通过内皮激活和应激指数（EASIX）评估的内皮功能障碍可预测慢性心力衰竭患者的死亡风险。

Endothelial dysfunction assessed by the endothelial activation and stress index (EASIX) predicts risk of mortality in chronic heart failure patients.

作者信息

Estler Bent, Fröhlich Hanna, Täger Tobias, Hund Hauke, Frey Norbert, Luft Thomas, Frankenstein Lutz

机构信息

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

出版信息

Int J Cardiol. 2025 Nov 1;438:133566. doi: 10.1016/j.ijcard.2025.133566. Epub 2025 Jul 3.

DOI:10.1016/j.ijcard.2025.133566

PMID:40617481

Abstract

BACKGROUND

Endothelial dysfunction accompanies chronic heart failure (CHF) but is hard to quantify in routine practice. The Endothelial Activation and Stress Index (EASIX), calculated from creatinine, lactate dehydrogenase, and platelets, predicts mortality and complications in conditions like allogeneic stem cell transplantation, COVID-19, and coronary artery disease. Aim To evaluate if EASIX is a prognostic biomarker in patients with CHF.

METHODS

Training (n = 1796) and validation cohorts (n = 1796) included all patients from the outpatients' CHF registry of the University of Heidelberg, Germany, with available laboratory parameters for EASIX calculations at first clinical presentation. Five-year overall survival was assessed by multivariable Cox regression adjusting for age, sex, New York Heart Association (NYHA) score, etiology of heart failure, heart failure category, and NT- proBNP as covariates. Fractional polynomials modeled non-linear relationships, and prognostic performance was evaluated using the Brier score and concordance index.

RESULTS

EASIX moderately correlated with NT- proBNP, NYHA stage and left ventricular ejection fraction (LVEF), and associated with increased hazard of death in both cohorts (hazard ratio (HR) per log2 increase: training 1.51 (1.14-2.01), p < 0.01; validation 1.59 (1.25-2.01, p < 0.001). The effect was consistent across all etiologies, classes and stages of heart failure as assessed by fractional polynomials. Pre-established EASIX cut-offs independently predicted increased risk of mortality (cut-off 2.32: training: HR 2.14 (1.52-3.02), p < 0.001; validation: HR 3.34 (1.88-5.93), p < 0.0001). Both models (continuous and discrete EASIX values) were validated in the validation cohort using integrated Brier score and C-index.

CONCLUSIONS

EASIX is a novel biomarker to predict risk of mortality in patients with CHF.

摘要

背景

内皮功能障碍伴随慢性心力衰竭（CHF），但在常规临床实践中难以量化。内皮激活与应激指数（EASIX）由肌酐、乳酸脱氢酶和血小板计算得出，可预测异基因干细胞移植、COVID-19和冠状动脉疾病等情况下的死亡率和并发症。目的：评估EASIX是否为CHF患者的预后生物标志物。

方法

训练队列（n = 1796）和验证队列（n = 1796）纳入了德国海德堡大学门诊CHF登记处的所有患者，这些患者在首次临床表现时具有可用于计算EASIX的实验室参数。通过多变量Cox回归评估五年总生存率，对年龄、性别、纽约心脏协会（NYHA）评分、心力衰竭病因、心力衰竭类别和NT-proBNP作为协变量进行调整。分数多项式用于模拟非线性关系，并使用Brier评分和一致性指数评估预后性能。

结果

EASIX与NT-proBNP、NYHA分级和左心室射血分数（LVEF）中度相关，且与两个队列中死亡风险增加相关（每log2增加的风险比（HR）：训练队列1.51（1.14 - 2.01），p < 0.01；验证队列1.59（1.25 - 2.01），p < 0.001）。分数多项式评估显示，该效应在心力衰竭的所有病因、类别和阶段均一致。预先设定的EASIX临界值可独立预测死亡风险增加（临界值2.32：训练队列：HR 2.14（1.52 - 3.02），p < 0.001；验证队列：HR 3.34（1.88 - 5.93），p < 0.0001）。使用综合Brier评分和C指数在验证队列中对两个模型（连续和离散的EASIX值）进行了验证。