Author + information
- Gerasimos Siasos,
- Dimitris Tousoulis,
- Marina Zaromitidou,
- Evangelos Oikonomou,
- Konstantinos Maniatis,
- Stamatis Kioufis,
- Eleni Kokkou,
- Athanasios G. Papavassiliou and
- Christodoulos Stefanadis
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, arterial stiffness and cardiovascular outcome in patients with CAD treated with clopidogrel regimen.
We consecutively enrolled 353 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. High on treatment platelet reactivity was evaluated using VerifyNow Assay. CYP2C19*2 genotyping was performed by real–time polymerase chain reaction. Patients were followed for a mean time of 14 months.
From the 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 a marginally association between carriers of at least one loss of function allele and the occurrence of primary end point (for carriers HR=1.91, 95%C.I. 0.99 to 3.66, p=0.05). In addition, there was no difference in FMD (4.86±2.41% vs. 4.80±2.14%, p=0.83), PWV (8.63±2.37m/sec vs. 8.91±2.14m/sec, p=0.30) and AIx values (22.75±10.47% vs. 24.15±8.51%, p=0.18) between carriers and non carriers respectively. Finally, subjects with high on treatment platelet reactivity had significantly impaired PWV (8.71±2.22 m/sec vs. 7.71±1.77 m/sec, p=0.02) and AIx (25.37±8.81% vs. 20.99±10.51%, p=0.03).
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 a reduced–function CYP2C19 allele had a higher rate of major adverse cardiovascular events. Finally, increased platelet reactivity is associated with impaired arterial stiffness in CAD patients.
Special Session North, Room 120
Sunday, March 10, 2013, 11:45 a.m.–Noon
Session Title: Young Investigator Awards Competition: Physiology, Pharmacology and Pathology
Abstract Category: Physiology, Pharmacology, Pathology
Presentation Number: 403–8
- 2013 American College of Cardiology Foundation