BACKGROUND Nitric oxide plays an important role in the regulation of basal vascular tone and cardiac myocyte function. We investigated the NOS3-786T>C polymorphism in chronic heart failure (CHF) and its effects on long-term mortality. METHODS Ninety-one patients with CHF who were referred to the Department of Cardiology of Siyami Ersek Cardiovascular and Thoracic Surgery Center for cardiopulmonary exercise testing between April 2001 and January 2004 and 30 controls were enrolled in this study. Patient were followed prospectively for a period of 1 to 12 years. RESULTS Patients and controls were divided into three groups: TT, TC and CC, according to their NOS3-786T>C polymorphism. We noted that there was no significant difference in the genotype distribution between patients and controls. There was also no significant difference in endothelial nitric oxide synthase (eNOS) gene polymorphism between ischemic HF and nonischemic HF. During the follow-up period, 61 (67%) deaths occurred. The nonsurvivor group had lower left ventricular ejection fraction (LVEF) (p = 0.01), reduced peak oxygen consumption (p = 0.04) and were of older age (p = 0.001). Age, LVEF, peak oxygen consumption and genotype were found to be predictors of mortality (p < 0.05). Additionally, mortality was significantly increased in -786CC genotype patients compared to TT genotype patients (hazard ratio = 2.2; p = 0.03). By multivariate analysis, age and eNOS genotype were determined to be significant independent predictors of death. Additionally, Kaplan-Meier analysis confirmed that homozygote -786C genotype was associated with an increased risk of death (χ2 = 4.6, p = 0.03). CONCLUSIONS Our findings showed that the NOS3-786T>C polymorphism was associated with an increased risk of mortality in patients with CHF.

Background: Metabolic syndrome (MetS) is a leading risk factor for coronary artery disease (CAD) in women. Reduced paraoxonase 1 (PON1) activity may play a role in the pathogenesis of atherosclerosis through increased susceptibility to lipid peroxidation in patients with MetS.Aim: To examine whether there is a relationship between serum PON1 activity and MetS in women.Method: The study group consisted of 54 women with MetS. The NCEP ATP III guidelines were used to define MetS. The control group consisted of 65 women without MetS and CAD. All patients from the MetS group underwent coronary angiography.Results: The PON1 activity and salt-stimulated PON1 activity were not significantly altered in women with MetS when compared to controls (p = 0.902, p = 0.877, respectively). There was no significant difference in PON1 activity (p = 0.159), and salt-stimulated PON1 activity (p = 0.139) between diabetics and non-diabetics. In the MetS group, patients with CAD (n = 16) had significantly reduced PON1 activity and salt-stimulated PON1 activity compared to MetS patients without CAD (p = 0.008 and p = 0.004, respectively).Conclusions: Serum PON1 activity is significantly reduced in women with CAD and MetS. MetS per se does not alter serum PON1 activities.

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.

Aim of this study was to investigate the possible relationship between ACE and/or PON1 M55L, Q192R genetic polymorphisms and subjects with Coronary Heart Disease (CHD) and/or syndrome X (SX) when compared to the control group. ACE I/D, PON1 M55L and Q192R genetic polymorphisms, Body Mass Index (BMI) and biochemical parameters were investigated in subjects with CHD (n = 19), SX (n = 34) and healthy subjects (n = 26). All of the subjects were nonsmokers. According to the unrelated group t-test results; BMI, HDL-C and TG values were found to be slightly different in SX and control subjects but there was no significant difference in LDL-C and TC values. According to the Mann Whitney U-test results, BMI, TC, HDL-C and LDL-C values were found to be significantly different among CHD and control group subjects, but there was no difference in TG values. The results of this study indicates that ACE, PON1 192 and PON1 55 gene polymorphisms are not related to genetic susceptibility to SX and/or CHD in non-smokers. Obviously, the interpretation of these finding is difficult due to the small sample size and larger group studies are needed for more definitive conclusions.

The relationship between angiotensin-converting enzyme (ACE) gene polymorphism and type I aortic dissection was examined in 205 unrelated hypertensives. A total of 94 patients underwent emergency repair due to type I aortic dissection, confirmed by computed tomography, and the remaining 111 were controls. Polymerase chain reaction was used to confirm that ACE gene polymorphism was due to insertion (I) or deletion (D) of a 287 base pair (bp) DNA sequence within intron 16. The genotype distribution and allele frequency of ACE I/D polymorphism between patients and controls were not statistically significant. When the frequency of at least one D allele carrier (DD or ID genotype) was compared with the II homozygous genotype, there was also no significant difference between the study groups. The findings revealed no association between ACE I/D polymorphism and aortic dissection. We conclude that I/D mutation of the ACE gene does not seem to be a risk factor for aortic dissection.

Objectives In this study, we aimed to investigate the relationship between T-786C polymorphism of the endothelial nitric oxide synthase (eNOS) gene and slow coronary flow (SCF).Study design A total of 56 patients with SCF but otherwise normal coronary arteries (mean age 48 9 years) and 37 controls with normal coronary angiograms (mean age 50 12 years) were enrolled in the study. Screening for the eNOS T-786C polymorphism was performed by restriction fragment length polymorphism methodology.Results In normal coronary artery and SCF groups, TT genotype frequency was 23 (62.2%) versus 22 (39.3%), TC heterozygote genotype frequency was 11 (29.7%) versus 30 (53.6%), and CC homozygote genotype frequency was 3 (8.1%) versus 4 (7.1%), respectively (P=0.07). In dominant model statistical analysis, total CC and CT genotype frequency in control and study groups was found to be 14 (37.3%) versus 34 (60.7%), respectively (P=0.025). A positive correlation was found between the mean thrombolysis in myocardial infarction frame count and C allele in patients with SCIF (r=0.21, P=0.043).Conclusion We concluded that the T-786C polymorphism of eNOS gene might be a risk factor for the SCF.

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 α (Hu TNF-α), 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-α, 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-α 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-α 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.

Increased coronary artery disease (CAD) risk is well established in diabetes mellitus (DM). Paraoxonase (PON) enzyme is known to have protective effects on lipid peroxidation. This study aimed to investigate the changes in PON activity levels with duration of DM as well as the role of PON activity in progression of CAD. Eighty-four consecutive diabetic patients (mean age 58 years, 46 men) who underwent coronary angiography for diagnostic purposes were examined. Before the angiography, fasting venous blood samples were taken for PON enzyme activity, thiobarbituric acid reactive substances (TBARS), and routine biochemical parameters. Severity and extent of coronary atherosclerosis were scored numerically using the Gensini scoring system. The population was divided into three groups according to Gensini score: Group 1, mild CAD; Group 2, moderate CAD; Group 3, severe CAD. Group 1 had higher PON levels and shorter DM duration than those of Group 3. Gensini score was significantly correlated with, PON activity (r = −0.361) and apo-AI (r = −0.375). TBARS (r = −0.290) and the duration of DM (r = −0.336) also showed a significant correlation with PON activity levels. Also, multivariate linear regression and Pearson correlation analyses showed that PON activity (P = 0.04), apo-AI levels (P = 0.01), and the duration of DM (P = 0.003) were significantly associated with Gensini score. Paraoxonase activity decreases parallel to DM duration. The lack of protective effect of PON enzyme on lipid peroxidation may be a factor in acceleration of CAD in DM.

Left ventricular (LV) systolic and diastolic parameters derived from Doppler echocardiography have been used widely to predict functional capacity but diastolic filling is affected by various factors. Tissue Doppler imaging (TDI) that records systolic and diastolic velocities within the myocardium and at the corners of the mitral annulus, has been shown to provide additional information about regional and global LV function. The goal of this study was to examine whether TDI-derived parameters add incremental value to other standard Doppler echocardiographic measurements in predicting exercise capacity. The study enrolled 59 consecutive patients with stable congestive heart failure (CHF). The etiology of heart failure was coronary artery disease in 42 patients and dilated cardiomyopathy in 17. Twenty-three age-matched healthy subjects were recruited as controls. Conventional echocardiographs and TDI were obtained. Early (Ea) and late (Aa) diastolic and systolic (Sa) mitral annulus velocities, the Ea/Aa and E/Ea ratios, were measured by pulsed wave TDI placed at the septal side of the mitral annulus and results were compared with results of cardiopulmonary exercise testing. Systolic and early diastolic velocities of mitral annulus were decreased and the E/Ea ratio was increased in the restrictive group as compared to controls (P = 0.02, P = 0.03, P < 0.001, respectively) but there was no significant difference in late diastolic velocity and the Ea/Aa ratio between the restrictive group and controls. The average peak VO2 of the patients were 14.9 ± 4.9 ml/min per kg. Achieved peak VO2 of the patients with E/Ea ratio ≤7.5 was 17.4 ± 5 vs 12.2 ± 3 ml/min per kg for those with E/Ea >7.5 (P < 0.001). Interestingly, the patients with the nonrestrictive pattern and E/Ea ratio >7.5 had reduced exercise capacity, as did the group with restrictive LV filling patterns (12.8 ± 3.3 vs 12.9 ± 4.0 ml/min per kg, P = 0.9). Similarly, there was no significant difference in the mean exercise capacity between the patients with a nonrestrictive pattern vs restrictive pattern with E/Ea ratio ≤7.5 (16.1 ± 5.0 vs 15.4 ± 5.1 ml/min per kg, P = 0.78). Univariate analysis demonstrated that the peak Sa (r = 0.30, P = 0.03), peak Ea (r = 0.38, P = 0.004) and peak Aa (r = 0.35, P = 0.009) correlated significantly with maximum exercise capacity. No relationship was observed between the Ea/Aa ratio and peak VO2 (r = −0.09, P = 0.48). By multivariate analysis, including age and heart rate, the E/Ea ratio was found to be an independent prognostic factor at peak VO2 (P < 0.001. In contrast, the comparison of the maximum transmitral early diastolic velocity and the mitral annulus TDI velocity, that is E/Ea ratio, had strong correlation with peak VO2 (r = −0.46, P < 0.001). Receiver operating characteristic (ROC) analysis was performed for prediction of limited exercise capacity from the E/Ea ratio. An E/Ea ratio ≤7.5 was able to predict peak VO2 ≤14 ml/min per kg with a sensitivity of 84% and a specificity of 74%. If restrictive pattern or an E/Ea ratio >7.5 was used, 21 out of 24 patients in the reduced exercise capacity group were identified with 16 false positives in the preserved exercise capacity group (P = 0.001). Mitral annular systolic and diastolic velocities of TDI were associated with cardiopulmonary exercise capacity in patients with LV systolic dysfunction. Index of the E/Ea ratio was found to be the most powerful predictor of peak oxygen uptake.

BACKGROUND:Elevated plasma homocysteine (Hcy) concentrations are associated with an increased risk of vascular disease. Hcy is known to inhibit endothelial cell proliferation in vitro. The purpose of the present study was to investigate the role of plasma Hcy concentrations on development of collateral circulation in single-vessel chronic total occlusion.METHODS AND RESULTS:Collateral status was determined by Rentrop's classification. Of 817 patients, 56 cases of pure single-vessel chronic total occlusion were studied. Plasma Hcy concentrations in patients with single-vessel total coronary occlusion were higher compared with controls (17.3 +/-12.6 micromol/L vs 10.9+/-4.9 micromol/L, p=0.015). There was no significant difference in plasma Hcy concentrations of the good and poor collateral groups (17.2+/-13.7 micromol/L vs 15.3+/-9.3 micromol/L, p=0.834). Plasma Hcy concentrations in individual Rentrop subclasses 0, 1, 2 and 3 were as follows: 15.9 +/-9.1, 16.3+/-12.4, 17.1+/-14.1 and 20.1+/-13.5 micromol/L (p=0.893). There was a positive linear correlation between Rentrop subclass and angina pectoris duration (r=0.41, p=0.003). Angina pectoris duration was the only independent variable affecting the development of coronary collaterals in the present study (odds ratio [confidence interval]: 1.85 [1.12-2.91], p=0.014).CONCLUSION:Patients with single-vessel chronic total occlusion had higher plasma Hcy concentrations than controls, but similar Hcy concentrations when compared according to the presence of poor or good coronary collaterals. There is a lack of association between plasma Hcy concentration and coronary collateral status in the current study.

Glycoprotein IIb/IIIa inhibitor therapy during primary percutaneous coronary intervention (PCI) decreases the incidence of major adverse cardiac events. These effects directly result from the level of platelet inhibition. It was shown that standard dosing of tirofiban is insufficient for optimal platelet inhibition. We sought to determine the efficacy and safety of single high-dose bolus (HDB) tirofiban with high-dose clopidogrel loading in primary PCI in acute ST elevation myocardial infarction. A total of 100 patients (mean age 55.2 ± 9.9 years, male/female = 86/14) undergoing primary PCI, pretreated with clopidogrel (450 mg) and aspirin (325 mg), were consecutively randomized into two groups. Group I (n = 50) received a standard dose bolus of tirofiban (10 µg/kg/3 min) with 24-h infusion at a rate of 0.15 µg/kg/min. Group II received single HDB tirofiban (25 µg/kg/3 min). The assessed angiographic, clinical, and echocardiographic endpoints were: initial and final Thrombolysis in Myocardial Infarction (TIMI) grade flow (TGF), corrected TIMI frame count (CTFC), ST-segment resolution (STR) at 90 min, in-hospital bleeding complications, echocardiographic left ventricular ejection fraction (LVEF), death, reinfarction, and repeat target vessel revascularization at 1 month. Platelet function inhibition was measured using PFA-100 (Behring-Dade, Liederbach, Germany) with a test cartridge unit containing a membrane coated with 2 µg of equine Type I collagen and 50 µg adenosine diphosphate before, and 10 min, 2, 4, 6, 12, and 24 h after the bolus of the tirofiban in the first 10 cases of each group. There were no significant differences in baseline characteristics between groups. Initial TGF III was more frequent (24% vs 8%, P = 0.029) and the value of CTFC was lower (75 ± 34 vs 89 ± 25, P = 0.03) in group II. Postprocedural TGF, CTFC, STR, bleeding complications, and LVEF at 1 month were not different between the two groups. There was a higher rate of reinfarction in group II (8%) compared with group I (2%), but this difference was not statistically significant (P > 0.05). The results of platelet function analyses showed that group II patients had significantly prolonged platelet function assay closure times (299 ± 6 s) compared with group patients (236 ± 97 s) at 10 min after the bolus dose (P = 0.04). However, after the first dose between 2 and 24 h, PFA closure times were significantly prolonged in patients with tirofiban infusion. High-dose bolus of tirofiban seems to be safe and more effective than conventional dose at the periprocedural time, whereas continuous infusion of tirofiban may be necessary in the first 24 h before stable and safe antiplatelet status is reached with clopidogrel. However, safety and efficacy of HDB tirofiban and high-loading-dose clopidogrel together with tirofiban infusion requires further studies with a larger population.

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 (≥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.