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European Heart Journal 2004 25(18):1620-1625; doi:10.1016/j.ehj.2004.06.036
Copyright © 2004 by the European Society of Cardiology.
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Clinical research

The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure

Lothar Rössiga, Stephan Fichtlscherera, Christopher Heeschena, Jürgen Bergerb, Stefanie Dimmelera,* and Andreas M. Zeihera

a Division of Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
b Institute of Mathematics and Computer Science in Medicine, University of Hamburg, Hamburg, Germany

Received January 19, 2004; revised June 9, 2004; accepted June 24, 2004 * Corresponding author. Tel.: +49-696-301-7440; fax: +49-696-301-7113 (E-mail: dimmeler{at}em.uni-frankfurt.de).

AIM: Systemic inflammation with elevated serum levels of circulating pro-inflammatory cytokines is a major determinant of prognosis in heart failure (HF). Since serum of patients with HF induces apoptosis of endothelial cells (EC), we aimed to determine whether the pro-apoptotic activity in the serum may predict prognosis of patients with HF.

METHODS AND RESULTS: We measured the pro-apoptotic activity in the serum of 48 patients with HF of different aetiology by an ex vivo cell culture assay and subsequently monitored these patients for the single endpoint all-cause mortality. During follow-up, 16 patients died and 11 patients received a heart transplant. Survivors had a lower pro-apoptotic serum activity (P=0.007). By univariate analysis, pro-apoptotic serum activity, NYHA class, pro-BNP, low blood pressure, and creatinine levels were significantly associated with mortality. In a multivariable stepwise Cox-regression model, the pro-apoptotic serum activity (adjusted hazard ratio, HR=1.85 per %, P=0.008), elevated pro-BNP levels (HR=9.35 per log[pro-BNP], P=0.001), and low blood pressure (HR=0.96 per mmHg, P=0.041) remained as independent predictors of death.

CONCLUSION: In this exploratory study, the pro-apoptotic serum capacity is independently associated with a worse prognosis in patients with HF, suggesting that the assessment of serum-induced EC apoptosis could provide an integrative estimate of the deleterious effects of various pro-inflammatory cytokines and other cytotoxic factors in HF.


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