Association of endothelial activation and stress index with all-cause and cardiovascular mortality in patients with diabetic kidney disease: a population-based prospective study

Emerging evidence suggests a potential role of endothelial activation and oxidative stress in the pathogenesis of diabetic kidney disease (DKD). Endothelial activation and stress index (EASIX) is a reliable alternative biomarker of endothelial dysfunction. We aimed to investigate the relationship between the EASIX and both all-cause and cardiovascular mortality in individuals with DKD. Data were extracted from the National Health and Nutrition Examination Survey database. Multivariable Cox proportional hazards models were applied to assess the relationship between EASIX and mortality. Kaplan-Meier survival curves, Subgroup analyses, receiver operating characteristic curves, and sensitivity analyses were conducted. Additionally, restricted cubic spline analysis was employed to elucidate the nonlinear relationships between EASIX and hazard ratio in DKD patients. A total of 1700 participants were included in this study. Over a median follow-up of 87.6 months, 571 all-cause deaths were recorded. The highest EASIX group showed higher hazard ratios for all-cause and cardiovascular mortality in both crude and multivariable-adjusted models. In the fully adjusted model, the hazard ratios for the highest EASIX group were 1.59 (95% CI: 1.24–2.03; p < 0.001) for all-cause mortality and 1.67 (95% CI: 1.09–2.54; p = 0.018) for cardiovascular mortality, compared to the lowest tertile. Furthermore, a nonlinear relationship was observed, with a sharp increase in all-cause mortality risk beyond an EASIX threshold of 0.619. The results showed EASIX as an independent predictor of all-cause and cardiovascular mortality in DKD patients and further revealed that a non-linear positive correlation exists between EASIX and both all-cause mortality and a linear relationship with cardiovascular mortality in DKD patients.