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European Heart Journal Advance Access originally published online on February 4, 2009
European Heart Journal 2009 30(7):789-796; doi:10.1093/eurheartj/ehp004
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Prognostic value of apoptosis markers in advanced heart failure patients

Alexander Niessner1, Philipp J. Hohensinner1, Kathrin Rychli1, Stephanie Neuhold1, Gerlinde Zorn1, Bernhard Richter1, Martin Hülsmann1, Rudolf Berger1, Deddo Mörtl1, Kurt Huber2, Johann Wojta1,* and Richard Pacher1

1 Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
2 Department of Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria

Received 13 April 2008; revised 11 December 2008; accepted 5 January 2009; online publish-ahead-of-print 4 February 2009.

* Corresponding author. Tel: +43 1 40400 2247, Fax: +43 1 40400 4216, Email: johann.wojta{at}meduniwien.ac.at

Aims: Apoptosis plays an important role in the progression of heart failure (HF). The purpose of this study was to assess whether the pro-apoptotic molecules apoptosis-stimulating fragment (FAS, CD95/APO-1) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) predict event-free survival of HF patients.

Methods and results: We assayed soluble (s)FAS and sTRAIL levels in 351 patients with advanced HF. During the median follow-up time of 16 months, 175 patients (50%) experienced the composite endpoints: rehospitalization and death. The hazard increased with sFAS concentrations, with a hazard ratio of 2.3 comparing fourth and first quartiles. This association remained significant after adjustment for B-type natriuretic peptide (BNP) and other risk factors in a Cox regression model (P = 0.014). Patients with high sFAS but low BNP had a comparable event-free survival rate with those with elevated BNP only (P = 0.78). Conversely, high sTRAIL concentrations were related to a better prognosis. Particularly, the risk of mortality dropped by 70% in the fourth quartile of sTRAIL (P = 0.001, multivariable Cox regression model).

Conclusion: sFAS is an independent risk predictor in advanced HF patients. It may be of particular value for the identification of high-risk patients in addition to BNP. Conversely, sTRAIL appears to be protective and could be an interesting therapeutic agent.

Key Words: TRAIL • FAS • Apoptosis • Heart failure • Cardiomyopathy


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