Effects of CYP2C19 genotype on vascular function in patients with coronary artery disease receiving clopidogrel

Abstract

Purpose: The role of CYP2C19*2 polymorphism in plasma clopidogrel active drug metabolite concentrations, in platelet inhibition and in cardiovascular prognosis has come under question in recent studies. We examined the impact of functional genetic polymorphism CYP2C19*2 on endothelial function and arterial stiffness in patients with CAD treated with clopidogrel regimen. Methods: We consecutively enrolled 408 patients with stable CAD receiving clopidogrel regimen (75mg/d), one month after percutaneous coronary intervention. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as an index of arterial wave reflections. CYP2C19*2 genotyping was performed by real-time polymerase chain reaction. High on treatment platelet reactivity was evaluated using VerifyNow Assay. VerifyNow reports its results in P2Y12 reaction units (PRU) and the diagnostic cut-off value is 230 PRU. Results: From the study population 150 patients (36.8%) were carriers of at least one CYP2C19*2 reduced-function allele and 258 patients (63.2%) were non carriers. There was no statistically significant difference between carriers and non carriers in age, male sex and the presence of hyperlipidemia, diabetes mellitus, arterial hypertension, in smoking habits, in anticoagulant and statin treatment. Importantly, there was no difference in FMD (4.88±2.34% vs. 4.83±2.21%, p=0.83), PWV (8.53±2.54m/sec vs. 8.85±2.33m/sec, p=0.19) and AIx values (22.87±10.04% vs. 23.82±8.43%, p=0.31) between carriers and non carriers respectively. Finally, carriers of two CYP2C19*2 reduced-function allele had significantly increased PRU (292±53 vs. 198±83, p=0.007). Conclusions: The presence of CYP2C19*2 loss of action polymorphism displays no impact on arterial wall properties in patients with CAD treated with clopidogrel regimen. Moreover, carriers of two CYP2C19 reduced-function alleles had significantly increased platelet reactivity.