title: Evaluation of the F2R IVS-14A/T PAR1 polymorphism with subsequent cardiovascular events and bleeding in patients who have undergone percutaneous coronary intervention.
abstract: Abnormal platelet reactivity is associated with recurrent ischemia and bleeding following percutaneous coronary intervention (PCI). Protease-activated receptor-1 (PAR1), encoded by F2R, is a high affinity thrombin receptor on platelets and the target of the antiplatelet drug vorapaxar. The intronic single nucleotide polymorphism F2R IVS-14 A/T affects PAR1 receptor density and function. We hypothesized that carriers of the T allele, who have been shown to have decreased platelet reactivity, would be at lower risk for thrombotic events, but higher risk for bleeding following PCI. Using BioVU, the Vanderbilt DNA repository linked to the electronic medical record, we studied 660 patients who underwent PCI for unstable or stable coronary artery disease. Primary outcome measures were major adverse cardiovascular events (MACE, composite of revascularization, MI, stroke, death) and bleeding (assessed by Bleeding Academic Research Consortium scale) over 24 months. The minor allele (T) frequency was 14.8 %. There were no genotypic differences in the frequency of MACE (33.7, 28.8, and 31.6 % for A/A, A/T, and T/T respectively, P = 0.50) or bleeding (15.7, 14.7, and 18.8 % for A/A, A/T, and T/T respectively, P = 0.90). In a Cox regression model, fully adjusted for age, race, sex, BMI, and smoking status, carrying a T allele was not associated with MACE (HR 1.19, 95 % CI 0.89-1.59, P = 0.23) or bleeding (HR 0.73, 95 % CI 0.37-1.4, P = 0.34). In conclusion, in our population, F2R IVS-14 PAR1 variability does not affect risk of MACE or bleeding following PCI.
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Eitan A
authors.initials: EA
authors.lastname: Friedman
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Luisa
authors.initials: L
authors.lastname: Texeira
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.|Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Delaney
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Weeke
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Lynch
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Ehab
authors.initials: E
authors.lastname: Kasasbeh
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Frank E
authors.initials: FE
authors.lastname: Harrell
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Josh C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Hamm
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.|Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.|Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.|Vanderbilt Heart and Vascular Institute, 2220 Pierce Avenue, 383 PRB, Nashville, TN, 37232-6300, USA.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA. john.cleator@vanderbilt.edu.|Department of Pharmacology, Vanderbilt University, Nashville, TN, USA. john.cleator@vanderbilt.edu.|Vanderbilt Heart and Vascular Institute, 2220 Pierce Avenue, 383 PRB, Nashville, TN, 37232-6300, USA. john.cleator@vanderbilt.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Cleator
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000235:genetics* / Q000401:mortality / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics / Q000401:mortality; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D044463:Receptor, PAR-1 / Q000235:genetics*; D020521:Stroke / Q000209:etiology / Q000235:genetics / Q000401:mortality
chemical_list: D044463:Receptor, PAR-1
keywords: Bleeding; Ischemia; PAR-1; PAR1; PCI; Percutaneous coronary intervention; Protease-activated receptor-1; Thrombosis