Linking disease severity and mortality in obstructive sleep apnea: the role of the endothelial activation and stress index.

BACKGROUND: Systemic inflammation and endothelial dysfunction are implicated in adverse outcomes in obstructive sleep apnea (OSA), yet accessible biomarkers linking disease severity with long-term risk remain limited. The Endothelial Activation and Stress Index (EASIX) has been associated with mortality in various settings, but its role in OSA is unclear. METHODS: We analyzed data from 9,797 participants in the National Health and Nutrition Examination Survey (NHANES) to investigate the association between EASIX and all-cause and cardiovascular mortality using weighted Cox regression and restricted cubic spline models. Machine learning models were further developed to assess predictive performance and interpret feature importance using SHAP. In addition, a hospital-based cross-sectional clinical dataset (n = 258) was used to examine the relationship between EASIX and OSA severity indices, including the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). RESULTS: Higher EASIX levels were independently associated with increased risks of all-cause and cardiovascular mortality. Distinct dose-response patterns were observed, with a nonlinear association for all-cause mortality and a linear relationship for cardiovascular mortality. Machine learning models demonstrated strong predictive performance, with EASIX identified as a key contributor by SHAP analysis. In the clinical dataset, EASIX was significantly associated with both AHI and ODI, indicating a close relationship with OSA severity. CONCLUSIONS: EASIX is associated with both mortality and disease severity in OSA, suggesting its potential as a practical biomarker for risk stratification and integrated clinical assessment.