Early Menopause and Cardiovascular Disease Risk in Women With or Without Type 2 Diabetes: A Pooled Analysis of 9,374 Postmenopausal Women

Abstract

OBJECTIVE <p>Early menopause may be associated with higher cardiovascular disease (CVD) risk. Type 2 diabetes (T2DM), coupled with early menopause, may result in even greater CVD risk in women. We examined CVD risk in women with early compared to normal-age menopause, with and without T2DM overall and by race/ethnicity.</p> <p>RESEARCH DESIGN AND METHODS</p> <p>We pooled data from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. We included women with data on menopausal status, menopausal age, and T2DM, excluding pre- or peri-menopausal women, and those with prevalent CVD. Outcomes included incident coronary heart disease (CHD), stroke, heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD; CHD or stroke). We estimated the risk associated with early (<45 years) compared to normal-age menopause using Cox proportional hazards models. Covariates included age, race/ethnicity, education, body mass index, blood pressure, cholesterol, smoking, alcohol consumption, antihypertensive medication, lipid-lowering medication, hormone therapy use, and pregnancy history. </p> <p>RESULTS </p> <p>We included 9,374 postmenopausal women for a median follow-up of 15 years. We observed 1,068 CHD, 659 stroke, 1,412 HF and 1,567 ASCVD events. <a>T2DM significantly modified the effect of early menopause on CVD ris</a>k. Adjusted HRs for early menopause and the outcomes were greater in women with T2DM versus without (CHD 1.15, 1.00-1.33 vs 1.09, 1.03-1.15; stroke 1.21, 1.04-1.40 vs 1.10, 1.04-1.16; ASCVD 1.29, 1.09-1.51 vs 1.10, 1.04-1.17; HF 1.18, 1.00-1.39 vs 1.09, 1.03-1.16)). <a>The modifying effect of T2DM on the association between early menopause and ASCVD was only statistically significant in black compared to white women.</a></p> <p>CONCLUSION</p> <p>Early menopause was associated with increased risk for CVD in postmenopausal women. T2DM may further augment the risk, particularly in black women. </p>