Combined effect of menopause and cardiovascular risk factors on death and cardiovascular disease: a cohort study

BACKGROUND: Observational studies suggest that early menopause is associated with increased risk of death and cardiovascular disease (CVD); however, the results of these studies have been inconsistently. We aimed to assess the association of menopause with death and CVD and whether this association was modified by cardiovascular risk factors. METHODS: The study population was women age 35–64 years living in two communities of Beijing who were enrolled in the Chinese Multi-provincial Cohort Study in 1992. Participants were followed until first cardiovascular event, death, or the end of follow-up (2018). Self-reported age at menopause was recorded. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of death and CVD after adjusting for baseline covariates of age, family history of CVD, and white blood cell count, as well as time-varying covariates of menopause, use of oral estrogen, and conventional risk factors. Additionally, we assessed the combined effect of age at menopause and risk factors on the primary endpoint. RESULTS: Of 2104 eligible women, 124 died and 196 had a first CVD event (33 fatal CVD and 163 non-fatal CVD). Compared with women who experienced menopause at age 50–51 years, the risk of death was higher in women with menopause at age 45–49 years (HR 1.99, 95% CI 1.24–3.21; P = 0.005), and the risk of ischemic stroke was higher in women with menopause at age < 45 years (HR 2.16, 95% CI 1.04–4.51; P = 0.04) and at age 45–49 years (HR 2.05, 95% CI 1.15–3.63; P = 0.01). Women who had menopause before age 50 years and at least one elevated risk factor at baseline had a higher risk of death (HR 11.10, 95% CI 1.51–81.41; P = 0.02), CVD (HR 3.98, 95% CI 1.58–10.01; P = 0.003), ischemic CVD (HR 4.53, 95% CI 1.63–12.62; P = 0.004), coronary heart disease (HR 8.63, 95% CI 1.15–64.50; P = 0.04), and stroke (HR 2.92, 95% CI 1.03–8.29; P = 0.04) than those with menopause at age 50–51 years and optimal levels of all risk factors. CONCLUSIONS: Earlier menopause may predict death and ischemic stroke. Furthermore, there is a combined effect of earlier menopause and elevated risk factors on death and CVD.