The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis

Rüdiger Blindt; Katja Stellbrink; Anita de Taeye; Robert Müller; Paul Kiefer; Eray Yagmur; Christian Weber; Malte Kelm; Rainer Hoffmann

doi:10.1160/TH07-05-0324

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2007; 98(06): 1329-1334
DOI: 10.1160/TH07-05-0324

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis

Rüdiger Blindt

¹Department of Cardiology, University Hospital Aachen, Germany

,

Katja Stellbrink

¹Department of Cardiology, University Hospital Aachen, Germany

,

Anita de Taeye

¹Department of Cardiology, University Hospital Aachen, Germany

,

Robert Müller

²Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Aachen, Germany

,

Paul Kiefer

²Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Aachen, Germany

,

Eray Yagmur

²Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Aachen, Germany

,

Christian Weber

³Institute of Cardiovascular Molecular Research (IMCAR), University Hospital Aachen, Germany

,

Malte Kelm

¹Department of Cardiology, University Hospital Aachen, Germany

,

Rainer Hoffmann

¹Department of Cardiology, University Hospital Aachen, Germany

› Institutsangaben

Abstract

Summary

Low-response to the P2Y12 adenosine diphosphate (ADP)-receptor antagonist clopidogrel was suggested to correspond to a higher incidence of stent thrombosis (ST). This prospective observational study assessed the capability of two platelet function assays, e.g. direct measurement of the phosphorylation status of vasodilator-stimulated phosphoprotein (VASP) and ADP-induced platelet aggregation for definition of the individual risk to develop ST. Ninety-nine patients with an elevated high risk to develop ST were enrolled. All patients received a dual antiplatelet therapy consisting of 100 mg aspirin and 75 mg clopidogrel during an observation period of six months. Flow cytometry of VASP phosphorylation and densitometrically-determined measurement of ADP-induced platelet aggregation was performed 72–96 hours after stent implantation. These data were related to angiographically confirmed ST. Nine patients suffered from angiographically confirmed ST (9.1%). The meanVASP-platelet reactivity indices (VASP-PRI) and values for ADP-induced platelet aggregation in the ST group were significantly higher (60.8 ± 13.0 and 60.9 ± 13.1, respectively) compared to patients without ST (41.3 ± 14.0 and 50.8 ± 14.4, P<0.001 vs. 0.048, respectively). There was a fair correlation between both methods using non-linear regression analysis (r=0.332). In a multivariate analysis, VASP was the only independent predictor of ST and was superior to previously identified angiographic parameters. Receiver- operator characteristic (ROC) curve analysis revealed a cut-off value for VASP-PRI of <48% to be associated with low risk of ST. In conclusion, determination ofVASP phosphorylation is superior to conventional platelet aggregometry and angiographic parameters for assessing the risk of ST. Patients with a VASP-PRI >48% seem to have a significantly increased risk.

Keywords

Stent thrombosis - VASP phosphorylation - platelet aggregometry - clopidogrel

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Referenzen

References
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