Association of Endothelial Activation and Stress Index (EASIX) with long-term mortality in type 2 diabetes patients with coronary heart disease: A prospective national cohort study

Endothelial dysfunction is prevalent in type 2 diabetes mellitus (T2DM) with coronary heart disease (CHD), increasing cardiovascular risk. The Endothelial Activation and Stress Index (EASIX) is a novel composite biomarker, yet its prognostic value in this comorbid population remains unclear. In this prospective cohort study, we analyzed 909 participants with T2DM and CHD from National Health and Nutrition Examination Survey 1999 to 2010, followed until 2019. EASIX was calculated using lactate dehydrogenase, creatinine, and platelet count. Multivariable Cox regression and Fine-Gray competing-risk models assessed associations between EASIX and all-cause and cardiovascular mortality, respectively. Time-dependent C-statistic, net reclassification improvement, and integrated discrimination improvement evaluated the incremental prognostic value of EASIX beyond established risk factors. During a median follow-up of 111 months, 617 all-cause and 251 cardiovascular deaths occurred. Higher EASIX levels were significantly associated with increased mortality risks. In fully adjusted models, the highest quartile had a hazard ratio of 1.93 (95% confidence interval = 1.48-2.50) for all-cause mortality and a subdistribution hazard ratio of 1.56 (95% confidence interval = 1.05-2.33) for cardiovascular mortality compared with the lowest quartile. Restricted cubic spline analysis revealed a significant nonlinear positive relationship. Adding EASIX to a base model (age, HbA1c, and estimated glomerular filtration rate) significantly improved the C-statistic, net reclassification improvement, and integrated discrimination improvement for both outcomes (all P < .001). Elevated EASIX levels are independently associated with higher all-cause and cardiovascular mortality in patients with T2DM and CHD. In this population, its inclusion in risk assessment protocols enhances the predictive value for long-term clinical outcomes.