Abstract 127: Premenopausal Cardiovascular Disease is Associated With Early Natural Menopause

Abstract

Introduction: Early menopause has been associated with an increased risk of cardiovascular disease (CVD), but few studies have examined the converse, i.e., whether CVD events that occurred before menopause were linked to early natural menopause. Methods: Pooled participant-level data (177 131 women) from nine studies that contributed to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) consortium were included. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of non-fatal premenopausal CVD events (including coronary heart disease (CHD) and stroke events) and age at natural menopause. Age at menopause was categorised as <45 (early), 45-49, 50-51(reference), 52-53 and ≥54 years. Age at onset of premenopausal CVD events was grouped as <35, 35-39 and ≥40 years. Women who experienced no premenopausal CVD event were used as the reference group. Results: Overall, there were 1561 (0.9%) non-fatal premenopausal CVD events (including 1130 CHD and 469 stroke events). The mean age at onset of premenopausal CVD was 41.3 years (standard deviation: 8.2 years, median 44.0 years). Compared with women without experiencing any premenopausal CVD events, women who experienced premenopausal CVD, CHD or stroke before age 35 years had 2-fold increased risk of experiencing early menopause (<45 years), with adjusted RRR (95%CI) of 1.92 (1.17, 3.14), 1.86 (1.01, 3.43), 2.17 (1.43, 3.30) respectively, whereas women with premenopausal CVD after age 40 years were more likely to experience normal menopause at age around 51 years. The associations remained after adjusting for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension status and family history of CVD. Conclusions: In conclusion, women with premenopausal CVD events that occurred before age 35 years had twice the risk of having early menopause. Shared genetic and environmental factors, as well as compromised vasculature after CVD events may play a role.