What question did this study set out to answer?

This research aims to clarify the relationship between endothelial activation, as measured by EASIX, and cardiometabolic multimorbidity (CMM).

April 12, 2026Open Access

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

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Cardiometabolic multimorbidity (n=20040). Intervention: Endothelial Activation and Stress Index (EASIX). Primary outcome: Cardiometabolic multimorbidity (CMM) (OR 1.39, 95% CI 1.19-1.64, p=<.001).

Key Result

Each unit increase in natural logarithmic transformed EASIX was associated with a 39% increased risk of cardiometabolic multimorbidity (OR 1.39; 95% CI 1.19-1.64; P<0.001).

Key Points

This research aims to clarify the relationship between endothelial activation, as measured by EASIX, and cardiometabolic multimorbidity (CMM).
Analyzed data from NHANES 2003-2020 with 20,040 adult participants.
Calculated EASIX using lactate dehydrogenase, creatinine, and platelet count.
Employed weighted logistic regression and restricted cubic spline models to measure associations.
Conducted subgroup analyses based on hyperuricemia's effect on the relationship.
Each unit increase in Ln-EASIX is linked to a 39% higher risk of CMM.
A significant positive association is found when Ln-EASIX is greater than -0.916.
EASIX demonstrated a good predictive ability for CMM, with an area under the curve of 0.66.

Study Design

Type

Cross-Sectional (n=20,040)

Multicenter

Yes

Structured PICO

Is the Endothelial Activation and Stress Index (EASIX) associated with an increased risk of cardiometabolic multimorbidity in adults?

Population

20,040 adult participants from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2020

Intervention

Endothelial Activation and Stress Index (EASIX), calculated as lactate dehydrogenase (U/L) × creatinine (mg/dL) / platelet count (10^9/L)

Outcome

Cardiometabolic multimorbidity (CMM), defined as the co-occurrence of 2 or more cardiometabolic diseases, including type 2 diabetes mellitus, myocardial infarction, and strokecomposite

Higher levels of the Endothelial Activation and Stress Index (EASIX) are significantly associated with an increased prevalence of cardiometabolic multimorbidity, suggesting its potential utility as a biomarker for identifying high-risk individuals.

Main Result

Effect estimate: OR 1.39 (95% CI 1.19-1.64)

p-value: p=<.001

Abstract

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 −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 (10 9 /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.