CYP2C19 and CYP3A4 activity and ADP-induced platelet reactivity in prasugrel- or ticagrelor-treated STEMI patients: monocentric study in PRAGUE-18 trial participants.

We assessed the contribution of CYP2C19 and CYP3A4 metabolic activity to the ADP-induced platelet aggregation 1h and 24h after a loading dose of 60 mg prasugrel or 180 mg ticagrelor in patients with ST-elevation myocardial infarction (STEMI). Further, we assessed the contribution of CYP2C19 polymorphisms and medication to the CYP enzymatic activity.Patients with STEMI were randomly assigned to the treatment with prasugrel (n = 51) or ticagrelor (n = 46). Metabolic activity of CYP2C19 and CYP3A4 was assessed by the rate of 5-hydroxylation and sulfoxidation of lansoprazole. Further, patients were genotyped for CYP2C19 *2 and *17 alleles.In prasugrel-treated patients, high ADP-induced platelet reactivity 1h after the loading dose positively correlated with 5OH-lansoprazole/lansoprazole ratio (r = 0.44, p = 0.002), a marker of CYP2C19 metabolic activity, and negatively with lansoprazole-sulfone/lansoprazole ratio, which reflects CYP3A4 metabolic activity (r = -0.35, p = 0.018).CYP2C19 poor metabolizers had lower 5OH-lansoprazole/lansoprazole ratio and higher lansoprazole-sulfone/lansoprazole ratio, but without any effect on the ADP-induced platelet reactivity. The treatment with amiodarone, a CYP3A4 inhibitor, influenced neither the metabolic ratios nor the ADP-induced platelet reactivity.The CYP3A4 and CYP2C19 metabolic activity is associated with ADP-induced platelet reactivity in prasugrel-treated, but not ticagrelor-treated patients with STEMI.

Conservative versus invasive treatment in hypertrophic obstructive cardiomyopathy: an echocardiography study.

AIM AND METHODS: The aim of our study was to compare the development of echocardiographic parameters and functional status of patients with hypertrophic obstructive cardiomyopathy (HOCM) treated conservatively (n = 41) or by alcohol septal ablation (ASA; n = 39). RESULTS: Left ventricular outflow tract gradient (LVOTG) decreased in the first year by 53.7±36.4 mmHg in ASA group versus 5.5±47.1 mmHg in conservatively treated group (p<0.001), in the third year by 53.1±41.4 mmHg versus 23.9±42.7 mmHg (p = NS) and in the fifth year, the reduction of LVOTG was 52.1±44.5 mmHg in ASA group and 3.0±63.2 mmHg in conservatively treated group (p<0.05).Change in NYHA class in the first year was -1.1±0.4 versus 0.1±0.5, in the third year -1.0±0.6 versus 0.1±0.4 and in the fifth year -0.8±0.5 versus 0.1±0.4 (all p<0.001). CONCLUSION: Our results showed for the first time that decline of LVOTG after ASA creates a favorable left ventricle remodeling and leads to significant improvement of functional status of HOCM patients in comparison with conservative treatment (Tab. 3, Fig. 2, Ref. 42).

Association between three single nucleotide polymorphisms in eotaxin (CCL 11) gene, hexanucleotide repetition upstream, severity and course of coronary atherosclerosis.

The impact of three single-nucleotide polymorphisms in eotaxin (SCYA11) gene promoter (-426C>T and -384A>G) and first exon (67G>A) and recently described hexanucleotide (GAAGGA)(n) 10.9 kb upstream on coronary atherosclerosis was investigated. Elective coronary angiography of 1050 consecutive subjects was performed. All patients were genotyped for the three SNPs. In a subset of the first 472 samples, the number of (GAAGGA)(n) repetitions was determined. For further evaluation, short and long variants were distinguished; the borderline corresponded with the median value of all alleles: ≤8 repetitions were considered as short sequence, ≥9 repetitions as long. Patients with bronchial asthma or insignificant atherosclerosis were excluded; the remaining group of 933 subjects was further investigated. Patients were grouped according to the form of CAD (ACS vs. stable angina) and the number of diseased vessels. The GG variant of 67 G>A polymorphism was associated with acute form of CAD compared to stable angina (p=0.0011, p(corr.)=0.013). The number of (GAAGGA)(n) repetitions in our set of patients ranged from 3 to 12. There were no subjects with 4 or 5 repetitions. The frequency of short repetition alleles increased with the number of affected vessels (1 vs. 3 diseased vessels: p=0.0043, p(corr)=0.034). In our study, the (GAAGGA)(n) hexanucleotide was associated with the severity of CAD. The 67 GG was associated with acute form of CAD. None of the two SNPs in eotaxin promoter had any relation to CAD. The number of (GAAGGA)(n) repetitions can thus be a novel genetic marker of the extent of CAD.

Difference in angiotensinogen haplotype frequencies between chronic heart failure and advanced atherosclerosis patients - new prognostic factor?

Numerous association studies have been involved in studying the angiotensinogen (AGT) variants, AGT plasma levels and relations to cardiovascular diseases, such as hypertension, myocardial infarction, coronary heart disease. To investigate a role of AGT G(-6)A and M235T genetic variants for chronic heart failure (CHF) and advanced atherosclerosis (AA), a total of 240 patients with CHF and 200 patients with AA of the Czech origin were evaluated for the study. The study shows the role of polymorphism AGT G(-6)A in genetic background among advanced atherosclerosis patients and chronic heart failure patients (Pg=0.001). This difference was also observed in comparison of AA patients with subgroup of CHF with dilated cardiomyopathy (Pg=0.02; Pa=0.009), and ischemic heart disease (Pg=0.007). The greatest difference between triple-vessel disease and chronic heart failure groups was observed in frequency of GT haplotype (P<0.001) and GGMT associated genotype (P<0.001). Retrospectively, we found the same trend when the subgroups of CHF were compared to AA group (AA vs. IHD with CHF P<0.001; AA vs. DCM P<0.001). These results suggest AGT genetic variants as a risk factor for chronic heart failure compared to advanced atherosclerosis disease without heart failure, with a strong difference between IHD patients and chronic heart failure patients with ischemic heart disease, especially in haplotypes and associated genotypes.