Joint Association of Functional Impairment and Depression with Advanced Cardiovascular–Kidney–Metabolic Syndrome: A Cross-Sectional and Cohort Study Using Two Large Datasets

Background: Unfavorable cardiovascular–kidney–metabolic (CKM) status represents a major contributor to all-cause deaths. Our study sought to investigate the joint association of functional impairment and depression with advanced CKM syndrome among individuals of middle and old age. Methods: Participants for the cross-sectional analysis were drawn from the National Health and Nutrition Examination Survey (NHANES) in the United States, while those for the cohort analysis were selected from the China Health and Retirement Longitudinal Study (CHARLS). To analyze the independent and joint associations of functional impairment, depression, and their comorbidity with advanced CKM syndrome, multivariable logistic regression was performed. Subgroup analyses were performed to evaluate effect variations and interactions. Results: In the NHANES sample, the coexistence of instrumental activities of daily living (IADL)/basic activities of daily living (BADL) impairment and depression showed a significant positive association with advanced CKM syndrome (IADL and depression: odds ratio [OR] = 4.843, 95% confidence interval [CI]: 2.505, 9.366; BADL and depression: OR = 4.394, 95% CI: 2.281, 8.464); In the CHARLS cohort, the coexistence of IADL/BADL impairment and depression showed a stronger association with advanced CKM syndrome (IADL and depression: OR = 2.259, 95% CI: 1.517, 3.319; BADL and depression: OR = 2.287, 95% CI: 1.501, 3.419). Conclusions: The presence of functional impairment and depression is significantly associated with advanced CKM syndrome. Screening for coexisting functional impairment and depression may help identify individuals who are more likely to develop advanced CKM syndrome.