ArticleMedicine2026
Endothelial Activation Stress Index and risk of all-cause and cardiovascular mortality in early-stage cardio-renal-metabolic syndrome: A nationwide retrospective cohort study.
Article in Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Endothelial dysfunction plays a central role in the pathophysiology of cardiovascular, renal, and metabolic diseases. The Endothelial Activation Stress Index (EASIX) has emerged as a promising prognostic marker in endothelial-related disorders. This study aimed to evaluate the association between EASIX and the risks of all-cause and cardiovascular mortality in individuals with cardio-renal-metabolic (CKM) syndrome stages 0 to 3. Data were obtained from the National Health and Nutrition Examination Survey 2005 to 2010 and 2015 to 2018 cycles. A total of 7046 participants with CKM stages 0 to 3 were included. EASIX was calculated as lactate dehydrogenase × creatinine/platelet count. The primary outcome was cardiovascular mortality, and the secondary outcome was all-cause mortality, ascertained through linkage to the National Death Index. The optimal cutoff value of EASIX was determined using maximally selected rank statistics. Associations were assessed using survey-weighted Cox proportional hazards models, restricted cubic splines, and subgroup analyses. Predictive performance was evaluated using time-dependent receiver operating characteristic curves. Mediation analysis and competing risk models were also performed. Higher EASIX (≥0.64) was significantly associated with increased risks of cardiovascular mortality (adjusted hazard ratio = 1.65, 95% confidence interval = 1.11-2.46) and all-cause mortality (adjusted hazard ratio = 1.45, 95% confidence interval = 1.16-1.81). Restricted cubic spline analysis revealed a significant nonlinear relationship between EASIX and mortality (P < .001). Kaplan-Meier curves showed lower survival probabilities in the high-EASIX group (log-rank P < .0001). The association remained consistent across subgroups. EASIX demonstrated good predictive performance for 1-, 3-, and 5-year mortality. Mediation analysis indicated that chronic kidney disease accounted for approximately 30% to 35% of the observed associations. Competing risk analysis confirmed the independent association between EASIX and cardiovascular mortality. EASIX is a simple and robust predictor of all-cause and cardiovascular mortality in patients with CKM stages 0 to 3, and may facilitate early risk stratification and personalized management.
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