Prognostic significance of active and modified forms of endothelin 1 in patients with heart failure with reduced ejection fraction

Stephen S. Gottlieb, Kristie Harris, John Todd, Joel Estis, Robert H. Christenson, Victoria Torres, Kerry Whittaker, Heather Rebuck, Andrew Wawrzyniak, David S. Krantz

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)292-296
Number of pages5
JournalClinical Biochemistry
Volume48
Issue number4-5
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

Fingerprint

Endothelin-1
Biomarkers
Heart Failure
Assays
Hemodynamics
Hospitalization
Vascular Endothelial Growth Factor A
Half-Life
Galectin 3
Mortality
Endothelins
Physiology
Kaplan-Meier Estimate
Survival Analysis
Regression analysis
Logistics
Interleukin-6
Logistic Models
Regression Analysis
Inflammation

Keywords

  • Congestive
  • Endothelin
  • Heart failure
  • Prognosis

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Prognostic significance of active and modified forms of endothelin 1 in patients with heart failure with reduced ejection fraction. / Gottlieb, Stephen S.; Harris, Kristie; Todd, John; Estis, Joel; Christenson, Robert H.; Torres, Victoria; Whittaker, Kerry; Rebuck, Heather; Wawrzyniak, Andrew; Krantz, David S.

In: Clinical Biochemistry, Vol. 48, No. 4-5, 01.03.2015, p. 292-296.

Research output: Contribution to journalArticle

Gottlieb, SS, Harris, K, Todd, J, Estis, J, Christenson, RH, Torres, V, Whittaker, K, Rebuck, H, Wawrzyniak, A & Krantz, DS 2015, 'Prognostic significance of active and modified forms of endothelin 1 in patients with heart failure with reduced ejection fraction', Clinical Biochemistry, vol. 48, no. 4-5, pp. 292-296. https://doi.org/10.1016/j.clinbiochem.2014.12.012
Gottlieb, Stephen S. ; Harris, Kristie ; Todd, John ; Estis, Joel ; Christenson, Robert H. ; Torres, Victoria ; Whittaker, Kerry ; Rebuck, Heather ; Wawrzyniak, Andrew ; Krantz, David S. / Prognostic significance of active and modified forms of endothelin 1 in patients with heart failure with reduced ejection fraction. In: Clinical Biochemistry. 2015 ; Vol. 48, No. 4-5. pp. 292-296.
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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.

PY - 2015/3/1

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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

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