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Joint effects of depression, lipid metabolic dysfunction, and their trajectories on incident cardiometabolic multimorbidity: a prospective multi-cohort analysis from two national cohorts
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DOI：10.1186/s12944-026-03008-y.png)
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Abstract
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Cardiometabolic multimorbidity (CMM) imposes a growing public health burden on middle-aged and older adults. Depression and lipid metabolic dysfunction are modifiable risk factors for CMM, yet their joint effects and dynamic co-trajectories on CMM risk across diverse ageing populations remain poorly understood. This prospective multicohort study used individual-level data from the China Health and Retirement Longitudinal Study (CHARLS) and the English Longitudinal Study of Ageing (ELSA). Two analytical risk sets were defined to support static and dynamic analyses. Metabolic status was assessed using the atherogenic index of plasma (AIP) and remnant cholesterol (RC); depressive symptoms were measured by the Centre for Epidemiologic Studies Depression Scale (CES-D). Cox proportional hazards regression, counterfactual population attributable fractions (PAF), interaction analyses, and trajectory analyses were applied to examine associations between depression, metabolic status, and incident CMM. Multiple sensitivity analyses confirmed robustness. Depression and metabolic dysfunction each independently increased CMM risk, and their co-occurrence conferred the highest risk (AIP, fully adjusted: CHARLS HR = 1.71, 95% CI 1.45–2.01; ELSA HR = 1.55, 95% CI 1.26–1.89), with consistent findings for RC. In the dynamic analysis, persistent co-exposure to elevated metabolic burden and depression was associated with the greatest CMM risk in CHARLS (HR = 2.78, 95% CI 1.73–4.45), with a consistent directional pattern in ELSA. Depression and lipid metabolic dysfunction independently and jointly increase incident CMM risk across two nationally representative ageing cohorts. Integrating mental health screening and metabolic assessment into CMM primary prevention may offer meaningful reductions in disease burden across diverse ageing populations.
Keywords:
Cardiometabolic multimorbidity
Depression
Atherogenic index of plasma
Multi-cohort study
Middle-aged and older adults
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