Endothelial Activation Stress Index predicts all-cause and cardiovascular mortality in patients with diabetes: A nationwide study

Introduction

Evidence suggests that the Endothelial Activation and Stress Index (EASIX) predicts mortality in endothelium-related conditions, but its link to mortality risk in diabetes remains unclear. This study investigates the association between EASIX and mortality risk in diabetes patients.

Methods

We included 3,252 diabetes patients from seven National Health and Nutrition Examination Survey cycles (2003–2016). Mortality data were sourced from National Death Index records. Restricted cubic spline (RCS) regression assessed the EASIX-mortality risk relationship, while the maximally selected rank statistics method (MSRSM) identified the optimal EASIX cutoff for survival outcomes. Weighted multivariable Cox regression models evaluated the association of EASIX with all-cause and cardiovascular mortality.

Results

Over a median follow-up of 91 months, 895 (27.5%) of 3,252 diabetes patients died, including 260 (8.0%) from cardiovascular and 635 (19.5%) from noncardiovascular causes. RCS analysis showed a positive association between EASIX and both all-cause and cardiovascular mortality. Each one-unit EASIX increase raised all-cause and cardiovascular mortality risks by 27% and 24%, respectively. MSRSM classified patients into higher (>0.70) and lower (≤0.70) EASIX groups. Those with higher EASIX had a significantly greater risk of all-cause (HR 1.56, 95% CI 1.21–2.01) and cardiovascular mortality (HR 2.05, 95% CI 1.33–3.16). Time-dependent receiver operating characteristic analysis showed AUCs for 1-, 3-, 5-, and 10-year survival were 0.78, 0.72, 0.70, and 0.69 (all-cause) and 0.90, 0.81, 0.76, and 0.73 (cardiovascular).

Conclusions

Elevated EASIX is independently associated with increased all-cause and cardiovascular mortality in diabetes patients, highlighting its potential as a valuable clinical biomarker.