Endothelial dysfunction and long-term survival in cardiovascular-kidney-metabolic syndrome stages 0–3: An EASIX-based national cohort study

ObjectiveTo assess the association of the endothelial activation and stress index (EASIX) with all-cause and cardiovascular mortality in adults at cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3.MethodsThis retrospective analysis of a population-based cohort included 10,885 adults aged ≥30 years from NHANES 1999-2018, with mortality follow-up through 2019. EASIX was calculated as lactate dehydrogenase × creatinine/platelet count. Survey-weighted Cox models, restricted cubic splines, subgroup analyses and sensitivity analyses evaluated mortality associations.ResultsDuring a median follow-up of 97 months, 1,122 participants died, including 295 from cardiovascular causes. Each one-unit increase in EASIX was associated with all-cause mortality (adjusted hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.24-1.61) and cardiovascular mortality (HR 1.30, 95% CI 1.13-1.49). There was no evidence of non-linearity for all-cause mortality (P = 0.466), while the cardiovascular association was non-linear (P = 0.008). Associations persisted after additional lifestyle adjustment. CKM-stage interactions were not significant in the full cohort.ConclusionsHigher EASIX was associated with greater all-cause and cardiovascular mortality in CKM stages 0-3. Its potential role in clinical risk assessment warrants further validation.