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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.

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.

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.

Obese patients may have a phase of asymptomatic left ventricular dysfunction. A combined myocardial performance index (MPI) has been demonstrated to be a useful index to estimate left ventricular function and to predict the prognosis of patients with heart failure. The objective of the study was to determine the influence of weight loss on MPI. A total of 18 obese patients (3 men, 15 women, mean age 49.6 +/- 5.5 years, body mass index [BMI] >30 kg/m(2)) were investigated in the study. All patients were treated with a multidisciplinary approach consisting of a hypocaloric diet and orlistat therapy (120 mg three times daily), and all of them underwent two-dimensional and Doppler echocardiographic examination two times before starting the study and after a period of weight loss. Using echo-Doppler methods, ejection fraction, peak velocities of early (E) and late (A) diastolic filling, the E/A ratio, deceleration time (DT), isovolumic contraction time (IVCT), isovolumic relaxation time, ejection time, and MPI were measured. The MPI was obtained by subtraction ejection time from the interval between cessation and onset of the mitral flow. All patients lost at least 10% of their initial body weight, with a mean decrease of 10.8 +/- 3.7 kg. This was associated with significant reductions in BMI with a mean decrease 4.5 +/- 1.4 kg/m(2). Compared with baseline, after weight loss the E/A ratio of 1.01 +/- 0.22 before treatment increased to 1.17 +/- 0.26 (P = 0.012), left ventricular mass index decreased from 88 +/- 23 to 82 +/- 19 g/m(2) (P = 0.028), IVCT from 71 +/- 20 to 53 +/- 30 ms (P = 0.004), DT from 233.65 +/- 38.14 to 196.72 +/- 47.73 s (P = 0.004), and MPI from 0.63 +/- 0.13 to 0.50 +/- 0.13 (P = 0.0001). Weight loss ameliorates MPI and seems to be a clinically relevant measurement of left ventricular global function, and may prove to be a valuable tool in assessing the risk of developing heart failure.

Glycoprotein IIb/IIIa receptor inhibition prevents the major cardiac events and improves the prognosis of patients with acute coronary syndromes. The purpose of the study was to evaluate the effects of tirofiban on clinical stabilization parameters in patients with unstable angina (UA) and non-Q-wave myocardial infarction (MI). Eighty-three patients presenting with prolonged ongoing chest pain and ST segment depression were included in the study. Forty-two patients were randomized to aspirin and heparin therapy, and 41 patients to tirofiban therapy in addition to the aspirin and heparin therapy. The interval between the initiation of the treatment and the disappearance of angina, recovery time of ST segment depression, creatine kinase-MB (CK-MB) levels, onset of decrease and normalization of CK-MB, and frequency of in-hospital major cardiac events were compared. The interval between initiation of the treatment and the disappearance of angina was significantly shorter in the tirofiban group (3.5 +/- 4.2 vs 9.1 +/- 8.6 h, P << 0.001). Recovery time of ST depression was also significantly shorter in the tirofiban group (5.1 +/- 7.3 vs 12.3 +/- 11.5 h, P << 0.05). The peak CK-MB values were significantly lower in the non-Q-wave MI and UA subgroups of tirofiban than in the heparin group ( P = 0.04 for both). The onset of the CK-MB decrease was significantly earlier in the tirofiban group (15 +/- 14 vs 24 +/- 15 h, P = 0.02). The normalization time of the CK-MB was relatively shorter in the tirofiban group but without statistical significance (50 +/- 22 vs 60 +/- 25 h). The tirofiban group had a lower frequency of total major cardiac events (26% vs 54%, P = 0.01), acute MI (2.4% vs 19%, P = 0.03), and recurrent angina (26% vs 50%, P = 0.04). The frequency of death and urgent revascularization did not differ between the groups. Tirofiban, in addition to heparin, provides earlier clinical stability and prevents major in-hospital cardiac events in patients with UA and non-Q-wave MI as compared to heparin therapy alone.