Abstract 15708: Effects of CYP2C19 Genotype on Arterial Wall Properties in Patients with Coronary Artery Disease Receiving Clopidogrel
Background: The clinical benefit of clopidogrel has been attributed to its inhibition of platelet activation and aggregation. Clopidogrel requires transformation into an active form by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. Though, clopidogrel treatment has also pleiotropic vasoprotective effects, such as modulation of vascular tone, improvement of endothelial function, as well as inhibition of inflammation and oxidative stress. We tested the impact of CYP2C19*2 genetic polymorphism on endothelial function and arterial stiffness in patients with coronary artery disease (CAD) treated with clopidogrel regimen.
Methods: We consecutively enrolled 353 patients with stable CAD, receiving clopidogrel regimen (75mg/d). CAD patients were divided in two groups. Endothelial function was evaluated by flow-mediated dilation (FMD). 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.
Results: In the total study population, 131 patients (37.1%) were carriers of at least one CYP2C19*2 reduced-function allele and 222 patients (62.9%) were non carriers. There was no statistically significant difference between carriers and non carriers in age, male sex and the presence of dyslipidemia, statin use, diabetes mellitus, arterial hypertension, and in smoking habits (p=NS for all). Importantly, there was no difference in FMD (4.94 ±2.29% vs. 4.88±2.01%, p=0.77), PWV (8.63±2.37m/sec vs. 8.91±2.13m/sec, p=0.28) and AIx values (22.75±10.47% vs. 24.20±8.51%, p=0.16) between carriers and non carriers respectively.
Conclusion: CYP2C19*2 polymorphism does not affect endothelial function and arterial wall properties in patients with CAD treated with clopidogrel. These findings supports the notion that clopidogrel either directly or indirectly via its active metabolite, may affect vascular function by direct stimulation of NO-dependent vasodilation, irrespectively of its platelet inhibitory action.
- © 2012 by American Heart Association, Inc.