Murat Tulmac

Asymmetrical dimethylarginine level in atrial fibrillation

Objective — Atrial fibrillation (AF) is known to be related with increased risk of thromboembolic events. Asymmetrical dimethylarginine (ADMA), which is an endogenous inhibitor of nitric oxide synthase (NOS), can cause endothelial dysfunction by decreasing nitric oxide (NO) and lead to increased risk of thrombosis. In the present study our aim was to compare plasma levels of ADMA in patients with acute onset (< 24 hours) and chronic AF (> 1 year) to determine the risk of thrombosis. Method — 17 patients with the first detected attack of AF within the first 24 hours of presentation (group I), 25 patients who had permanent chronic AF lasting at least 1 year or more (group II) and 18 healthy persons as the control group (group III) were included in the study. For each patient the plasma ADMA, L-arginine, symmetrical dimethylarginine (SDMA) concentrations were measured by high-performance liquid chromatography in venous blood samples collected before cardioversion. We compared the plasma ADMA, L-arginine and SDMA concentrations between the groups. Results — Plasma L-arginine (78.18 ± 28.29 vs. 73.14 ± 14.11 vs. 71.03 ± 21.31, P = 0.549) and plasma SDMA concentrations (0.38 ± 0.18 vs. 0.42 ± 0.21 vs. 0.32 ± 0.24, P = 0.224) were similar in all groups. There was a significant difference between plasma ADMA concentrations (0.76 ± 0.27 vs. 0.50 ± 0.26 vs. 0.36 ± 0.20, P < 0.001) among the groups.When we compared plasma ADMA levels between the subgroups, we also found a significant difference (P = 0.002 when comparing group I and group II, P < 0.001 when comparing of group I and group III, P = 0.042 when compareng of group II and group III). Conclusion — ADMA levels in patients with acute onset AF were significantly increased when compared with patients with chronic AF and the healthy control group indicating the presence of endothelial dysfunction and a prothrombotic state even in a very early phase of AF.

Lack of Association Between Matrix Metalloproteinase-9 and Endothelial Nitric Oxide Synthase Gene Polymorphisms and Coronary Artery Disease in Turkish Population

Polymorphic variants of genes encoding proteins involved in vascular remodeling may genetically diverge among different populations and play a role in the susceptibility to the coronary artery disease (CAD). MMP-9-1562 C/T (rs3918242), eNOS T-786C (rs2070744), and Glu298Asp (rs1799983) are among the most studied of these polymorphisms. The aim of this study was to determine the relationship between CAD and these polymorphisms in the Turkish population. The analysis included 146 CAD+ and 122 CAD- individuals. Genomic DNA was isolated from whole blood and genotyping was performed by the PCR-RFLP method. No significant associations were found between -1562 C/T (p = 0.557), Glu298Asp (p = 0.432), and -786 T/C (p = 0.055) polymorphisms and CAD. The distribution of each haplotype also did not differ between CAD+ and the CAD- samples (p > 0.05). The present investigation is the first to study an association between -1562 C/T polymorphism and CAD in the Turkish population. In conclusion, no appreciable differences between CAD+ and CAD- samples were found in terms of polymorphisms mentioned above.

Bilirubin levels and the burden of coronary atherosclerosis in patients with STEMI.

We investigated whether serum bilirubin level (a marker of heme oxygenase activity) is a predictor of high levels of SYNTAX score (SXscore) in patients with acute myocardial infarction. Patients (n = 281; male 77%; mean age 60 ± 12) who were admitted with ST-elevation myocardial infarctions (STEMIs) were enrolled. Patients were divided into 2 groups. Group 1 was defined as SXscore <22 and group 2 was defined as SXscore ≥22. Total bilirubin levels were significantly higher in the high-SXscore group than in the low-SXscore group (0.86 ± 0.42 vs 1.02 ± 0.51, P = .005). A significant correlation was detected between total bilirubin and SXscore (r = .42; P = .001). At multivariate analysis, total bilirubin (odds ratio: 1.86, 95% confidence interval 1.04-3.35; P = .038) was an independent risk factor for high SXscore in patients with STEMI. In conclusion, serum bilirubin level is independently associated with SXscore in patients with STEMI.

Renal dysfunction is the most important predictor of the extent and severity of coronary artery disease in patients with diabetes mellitus.

ObjectivesDiabetic patients tend to have more extensive and diffuse coronary artery disease (CAD) that may contribute to the less favorable outcomes in them. The aim of this study was to elucidate the predictors of the angiographic severity and extent of CAD in patients with diabetes. MethodsA total of 203 diabetic patients (116 men; mean age, 61.9±10.8) who were referred for a first coronary angiogram were included. The extent and severity of CAD was assessed in several ways. The first was a simple classification in one-vessel, two-vessel, and three-vessel disease scoring system. The total numbers of segments with ≥20 and ≥50% stenosis were calculated as CASS 20 and CASS 50 scores, respectively. Hamsten and Gensini scores were also calculated. ResultsOf the 203 patients included in the study, 175 (86.2%) had CAD. Multivariate ordinal logistic regression analysis showed that age (Wald 5.741, P=0.017), glomerular filtration rate (Wald 5.032, P=0.025), previous myocardial infarction (Wald 10.955, P=0.001), and family history of CAD (Wald 7.236, P=0.007) were independent predictors of the severity of CAD, as assessed by the clinical zero-vessel to three-vessel disease scoring system. On stepwise multiple linear regression analysis, glomerular filtration rate was an independent predictor of the CASS 20 (r=−0.221, P=0.004), CASS 50 (r=−0.239, P=0.005), Gensini (r=−0.328, P<0.001), and Hamsten (r=−0.320, P<0.001) scores. Previous myocardial infarction was an independent predictor of the CASS 50 (r=0.355, P<0.001), Gensini (r=0.350, P<0.001), and Hamsten (0.256, P<0.001) scores. Age and sex were independent predictors for the CASS 50 (r=0.174, P=0.039; r=0.172, P=0.016, respectively) and Hamsten (r=0.212, P=0.011; r=0.244, P=0.001, respectively) scores. ConclusionRenal function is one of the most important factors associated with the extent and severity of coronary atherosclerosis, whereas classical coronary risk factors and the degree of metabolic control were not associated with the severity of coronary atherosclerosis in diabetic patients.

An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.

The Role of Matrix Metalloproteinase-2 Promoter Polymorphisms in Coronary Artery Disease and Myocardial Infarction

The matrix metalloproteinase (MMP) family are key enzymes involved in the breakdown of the extracellular matrix in normal physiological processes, including tissue remodeling, and disease processes, such as arthritis and metastasis. The promoter polymorphism in the MMP2 gene may be responsible for multiple diseases related to extracellular matrix degradation. Therefore, we aimed to investigate the relationship between genotypes or haplotypes of -1575 G/A, -1306 C/T, -790 T/G, and -735 C/T promoter polymorphisms and coronary artery disease (CAD) with or without myocardial infarction (MI) history. This study included 298 patients with angiographically confirmed CAD and 299 age matched controls. Genomic DNA was isolated from whole blood and genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. No significant associations were found between -1575 G/A, -1306 C/T, and -790 T/G polymorphisms and CAD with or without MI history. However, the frequency of the -735 TT genotype was significantly lower in the controls than in the patients with MI alone when compared with the CC genotype (p=0.021). Only the distribution of the ACGC haplotype in CAD patients exhibited a significant difference than that in controls (p<0.05). The distribution of other haplotypes did not differ between CAD patients and controls. The present investigation is the first report to detect an association between MMP2 promoter polymorphisms and CAD with or without MI history in the Turkish population. Further case-control studies in CAD development might be contributed to clarify the role of these polymorphisms.

Serum paraoxonase 1 activity, asymmetric dimethylarginine levels, and brachial artery flow-mediated dilatation in women with polycystic ovary syndrome

OBJECTIVE To evaluate endothelial function via serum asymmetric dimethylarginine (ADMA) levels, paraoxonase 1 (PON1) activity, and brachial artery flow-mediated dilatation (FMD) in women with polycystic ovary syndrome (PCOS). DESIGN Prospective case-control study. SETTING University hospital. PATIENT(S) Thirty patients with PCOS with a mean age of 24.33 ± 4.50 years and 30 healthy controls matched for body mass index (BMI) and age. INTERVENTION(S) Endothelial function was assessed biochemically with serum ADMA levels and serum PON1 activity and functionally with brachial artery FMD by ultrasonography. MAIN OUTCOME MEASURE(S) Serum ADMA levels, serum PON1 activity, brachial artery FMD, hormonal and biochemical parameters. RESULT(S) Patients with PCOS had higher levels of free testosterone and insulin, and higher waist-hip ratio and Ferriman Gallwey scores when compared with the controls. Fasting glucose and homeostasis model assessment of insulin resistance were not different between the groups. There was no statistically significant difference in ADMA levels between two groups. Serum PON1 activity and brachial artery FMD were statistically significantly lower in women with PCOS. There was negative correlation between ADMA and PON1 in patients with PCOS. CONCLUSION(S) Serum PON1 activity and brachial artery FMD, as markers of endothelial dysfunction and cardiovascular risk, were statistically significantly lower in women with PCOS compared with healthy controls matched for age and BMI. Endothelial dysfunction may be seen at earlier ages in patients with PCOS.

Markers of Endothelial Dysfunction and Evaluation of Vascular Reactivity Tests in Behçet Disease

We assessed endothelial dysfunction (ED) in patients with Behcet disease (BD; n = 40) and healthy controls (n = 20). Serum lipid, homocysteine, asymmetric dimethylarginine (ADMA) and high-sensitivity C-reactive protein (hsCRP) levels, erythrocyte sedimentation rates (ESRs), and ultrasonographic flow-mediated dilatation (FMD) were measured. Mean hsCRP, ESR, homocysteine, and ADMA were significantly higher in the BD group (P < .001 for all). Patients with active BD had higher serum levels of hsCRP, homocysteine, and ESR compared with those in remission (P < .001, P < .001, and P = .005, respectively). Flow-mediated dilatation was significantly lower in patients with BD than in controls (P = .001). Flow-mediated dilatation correlated negatively with BD duration and serum ADMA levels (P < .001, r = −.745 and P < .001, r = −.682); a positive correlation was seen between serum ADMA levels and BD duration (P < .001, r = .552). Only stepwise multivariate regression analysis revealed BD duration to have a significant effect on FMD. Flow-mediated dilatation, in conjunction with markers of inflammation, may evaluate ED in patients with BD.

Copeptin level and copeptin response to percutaneous balloon mitral valvuloplasty in mitral stenosis.

We aimed to investigate copeptin levels in mitral stenosis (MS) patients and the behavior of copeptin after hemodynamic improvement achieved by percutaneous balloon mitral valvuloplasty (PBMV). The study involved 29 consecutive symptomatic patients with moderate to severe rheumatic MS who underwent PBMV. Twenty-eight age- and gender-matched healthy volunteers composed the control group. Blood samples for copeptin were obtained immediately before and 24 h after PBMV, centrifuged, then stored at -70°C until assayed. The copeptin level of the patient group was statistically different from that of the control group (61.8 ± 34.4 and 36.8 ± 15.2 pg/ml, respectively; p = 0.001). PBMV resulted in a significant increase in mitral valve area and a significant decrease in transmitral gradient as well as systolic pulmonary artery pressure. While hemodynamic relief was obtained, we detected a statistically significant decline in copeptin levels 24 h after PBMV compared to the baseline levels (from 61.8 ± 34.4 to 44.1 ± 18.2 pg/ml; p = 0.004).

Effect of overnight nasal continuous positive airway pressure treatment on the endothelial function in patients with obstructive sleep apnea.

OBJECTIVE In this prospective study, we aimed to investigate acute effect of nasal continuous positive airway pressure (CPAP) therapy on the endothelial function of patients with obstructive sleep apnea syndrome (OSA) by using brachial artery flow mediated dilatation (FMD) method. METHODS Newly diagnosed thirty OSA patients with ages between 29 and 72 years were included in this study. FMD and high sensitivity C-reactive protein (hsCRP) values of patients obtained before and after CPAP dose titration test were compared with paired samples t test or Wilcoxon signed ranks test. RESULTS With CPAP therapy apnea hypopnea indices were reduced (60.6±24.9/h vs. 9.6±7.9/h; p<0.001) and oxygen desaturation indices recovered (50±27/h vs. 6±7/h; p<0.001). Heart rates of patients decreased after CPAP therapy (80±10/min vs. 73±8/min; p=0.003). FMD values significantly increased after CPAP (8.55±5.82 percent vs. 12.08±7.17 percent; p=0.003). HsCRP values after CPAP were not different from baseline values. CONCLUSION Acute improvement of the endothelial function with one night CPAP therapy suggests endothelial dysfunction in OSA patients to be result of acute pathophysiologic factors. In intermediate and severe OSA patients, CPAP therapy may be considered in acute treatment of diseases associated with endothelial dysfunction.