canadian Longitudinal Study on Aging

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