The thrombin generation is associated with the PlA1/A2 β3 integrin polymorphism in aspirin-treated patients with coronary artery disease: a role of statins

Abstract

Introduction: The PlA2 allele is present in about 20–30% of European population. This allele has been associated with resistance to the antithrombotic action of aspirin in healthy PlA2 carriers

Objectives: To evaluate the functional association of the PlA1/A2 polymorphism of β3 intergrins with increased thrombin generation and platelet activation in patients with coronary artery disease (CAD), treated with low-dose aspirin and whether the effect of this polymorphism is modulated by statin administration. Patients and methods. In 31 patients (25 M, 6 F) with CAD, aged 47 to 76 years, the thrombin-antithrombin complex generation (TAT) and the soluble form of CD40 ligand level (sCD40L) in blood collected every 60 seconds at sites of standardized microvascular injury were determined.

Results: Coronary angiography revealed ≥1 major epicardial artery stenosis (≥50%) in all patients. Genotyping determined 18 subjects homozygous for PlA1 and 13 PlA2 heterozygous carriers. Homozygous PlA1 subjects exhibited increased fibrinogen levels compared with PlA2 carriers (4.2 [IQ 2.39] g/l vs. 2.5 [0.73] g/l, p <0.05). Maximal TAT level observed 6 min after microvascular injury was higher in PlA2 carriers (p = 0.01). Maximal sCD40L did not differ between PlA1/A1 subjects and PlA2 carriers. The PlA2 allele did not alter the velocity of TAT production and sCD40L release. The analysis of the area under the concentration vs. time curve for TAT revealed that PlA2 carriers exhibited increased thrombin generation compared with PlA1A1 subjects (by 17.5%, p <0.05). Subjects treated with statins (n = 12) had lower TAT generation and sCD40L release than non-treated (by 20%, p <0.005 and 23%, p <0.005, respectively). This effect was not altered by the PlA2 presence.

Conclusions: In a model of microvascular injury the PlA1/A2 polymorphism influenced thrombin formation but not platelet activation in CAD patients treated with low-dose aspirin. The PlA2 allele did not alter the beneficial effect of statins on blood coagulation.