Relationship between depressive symptom trajectories and cardiovascular disease risk in middle-aged and older adults with cardiovascular-kidney-metabolic syndrome stages 0–3

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome underscores the interlinked pathophysiology of metabolic dysregulation, chronic kidney disease, and cardiovascular disease (CVD). Although depression is a key psychosocial factor, evidence linking its longitudinal trajectories to incident CVD among middle-aged and older adults with CKM stages 0-3 remains limited. METHODS: We conducted a prospective cohort study using data from the China Health and Retirement Longitudinal Study (CHARLS) collected between 2011 and 2020, including participants at CKM stages 0-3. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) across the 2011, 2013, and 2015 waves. Group-based trajectory modeling (GBTM) was applied to identify depressive symptom trajectories. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD (including heart disease and stroke). RESULTS: Among 6,152 participants (49% male, median age 58.0 years), 1,080 incident CVD events occurred during the follow-up. We identified three distinct depressive symptom trajectories: Low-stable, Moderate-stable, and Persistently-high. The cumulative incidence of CVD across these groups was 13.0%, 17.3%, and 23.1%, respectively (P < 0.001). Relative to the Low-stable group, fully adjusted Cox models revealed a significantly higher risk of incident CVD in both the Moderate-stable (HR = 1.36; 95% CI: 1.16-1.60) and Persistently-high (HR = 1.88; 95% CI: 1.57-2.24) groups. Consistent risk elevations were observed for coronary heart disease and stroke analyzed separately. CONCLUSION: In Chinese middle-aged and older adults with CKM stages 0-3, depressive symptom trajectories are heterogeneous. Both Persistently-high and Moderate-stable trajectories of elevated depressive symptoms are independently associated with an increased risk of incident CVD.