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2015 ; 48
(4-5
): 292-6
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Prognostic significance of active and modified forms of endothelin 1 in patients
with heart failure with reduced ejection fraction
#MMPMID25541019
Gottlieb SS
; Harris K
; Todd J
; Estis J
; Christenson RH
; Torres V
; Whittaker K
; Rebuck H
; Wawrzyniak A
; Krantz DS
Clin Biochem
2015[Mar]; 48
(4-5
): 292-6
PMID25541019
show ga
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, TNF?, 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.