The association of beta-fibrinogen 455 G/A gene polymorphism with left atrial thrombus and severe spontaneous echo contrast in atrial fibrillation.

OBJECTIVE: The role of coagulation parameters left atrial thrombus formation in atrial fibrillation has not been investigated before. We aimed to investigate the association between the beta-fibrinogen gene polymorphism or glycoprotein IIIa gene polymorphism and presence of left atrial (LA) thrombus or spontaneous echo contrast (SEC) in patients with atrial fibrillation (AF). METHODS: Forty-seven patients with AF, in whom transesophageal echocardiography was performed, were included to this cross-sectional observational study. Patients were divided in two groups; those with LA thrombus (n=24) were assigned to group 1 and those without thrombus in group 2 (n=23). DNA analysis was conducted to determine gene polymorphism in all patients. Mann-Whitney U test or Chi-square tests were used for statistical analysis. RESULTS: There were no significant differences between groups regarding to demographic and clinical characteristics. The frequency of beta-fibrinogen 455 G/A polymorphism was higher (37.5%) in group 1 as compared to group 2 (15.1%) but it did not reach statistical difference (p=0.23). When we added patients with severe SEC in the study group (patients with severe SEC and/or thrombus n=27) the difference (44.40%-10%) reached the statistical difference (p=0.01). Glycoprotein IIIa Pl A1/A2 polymorphism was not different between groups with (p=0.82) or without SEC (p=0.73). CONCLUSION: In patients with atrial fibrillation, beta-fibrinogen 455 G/A gene polymorphism is associated with the presence of left atrial thrombus and severe SEC. Beta-fibrinogen 455 G/A gene polymorphism may be a promising marker for the prediction of thromboembolism risk in patients with atrial fibrillation.

Influence of carvedilol on serum digoxin levels in heart failure: is there any gender difference?

OBJECTIVE: The activity of the human cytochrome P450 and P-glycoprotein (P-gp) changes according to gender. The present study evaluated the effect of gender on the influence of carvedilol on serum digoxin levels in patients with heart failure. METHODS: Twenty-four patients (12 female and 12 male) with New York Heart Association class II-III heart failure were included in the study. Patients were taking oral digoxin (0.0625-0.25 mg, once a day) and were administered oral carvedilol (6.25 mg, two times daily) for 7 days. RESULTS: In the male group, carvedilol led to statistically significant increases in the area under the concentration time curve to 16 h (AUC(0-16h)) and the peak concentration (C(max)) for digoxin, with no change in time to peak (t(max))(AUC(0-16h)= 24.1+/-9.2 ng.h/ml vs. 15.4+/-5.8 ng.h/ml, p<0.001, C(max)=2.2+/-1.0 ng/ml vs. 1.6+/-0.6 ng/ml, p<0.01, t(max)=2.4+/-2.2 h vs. 2.1+/-1.0 h, p>0.05). In the female group, carvedilol administration did not cause statistically significant change in the AUC(0-16h), C(max), or t(max) for digoxin (p>0.05). In the male group, carvedilol resulted in a significant increase in the AUC(0-16h) and C(max) for digoxin compared with the female group (AUC(0-16h)=24.1+/- 9.2ng.h/ml vs. 17.0+/-6.8 ng.h/ml, C(max)=2.2+/-1.0 ng/ml vs. 1.5+/-0.6 ng/ml, p<0.05, respectively). CONCLUSION: Men seem to have a higher activity relative to women for the drug efflux transporter P-gp. Our results suggest that carvedilol will cause drug interaction with digoxin following the inhibition of P-gp-mediated transcellular transport of digoxin in males.

The relationship between angiotensin converting enzyme gene polymorphism, coronary artery disease, and stent restenosis: the role of angiotensin converting enzyme inhibitors in stent restenosis in patients with diabetes mellitus.

Patients with diabetes mellitus (DM) have advanced atherosclerosis compared with nondiabetics. Restenosis after intracoronary stent implantation occurs frequently in diabetic patients. Angiotensin II is an important growth factor for the development of neointimal hyperplasia after vascular injury. The aim of our study was to evaluate the relationships between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and coronary artery disease (CAD) and stent restonosis in diabetic patients. One hundred and thirty consecutive patients with CAD and 47 consecutive patients (14 males, mean age, 58.0 +/- 10.0) without CAD were enrolled in the study. All patients had type 2 (noninsulin dependent) DM. The patients with CAD underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting. Ninety-four (59 males, mean age, 60.3 +/- 9.8) underwent control coronary angiography at the end of the follow-up period (mean duration, 9.1 +/- 2.9 months). ACE gene I/D genotyping was identified in all patients. No significant difference was found among patients with and without CAD with respect to ACE gene I/D polymorphism (P = 0.460). In the control coronary angiography, stent restenosis and new lesion development were comparable in each genotyping subgroup. However, a significant relationship was observed between restenosis and the use of ACE inhibitors (ACEI) in patients with D allele (ACEI ratio, 43.5% in the restenosis group and 56.5% in non-restenotic group, P < 0.05). We did not find any relationship between ACE gene I/D polymorphism and CAD and stent restenosis and new lesion development in diabetic patients. On the other hand, ACEI treatment may reduce stent restenosis in type 2 diabetic patients with D allele (DD or ID).