title: Prognostic significance of active and modified forms of endothelin 1 in patients with heart failure with reduced ejection fraction.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: sgottlie@medicine.umaryland.edu.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Gottlieb
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, USA; Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Kristie
authors.initials: K
authors.lastname: Harris
authors.affiliation: Singulex Inc., Alameda, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Todd
authors.affiliation: Singulex Inc., Alameda, CA, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Estis
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Christenson
authors.affiliation: Singulex Inc., Alameda, CA, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Torres
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Whittaker
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Rebuck
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wawrzyniak
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Krantz
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D006760:Hospitalization / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D011379:Prognosis; D013318:Stroke Volume / Q000502:physiology*
chemical_list: D015415:Biomarkers; D019332:Endothelin-1
keywords: Congestive; Endothelin; Heart failure; Prognosis