Sex Differences in the Association Between Depression and Incident Cardiovascular Disease

Background Depression is a known risk factor for cardiovascular disease (CVD), but the potential sex differences in this association remain unclear. Objectives The aim of this study was to investigate the association between depression and subsequent CVD events, and to explore potential sex differences. Methods We conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4,125,720 individuals aged 18 to 75 years without a history of cardiovascular disease or renal failure and missing data at baseline. Participants were followed up for a mean of 1,288 days to assess the association between depression and subsequent CVD events, such as myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Results Our analysis revealed a significant association between depression and subsequent composite CVD events in both men and women, with a stronger association observed in women. The HR for the composite endpoint was 1.64 (95% CI: 1.59-1.70) in women and 1.39 (95% CI: 1.35-1.42) in men after multivariable adjustment (P for interaction <0.001). Furthermore, the individual components of the composite endpoint were also associated with depression in both men and women, each of which was also observed to be more strongly associated in women. Conclusions Our study provides evidence of a significant association between depression and subsequent CVD events in both men and women, with a more pronounced association observed in women. These findings highlight the importance of addressing depression and tailoring prevention and management strategies according to sex-specific factors.