Abstract 12035: Cytochrome P450 Polymorphism and Endothelial Dysfunction Additively Correlates With Adverse Cardiovascular Events in Patients With Coronary Heart Disease
Introduction: CYP2C19 polymorphism correlates with adverse cardiovascular events in patients following coronary stent implantation. Endothelial dysfunction has recently been reported to predict clinical outcome in coronary heart disease patients.
Hypothesis: We hypothesized that additional evaluation of endothelial function to CYP2C19 polymorphism would further improve risk stratification.
Methods: We enrolled 434 patients after coronary stents. All patients received aspirin and clopidogrel. CYP2C19 genotype was examined, and we defined Carrier as having at least one loss-of-function (LOF) allele. Peripheral endothelial function by reactive hyperemia peripheral arterial tonometry (RH-PAT) was examined, and we used the median value of RH-PAT index (RHI) to divide subjects into low and high RHI. Thus, subjects were divided into four groups: Carrier, low RHI, (n=135), Carrier, high RHI (n=150), non-Carrier, low RHI (n=82), and non-Carrier, high RHI (n=67). The endpoint was a composite of cardiovascular death, myocardial infarction, stroke, unstable angina, urgent revascularization, and hospitalization for heart failure.
Results: A total of 63 patients had a cardiovascular event. Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in Carrier subjects with low RHI (log-rank test: P=0.003). Multivariate Cox proportional hazards analysis identified Carrier (hazard ratio [HR]: 2.008; 95% confidence interval [CI]: 1.107 to 3.645; P=0.022), low RHI (HR: 2.116; 95% CI: 1.241 to 3.608; P=0.006), and peripheral arterial disease (HR: 2.246; 95% CI: 1.246 to 4.048; P=0.007) as independent predictors of future cardiovascular events.
Conclusions: CYP2C19 polymorphism and endothelial dysfunction independently correlated with clinical outcome, and an additional evaluation of endothelial function to CYP2C19 polymorphism improved risk stratification after coronary stent implantation.
- Percutaneous coronary intervention (PCI)
- Endothelial function
- Coronary heart disease
Author Disclosures: N. Tabata: None. S. Hokimoto: None. T. Akasaka: None. Y. Arima: None. K. Kaikita: None. K. Nakagawa: None. H. Ogawa: Other Research Support; Modest; AstraZeneca, Astellas, Boehringer lngelheim, Bristol-Myers Squibb, Daiichi Sankyo, Dainippon Sumitomo Pharma, Kowa, MSD, Novartis, Pfizer, Sanofi, Takeda. Other Research Support; Significant; Bayer, Chugai, Otsuka. Honoraria; Modest; AstraZeneca, Bayer, Pfizer, Sanofi, Takeda. Honoraria; Significant; Daiichi Sankyo, MSD.
- © 2014 by American Heart Association, Inc.