Joint Trajectories of Physical Activity and Depressive Symptoms and Incident Cardiometabolic Multimorbidity: A Multi‐Cohort Study

BACKGROUND: Physical activity and depressive symptoms have each been associated with cardiometabolic multimorbidity (CMM), but evidence on their joint longitudinal trajectories across diverse ageing populations remains limited. METHODS: We used harmonized data from four population-based ageing cohorts, including ELSA, HRS, SHARE, and CHARLS. Among 29 523 adults aged 45 years or older, joint trajectories of physical activity and depressive symptoms were identified across three trajectory-defining survey waves using the KmL3D algorithm. Cox proportional hazards models were used to examine associations with incident CMM, defined as the coexistence of two or more of hypertension, diabetes, heart disease, and stroke. Sensitivity and supplementary analyses included proportional hazards diagnostics, time-stratified and extended Cox models, early-event exclusion analyses, conservative covariate adjustment, BMI exclusion, extended covariate models, Z-score-standardized trajectory re-analysis, and E-value calculation. RESULTS: Four joint trajectory phenotypes were identified within each cohort. Participants in trajectories characterised by lower physical activity and high depressive symptoms had the highest risk of incident CMM compared with the cohort-specific reference trajectory: ELSA, HR 2.15 (95% CI, 1.67-2.77); HRS, HR 1.46 (95% CI, 1.22-1.74); SHARE, HR 1.85 (95% CI, 1.69-2.03); and CHARLS, HR 2.28 (95% CI, 1.52-3.44). Findings were directionally consistent across sensitivity analyses. CONCLUSIONS: Joint trajectories of physical activity and depressive symptoms were associated with incident CMM across four international ageing cohorts. Combined behavioural and psychological profiles may help inform CMM risk stratification in middle-aged and older adults.