Association of age at menopause with cardiovascular disease and mortality:insights from NHANES and a clinical cohort

BACKGROUND: Age at menopause is closely associated with cardiovascular disease and mortality, whereas the underlying mechanisms remain unclear. This study employed mediation analysis to explore potential pathways underlying this association. METHODS: Natural postmenopausal women were identified from the NHANES database to assess the association between age at menopause and cardiovascular disease and mortality. Mediation analysis was performed to identify potential mediators. A hospital-based cohort was used for a supportive analysis. RESULTS: Compared with women with menopause at 50-51 years, those with menopause before 40 years had a higher prevalence of cardiovascular disease and increased risks of all-cause and cardiovascular mortality. Dose-response analysis indicated that each one-year decrease in age at menopause was associated with 3%, 3%, and 4% increases in cardiovascular disease prevalence, all-cause mortality, and cardiovascular mortality, respectively. Mediation analysis showed that total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), hypertension, and glycated hemoglobin partially mediated the association between age at menopause and adverse outcomes. A hospital-based cohort study further supported these findings. CONCLUSION: Early menopause is significantly associated with higher cardiovascular disease prevalence, all-cause mortality, and cardiovascular mortality, and this association is partially mediated by metabolic dysregulation.