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Increased mortality with elevated plasma endothelin-1 in acute heart failure: An ASCEND-HF biomarker substudy
Perez, Antonio L. Grodin, Justin L. Wu, Yuping Hernandez, Adrian F. Butler, Javed Metra, Marco Felker, G. Michael Voors, Adriaan A. McMurray, John J. V. Armstrong, Paul W.
Perez, Antonio L.
Grodin, Justin L.
Wu, Yuping
Hernandez, Adrian F.
Butler, Javed
Metra, Marco
Felker, G. Michael
Voors, Adriaan A.
McMurray, John J. V.
Armstrong, Paul W.
Abstract
Aims: Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in pulmonary and systemic hypertension, as well as ventricular dysfunction, through effects on vascular smooth muscle, the kidneys, and cardiomyocytes. We aimed to determine the association between serial ET-1 levels and acute heart failure patient outcomes. Methods and results: We measured plasma ET-1 at baseline, 48–72 h, and 30 days in a cohort of 872 patients hospitalized with acute heart failure from the ASCEND-HF trial (randomized to nesiritide vs. placebo), and its association with 30-day mortality, 180-day mortality, in-hospital death or worsening heart failure, and 30-day mortality or rehospitalization. Median ET-1 was 7.6 [interquartile range (IQR) 5.9–10] pg/mL at baseline, 6.3 (IQR 4.9–8.1) pg/mL at 48–72 h, and 5.9 (IQR 4.7–7.9) pg/mL at 30 days (P < 0.001). Baseline and 48–72 h ET-1 were found to be independently associated with 180-day mortality in a multivariable analysis [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.3–2.0, P < 0.001 and HR 1.5, 95% CI 1.2–1.9, P = 0.001, respectively, log-transformed]. ET-1 that was measured at 48–72 h was also independently associated with death or worsening heart failure prior to discharge [odds ratio (OR) 1.6, 95% CI 1.03–2.4, P = 0.03]. These independent associations remained significant after including NT-proBNP in the multivariable analysis. Conclusions: We observed an independent association between elevated ET-1 and short-term in-hospital clinical outcomes and 180-day mortality in hospitalized patients with acute heart failure ET-1 provided additional prognostic information which was incremental to that yielded by NT-proBNP.
Keywords
endothelin-1, acute heart failure, prognosis
Date
2016
Type
Journal article
Journal
European Journal of Heart Failure
Book
Volume
18
Issue
3
Page Range
290-297
Article Number
ACU Department
Collections
Relation URI
DOI
Source URL
Event URL
Open Access Status
License
File Access
Controlled