Association between Depressive Symptoms and Incidence of Stroke in a Population with Cardiovascular - Kidney - Metabolic Syndrome Stage 0–3: A Nationwide Prospective Cohort Study (Preprint)

BACKGROUND The association between depressive symptoms and cardiovascular diseases is well established. However, their impact on the incidence of stroke in individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome remains unclear. OBJECTIVE This study aims to investigate the impact of depressive symptoms at different stages of CKM syndrome on the incidence of new-onset stroke. METHODS This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS). Depressive symptoms at baseline were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) , with stroke incidence determined through standardized follow-up questionnaires. Cox regression and restricted cubic spline (RCS) regression were used to evaluate the association between depressive symptoms and stroke risk. RESULTS The analysis included 9,593 participants (54.92% male, mean age 60.89 ± 9.39 years), classified into CKM stages 0–3. Fully adjusted Cox regression showed that each one-point increase in depressive score was associated with a 3% higher stroke risk (HR: 1.03; 95% CI: 1.02–1.04; P < 0.0001). RCS regression confirmed a significant positive linear relationship between depressive symptoms and stroke incidence (P < 0.001). CONCLUSIONS This cohort study demonstrates a positive linear association between depressive symptoms and increased stroke incidence in individuals with CKM syndrome (Stages 0–3). These findings highlight the importance of emotional health management, suggesting that effective depression treatment may help reduce stroke risk through inflammation reduction and lifestyle improvements.