Social Isolation Trajectories Spanning Childhood to Adulthood and Mortality Risk in CKM Syndrome: Evidence From...

Social isolation is increasingly recognized as a critical determinant of health. This study aimed to systematically evaluate the association between social isolation trajectories spanning childhood to adulthood and all-cause mortality in patients with cardiovascular-kidney-metabolic (CKM) syndrome stages 1-4 and to investigate the potential mediating role of renal function.

We analyzed data from 5019 participants aged 45 years or older with CKM stages 1-4 from the China Health and Retirement Longitudinal Study (CHARLS). Four life-course social isolation trajectories were identified: no isolation, childhood-only, adulthood-only, and persistent isolation. Cox proportional hazards models and exploratory mediation analyses were used to assess all-cause mortality risk and potential mediating effects. Additionally, Kaplan-Meier curves, subgroup analyses, and sensitivity analyses were performed.

Persistent isolation was linked to an elevated likelihood of all-cause mortality (HR = 1.92, 95% CI: 1.25-2.97). The mediation analysis suggested that cystatin C contributed to the pathway linking persistent isolation with mortality, explaining 6.31% of the overall effect (p < 0.05).

Persistent social isolation shows a clear association with elevated mortality risk among middle-aged and older Chinese individuals living with CKM syndrome, and this association is partially explained by cystatin C levels, serving as a potential mechanistic link. Integrating long-term psychosocial assessment into CKM risk stratification and management is crucial.