Premature Menopause and Lifetime Risk of Coronary Heart Disease

Importance Premature onset of menopause is associated with increased short-term risk of coronary heart disease (CHD), but the associated long-term CHD risk and whether this differs by self-identified race are not known. Objective To calculate lifetime risk estimates of incident CHD and to estimate years lived free of and with CHD by premature menopause status stratified by self-identified race. Design, Setting, and Participants This prospective population-based cohort study was conducted with 163 600 person-years of follow-up, from 1964 to 2018. Individual-level data from postmenopausal women (aged 55-69 years) who self-identified their race as Black or White across 6 US cohorts were included. All participants were free of CHD at baseline and had data on menopausal status and CHD outcomes. Individuals who self-reported surgically induced menopause were excluded. Exposure Premature onset of natural menopause (age <40 years). Main Outcome and Measures The primary outcome was CHD (fatal and nonfatal myocardial infarction). The following analyses were performed: (1) modified Kaplan-Meier analysis to estimate lifetime risks, (2) adjusted competing Cox models to estimate joint cumulative risks for CHD or non-CHD death, and (3) Irwin restricted mean survival time to estimate mean years lived free of CHD and with CHD. Results Of the 3522 Black women and 6514 White women included, mean (SD) age at baseline was 61.2 (4.3) years and 60.0 (4.4) years, respectively. Premature natural menopause occurred more frequently in Black women (545 [15.5%]) compared with White women (313 [4.8%]). Premature menopause was associated with a higher lifetime risk of incident CHD, with hazard ratios of 1.41 (95% CI, 1.04-1.90) for Black women and 1.39 (95% CI, 1.03-1.87) for White women. Mean years lived free of CHD were 18.2 years (95% CI, 17.5-18.9) for Black women with premature menopause compared to 19.1 years (95% CI, 18.8-19.4) for Black women without premature menopause; a similar pattern was seen in White women with and without premature menopause, but neither met statistical significance. Conclusions and Relevance In this cohort study, premature menopause was associated with 40% higher lifetime risk of CHD in Black and White women. This suggests that premature onset of menopause is an important risk-enhancing factor for lifetime risk and should be routinely assessed in clinical practice to consider intensification of preventive efforts.