TY - JOUR
T1 - Prognostic significance of active and modified forms of endothelin 1 in patients with heart failure with reduced ejection fraction
AU - Gottlieb, Stephen S.
AU - Harris, Kristie
AU - Todd, John
AU - Estis, Joel
AU - Christenson, Robert H.
AU - Torres, Victoria
AU - Whittaker, Kerry
AU - Rebuck, Heather
AU - Wawrzyniak, Andrew
AU - Krantz, David S.
N1 - Funding Information:
This study was supported by NHLBI grant 1R01 HL085730 .
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Objectives: 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. Design and 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. •Endothelin 1 predicted mortality & hospitalizations in heart failure; addition of other biomarkers did not improve the model.
AB - Objectives: 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. Design and 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. •Endothelin 1 predicted mortality & hospitalizations in heart failure; addition of other biomarkers did not improve the model.
KW - Congestive
KW - Endothelin
KW - Heart failure
KW - Prognosis
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U2 - 10.1016/j.clinbiochem.2014.12.012
DO - 10.1016/j.clinbiochem.2014.12.012
M3 - Article
C2 - 25541019
AN - SCOPUS:84924580810
VL - 48
SP - 292
EP - 296
JO - Clinical Biochemistry
JF - Clinical Biochemistry
SN - 0009-9120
IS - 4-5
ER -