Ibrahim Halil Altiparmak

The association of serum prolidase activity with the presence and severity of coronary artery disease.

ObjectivesProlidase is a cytosolic exopeptidase that cleaves iminodipeptides with carboxy-terminal proline or hydroxyproline and plays major role in collagen turnover. Collagen is the essential content in atherosclerotic plaque playing a key role in the stability/instability of and progression of coronary artery disease (CAD). Consequently, in this study we sought to determine serum prolidase activity and markers of oxidative stress such as lipid hydroperoxide and total free sulfhydryl in CAD. Design and methodsWe have evaluated 199 patients with CAD and 122 control cases with clinical, electrocardiographic, and laboratory investigation. We have measured serum prolidase activity and serum total free sulfhydryl levels spectrophotometrically. Serum lipid hydroperoxide levels were determined with ferrous ion oxidation-xylenol orange method. We assessed the association of serum prolidase activity with the presence and severity of CAD and clinical characteristics, and laboratory parameters. ResultsSerum prolidase activity (52.5±5.6 vs. 46.7±5.1 U/l, respectively, P<0.001) and serum lipid hydroperoxide levels were significantly increased in patients with CAD compared with control cases whereas, serum total free sulfhydryl levels were significantly decreased in patients with CAD compared with control cases. Serum prolidase activity and total free sulfhydryl levels were independent predictors of the presence of CAD [(χ2=75.532, ß=0.212, P=0.003) and (χ2=25.969, ß=−30.486, P=0.019), respectively] and Gensini score [(&bgr;=0.276, P<0.001) and (&bgr;=−0.274, P<0.001), respectively]. Independent predictors of serum prolidase activity were serum high-density lipoprotein cholesterol (&bgr;=−0.138, P=0.023) and urea levels (&bgr;=0.146, P=0.036), and Gensini score (&bgr;=0.317, P<0.001). ConclusionFindings of this study have shown that serum prolidase activity is significantly associated with the presence and severity of CAD, and elevated serum prolidase activity might be an independent predictor of coronary atherosclerosis.

The relation of serum thiol levels and thiol/disulphide homeostasis with the severity of coronary artery disease

BACKGROUND The balance of oxidant and antioxidant status plays a key role in the coronary artery diseases (CAD). Thiol is one of the most important antioxidant barriers in humans, and thiol/disulphide homeostasis is a novel oxidative stress marker. AIM We aimed to investigate the relation of serum thiol levels and thiol/disulphide homeostasis with the presence and severity of CAD. METHODS A total of 161 patients who underwent coronary angiography owing to stable angina pectoris were consecutively enrolled. They were divided into three groups. Group I - 47 age- and gender-matched subjects with normal coronary angiography (control); group II - 71 newly diagnosed CAD patients with noncritical stenosis; and group III - 43 newly diagnosed CAD patients with critical stenosis. Serum native thiol, total thiol, and disulphide levels were measured, and disulphide/thiol ratios were calculated. Gensini scores were calculated in CAD patients. RESULTS While the highest thiol levels were found in group I, the lowest one was observed in group III (p < 0.001). Total and native thiol levels were significantly lower in group II than in group I (p < 0.001 for each), but they increased considerably in group II compared with group III (p = 0.031 and p = 0.028, respectively). Disulphide levels decreased in group II and III compared with group I (p < 0.001 for each). No statistically significant changes were observed in disulphide/thiol ratios (p > 0.05). Gensini scores were negatively correlated with total and native thiols, and positively with age and dyslipidaemia. Stepwise linear regression analyses showed that native thiol was an independent predictor in the final model for Gensini score. Receiver operating characteristic curve analysis demonstrated that thiol values of 310.7 or below could predict CAD with 89% sensitivity and 85% specificity (AUC = 0.918; 95% CI 0.870-0.965). CONCLUSIONS While the disulphide/thiol ratio did not change significantly, decreased native thiol levels were associated with the presence and severity of CAD. This result indicates that the reduction of thiols may be an important factor in the development of CAD.

Epicardial fat thickness and oxidative stress parameters in patients with subclinical hypothyroidismhypothyroidism

Introduction Thyroid disorders are known to be a risk factor for cardiovascular diseases. Epicardial fat thickness (EFT) and oxidative stress are also believed to be major risk factors for cardiovascular events. The aim of this study was to evaluate the possible relationship between oxidative stress parameters and EFT in patients with subclinical hypothyroidism (SCH). Material and methods A total of 60 individuals (30 patients with SCH and 30 healthy controls) were recruited for the study. The EFT and oxidative stress parameters of all participants were analyzed at baseline; the same were analyzed in SCH patients after achievement of a euthyroid state. Results Compared to healthy subjects, SCH patients had significantly higher EFT and oxidative stress parameters (p < 0.05 for all). EFT and oxidative stress parameters both decreased after treatment, but only the decrease of EFT levels was statistically significant after thyroid hormone replacement (p < 0.05). Serum EFT levels were not significantly correlated with oxidative stress index (r = 0.141, p = 0.458). Conclusions Previous studies have demonstrated that visceral adipose tissue and oxidative stress are major risk factors for cardiovascular events; our study demonstrated that EFT, a visceral adipose tissue, and oxidative stress parameters were higher, and could be used as an indicator for cardiovascular diseases in patients with SCH.

The association between plasma thiol levels and left ventricular diastolic dysfunction in patient with hypertension

The balance of oxidant and antioxidant status plays an important role in the left ventricular diastolic dysfunction (LVDD) in patients with hypertension (HT). Thiol is an important part of antioxidant system in the body. The aim of this study was to investigate the relationship between plasma thiol levels and LVDD in patients with HT. A total of 138 patients with newly diagnosed essential hypertensive and 20 age-gender matched subjects as control group enrolled in the study. After echocardiographic assessment, the hypertensive patients were divided into three groups: Group 1: without LVDD (n = 41); group 2: with LVDD grade 1 (n = 57); and group 3: with LVDD grade 2 (n = 40). Plasma thiol, lipid and glucose levels were measured in all subjects. Plasma thiol levels were significantly different between the groups (all of p < 0.05). While the lowest thiol level was in the group 3, the highest level was in the control group. The presence of LVDD was correlated with age, systolic and diastolic blood pressure, thiol levels, and history of coronary artery disease and hyperlipidemia (all of p < 0.05). Age and thiol were however independent predictors of LVDD in multivariate analyses (β = 0.318, p < 0.001, and β = − 0.314, p < 0.001, respectively). ROC-curve analysis revealed that thiol levels over 163 μmol/L predict LVDD in hypertensive patients with 75% sensitivity and 70% specificity (AUC = 0.783; 95% CI: 0.714–0.852). Plasma thiol is an independent predictor for the presence of LVDD. This suggests that thiol plays a role in the pathogenesis of diastolic function. Increased thiol levels may provide protection against the development of diastolic dysfunction.

Evaluation of thiol levels, thiol/disulfide homeostasis and their relation with inflammation in cardiac syndrome X.

ObjectivesCardiac syndrome X (CSX) is characterized by the presence of myocardial ischemia in the absence of coronary artery stenosis on angiograms. Its relation to oxidative stress and inflammation is well known. There are no data on thiols and their relation with inflammation in CSX. The aim of this study was to investigate thiol levels and thiol/disulfide homeostasis in CSX patients. Materials and methodsFifty consecutive patients who had documented myocardial ischemia and normal coronary angiogram (CSX group), and 45 age-matched and sex-matched consecutive patients who had normal coronary angiogram without myocardial ischemia (control group) were enrolled in this study. C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), native thiol, total thiol, and disulfide levels were measured and disulfide/thiol ratios were calculated in all patients. ResultsDemographic, clinical, basic laboratory, and echocardiographic characteristics were similar in the two groups (P>0.05). Serum total thiol, native thiol, and disulfide levels decreased significantly in the CSX group compared with the control group (P<0.001). CRP and NLR increased significantly in the CSX group compared with the control group (P<0.001). Although disulfide/native thiol levels increased in the CSX group, this reduction did not reach statistical significance (5.8 vs. 5.5, P>0.05). The reduction of thiols was correlated negatively with CRP and NLR (P<0.001). Although univariate logistic regression analyses showed that serum total and native thiol levels, CRP and NLR were independent predictors for CSX estimation, stepwise multivariate logistic regression analysis showed only total thiol levels as an independent predictor for CSX (odds ratio=0.966, 95% confidence interval: 0.950–0.982, P<0.001). Also, receiver operating characteristic curve analysis showed that serum total thiol values of 338.4 or below could predict the CSX with 86% sensitivity and 84% specificity (area under curve=0.903; 95% confidence interval: 0.842–0.965). ConclusionSerum total thiol levels decreased significantly in CSX and this reduction independently predicted CSX with strong sensitivity and specificity. This suggests that the reduction in thiols along with increased inflammation may play a pathophysiological role in the development of CSX.

High aortic pulse-wave velocity may be responsible for elevated red blood cell distribution width in overweight and obese people: a community-based, cross-sectional study.

Summary Background: Obesity and overweight are risk factors for atherosclerosis. Red blood cell distribution width (RDW) is associated with subclinical cardiac diseases. The aim of this study was to investigate the association between RDW and aortic stiffness in overweight or obese subjects. Methods: A total of 101 overweight or obese subjects without overt cardiovascular disorders, and 48 healthy controls were enrolled. RDW, aortic pulse-wave velocity (PWV) and augmentation index 75 (Aix75) were evaluated. The case subjects were divided into two sub-groups according to PWV values; ≥ 10 m/s in group I, and < 10 m/s in group II. Bivariate correlation and multiple regression analyses (stepwise) were performed. Results RDW and PWV were considerably increased in the case groups compared with the controls. RDW was significantly increased in group I compared with group II and the controls [median 12.0 m/s, interquartile range (IQR): 10.5–17.5; median 11.7 m/s, IQR: 10.2–14.2, and median 11.4 m/s, IQR: 9.6–15.5, p < 0.05, respectively]. Resting heart rate and age were higher in group I than group II (81 ± 11 vs 74 ± 12 beats/min and 41 ± 120 vs 36 ± 9 years, respectively, p < 0.05). Regression analyses revealed that while log-RDW, age and resting heart rate were independent predictors for aortic PWV, log-RDW was the most important predictor in the final model. Conclusions: RDW, resting heart rate and age independently predicted arterial stiffness, and RDW may be useful to provide an early recognition of subclinical atherosclerosis in overweight and obese individuals.

Usefulness of the epicardial fat tissue thickness as a diagnostic criterion for geriatric patients with metabolic syndrome

Objective To evaluate the epicardial fat tissue thickness (EFTT) as a diagnostic criterion for geriatric patients with metabolic syndrome (MetS). Methods Sixty geriatric patients over 65 years of age were recruited for the study. Patients were divided into two groups: Group 1 (n = 30) consisted of patients with MetS; Group 2 (n = 30) consisted of patients without MetS. Echocardiography was used to measure EFTT in all patients, and blood samples were analyzed for biochemical parameters. Results Compared to Group 2, EFTT levels of Group 1 were statistically higher (P < 0.05). In a binary logistic regression analysis, EFTT levels served as the independent factor for metabolic syndrome (B = 17.35, SE = 4.93, Wald = 12.36, P < 0.001). Receivers operating characteristic Curve (ROC-curve) analysis revealed that EFTT predicted MetS with 96.7% sensitivity and 86.7% specificity above the level of 7.3 mm [area under the curve = 0.969; 95% confidence interval (CI): 0.928–1.00]. Conclusions The present study demonstrated that serum EFTT levels were higher in geriatric patients with MetS and can therefore be used as a diagnostic criterion for MetS.

The relation of serum paraoxonase-1 activity with isolated coronary artery ectasia: an observational study

OBJECTIVE Coronary artery ectasia (CAE) is a congenital or acquired anomaly characterized with localized or diffuse dilatations of coronary arteries. Paraoxonase (PON-1) is a high-density lipoprotein-cholesterol (HDLC) associated antioxidant enzyme that prevents atherosclerosis. The aim of this study was to investigate serum paraoxonase-1 enzyme activity (SPA) in patients with CAE in comparison patients with coronary artery disease (CAD) and normal coronary arteries. METHODS We have evaluated 44 patients with isolated IKAE, 40 cases with normal coronary arteries (NCA), 40 cases with critical CAD (CAD) and 40 cases with minimal CAD (MCAD) in this cross-sectional observational study. Demographic and biochemical data of patients were collected. SPA was determined spectrophotometrically. Among-group comparisons, ANOVA, Kruskal-Wallis and Chi-square tests were used; Bonferroni test was used for post-hoc analysis, Pearsons correlation analysis to determine the parameters associated with the SPA. RESULTS There were no differences among groups with regard to age, sex, presence of diabetes, hypertension and smoking (p>0.05 for all). The highest HDLC was detected in patients with NCA and lowest HDLC was detected in patients with CAD (respectively 52±15 mg/dL; 41±16 mg/d L, p=0.021). CAD and CAE groups were similar with respect to HDLC levels (p>0.05). The highest SPA level was detected in patients with NKA and the lowest SPA level was detected in patients with CAD (respectively 250.78±59.37U/L; 163.39±49.28 U/L, p=0.005). CAD and CAE groups were similar with respect to SPA levels (p>0.05). CONCLUSION Both decreased SPA and decreased HDLC levels are closely related to the development of the CAE similar to CAD.

The Relation Between Epicardial Fat Tissue Thickness and TSH Receptor Antibody in Hyperthyroidism

BACKGROUND Although hyperthyroidism may be associated with atherosclerosis, its pathogenesis is not well known. TSH receptor antibody (TRAb) has been shown to be responsible for increased orbital fat tissue in Graves ophthalmopathy. Epicardial fat tissue thickness (EFT) has been found to be increased in case of overt hyperthyroidism. In our study, we aimed to investigate if TRAb is associated with the increased EFT in newly diagnosed hyperthyroidism. METHODS Twenty six TRAb positive (group 1) and 26 TRAb negative (group 2) newly diagnosed patients with hyperthyroidism, and 26 healthy control subjects (group 3) were enrolled. EFT was measured by the same cardiologist using an echocardiography device. Serum TRAb levels were measured by the radio-receptor assay and levels above 1.75 IU/L were considered as positive. RESULTS There was no difference among groups in terms of age, gender and body mass index. Although there was no significant difference between group 1 and 2, both group 1 (0.38±0.15 cm) and group 2 (0.4±0.17 cm) had significantly higher EFT levels when compared to group 3 (0.25±0.06 cm) (p=0.004 and p=0.001, respectively). However we did not find any correlation between TRAb and EFT levels. CONCLUSION The results of our study suggested that EFT was increased in hyperthyroidism and this increasing was not dependent of TRAb level. EFT elevation might be depending directly to the cardiovascular effects of hyperthyroidism.

Red Cell Distribution Width and Hemorrhagic Events Related to Dabigatran Use.

bleeding, are closely related to its plasma concentrations [5] . Zhang et al. [1] found that patients with a high RDW had a significantly lower creatinine clearance than those with a low RDW. Although there is no linear relationship between RDW and creatinine clearance, the low creatinine clearance could have led to the high plasma concentration of dabigatran in the patients with a high RDW. However, if more patients had been included in the study, perhaps a reverse linear correlation between RDW and creatinine clearance would have been observed. On the other hand, Table 1 of Zhang et al. [1] shows that the high-RDW group had a lower hemoglobin level, were of advanced age, and were predominantly female. These findings support that the mechanism underlying a high RDW may be multifactorial. Recently, most of the studies on RDW have revealed a high RDW to be associated with a poor outcome in many clinical disorders including AF and other cardiovascular diseases [4, 6, 7] . Though the exact reason for elevated RDW has not been discovered, mechanisms such as inflammation, oxidative stress, poor nutritional status, a decrease in or malfunction regarding erythropoietin production, and anisocytosis have been asserted [4, 7–9] . Therefore, to at least explain the association of high RDW with inflammation, Zhang et al. [1] could have worked with other inflammatory parameters in this study, such as high-sensitivity C-reactive protein, the neutrophil-toWe read the paper by Zhang et al. [1] , entitled ‘‘Prognostic Value of Red Blood Cell Distribution Width on Bleeding Events in Nonvalvular Atrial Fibrillation Patients Taking Dabigatran (110 mg b.i.d.) after Catheter Ablation’’ in this issue of Cardiology, with great interest, and we thank them for their striking investigation. It is known that atrial fibrillation (AF) is the most frequently observed arrhythmia in daily clinical practice and that it has an increased risk of thromboembolic stroke as well as high cardiovascular morbidity and mortality [2] . Thus, the management of AF is very important, especially in terms of preventing thromboembolic events. Recently, studies have reported that a high red blood cell distribution width (RDW) is associated with a poor prognosis and bleeding events in patients with AF [3, 4] . The investigation by Zhang et al. [1] is a well-designed research study. The investigators discovered that RDW could predict hemorrhagic complications in patients taking dabigatran. However, as they themselves state, their study had its limitations, the most important being the short follow-up time (3 months) and the use of only a low dose of dabigatran (110 mg twice a day). They found only minor hemorrhages (13 cases) in their study population [1] . We wonder if the outcome would have been the same with a 150-mg dose dabigatran or if patients had been followed for a longer time. It is also well known that the side effects of dabigatran, including Received: September 30, 2016 Accepted: October 1, 2016 Published online: November 10, 2016