Associations of Life‐Course Social Isolation Trajectories and Depressive Symptoms With the Risk of Incident Cardiovascular Disease: A Prospective Cohort Study

Background Social isolation is increasingly recognized as a fundamental determinant of health. This study aimed to comprehensively examine the associations between social isolation trajectories spanning from childhood through adulthood and the risk of incident cardiovascular disease (CVD) among middle‐aged and older adults in China, while further exploring the potential mediating role of depressive symptoms in these relationships. Methods We analyzed data from 6858 participants using the 2014 life‐course survey and 2015–2020 follow‐up waves of the China Health and Retirement Longitudinal Study (CHARLS). Trajectories were constructed based on the cross‐classification of social isolation status in childhood and adulthood. Exposures were assessed using cumulative composite scores, and incident CVD outcomes were identified via self‐reported physician diagnoses. Multivariable logistic regression models were applied to estimate the odds of incident CVD, alongside mediation analyses to quantify potential indirect effects. Subgroup analyses and a comprehensive set of sensitivity analyses were additionally conducted to assess the robustness of the findings. Results Four distinct life‐course social isolation trajectories were identified: no isolation, childhood‐only, adulthood‐only, and persistent isolation. Persistent social isolation was associated with significantly elevated odds of incident CVD (OR = 1.53, 95% CI: 1.16–2.01). Mediation analyses indicated that depressive symptoms accounted for a meaningful proportion of this association, explaining 16.28% of the relationship with CVD and 14.70% of the association with stroke. Analyses of secondary outcomes further demonstrated that childhood social isolation (OR = 1.44, 95% CI: 1.16–1.79), childhood‐only isolation (OR = 1.36, 95% CI: 1.08–1.72), and persistent isolation (OR = 1.79, 95% CI: 1.19–2.71) were each independently associated with increased odds of incident stroke. Conclusions Persistent social isolation was associated with an increased risk of incident CVD among middle‐aged and older adults in China, with this relationship being partially mediated by depressive symptoms. These findings underscore the importance of incorporating long‐term psychosocial assessments into CVD risk stratification and management strategies.