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Levels of von Willebrand factor antigen and von Willebrand factor cleaving protease (ADAMTS13) activity predict clinical events in chronic heart failure

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH09-01-0036
Issue: 2009: 102/3 (Sep) pp. 421-610
Pages: 573-580

Levels of von Willebrand factor antigen and von Willebrand factor cleaving protease (ADAMTS13) activity predict clinical events in chronic heart failure

Tímea Gombos1; Veronika Makó1; László Cervenak1; Jana Papassotiriou2; Jan Kunde2; Jolán Hársfalvi3; Zsolt Förhécz1; Zoltán Pozsonyi1; Gábor Borgulya4; Lívia Jánoskuti1; Zoltán Prohászka4

1IIIrd Department of Internal Medicine, Semmelweis University, Budapest, Hungary; 2Department of Research, BRAHMS Aktiengesellschaft, Neuendorfstr. 25, D-16761 Hennigsdorf, Germany; 3Clinical Research Center, University of Debrecen, Debrecen, Hungary; 4Research Group of Inflammation Biology and Immunogenomics, Hungarian Academy of Sciences, Budapest, Hungary

Summary

Decreased activity of ADAMTS13, the von Willebrand factor (VWF) cleaving protease, was recently reported in cardiovascular diseases and in hepatic failure. Chronic heart failure (CHF) is characterised by abnormalities of left ventricular function accompanied by the failure of the liver and dysregulation of endothelial activation. Therefore, the aim of our study was to measure ADAMTS13 activity in CHF, and determine the prognostic value of VWF and ADAMTS13 on major clinical events in CHF. ADAMTS13 activity (measured by FRETS-VWF73 substrate) was decreased in CHF (n = 152, left ventricular ejection fraction <45%), and it correlated negatively with B-type natriuretic peptide (BNP) NYHA (New York Heart Association) classes, markers of synthetic capacity of the liver and endothelial dysfunction (all p<0.005). Both, high VWF:Ag levels (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.189–1.943), and low ADAMTS13/VWF:Ag ratios (HR 0.70, 95% CI 0.58–0.84) independently and significantly predicted short-term (1 year followup) clinical adverse events in heart failure (HF). Decreased activity of ADAMTS13 with concomitant high VWF:Ag levels is a significant independent predictor of clinical events in CHF. The levels of the two molecules may integrate the impaired synthetic capacity of the liver and the disturbed endothelial regulation and can therefore be a useful tool to predict clinical events in CHF.

Keywords

Endothelial dysfunction, Heart failure, von Willebrand factor, ADAMTS13, hepatic failure

DOI

http://dx.doi.org/10.1160/TH09-01-0036

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