Association of long-term depressive burden with incident cardiometabolic multimorbidity: a prospective study in middle-aged and older adults across three continents

Background Cardiometabolic multimorbidity (CMM) is a growing concern as global population ages. Although baseline depression is a recognised risk factor for chronic diseases, the dynamic and cumulative effect of depression on CMM remains unclear. We aimed to evaluate the longitudinal association between long-term depressive burden and the risk of incident CMM.Methods This study included 51,416 participants from three large prospective cohorts conducted in China, the USA, and Europe. Incident CMM was defined as co-occurrence of two or more of heart disease, stroke, and diabetes. Long-term depressive burden was assessed by changes in depression and cumulative depressive scores during baseline and first follow-up assessments. Cox proportional hazards model, adjusted for sociodemographic, health status, and lifestyle behaviour factors, was performed to assess incident CMM associated with long-term depressive burden. Subgroup analyses by age and sex were further conducted to evaluate potential effect modification.Results During the follow-up period, a total of 2,689 incident CMM cases were documented: 238 in China (average follow-up = 7.61 ± 2.18 years), 829 in the USA (6.81 ± 1.89 years), and 1,622 in Europe (6.00 ± 2.20 years). Depression progression was associated with elevated risks of incident CMM in China (hazard ratio (HR) = 1.474; 95% confidence interval (CI) = 1.002-2.168), the USA (HR = 1.325; 95% CI = 1.006-1.744), and Europe (HR = 1.456; 95% CI = 1.258-1.686). Conversely, depression remission correlated with a reduced risk in China (HR = 0.558; 95% CI = 0.357-0.874) and Europe (HR = 0.764; 95% CI = 0.633-0.923). The CMM risk increased with each SD increase in cumulative depressive scores. Sex was found to modify these associations in the USA and Europe, with a more pronounced impact in females.Conclusions Severe long-term depressive burden is associated with a higher risk of incident CMM, whereas remission from depression correlates with a relatively lower risk. These findings suggest that tracking the longitudinal dynamics of depression may serve as a valuable indicator for identifying individuals at an elevated risk of incident CMM.