Sex-Specific Associations Between Depression and Cardiovascular-Kidney-Metabolic Syndrome Progression: A National Cohort Study

AIMS: Depressive symptoms are common in women and men with cardiovascular-kidney-metabolic (CKM) syndrome components, yet their prognostic relevance to CKM progression remains unclear. We therefore investigated the sex-specific associations between depressive symptoms and the risk of CKM progression in a national cohort of middle-aged and elderly adults. METHODS AND RESULTS: A total of 5035 participants aged ≥45 years with CKM Stages 0-3 were enrolled. Depressive symptoms were measured using the 10-item Center for Epidemiologic Studies Depression (CESD-10) scale, with scores <10 classified as low and ≥10 as high depressive symptoms. Cardiovascular-kidney-metabolic progression was defined as an increase of at least one CKM stage during 4-year follow-up. The mean age of the study population was 58.7 (8.6) years, and 53.2% were women. Women had higher baseline CESD-10 scores than men (8.0 [4.0, 13.0] vs. 6.0 [3.0, 10.0]). Cardiovascular-kidney-metabolic progression occurred in 898 (33.5%) female and 742 (31.5%) male participants. A significant positive linear association between depressive symptoms and CKM progression was observed in women, but not men [per five-point increase: women, adjusted OR (aOR), 1.12; 95% CI, 1.05-1.20; men, aOR, 1.00; 95% CI, 0.92-1.08; P for interaction = 0.028]. Accordingly, women with high depressive symptoms had a significantly increased CKM progression risk compared with those with low depressive symptoms (aOR, 1.35; 95% CI, 1.14-1.60). CONCLUSION: Depressive symptoms are associated with CKM progression in a sex-specific manner, with significant effects observed only among women. These findings support adopting psychological interventions to delay CKM progression, particularly in female populations.