Abstract

Introduction: Cardiovascular disease (CVD) is the leading cause of death in women and early onset of menopause before the age of 40 years has been identified as a risk enhancer for future CVD events. Quantifying the magnitude of risk for premature CVD among women with early menopause may inform and guide the intensity of sex-specific preventive strategies. Methods: We included all women in the Coronary Artery Risk Development in Young Adults (CARDIA) study who attended a follow-up exam after the age of 40 years, had available data on menopausal status, and had not experienced premature CVD before 40 years. We performed multivariable Cox proportional hazards regression to examine the relationship between early onset of menopause defined as <40 years and incident CVD (coronary heart disease, peripheral arterial disease, stroke, and heart failure) prior to the age of 65 years. We performed Cox proportional hazards models and adjusted for risk factors levels at baseline: age, race, age at menarche, years of education, smoking status, body mass index, diabetes, hypertension, and total cholesterol: high-density lipoprotein ratio. Results: Among 2136 women with mean age of 43.0 (SD 3.0), 9.1% reported premature menopause before the age of 40 years (4.5% in white and 13.9% in black women). Over a median follow-up of 14.0 (IQR 11.5, 16.9) years, 81 premature CVD events occurred. Incidence rate (95% CI) of CVD was 6.46 (2.43, 17.22) and 1.41 (0.92, 2.17) per 1,000 per person-years for white women with and without early onset menopause, respectively; 4.94 (2.66, 9.16) and 3.92 (2.94, 5.24) per 1,000 person-years for black women with and without early onset menopause (FIGURE). Conclusions: In a population-based sample, white women with early onset of menopause had a 3-fold higher rate of premature CVD events, independent of perimenopausal risk factor levels. Interventions to intensify CVD prevention in at-risk women are needed following early onset of menopause.

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