The Prognostic Value of Big Endothelin-1 in More Than 2,300 Patients With Heart Failure Enrolled in the Valsartan Heart Failure Trial (Val-HeFT)

Serge Masson, Roberto Latini, Inder Anand, Simona Barlera, Dianne Judd, Monica Salio, Francesco Perticone, Giampaolo Perini, Gianni Tognoni, Jay N Cohn

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Background: Endothelin is elevated in heart failure and contributes to neurohormonal activation, hemodynamic deterioration, and cardiovascular remodeling. Here, we examined its prognostic value in a large population of patients with chronic heart failure. Methods and Results: Big endothelin-1 (Big ET-1) and 4 other neurohormones were measured at study entry in 2359 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) and their concentrations related to outcome over a median follow-up of 23 months. Baseline concentration of Big ET-1 (median 0.80 pmol/L) was proportional to severity of disease (New York Heart Association class, left ventricular structure and function). High circulating concentrations of brain natriuretic peptide (BNP), creatinine and bilirubin, advanced New York Heart Association class, elevated body mass index, and the presence of atrial fibrillation were independently associated to higher concentrations of Big ET-1. Big ET-1 (ranking second just behind BNP among neurohormonal factors) was an independent predictor of outcome defined as all-cause mortality (hazard ratio 1.49, 95% CI 1.20-1.84, P = .0003) or the combined endpoint of mortality and morbidity (hazard ratio 1.43, 95% CI 1.20-1.69, P < .0001) and provided incremental prognostic value compared with BNP. Conclusions: In a large population of patients with symptomatic heart failure, the circulating concentration of Big ET-1, a precursor of the paracrine and bioactive peptide ET-1, was an independent marker of mortality and morbidity. In this setting, BNP remained the strongest neurohormonal prognostic factor.

Original languageEnglish (US)
Pages (from-to)375-380
Number of pages6
JournalJournal of cardiac failure
Volume12
Issue number5
DOIs
StatePublished - Jun 1 2006

Fingerprint

Valsartan
Endothelin-1
Brain Natriuretic Peptide
Heart Failure
Mortality
Morbidity
Endothelins
Left Ventricular Function
Bilirubin
Atrial Fibrillation
Population
Neurotransmitter Agents
Creatinine
Body Mass Index
Hemodynamics
Peptides

Keywords

  • Clinical trial
  • Endothelin
  • Heart failure
  • Neurohormones
  • Prognosis

Cite this

The Prognostic Value of Big Endothelin-1 in More Than 2,300 Patients With Heart Failure Enrolled in the Valsartan Heart Failure Trial (Val-HeFT). / Masson, Serge; Latini, Roberto; Anand, Inder; Barlera, Simona; Judd, Dianne; Salio, Monica; Perticone, Francesco; Perini, Giampaolo; Tognoni, Gianni; Cohn, Jay N.

In: Journal of cardiac failure, Vol. 12, No. 5, 01.06.2006, p. 375-380.

Research output: Contribution to journalArticle

Masson, Serge ; Latini, Roberto ; Anand, Inder ; Barlera, Simona ; Judd, Dianne ; Salio, Monica ; Perticone, Francesco ; Perini, Giampaolo ; Tognoni, Gianni ; Cohn, Jay N. / The Prognostic Value of Big Endothelin-1 in More Than 2,300 Patients With Heart Failure Enrolled in the Valsartan Heart Failure Trial (Val-HeFT). In: Journal of cardiac failure. 2006 ; Vol. 12, No. 5. pp. 375-380.
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T1 - The Prognostic Value of Big Endothelin-1 in More Than 2,300 Patients With Heart Failure Enrolled in the Valsartan Heart Failure Trial (Val-HeFT)

AU - Masson, Serge

AU - Latini, Roberto

AU - Anand, Inder

AU - Barlera, Simona

AU - Judd, Dianne

AU - Salio, Monica

AU - Perticone, Francesco

AU - Perini, Giampaolo

AU - Tognoni, Gianni

AU - Cohn, Jay N

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Background: Endothelin is elevated in heart failure and contributes to neurohormonal activation, hemodynamic deterioration, and cardiovascular remodeling. Here, we examined its prognostic value in a large population of patients with chronic heart failure. Methods and Results: Big endothelin-1 (Big ET-1) and 4 other neurohormones were measured at study entry in 2359 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) and their concentrations related to outcome over a median follow-up of 23 months. Baseline concentration of Big ET-1 (median 0.80 pmol/L) was proportional to severity of disease (New York Heart Association class, left ventricular structure and function). High circulating concentrations of brain natriuretic peptide (BNP), creatinine and bilirubin, advanced New York Heart Association class, elevated body mass index, and the presence of atrial fibrillation were independently associated to higher concentrations of Big ET-1. Big ET-1 (ranking second just behind BNP among neurohormonal factors) was an independent predictor of outcome defined as all-cause mortality (hazard ratio 1.49, 95% CI 1.20-1.84, P = .0003) or the combined endpoint of mortality and morbidity (hazard ratio 1.43, 95% CI 1.20-1.69, P < .0001) and provided incremental prognostic value compared with BNP. Conclusions: In a large population of patients with symptomatic heart failure, the circulating concentration of Big ET-1, a precursor of the paracrine and bioactive peptide ET-1, was an independent marker of mortality and morbidity. In this setting, BNP remained the strongest neurohormonal prognostic factor.

AB - Background: Endothelin is elevated in heart failure and contributes to neurohormonal activation, hemodynamic deterioration, and cardiovascular remodeling. Here, we examined its prognostic value in a large population of patients with chronic heart failure. Methods and Results: Big endothelin-1 (Big ET-1) and 4 other neurohormones were measured at study entry in 2359 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) and their concentrations related to outcome over a median follow-up of 23 months. Baseline concentration of Big ET-1 (median 0.80 pmol/L) was proportional to severity of disease (New York Heart Association class, left ventricular structure and function). High circulating concentrations of brain natriuretic peptide (BNP), creatinine and bilirubin, advanced New York Heart Association class, elevated body mass index, and the presence of atrial fibrillation were independently associated to higher concentrations of Big ET-1. Big ET-1 (ranking second just behind BNP among neurohormonal factors) was an independent predictor of outcome defined as all-cause mortality (hazard ratio 1.49, 95% CI 1.20-1.84, P = .0003) or the combined endpoint of mortality and morbidity (hazard ratio 1.43, 95% CI 1.20-1.69, P < .0001) and provided incremental prognostic value compared with BNP. Conclusions: In a large population of patients with symptomatic heart failure, the circulating concentration of Big ET-1, a precursor of the paracrine and bioactive peptide ET-1, was an independent marker of mortality and morbidity. In this setting, BNP remained the strongest neurohormonal prognostic factor.

KW - Clinical trial

KW - Endothelin

KW - Heart failure

KW - Neurohormones

KW - Prognosis

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