Abstract Body: Objective: This study aimed to determine whether depression diagnosed prior to menopause independently predicts incident cardiovascular disease (CVD) after menopause, addressing an important gap in understanding the long-term cardiovascular consequences of midlife mental health.
Methods: A retrospective cohort study was conducted using the TriNetX Global Collaborative Network, which includes data from 155 large healthcare organizations. Two cohorts of postmenopausal women were identified: cohort 1 was comprised of women with depression diagnosed before menopause and without preexisting CVD, premature menopause, or conventional CVD risk factors (smoking, diabetes mellitus, essential hypertension, dyslipidemia, overweight/obesity, or family history of ischemic heart disease); cohort 2 included comparable women without depression prior to menopause. Propensity score matching was performed to balance baseline characteristics, including age at menopause, current age, and ethnicity. Risk differences and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to compare CVD incidence (composite of myocardial infarction, coronary heart disease, stroke, heart failure, and cardiovascular death) between cohorts. Kaplan–Meier survival analysis with log-rank testing assessed time to incident CVD, and Cox proportional hazards regression estimated hazard ratios (HRs).
Results: Initial queries identified 90,638 women in cohort 1 and 1,237,202 in cohort 2. After propensity score matching, 88,884 women were included in each cohort, with a mean (SD) age of 57.6 (11.4) years. Participants were observed for a maximum of 20 years after the onset of menopause, with a mean (median) follow-up 3.37 (2.23) years in cohort 1 and 3.31 (2.05) years in cohort 2. Compared with cohort 2, women with premenopausal depression had a significantly higher incidence of CVD after menopause (4.0% vs. 3.3%; RR = 1.23, 95% CI 1.17–1.29, p < .001). Premenopausal depression was associated with a significantly increased hazard of incident CVD over time (HR = 1.21, 95% CI 1.15–1.27, p < .001).
Conclusion: Among women without preexisting CVD or traditional cardiovascular risk factors before menopause, depression diagnosed prior to menopause was associated with a higher risk of developing CVD later in life. These findings suggest that premenopausal depression may serve as an independent and early indicator of cardiovascular risk in midlife women.