Association between the Endothelial Activation and Stress Index (EASIX) and all-cause and cardiovascular mortality in patients with diabetes and prediabetes
Enfa Zhao, Yiqing Chen, Hang Xie, R Wang, Yuan Gao, Bingtian Dong, Chaoxue Zhang
Abstract
BACKGROUND: Vascular endothelial impairment is crucial in diabetes and its cardiovascular complications, but clinically applicable endothelial function markers remain limited. We investigated the Endothelial Activation and Stress Index (EASIX), a novel biomarker calculated from lactate dehydrogenase, creatinine, and platelet count, for predicting mortality in diabetes and prediabetes populations. METHODS: /L). We employed multiple statistical approaches, including Kaplan-Meier survival analysis, multivariable Cox proportional hazards models, restricted cubic spline analysis, and stratified analysis to examine the relationship between EASIX and mortality outcomes. RESULTS: During a median follow-up of 90.2 months, 3,432 deaths occurred, including 1,128 cardiovascular-related deaths. Higher EASIX values were significantly associated with increased risks of all-cause and cardiovascular mortality (P for trend < 0.0001). In the fully adjusted model, the highest EASIX quartile (Q4) demonstrated significantly higher risks as compared to the lowest quartile (Q1): all-cause mortality (HR: 1.50, 95% CI 1.33-1.69) and cardiovascular mortality (HR: 1.72, 95% CI 1.38-2.14). Nonlinear relationships were observed between EASIX and mortality outcomes (P for nonlinearity < 0.001). While EASIX predicted outcomes in both populations, diabetic patients showed a more pronounced effect. Subgroup analyses revealed more significant associations in females (HR: 1.36, 95% CI 1.28-1.44) compared to males (HR: 1.18, 95% CI 1.13-1.22), and the association was modified by hypertension status (P for interaction = 0.002). CONCLUSION: EASIX emerges as an independent predictor of all-cause and cardiovascular mortality in diabetes and prediabetes patients. Its accessibility makes it a practical tool for identifying patients requiring intensive monitoring and intervention. The stronger associations in specific subgroups, particularly among diabetic patients and females, underscore the need for targeted approaches.