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Endothelial dysfunction assessed by the endothelial activation and stress index (EASIX) predicts risk of mortality in

Bent Estler1, Hanna Fröhlich1, Tobias Täger1

  • 1Department of Cardiology, Angiology and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

International Journal of Cardiology
|July 5, 2025
PubMed

Insights

The Endothelial Activation and Stress Index (EASIX) can predict mortality risk in chronic heart failure (CHF) patients. This novel biomarker, calculated from routine lab tests, offers valuable prognostic information for CHF management.

Area of Science:

  • Cardiology
  • Biomarker Discovery
  • Prognostic Medicine

Background:

  • Endothelial dysfunction is a hallmark of chronic heart failure (CHF) but lacks routine quantification.
  • The Endothelial Activation and Stress Index (EASIX) uses creatinine, lactate dehydrogenase, and platelets to predict outcomes in various conditions.
  • EASIX has shown prognostic value in conditions such as allogeneic stem cell transplantation, COVID-19, and coronary artery disease.

Purpose of the Study:

  • To investigate the prognostic utility of the Endothelial Activation and Stress Index (EASIX) in patients with chronic heart failure (CHF).
  • To determine if EASIX can serve as a novel biomarker for predicting mortality risk in CHF patients.

Main Methods:

  • Utilized training (n=1796) and validation (n=1796) cohorts from a CHF registry.
  • Assessed five-year overall survival using multivariable Cox regression, adjusting for clinical covariates.
  • Employed fractional polynomials for non-linear relationships and evaluated prognostic performance with Brier score and concordance index.

Main Results:

  • EASIX demonstrated a moderate correlation with NT-proBNP, NYHA stage, and LVEF.
  • Increased EASIX levels were associated with a significantly higher hazard of death in both cohorts (HR per log2 increase: 1.51-1.59).
  • Pre-established EASIX cut-offs independently predicted increased mortality risk (HRs ranging from 2.14 to 3.34).

Conclusions:

  • The Endothelial Activation and Stress Index (EASIX) is a novel and effective biomarker for predicting mortality risk in patients with chronic heart failure (CHF).
  • EASIX provides independent prognostic information, consistent across various heart failure etiologies and stages.
Abstract

Keywords:
Chronic heart failureCreatinineEASIXEndothelial activation and stress indexLactate dehydrogenasePlatelets

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