Beyond the change: exploring age of menopause, lifestyle, and cardiovascular risk in women

Abstract Background Premature/early menopause increases the risk of future cardiovascular disease (CVD); however, whether lifestyle can offset this risk is unknown. Purpose Investigate the association between premature/early menopause and incident CVD and whether a healthy lifestyle modifies this association. Methods The 45 and Up Study prospectively recruited participants aged ≥45 years (n=267,357) between 2005-2009. Our study included women without prior CVD and those reporting menopausal age at baseline. Primary outcome was incident CVD (self-reported heart disease/stroke) based on survey data1 at Wave 2 (2012-2015) and/or Wave 3 (2018-2020). Logistic regression models assessed associations of premature (age <40 years) and early (age 40-44 years) menopause with CVD, compared to standard menopause (age 50-52 years), adjusting for sociodemographic and clinical variables. Healthy lifestyle adherence was assessed using a score of five factors: smoking, physical activity, sitting, sleep, and diet. Interaction effects were analysed between menopause and healthy lifestyle adherence on CVD. Results We included 46,273 women (mean age 62.1±8.2 years), with 5,425(11.7%) incident CVD over 15-year follow-up. After adjustment, the CVD risk was higher in women with premature menopause (odds ratio (OR): 1.36, 95% confidence intervals (CI), 1.17-1.59; p<0.0001) and early menopause (OR: 1.15, 95% CI, 1.03-1.28; p=0.013) compared to standard menopause. Among all menopausal women, high versus low healthy-lifestyle adherence led to 20% lower CVD risk (OR: 0.80, 95% CI, 0.71-0.90; p=0.0003). In the subset of high-risk women with premature menopause, high versus low healthy lifestyle adherence led to 50% lower risk of CVD (OR: 0.50, 95% CI, 0.31-0.80, p=0.0040). The healthy lifestyle effect was not significantly different across menopause groups (p=0.71). Conclusion Early and premature menopause were independently associated with increased CVD risk. Healthy versus unhealthy lifestyle significantly attenuated the risk of CVD in all menopausal women, particularly in the highest risk group of women with premature menopause, reducing this risk by 50%. 1 Secure data access was provided through the Sax Institute’s Secure Unified Research Environment (SURE).