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European Heart Journal 2002 23(12):967-974; doi:10.1053/euhj.2001.2977
Copyright © 2002 by the European Society of Cardiology.
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Chromogranin A in heart failure. A novel neurohumoral factor and a predictor for mortality

C. Ceconia, R. Ferrarib,f1, T. Bachettia, C. Opasichc, M. Volterranid, B. Colomboe, G. Parrinellof and A. Cortie

a Cardiovascular Pathophysiology Research Centre, Salvatore Maugeri Foundation, IRCCS, Gussago, Italy
b Chair of Cardiology, University of Ferrara, Italy
c Medical Centre of Pavie, Salvatore Maugeri Foundation, IRCCS, Italy
d Medical Centre of Gussago, Salvatore Maugeri Foundation, IRCCS, Italy
e Department of Medical Statistics and Biometry, University of Brescia, Italy
f DIBIT, San Raffaele Scientific Institute, IRCCS, Milan, Italy

Received August 13, 2001; accepted August 22, 2001

Abstract

Background In chronic heart failure, several hormonal systems are activated with diagnostic and prognostic implications. We tested the hypotheses that serum Chromogranin-A (CgA)—a 49kDa acid protein present in the secretor granules of neuroendocrine cells—is increased in chronic heart failure and that CgA levels are a predictive factor for mortality.

Methods and Results In 160 patients with chronic heart failure, we measured serum CgA and other neuroendocrine hormones. The results showed that CgA is increased in chronic heart failure and the increase is related to the clinical severity of the syndrome: CgA levels in New York Heart Failure (NYHA) class II (median 146·9ng.ml–1, inter-quartiles 108·3–265·5) were significantly higher (P<0·05) than in class I (median 109·7ng.ml–1, inter-quartiles 96·7–137·6), and significantly lower (P<0·05) than in class III (median 279·0ng.ml–1, inter-quartiles 203·6–516·1). Class IV patients showed the highest serum levels of CgA (median 545·0ng.ml–1, inter-quartiles 231·8–1068·3), being statistically significantly different from class III patients (P<0·001). The association between survival and some recognized variables of prognostic significance, including CgA was also studied. The results showed that ejection fraction, noradrenaline, atrial natriuretic peptide, NYHA class and CgA were significant univariate prognosticators; however, in the multivariate analysis by the Cox proportional-hazard model, CgA and NYHA class were the only independent predictive factors for mortality (P<0·005, RR=1·22, 95% CI=1·06–1·41 andP =0·04, RR=1·58, 95% CI=1·02–2·46, respectively).

Conclusions CgA is a pro-hormone, precursor of several active fragments likely to exert biological effects in chronic heart failure. CgA serum levels are increased in patients with chronic heart failure and are a predictive factor for mortality.

Key Words: Heart failure, Chromogranin-A, neuroendocrine activation, mortality

f1 Correspondence: Prof. Roberto Ferrari, Dipartimento di Medicina Clinica e Sperimentale, Università di Ferrara, Corso Giovecca 203, 44100, Ferrara, Italy.

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