Abstract
BACKGROUND: Cardiometabolic multimorbidity (CMM) and depression are major health concerns, and the onset of either condition may heighten the risk of developing the other. OBJECTIVES: The goal of this study was to characterize the reciprocal associations between CMM and depression among middle-aged and older adults. METHODS: This multicohort study used harmonized data from 5 prospective cohorts from China, South Korea, the United States, the United Kingdom, and Europe. Cardiometabolic diseases (CMDs) (including diabetes, heart diseases, and stroke) and depression were assessed at baseline and at 7 to 8 years' follow-up. Lifestyle factors, including physical activity, alcohol consumption, and smoking status, were regarded as potential mediators. Two sets of analyses, CMM-depression analyses (n = 67,188) and depression-CMM analyses (n = 65,738), were conducted to explore the bidirectional associations between CMM and depression. RESULTS: In the CMM-depression analyses, 16,596 (24.7%) individuals developed depression. Participants with a single CMD (HR: 1.24; 95% CI:1.19-1.29) and CMM (HR: 1.52; 95% CI: 1.42-1.63) at baseline had higher risks of depression occurring. Physical activity and alcohol consumption significantly mediated 7.5% and 6.9% of the CMM-depression association, respectively. In the depression-CMM analyses, 1,461 (2.2%) participants developed CMM. The HR for developing CMM was 1.31 (95% CI: 1.14-1.50) in patients with depression, with increased risk of developing more CMDs. Physical activity and alcohol consumption mediated 12.0% and 7.1% of the depression-CMM association. The bidirectional relationships were more pronounced in Western countries than in Asian countries. CONCLUSIONS: CMM and depression were bidirectionally associated. The mediated effects of lifestyle factors were larger in the depression-lifestyle-CMM pathway than in the CMM-lifestyle-depression pathway.