The impact of CYP2C19*2, CYP4F2*3, and clinical factors on platelet aggregation, CYP4F2 enzyme activity, and 20-hydroxyeicosatetraenoic acid concentration in patients treated with dual antiplatelet therapy.

: The aim of the current study was to evaluate the impact of CYP2C192 (rs4244285), CYP4F23 (rs2108622), and nongenetic factors on platelet aggregation and to investigate the mechanism of CYP4F2's effect on platelet aggregation in the patients treated with dual antiplatelet therapy. A total of 146 patients were included in this study. Ticagrelor or clopidogrel were administered in a loading dose of 180 mg and 600 mg, respectively, in combination with aspirin (300 mg). Blood samples for analysis were taken the next morning after antiplatelet therapy induction. Clopidogrel users with the CYP2C1912 variant had higher platelet aggregation values (median 43, range 30-54%) compared with 11 wild-type carriers (median 33, range 15-77%; P = 0.009). Carriers of the CYP4F213 variant had higher platelet aggregation values than carriers of the 33 variant (median 34, range 8-70% vs. median 24.5, range 10-47%, P = 0.016, respectively). Higher CYP4F2 concentrations were detected in clopidogrel users than in ticagrelor users (median 3.6, range 1.6-22.0 ng/ml vs. median 2.3, range 1.6-27.2 ng/ml, P = 0.056, respectively) and in carriers of the CYP4F213 variant compared with carriers of the 11 variant (median 4.3, range 1.6-27.2 ng/ml vs. median 2.4, range 1.6-22.0 ng/ml, P = 0.009, respectively). No correlation between plasma 20-hydroxyeicosatetraenoic acid and CYP4F2 enzyme concentrations were detected (r = -0.045, P = 0.587). Our results proved that CYP2C192 might significantly affect antiplatelet function of clopidogrel. Plasma CYP4F2 concentrations were significantly lower in ticagrelor users than in clopidogrel users.

The impact of clinical and genetic factors on ticagrelor and clopidogrel antiplatelet therapy.

AIM: To determine clinically significant factors which may alter the effect of dual antiplatelet therapy with aspirin and ticagrelor or clopidogrel in patients who had undergone percutaneous coronary intervention and stent implantation. MATERIALS & METHODS: The study included 378 patients. All the patients had undergone percutaneous coronary intervention and stent implantation. Platelet aggregation and genotyping for CYP2C19 *2 (rs4244285) and CYP4F2 (rs2108622, rs1558139, rs3093135 and rs2074902) was performed. RESULTS: Significantly lower platelet aggregation values (%agr) were detected in ticagrelor users who carried CYP4F2 rs3093135 TT variant (14.67 ± 5.07%agr) versus AA (22.88 ± 6.30%agr), p = 0.0004, or AT (20.56 ± 6.51%agr), p = 0.0126. CONCLUSION: Results of the current study showed that CYP4F2 rs3093135 TT variant carriers had a higher antiplatelet effect of ticagrelor, and more frequently had nonprocedural bleeding during ticagrelor therapy, as compared with AA and AT variant carriers.

The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction.

OBJECTIVE: Data on the impact of PAI-1-675 4G/5G genotype for fibrinolysis during myocardial infarction are inconsistent. The aim of our study was to evaluate the association of clinical and genetic (PAI-1-675 4G/5G polymorphism) factors with coronary artery occlusion in patients with myocardial infarction. MATERIALS AND METHODS: PAI-1-675 4G/5G detection was achieved by using Sanger sequencing in a sample of patients hospitalized for stent implantation due to myocardial infarction. We categorized the patients into two groups: patients with coronary artery occlusion and patients without coronary artery occlusion according to angiographic evaluation. RESULTS: We identified n = 122 (32.4%) 4G/4G, n = 186 (49.5%) 4G/5G, and n = 68 (18.1%) 5G/5G PAI-1 genotype carriers. Univariate and multivariate analysis showed that only the 4G/5G genotype was associated with coronary artery occlusion (OR: 1.656 and 95% CI: 1.009-2.718, p = 0.046). CONCLUSIONS: Our results showed that carriers of PAI-1 4G/5G genotype with myocardial infarction have increased odds of coronary artery occlusion more than 1.6 times in comparison to the carriers of homozygous genotypes.

Effect of clinical factors and gene polymorphism of CYP2C19*2, *17 and CYP4F2*3 on early stent thrombosis.

AIM: To determine the main clinical and genetic factors having impact on early coronary stent thrombosis. MATERIALS & METHODS: Genotyping of CYP2C19*2, *17 and CYP4F2*3 in patients with (n = 31) and without stent thrombosis (n = 456) was performed. Clinical and genetic data were analyzed by binary logistic regression. RESULTS: Smoking (OR: 0.317; 95% CI: 0.131-0.767), high-density lipoprotein level in mmol/l (OR: 0.142; 95% CI: 0.040-0.506), CYP2C19*2*2 versus *1*1 and *1*2 genotype (OR: 11.625; 95% CI: 3.498-38.633), CYP4F2 AA versus GA and GG genotype (OR: 3.532; 95% CI: 1.153-10.822) were associated with early stent thrombosis. CONCLUSION: For the first time we have identified a clinically important polymorphism (CYP4F2 G1347A) that was independently associated with early stent thrombosis. Original submitted 18 August 2014; Revision submitted 10 November 2014.

The role of clinical parameters and of CYP2C19 G681 and CYP4F2 G1347A polymorphisms on platelet reactivity during dual antiplatelet therapy.

Dual antiplatelet therapy with aspirin and clopidogrel is used to lower the risk of arterial thrombosis. However, this strategy is not always successful owing to high interindividual variability in response to antiplatelet therapy. To evaluate an impact of CYP2C19 G681A and CYP4F2 G1347A polymorphisms and clinical factors on dual antiplatelet effect of clopidogrel and aspirin. Totally 89 patients who continued dual aspirin and clopidogrel antiplatelet therapy for at least of 14 days were included into the further study. Test for platelet aggregation was performed according to the classical Born method. Genotyping of CYP2C19*2 and CYP2C19*3 and CYP4F2*3 was done by using commercial probes from Applied Biosystems (UK). Patient age, weight and body weight index did not correlate significantly with platelet aggregation level both induced by ADP and epinephrine (P > 0.05). Serum concentration of creatinine, diabetes, angiotensin II receptor blockers, B-blockers, statin or omeprazole use had no significant effect on platelet aggregation. The users of angiotensin-converting enzyme inhibitors had lower platelet aggregation levels with epinephrine vs. nonusers: 28.80 ±â€Š13.25 vs. 51.15 ±â€Š23.50, P < 0.03, respectively. Platelet aggregation with ADP was higher in CYP2C19*1*2 genotype carriers than in CYP2C19*1*1 carriers (P = 0.01). Platelet aggregation with epinephrine was higher in CYP4F2 GA genotype carriers than in GG (P = 0.04) or AA (P = 0.01) carriers. Our study confirms that CYP2C19 G681A genotype has an impact on antiplatelet effect of clopidogrel. The novelty is that the platelet aggregation after induction with epinephrine is influenced by CYP4F2 G1347A genotype.

Prognostication of long-term outcomes for patients with ischemic heart disease.

UNLABELLED: Cardiovascular disease, including coronary heart disease (CHD), is the leading cause of death among elderly adults across many European countries. In 2005, the Clinic of Cardiology, Hospital of Lithuanian University of Health Sciences (former Kaunas University of Medicine), started to gather the clinical data of patients with acute and chronic coronary syndromes according to the standards set by the Cardiology Audit and Registration Data Standards Project. THE AIM OF OUR STUDY was to evaluate one-year mortality after inpatient treatment for acute and chronic coronary syndromes in different risk groups. MATERIAL AND METHODS: A total of 3268 patients who were treated for coronary heart disease - acute myocardial infarction, unstable angina, stable angina--at the Clinic of Cardiology, Hospital of Lithuanian University of Health Sciences (former Kaunas University of Medicine) in 2005 were randomly selected. Clinical data of the patients were collected by means of a standardized questionnaire. After one year, 1908 patients were reexamined, and predominant symptoms, treatment during one-year period, outcomes were evaluated. RESULTS: Multiple logistic regression analysis revealed that one-year mortality after acute coronary syndromes was most influenced by age of 70-80 years, history of stroke, Killip class III-IV, and reduced high-density lipoprotein cholesterol levels. For patients who were treated for chronic coronary syndromes, reduced EF (<40%) and increased heart rate (>70 beats per minute) were the strongest independent predictors of one-year mortality. CONCLUSION: A scoring system for the assessment of mortality risk within one year for patients with acute and chronic coronary syndromes was constructed, which could be useful for cardiologists as well as family physicians for risk evaluation in inpatient and outpatient settings.