Depression Symptoms and Advanced Cardiovascular–Kidney–Metabolic Syndrome in U.S. Adults: The Moderating Role of Sex

Objective: To examine the association between depressive symptoms and advanced cardiovascular-kidney-metabolic (CKM) syndrome among U.S. adults and to determine whether this association differs by demographic, socioeconomic, and behavioral factors. Methods: This cross-sectional study used National Health and Nutrition Examination Survey data. Depressive symptoms were assessed using the Patient Health Questionnaire-9. CKM stages were defined using the American Heart Association framework and categorized as nonadvanced CKM, stages 0 to 2, versus advanced CKM, stages 3 to 4. Survey-weighted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for advanced CKM. Interaction terms tested effect modification by age, sex, race and ethnicity, poverty-income ratio, education, and smoking status. Results: The study included 30,244 adults. Overall, 16% of adults had advanced CKM, and 8% had depressive symptoms. In fully adjusted sex-stratified models, depressive symptoms were associated with higher odds of advanced CKM among women (OR, 2.24; 95% CI, 1.74–2.88) and men (OR, 1.75; 95% CI, 1.34–2.28). Interaction estimates indicated a stronger association among women (OR, 1.58; 95% CI, 1.12–2.23; P =0.010) and a weaker association at age ≥65 versus 30–49 years (OR, 0.42; 95% CI, 0.27–0.67; P <.001). Conclusions: Depressive symptoms were associated with higher odds of advanced CKM in both women and men, with a stronger association among women and a weaker association at ages ≥65 versus 30–49. These findings support integrating mental health screening into cardiometabolic and kidney disease prevention strategies, emphasizing age- and sex-specific vulnerabilities.