Association between the endothelial activation and stress index and cardiometabolic multimorbidity: Results from the NHANES 2003 to 2020.

Cardiometabolic multimorbidity (CMM) poses a significant global health burden, with endothelial dysfunction being a shared pathophysiological mechanism. The Endothelial Activation and Stress Index (EASIX) is a novel and powerful marker reflecting endothelial function, but its association with CMM remains unclear. In the fully adjusted model, each unit increase in natural logarithmic transformed (Ln)-EASIX was associated with a 39% increased risk of CMM (odds ratios = 1.39, 95% confidence intervals: 1.19-1.64, P < .001). A nonlinear L-shaped dose-response relationship was observed in restricted cubic spline model. Threshold effect revealed a significant positive association between Ln-EASIX and CMM risk when Ln-EASIX > -0.916 (odds ratios = 1.857, 95% confidence intervals: 1.615-2.133, P < .001). Subgroup analyses demonstrated that hyperuricemia significantly modified the association between Ln-EASIX and CMM. The area under the curve was 0.66, showing that EASIX has good prediction ability for CMM. EASIX is significantly and positively associated with the prevalence of CMM, suggesting its potential role as a biomarker for identifying high-risk individuals and underscoring the importance of endothelial dysfunction in CMM. This study utilized data from the National Health and Nutrition Examination Survey 2003 to 2020, including 20,040 adult participants. EASIX was calculated as lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelet count (109/L). CMM was defined as the co-occurrence of 2 or more cardiometabolic diseases, including type 2 diabetes mellitus, myocardial infarction, and stroke. Weighted logistic regression models, restricted cubic spline regression model, subgroup analyses were employed to assess the association. The receiver operating characteristic curve and area under the curve were used to assess the predictive power of EASIX.