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

被引:42
作者
Gombos, Timea [1 ]
Mako, Veronika [1 ]
Cervenak, Laszlo [1 ]
Papassotiriou, Jana [2 ]
Kunde, Jan [2 ]
Harsfalvi, Jolan [3 ]
Forhecz, Zsolt [1 ]
Pozsonyi, Zoltan [1 ]
Borgulya, Gabor [4 ]
Janoskuti, Livia [1 ]
Prohaszka, Zoltan [4 ]
机构
[1] Semmelweis Univ, Dept Internal Med 3, H-1125 Budapest, Hungary
[2] BRAHMS Aktiengesell, Dept Res, D-16761 Hennigsdorf, Germany
[3] Univ Debrecen, Clin Res Ctr, H-4012 Debrecen, Hungary
[4] Hungarian Acad Sci, Res Grp Inflammat Biol & Immunogenom, Budapest, Hungary
关键词
Heart failure; ADAMTS13; von Willebrand factor; endothelial dysfunction; hepatic failure; THROMBOTIC THROMBOCYTOPENIC PURPURA; HEMOLYTIC-UREMIC SYNDROME; MULTIORGAN FAILURE; ENDOTHELIAL-CELLS; LIVER DISTURBANCE; METALLOPROTEASE; RISK; VWF; INFLAMMATION; DYSFUNCTION;
D O I
10.1160/TH09-01-0036
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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% Cl 0.58-0.84) independently and significantly predicted short-term (I 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.
引用
收藏
页码:573 / 580
页数:8
相关论文
共 39 条
[1]   Cachexia in chronic heart failure: prognostic implications and novel therapeutic approaches. [J].
Akashi Y.J. ;
Springer J. ;
Anker S.D. .
Current Heart Failure Reports, 2005, 2 (4) :198-203
[2]   Measurement of the binding forces between von Willebrand factor and variants of platelet glycoprotein Ibα using optical tweezers [J].
Arya, M ;
López, JA ;
Romo, GM ;
Dong, JF ;
McIntire, LV ;
Moake, JL ;
Anvari, B .
LASERS IN SURGERY AND MEDICINE, 2002, 30 (04) :306-312
[3]   Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex:: studies using optical tweezers [J].
Arya, M ;
Anvari, B ;
Romo, GM ;
Cruz, MA ;
Dong, JF ;
McIntire, LV ;
Moake, JL ;
López, JA .
BLOOD, 2002, 99 (11) :3971-3977
[4]   Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow [J].
Bernardo, A ;
Ball, C ;
Nolasco, L ;
Moake, JF ;
Dong, JF .
BLOOD, 2004, 104 (01) :100-106
[5]   A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders [J].
Besbas, N. ;
Karpman, D. ;
Landau, D. ;
Loirat, C. ;
Proesmans, W. ;
Remuzzi, G. ;
Rizzoni, G. ;
Taylor, C. M. ;
Van de Kar, N. ;
Zimmerhackl, L. B. .
KIDNEY INTERNATIONAL, 2006, 70 (03) :423-431
[6]   Inflammation-associated ADAMTS13 deficiency promotes formation of ultra-large von Willebrand factor [J].
Bockmeyer, Clemens L. ;
Claus, Ralf A. ;
Budde, Ulrich ;
Kentouche, Karim ;
Schneppenheim, Reinhard ;
Loesche, Wolfgang ;
Reinhart, Konrad ;
Brunkhorst, Frank M. .
HAEMATOLOGICA, 2007, 93 (01) :137-140
[7]   High von Willebrand factor levels increase the risk of first ischemic stroke -: Influence of ADAMTS13, inflammation, and genetic variability [J].
Bongers, Tamara N. ;
de Maat, Moniek P. M. ;
van Goor, Mary-Lou P. J. ;
Bhagwanbali, Vinod ;
van Vilet, Huub H. D. M. ;
Garcia, Encarna B. Gomez ;
Dippel, Diederik W. J. ;
Leebeek, Frank W. G. .
STROKE, 2006, 37 (11) :2672-2677
[8]   Sudden unexpected cardiac death: Methods and results of a national pilot survey [J].
Bowker, TJ ;
Wood, DA ;
Davies, MJ .
INTERNATIONAL JOURNAL OF CARDIOLOGY, 1995, 52 (03) :241-250
[9]   Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease [J].
Caprioli, J ;
Castelletti, F ;
Bucchioni, S ;
Bettinaglio, P ;
Bresin, E ;
Pianetti, G ;
Gamba, S ;
Brioschi, S ;
Daina, E ;
Remuzzi, G ;
Noris, M .
HUMAN MOLECULAR GENETICS, 2003, 12 (24) :3385-3395
[10]  
CEJKA J, 1982, CLIN CHEM, V28, P1356