Linking social isolation to excess mortality in stroke survivors: a population-based investigation of inflammation indicators

BACKGROUND: Social isolation is a common yet under-recognized risk factor among stroke survivors that has been linked to adverse long-term health outcomes. OBJECTIVE: To investigate the association between social isolation and mortality in this population and evaluate the role of systemic inflammation as a potential mediator. METHODS: This retrospective cohort study leveraged data from 1,284 participants aged ≥ 40 years with a self-reported stroke history, drawn from the 1999-2018 National Health and Nutrition Examination Survey. The primary outcomes were all-cause and cardiovascular disease (CVD) mortality. Associations were evaluated using Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses assessed the contribution of the systemic inflammation response index (SIRI) to the association between social isolation and mortality outcomes. RESULTS: The weighted prevalence of social isolation was 15.72%. Over a median follow-up of 85 months, 605 (43.57%) deaths occurred. After multivariable adjustment, socially isolated participants had significantly increased hazards of all-cause mortality (HR = 1.57; 95%CI: 1.23-2.02) and CVD mortality (HR = 2.49; 95%CI: 1.67-3.72) compared to non-isolated individuals. Mediation analysis indicated that SIRI explained 10.40% and 5.37% of the association between social isolation and all-cause and CVD mortality, respectively. The population-attributable fraction of social isolation was 12.0% for all-cause mortality and 15.2% for CVD mortality. CONCLUSION: Social isolation is associated with a significantly elevated hazard of mortality in U.S. stroke survivors, a relationship partly mediated by systemic inflammation. These findings highlight social isolation as a critical, modifiable risk factor that should be integrated into comprehensive post-stroke care strategies.