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

Social isolation is a common yet under-recognized risk factor among stroke survivors that has been linked to adverse long-term health outcomes. To investigate the association between social isolation and mortality in this population and evaluate the role of systemic inflammation as a potential mediator. 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. 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. 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.