Gottlieb Stephen S, Harris Kristie, Todd John, Estis Joel, Christenson Robert H, Torres Victoria, Whittaker Kerry, Rebuck Heather, Wawrzyniak Andrew, Krantz David S
University of Maryland School of Medicine, Baltimore, MD, USA.
University of Maryland School of Medicine, Baltimore, MD, USA; Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Clin Biochem. 2015 Mar;48(4-5):292-6. doi: 10.1016/j.clinbiochem.2014.12.012. Epub 2014 Dec 23.
Concentrations of endothelin I (ET1) are elevated in CHF patients and, like other biomarkers that reflect hemodynamic status and cardiac pathophysiology, are prognostic. The Singulex assay (Sgx-ET1) measures the active form of ET1, with a short in vivo half-life and the Brahms assay measures C-terminal endothelin-1 (CT-ET1), a modified (degraded) product with longer half-life. We aimed to determine the prognostic importance of active and modified forms of endothelin 1 (Singulex and Brahms assays) in comparison with other commonly measured biomarkers of inflammation, hemodynamic status and cardiac physiology in CHF.
Plasma biomarkers (Sgx-ET1, CT-ET1, NTproBNP, IL-6, TNFα, cTnI, VEGF, hs-CRP, Galectin-3, ST2) were measured in 134 NYHA class II and III CHF patients with systolic dysfunction. Prognostic importance of biomarkers for hospitalization or death were calculated by both logistic regression and Kaplan-Meier survival analyses.
CT-ET1 (OR=5.2, 95% CI=1.7-15.7) and Sgx-ET1 (OR=2.9, CI=1.1-7.7) were independent predictors of hospitalization and death and additively predicted events after adjusting for age, sex, and other significant biomarkers. Other biomarkers did not improve the model. Similarly, in Cox regression analysis, only CT-ET1 (HR 3.4, 95% CI=1.4-8.4), VEGF (2.7, 95% CI=1.3-5.4), and Sgx-ET1 (HR 2.6, 95% CI=1.2-5.6) were independently prognostic.
Elevated concentrations of endothelin 1 predict mortality and hospitalizations in HF patients. Endothelin 1 was more prognostic than commonly obtained hemodynamic, inflammatory, and fibrotic biomarkers. Two different assays of endothelin 1 independently and synergistically were prognostic, suggesting either complementary information or extreme prognostic importance.
慢性心力衰竭（CHF）患者体内内皮素-1（ET1）浓度升高，与其他反映血流动力学状态和心脏病理生理学的生物标志物一样，具有预后价值。Singulex检测法（Sgx-ET1）测量的是ET1的活性形式，其体内半衰期较短；Brahms检测法测量的是C端内皮素-1（CT-ET1），这是一种半衰期较长的修饰（降解）产物。我们旨在确定内皮素-1的活性形式和修饰形式（Singulex和Brahms检测法）与其他常用于测量CHF炎症、血流动力学状态和心脏生理学的生物标志物相比，其预后重要性如何。
对134例纽约心脏协会（NYHA）心功能II级和III级且存在收缩功能障碍的CHF患者的血浆生物标志物（Sgx-ET1、CT-ET1、N末端脑钠肽前体（NTproBNP）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）、心肌肌钙蛋白I（cTnI）、血管内皮生长因子（VEGF）、高敏C反应蛋白（hs-CRP）、半乳糖凝集素-3、ST2）进行检测。通过逻辑回归和Kaplan-Meier生存分析计算生物标志物对住院或死亡的预后重要性。
CT-ET1（比值比（OR）=5.2，95%置信区间（CI）=1.7 - 15.7）和Sgx-ET1（OR=2.9，CI=1.1 - 7.7）是住院和死亡的独立预测因子，在调整年龄、性别和其他重要生物标志物后，二者相加可预测事件发生。其他生物标志物未改善该模型。同样，在Cox回归分析中，只有CT-ET1（风险比（HR）3.4，95%CI=1.4 - 8.4）、VEGF（2.7，95%CI=1.3 - 5.4）和Sgx-ET1（HR 2.6，95%CI=1.2 - 5.6）具有独立的预后价值。
内皮素-1浓度升高可预测心力衰竭患者的死亡率和住院率。内皮素-1比常用的血流动力学、炎症和纤维化生物标志物更具预后价值。两种不同的内皮素-1检测法具有独立且协同的预后价值，提示二者可能提供互补信息或具有极高的预后重要性。
