Copyright © 2004 by the European Society of Cardiology.
Clinical research
The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT
a Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche ‘Mario Negri’,Milan, Italy
b Cardiology Section, V.A. Medical Centre,Minneapolis, Minnesota, USA
c Novartis Pharmaceuticals Corporation,East Hanover, New Jersey, USA
d Cardiovascular Division, Department of Medicine, University of Minnesota Medical School,Minneapolis, Minnesota, USA
e Centro Studi ANMCO,Florence, Italy
* Correspondence to: Dr. Roberto Latini, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via Eritrea 62, 20157 Milan, Italy. Tel: +39.0239014454; Fax: +39 0233200049
E-mail address: latini{at}marionegri.it
Received 29 January 2003;
revised 1 October 2003;
accepted 30 October 2003
See page 281, for the editorial comment on this article
Abstract
Aims Plasma levels of individual neurohormones (NH) have been proposed as reliable indicators for risk stratification of patients with heart failure (HF). Mainly because of small sample size, the predictive value of different NH has never been compared, while taking into account demographic, clinical and echocardiographic markers of risk in HF.
Methods and results Plasma brain natriuretic peptide (BNP), norepinephrine (NE), renin activity (PRA), aldosterone (aldo) and endothelin were measured in 4300 patients before randomization in Val-HeFT. Univariate and multivariate Cox proportional hazard analyses were performed to investigate the relationship between NH and two primary study outcomes, mortality and combined mortality and morbidity (M/M). Higher baseline values for all NH were related to mortality and M/M, with univariate hazard ratios ranging from 1.13 [95% CI 0.99–1.30] (aldo) to 2.47 [2.13–2.87] (BNP) for mortality, and from 1.24 [1.11–1.39] (aldo) to 2.56 [2.28–2.89] (BNP) for M/M. In multivariate analyses, BNP had the strongest association with outcome, followed by NE and PRA. Patients with more activation of renin-angiotensin-aldosterone system tended to show greater benefit from valsartan; but the trend was not statistically significant.
Conclusion All the NHs evaluated in 4300 patients with stable moderate to severe HF were found to be significant markers of outcome, despite therapy with ACEi, BB and randomization to an angiotensin receptor blocker or placebo. Several of these markers have been implicated as contributors to progression of HF, but BNP, which is thought to be protective, was the most powerful indicator for poor outcome.
Key Words: Heart failure • Neurohormones • Outcome • Brain natriuretic peptide • Norepinephrine • Aldosterone • Renin • Endothelin
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