Systemic immune inflammation, physical function, and mortality in US adults: A prospective follow-up analysis of NHANES 2011 to 2014

Abstract

Physical functional limitations and sleep disturbances frequently co-occur in older adults, yet their joint mortality risks and the potential nonlinear dynamics of systemic inflammation remain unclear. This study investigated the joint associations of health behavior profiles (physical function and sleep) and the systemic immune-inflammation index (SII) with mortality, focusing on exploring nonlinear relationships. Data were obtained from 4548 individuals who participated in the National Health and Nutrition Examination Survey (2011–2014). Survey-weighted Cox proportional hazards models and restricted cubic splines with change-point diagnostics were used to characterize exposure-response relationships. Compared with healthy controls, participants with physical functional limitations exhibited >2-fold increases in the risks of all-cause mortality (hazard ratio: 2.44) and cardiovascular mortality (hazard ratio: 2.46). Concurrent sleep disturbances conferred minimal additional risk. The association of SII value with mortality was nonlinear. Risk remained stable at lower SII values but increased sharply beyond identified model-based turning points (SII ≈ 447–644 for all-cause mortality; SII ≈ 332–643 for cardiovascular mortality). Physical functional limitations are robustly associated with mortality, overshadowing the contribution of sleep disturbances. The identified model-based turning points reflect an inflection in mortality risk, suggesting a potential threshold effect in systemic inflammation. Specifically, the findings highlight a unique susceptibility of the cardiovascular system to low-level inflammation. Given the observational nature of this study, these turning points are exploratory and warrant external validation.