In this study, we investigated the contribution of vitamin K epoxide reductase (VKORC1) and cytochrome P450 2C9 (CYP2C9) genotypes, age, and body surface area (BSA) on warfarin dose requirements and in an adult Turkish population. Blood samples were collected from 100 Turkish patients with stable warfarin dose requirements and an international normalized ratio (INR) of the prothrombin time within the therapeutic range. Genetic analyses for CYP2C9 genotypes (*2 and *3 alleles) and VKORC1 -1639 G>A polymorphism were performed and venous INR determined. The mean warfarin daily dose requirement was higher in CYP2C9 homozygous wild-type patients, compared to those with the variant *3 allele (P < 0.05), similar to those with the variant *2 allele (P > 0.05) and highest in patients with the VKORC1 -1639 GG genotype compared to those with the GA genotype and the AA genotype (P < 0.01). The time to therapeutic INR was longer in CYP2C9 homozygous wild-type patients compared with those with the variant *2 and *3 alleles (P < 0.01), and longer in patients with the VKORC1 (position -1639) GG genotype compared with those with the GA genotype and the AA genotype (P < 0.01). The multivariate regression model including the variables of age (R (2) = 4.4%), BSA (R (2) = 27.4%), CYP2C9 (R (2) = 8.1%), and VKORC1 genotype (R (2) = 34.1%) produced the best model for estimating warfarin dose (R (2) = 60.4%). VKORC1 genotype and CYP2C9 polymorphism affect daily dose requirements and time to therapeutic INR in Turkish patients receiving warfarin for anticoagulation.

Previous studies revealed that there were various mutations on endothelial nitric oxide synthase (eNOS) gene and these mutations might be a risk factor for coronary artery disease (CAD), myocardial infarction (MI), and hypertension (HT). In this study, we aimed to investigate the relationship between eNOS gene polymorphism (T-786 C) and coronary artery disease in the Turkish population. Two hundred and eleven unrelated individuals (152 male, 59 female, mean age 59 years, range 27-85) whose angiographic examinations were performed in our hospital were enrolled into the study; 159 of these had angiographically determined coronary artery lesions (>or=50% stenosis at least in one vessel). Fifty-two individuals were free of coronary artery disease on their coronary angiography. The Gensini scoring system was used to determine the severity of the CAD. The polymerase chain reaction (PCR) method was used for genotyping the individuals. To determine the independent risk factors for coronary artery disease, multivariate logistic regression analysis was used. The variant distribution of the T-786 C polymorphism was as follows. For all individuals: TT 94 (44.5%), TC 88 (41.7%), CC 29 (13.8%); in CAD patients: TT 63 (39.6%), TC 73 (45.9%), CC 23 (14.5%); and in normal individuals: TT 31 (59.6%), TC 15 (28.8%), CC 6 (11.5%). There was a statistically significant difference in the variant distribution between CAD and normal individuals (P<0.05). On the other hand, when we compared the frequency of the at-least-one-C-allele carriers (CC+TC, dominant model) and TT homozygous, those with at least one C allele were more prevalent in CAD patients. The results were as follows. In coronary artery disease patients: CC+TC 96 (60.4%), TT 63 (39.6%); in normals: TC+CC 21 (40.4%), TT 31 (59.6%) (P<0.01). When we compared the allele distribution (T vs C, additive model) between CAD patients and normal controls, the results were as follows: T 0.625 vs 0.740, C 0.375 vs 0.260; there was also a statistically significant association between CAD and C allele (P<0.05). When we compared the means of the Gensini scores between each genotype of the T-786 C mutation, there was a statistically significant difference. The results were TT (48.6+/-37.3, median 43.0), TC (55.4+/-41.2, median 41.0), CC (77+/-43.6, median 80.0) (P<0.05). Multivariate logistic regression analysis revealed that C-dominant (CC+TC) individuals had 2.9-fold more likelihood to suffer from CAD (odds ratio: 2.902; confidence interval: 1.272-6.622) (P<0.05). We conclude that the T-786 C polymorphism of eNOS gene might be a risk factor for coronary artery disease in the Turkish population.

SUMMARYLeft atrial (LA) function is associated with left ventricular (LV) diastolic filling and cardiac output response to exercise. But the relation between LA function and exercise performance has not been adequately evaluated.The aim of this study was to investigate the relation between LA function and exercise capacity in dilated cardiomyopathy (DCM) with cardiopulmonary exercise testing.Forty-four patients with a left ventricular end-diastolic dimension (LVDd) ≥ 60 mm and an ejection fraction (EF) ≤ 40%, and in normal sinus rhythm were included in this study. Patients were divided into group 1 and group 2 according to their exercise peak oxygen uptake (VO 2 ) (group 1: peak VO 2 >14 mL/kg/min, group 2: peak VO 2 ≤ 14 mL/ kg/min). LA function indices were defined as follows: LA end-systolic diameter (LASd), end-diastolic diameter (LADd), LA systolic volume (LASV), LA diastolic volume (LADV), LA ejection volume (LAEV), and LA ejection fraction (LAEF).LASd, LADd, LASV, and LADV were significantly increased in group 2 (P < 0.001, P < 0.001, P < 0.05, P < 0.005). Group 1 had significantly higher LAEF (P < 0.001 ) and LVEF (P < 0.05). Group 2 had significantly shorter exercise duration, and decreased anaerobic threshold levels and minute ventilation volumes (P < 0.001, P < 0.001, P < 0.005 ). There was a positive correlation between peak VO 2 and LVEF (r = 0.46, P = 0.002), and LAEF (r = 0.61, P < 0.001), peak A wave velocity (r = 0.39, P = 0.009), E wave deceleration time (r = 0.56, P < 0.001), and isovolumic relaxation time (IVRT) (r = 0.35, P = 0.04). There was a negative correlation between peak VO 2 and LASd (r = -0.53, P < 0.001) LADd (r = -0.59, P < 0.001), LASVI (r = -0.34, P = 0.027), LADVI (r = -0.37, P = 0.001), and the E/A ratio (r = -0.41, P = 0.006), Decreased LAEF and increased LA sizes were associated with decreased peak VO 2 . The results clearly demonstrate that LA functions at rest are related to exercise performance in patients with heart failure. (Int Heart J 2005; 46: 123-131)

Inflammatory markers are elevated in acute coronary syndromes, and are also known to play a crucial role in the pathogenesis of neointimal proliferation and stent restenosis. Drug-eluting stents (DESs) have been shown to decrease stent restenosis in different studies. In this study, we aimed to investigate the effect of treatment with DESs on systemic inflammatory response in patients with unstable angina pectoris who underwent percutaneous coronary intervention (PCI). We compared plasma high-sensitivity C-reactive protein (hsCRP), human tumor necrosis factor alpha (Hu TNF-alpha), and interleukin 6 (IL-6) levels after DES (dexamethasone-eluting stent [DEXES], and sirolimuseluting stent [SES]) implantation with levels after bare metal stent (BMS) implantation. We performed PCI with a single stent in 90 patients (62 men; 59 +/- 9 years of age; n = 30 in the BMS group, n = 30 in the DEXES group, n = 30 in the SES group) who had acute coronary syndrome. Plasma hsCRP, Hu TNF-alpha, and IL-6 levels were determined before intervention and at 24 h, 48 h, and 1 week after PCI. The results were as follows. Plasma hsCRP levels at 48 h (11.19 +/- 4.54, 6.43 +/- 1.63 vs 6.23 +/- 2.69 mg/l, P = 0.001) after stent implantation were significantly higher in the BMS group than in the DES group; this effect persisted for 7 days (P = 0.001). Plasma Hu TNF-alpha levels at each time point were higher in the SES group than in the BMS and DEXES groups (P < 0.05). The time course of Hu TNF-alpha values was similar in all groups. Although IL-6 levels at baseline and at 24 and 48 h showed no statistically significant difference between the study groups, postprocedural values at 7 days were slightly statistically significant in the SES group (P = 0.045). Drug-eluting stents showed significantly lower plasma hsCRP levels after PCI compared with BMSs. This may reflect the potent effects of DESs on acute inflammatory reactions induced by PCI.

Background: Little is known about the relationship between exercise intolerance and lipid peroxidation in chronic heart failure (CHF) patients. This study was designed to investigate the relationship between exercise-induced plasma malondialdehyde (MDA) changes in CHF patients and to determine whether there is any association between plasma MDA levels and exercise capacity assessed by cardiopulmonary exercise testing. Methods: Cardiopulmonary exercise testing was applied to 31 CHF patients (16 ischemic, 15 idiopathic) and controls. Rest and peak exercise blood samples were analyzed for MDA. Results: Patients with CHF had elevation of plasma MDA levels during exercise compared with controls (p < 0.001 vs. p = 0.588). MDA change remained significant both in ischemic and idiopathic cardiomyopathy groups (p < 0.05 and p < 0.01, respectively). ΔMDA (peak exercise MDA – rest MDA) showed significant inverse correlation with peak oxygen consumption in patients with CHF. Conclusion: Lipid peroxidation is increased in patients with CHF during exercise regardless of etiology, and this increase is inversely related to oxygen consumption.