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: A total of 5,035 participants aged ≥45 years with CKM stages 0-3 were enrolled. Depressive symptoms were measured using the ten-item Center for Epidemiologic Studies Depression (CESD-10) scale, with scores <10 classified as low and ≥10 as high depressive symptoms. CKM progression was defined as an increase of at least one CKM stage during 4-years follow-up. RESULTS: 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]). CKM 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 5-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). CONCLUSIONS: 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.