Abstract 13172: Gender Differences in Impact of Vascular Endothelial Dysfunction or CYP2C19 Polymorphism on Clinical Outcome Following Coronary Stenting in Patients with Coronary Heart Disease
Background: Vascular endothelial dysfunction and CYP2C19 polymorphism are associated with increased risk of cardiovascular event in patients with coronary heart disease (CHD). The aim was to examine the gender differences in vascular endothelial dysfunction or CYP2C19 genotype on clinical outcomes following stent implantation.
Methods: We enrolled 600 patients following stent implantation, taking dual antiplatelet therapy. Patients were divided into male (n=426) and female (n=174) groups. Platelet reactivity (PR) by a light transmission aggregometry, reactive hyperemia index (RHI) using reactive hyperemia peripheral arterial tonometry as an index of endothelial dysfunction, and CYP2C19 polymorphism were examined. CYP2C19 genotype was classified into carrier (at least one CYP2C19 loss-of function allele carriage) and non-carrier. Cardiovascular event (cardiovascular death, myocardial infarction (MI), stroke, unstable angina, revascularization, intraprocedural thrombotic event and heart failure) was assessed according to male or female over 18 months follow-up.
Results: There were no significant differences in distribution of CYP2C19 carrier and non-carrier (78.9 vs. 64.3%, P=0.126), PR (4474 vs. 4223 AU*min, P=0.485) and clinical outcomes (17.8 vs. 16.7%, P=0.731) between male and female. In male group alone, the incidence of cardiovascular event was significantly associated with CYP2C19 carrier, renal failure, high PR, previous MI, and peripheral artery disease. While in female group alone, low RHI was significant (0.47 vs. 0.61, P=0.015). Multivariate analysis identified CYP2C19 carrier (HR, 1.908, 95% CI, 1.043-3.489; P=0.032), previous MI (HR, 1.918, 95% CI, 1.125-3.269, P=0.017), and peripheral artery disease (HR, 1.872, 95% CI, 1.079-3.247, P=0.026) as predictors of cardiovascular events in male group, while low RHI alone was a predictor in female (HR, 0.129, 95% CI, 0.021-0.811, P=0.029).
Conclusions: The impact of CYP2C19 polymorphism on clinical outcome is more significant in male, not female, while effect of endothelial dysfunction is more significant in female, not male, respectively. There are gender differences in impact of CYP2C19 genotype or endothelial dysfunction on clinical outcome in CHD patients.
Author Disclosures: S. Hokimoto: None. T. Akasaka: None. N. Tabata: 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.