Association between Cardiometabolic Multimorbidity and Depression Risk in Middle-aged and Older Chinese Adults: An Analysis Based on the China Health and Retirement Longitudinal Study (CHARLS) Database: A Prospective Cohort Study

Abstract Background Cardiometabolic multimorbidity (CMM) and depression are increasingly prevalent among middle-aged and older adults. However, prospective evidence regarding the association between CMM and subsequent depressive symptoms remains limited. This study aimed to examine this association among middle-aged and older Chinese adults. Methods This prospective cohort study included 10,726 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study, with baseline assessment in 2011 and follow-up through 2020. CMM was defined as the coexistence of at least two cardiometabolic diseases, including diabetes, heart disease, and stroke. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale, with a score ≥ 12 indicating depressive symptoms. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Interaction, propensity score, E-value, subgroup, machine learning, and sensitivity analyses were conducted to assess the robustness of the findings. Results Among the participants, 386 had CMM. The prevalence of depressive symptoms was higher in the CMM-positive group than in the CMM-negative group (38.6% vs. 33.0%, P = 0.022). After adjustment for demographic characteristics, lifestyle factors, clinical variables, and laboratory biomarkers, CMM was independently associated with an increased risk of depressive symptoms (HR 1.25, 95% CI 1.05–1.49, P = 0.011). Multiple propensity score analyses produced generally consistent positive associations, with the strongest estimate observed using inverse probability of treatment weighting (HR 1.52, 95% CI 1.29–1.79, P = 0.001). The E-value was 1.81 for the point estimate and 1.28 for the lower confidence limit. Evidence of additive interaction between CMM and cognitive dysfunction was observed. Boruta and SHAP analyses also identified CMM as an important predictor of depressive symptoms. The association remained significant after excluding participants with baseline depressive symptoms (HR 1.32, 95% CI 1.02–1.72, P = 0.037). Conclusions CMM was independently associated with an increased risk of depressive symptoms among middle-aged and older Chinese adults. These findings highlight the importance of incorporating routine depression screening and integrated mental health management into the care of individuals with CMM.