Endothelial Activation and Stress Index Predicts All‐Cause and Cardiovascular Mortality in Hypertensive Individuals: A Nationwide Study

Emerging evidence links the Endothelial Activation and Stress Index (EASIX) and mortality risk in coronary artery disease, but its relevance in hypertensive patients remains unclear. This study examines the association between EASIX and all-cause and cardiovascular mortality in hypertensive individuals. The analysis included 6138 hypertensive patients from seven National Health and Nutrition Examination Survey (NHNES) cycles (2003-2016), with mortality data obtained from the National Death Index (NDI). Over a median follow-up of 98 months, 1435 (23.4%) participants died, including 400 (6.5%) from cardiovascular causes. Restricted cubic spline analysis revealed a positive association between EASIX and both all-cause and cardiovascular mortality. Weighted multivariable Cox regression indicated that each 1-unit increase in EASIX corresponding to a 25% and 23% rise in mortality risk, respectively. Based on the optimal cutoff value determined using the maximally selected rank statistics method, participants were stratified into higher (>0.79) and lower (≤0.79) EASIX groups. Higher EASIX was significantly associated with increased all-cause mortality risk (HR 1.46, 95% CI 1.23-1.73, p < 0.0001). Higher EASIX scores were associated with increased cardiovascular mortality, especially in former/current smokers and those with diabetes/prediabetes. Time-dependent receiver operating characteristic analysis assessed the predictive accuracy of EASIX, yielding area under the curve (AUC) for 1-, 3-, 5-, and 10-year survival of 0.71, 0.67, 0.67, and 0.67 for all-cause mortality and 0.79, 0.73, 0.73, and 0.71 for cardiovascular mortality. In conclusion, elevated EASIX is independently associated with increased all-cause and cardiovascular mortality in hypertensive patients, suggesting its potential as a predictive biomarker in clinical practice.