Cardiometabolic changes in the menopause transition

Cardiovascular disease (CVD) remains the leading cause of death in women. Midlife cardiometabolic changes are a key contributor to this risk. Women experience an increase in cardiovascular (CV) risk beginning in the fifth decade of life, approximately 10 years later than men, which temporally aligns with the menopause transition. Many cardiometabolic alterations during perimenopause are not solely attributable to chronologic aging but are instead linked to ovarian aging. Recognizing menopause-related cardiometabolic changes provides clinicians with an opportunity to identify CV risk early and implement targeted prevention strategies. DOES THE TIMING AND TYPE OF MENOPAUSE AFFECT CARDIOVASCULAR DISEASE RISK? Natural menopause occurs at a mean age of 52 years; however, menopause occurring early (ages 40-45 y) or prematurely (before age 40 y) is consistently associated with higher rates of coronary heart disease, stroke, heart failure, and CV mortality. In a large, pooled analysis, there was a graded increase in CVD risk with earlier age at natural menopause compared with menopause at ages 50 to 51 years. Hazard ratios for incident CVD were 1.55 for premature (10 y since menopause), there may be an increase in CV risk. Since the results of the Women’s Health Initiative, two smaller randomized placebo-controlled trials (the Kronos Early Estrogen Prevention Study KEEPS and the Early versus Late Intervention Trial with Estradiol ELITE) evaluated whether HT compared with placebo could prevent CV disease by examining surrogate markers of coronary heart disease.9,10 Both studies found that HT initiated close to menopause (within 3-6 y) did not increase CV risk. KEEPS demonstrated neutral effects of low-dose estrogen on surrogate markers of coronary heart disease—carotid intima-media thickness (cIMT) and coronary artery calcium (CAC), whereas ELITE showed that estrogen initiated close to menopause significantly slowed cIMT progression without changes in CAC. These findings applied to normal arteries, which does not translate into clinically significant reductions in CV events and does not support the use of HT for CVD prevention. KEY SUMMARY POINTS The menopause transition represents a critical window for cardiometabolic risk identification and prevention. Cardiometabolic changes during the menopause transition contribute significantly to the rise in cardiovascular disease observed in midlife women. Early recognition and targeted intervention during this transition offer a unique opportunity to mitigate long-term cardiovascular risk and improve health outcomes for women. Lifestyle interventions remain foundational. CLINICAL RECOMMENDATIONS Incorporate menopause-specific factors into routine cardiovascular risk assessment, including age and type of menopause, blood pressure, lipid profile, glucose metabolism, body composition, and sleep quality. Consider menopause as a risk-enhancing factor when determining the intensity of preventive therapies. Use the American Heart Association’s Life’s Essential 8 to address lifestyle measures and modifiable risk factors (blood pressure, blood glucose, blood cholesterol, and sleep) that may improve long-term cardiovascular outcomes in women. Coming next in theStep-by-Stepseries: Jessica Caldwell, PhD, director of the Women’s Alzheimer’s Movement Prevention and Research Center at the Cleveland Clinic, reviews the physiologic basis for the cognitive complaints of menopausal women and offers strategies to share with patients to protect brain health.This article is part of the ongoing series Menopause Step-by-Step, a monthly Menopause education feature.11 The Editors of this series are Dr. Cynthia Stuenkel, Dr. Cheryl Cox Kinney, and Dr. Isaac Schiff.