Association between thrombin-activatable fibrinolysis inhibitor (TAFI) and clinical outcome in patients with unstable angina pectoris

Decrease of fibrinolytic potential is considered to be a risk factor for arterial thrombosis. The recently described thrombin-activatable fibrincilysis inhibitor (TAFI) attenuates fibrincilysis by cleaving of the C-terminal lysine residues from fibrin,thereby inhibiting tPA mediated plasminogen activation. The role of plasma TAR antigen (Ag) levels and gene polymorphisms in arterial thrombosis is still not elucidated. In this prospective study, the association between plasma TAR Ag levels and the TAR gene polymorphisms, Ala147Thr,Thr325Ile and 438A/G, with refractory unstable angina pectoris (UAP) was determined. The study population consisted of 209 patients with UAP of whom 76 were refractory and 133 non-refractory to medical treatment. In the same study population the contribution of these polymorphisms to plasma TAR Ag levels was determined. Plasma TAR Ag levels were significantly higher in non-refractory patients compared to refractory patients (geometric mean 114.4 and 105.6 U/dl respectively, p=0.042). Plasma TAR Ag levels in the lowest quartile resulted in a 2.6 fold (95% confidence interval 1.2-5.9) increased risk for refractory UAP compared to plasma TAR Ag levels in the upper quartile. The three studied TAR polymorphisms had an independent and additive effect on plasma TAR Ag levels. However, no significant association between the individual TAR polymorphisms and refractiveness was observed. In conclusion, in this study population plasma TAR Ag levels are significantly correlated with refractiveness in patients with UAR Furthermore, all three polymorphisms contribute independently to plasma TAR Ag levels, but not to refractiveness.