Abdullah Tekin

Efficacy of allopurinol pretreatment for prevention of contrast-induced nephropathy: a randomized controlled trial

BACKGROUND Contrast-induced nephropathy (CIN) remains a common complication of radiographic procedures. Radiocontrast agents can cause a reduction in renal function that may be due to reactive oxygen species. Conflicting evidence suggests that administration of antioxidants prevents CIN. METHODS We assessed the efficacy of allopurinol in preventing CIN. We prospectively randomized 159 patients with a serum creatinine concentration >1.1mg/dL undergoing cardiac catheterization/interventions to receive allopurinol (300 mg, p.o.) 24h before administration of radiocontrast agent and hydration (1mg/kg/hN/saline for 12h pre- and post-contrast, n=79), or hydration alone (1mg/kg/hN/saline for 12h pre- and post-contrast, n=80). RESULTS CIN occurred in 6 of 80 patients (7.5%) in the control group and no subjects in the allopurinol group (p=0.013). In the allopurinol group, median serum creatinine concentration decreased significantly from 1.43 mg/dL [1.1-4.15 mg/dL] to 1.35 mg/dL [0.7-4.15 mg/dl] at 48 h and to 1.27 mg/dL [0.66-4.37 mg/dL] at 4 days after radiocontrast administration (p<0.0001 and p<0.0001 compared with baseline, respectively). In the control group, median serum creatinine concentration decreased non-significantly from 1.48 mg/dL [1.1-2.96 mg/dL] to 1.43 mg/dL [0.73-3.02 mg/dL] and to 1.45 mg/dL [0.86-3.71 mg/dL] (p=0.045 and p=0.57, respectively) 48 h and 4 days after radiocontrast administration. CONCLUSIONS Prophylactic oral administration of allopurinol, along with hydration, may protect against CIN in high-risk patients undergoing coronary procedures.

Short- and long-term effect of simvastatin therapy on the heterogeneity of cardiac repolarization in diabetic patients

The interlead variability of QT interval in the 12-lead electrocardiogram, QT dispersion (QTd), has been shown to reflect dispersion of ventricular refractoriness and may provide a measure of arrhythmogenic potential in diabetic patients. QTd and heart rate corrected QTd (QTcd) were also proposed to be accurate predictors of cardiac death in patients with diabetes. In recent years, experimental and clinical evidence demonstrates that statins exert antiarrhythmic properties. Therefore, in the present study, we have examined whether simvastatin treatment has any effect on the QTd and QTcd in patients with diabetes mellitus. Sixty type 2 diabetic patients without known coronary artery disease and low-density lipoprotein cholesterol >100mg/dl and 30 age and sex-matched non-diabetic controls were included in a prospective study. Out of 60 diabetic patients, 30 were treated with simvastatin 40 mg/day for 1 year and the remaining 30 subjects were served as diabetic controls. No lipid lowering therapy was administered to the diabetic and the non-diabetic controls. QTd and QTcd of treated diabetics and the non-diabetic controls were measured at baseline, 6, 12 weeks and at 1 year. QTd and QTcd of the diabetic controls were obtained at baseline, 6 and 12 weeks. Both QTd and QTcd were significantly greater in patients with the diabetes than in the non-diabetic controls at baseline (52+/-13 ms vs. 41+/-12 ms, p<0.001 and 62+/-17 ms vs. 42+/-11 ms, p<0.001, respectively). Simvastatin therapy significantly decreased both QTd and QTcd at the end of first year compared to baseline (51+/-15 ms vs. 33+/-11 ms, p<0.001 and 60+/-18 ms vs. 38+/-12 ms, p<0.001, respectively). No significant change were found in QTd and QTcd in the non-diabetic (p=0.29 and p=0.87 by ANOVA, respectively) and in the diabetic controls (p=0.72 and p=0.57, by ANOVA, respectively). This study suggests for the first time that simvastatin treatment in diabetic patients with hyperlipidemia is associated with an improvement in the heterogeneity of cardiac repolarization. This may be one of the mechanisms for the reduction in clinical events reported in the survival studies with statins. Further prospective randomized studies are warranted to confirm our findings.

Left ventricular function in patients with polycystic ovary syndrome: a Doppler echocardiographic study.

PURPOSE Polycystic ovary syndrome (PCOS) is frequently accompanied by the presence of cardiovascular risk factors. The aim of this study was to determine and compare the echocardiographic profiles of patients with PCOS with those of healthy subjects by using conventional echocardiographic methods and tissue Doppler imaging. METHODS The study population consisted of 26 untreated patients with PCOS and 24 healthy controls who were mathced with respect to age and body mass index. In addition to standard two dimensional and M-mode measurements, color Doppler M-mode of left ventricular inflow propagation velocities (Vp), pulmonary venous flow measurements, transmitral valve flows and tissue Doppler imaging of the mitral annulus and basal wall were recorded. RESULTS There were no significant differences between patients with PCOS and control subjects with respect to ejection fraction, mitral E/A ratio, deceleration time, isovolumic relaxation time, Vp and pulmonary venous velocities. The tissue Doppler profiles of patients with PCOS were also found to be similar to those of controls. CONCLUSION This study suggests that there are no significant differences in certain conventional and tissue Doppler echocardiographic measures of cardiac function between patients with PCOS and healthy control subjects.

Does atorvastatin affect androgen levels in men in the era of very-low LDL targeting therapy?

BACKGROUND An adequate pool of free intracellular cholesterol is essential for steroidogenesis in gonads and LDL is the major source of cholesterol used in this pathway. Effect of peripheral LDL on the synthesis of steroids is dose dependent and although LDL levels around 100 mg/dl is demonstrated to be safe in terms of steroidogenesis, effect of LDL levels <70 mg/dl with higher doses of statins on steroidogenesis remains controversial. MATERIAL AND METHODS Androgen and gonadotropin levels are prospectively evaluated at baseline and after 12 weeks of treatment in 77 male coronary heart disease patients receiving high doses of atorvastatin (40-80 mg daily) targeting serum LDL levels <70 mg/dl and in 83 male coronary heart disease patients receiving regular doses of atorvastatin (10-20 mg daily) targeting serum LDL levels <100 mg/dl. RESULTS At the end of the study, mean LDL levels of the high and regular dose atorvastatin groups were 77+/-9 mg/dl and 98+/-10 mg/dl respectively. After twelve weeks of treatment, there were no significant alterations in serum total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone and follicle stimulating hormone levels between two groups. CONCLUSION High dose atorvastatin in order to reach serum LDL levels around 70 mg/dl seems to be as safe as regular doses in order to reach serum LDL levels around 100 mg/dl, in terms of gonadal steroidogenesis in men with coronary heart disease.

Short-term effects of fluvastatin therapy on plasma interleukin-10 levels in patients with chronic heart failure.

BackgroundExperimental data demonstrated that inflammatory mediators, such as pro-inflammatory and anti-inflammatory cytokines and their receptors might have important role in the development and the progression of heart failure (HF). Statins were shown to downregulate inflammatory cytokines in HF. Interleukin (IL)-10 is one of the most important anti-inflammatory cytokines. The effect of statin therapy on plasma IL-10 levels is not known in patients with HF. We conducted this study to investigate the effects of fluvastatin therapy on plasma IL-10 cytokine concentration in patients with HF. MethodsA total of 29 patients with ischemic HF were included in this prospective uncontrolled study. Patients were assigned to fluvastatin (80 mg/day) after baseline examinations. Determination of biochemical parameters including lipids, IL-10, and tumor necrosis factor-&agr; were performed at baseline and 12 weeks after the initiation of fluvastatin therapy. All participants also underwent symptom-limited exercise tolerance test at baseline and 12 weeks, and heart rate recovery (HRR) was calculated. ResultsA significant elevation in the plasma levels of IL-10 after 12 weeks of fluvastatin treatment (4.8±1.0 vs. 6.5±1.3 pg/ml, P=0.002) was observed. Plasma tumor necrosis factor-&agr; levels were significantly decreased after fluvastatin therapy (6.3±2.3 vs. 4.8±1.4 pg/ml, P=0.003). Fluvastatin therapy significantly improved HRR at 1 min after 12 weeks compared with baseline (19±7 vs. 24±9 bpm, P<0.001). A positive correlation between the change in the levels of IL-10 and the change in HRR at 1 min (r=0.57, P<0.001) was observed. ConclusionFluvastatin therapy might lead to an increase in plasma IL-10 levels and an associated improvement in vagal tonus as assessed by HRR at 1 min in patients with HF. These findings might partly explain the possible benefit observed in statin trials.

Investigation of the relationship between asthma and subclinical atherosclerosis by carotid/femoral intima media and epicardial fat thickness measurement

ABSTRACT Objective: Since asthma and atherosclerosis may share similar pathophysiological mechanism, this study is planned to investigate whether epicardial fat thickness (EFT), carotid and femoral intima media thicknesses, which are markers of subclinical atherosclerosis, are increased in patients with asthma. Methods: The study was designed as a cross-sectional study. A total of 154 participants (83 patients with asthma and 71 healthy volunteers) were enrolled into the study. Epicardial fat, carotid, and femoral intima media thicknesses were measured and recorded in both groups. The statistical difference between the two groups was examined. Results: Both carotid and femoral intima media thicknesses were significantly higher in patients with asthma compared to control group (5.52 ± 0.4 mm−1 vs. 5.36 ± 0.4 mm−1; p = 0.038 and 5.64 ± 0.4 mm−1 vs. 5.46 ± 0.5 mm−1; p = 0.036, respectively). However, there was not a significant difference in EFT between the groups [5.9 mm (5.3–6.6; IQR = 1.3) vs. 5.6 mm (4.7–6.5; IQR = 1.8); p = 0.1]. On comparison of control group and asthma subgroups (mild, moderate, and severe), there was a statistically significant difference among these four groups in terms of carotid and femoral intima media thicknesses (p = 0.002 and p < 0.001, respectively). Subgroup analyses showed that this difference was mainly due to patients with severe asthma. Conclusions: Carotid and femoral intima media thicknesses in asthmatic patients were found to be increased compared to the normal population. As a result, the risk of subclinical atherosclerosis in asthmatic patients may be high.

Comparison of Carvedilol and Metoprolol for Preventing Contrast-Induced Nephropathy after Coronary Angiography

Aims: Contrast-induced nephropathy (CIN) is one of the most common causes of hospital-acquired acute renal failure. Oxidative stress and vasoconstriction might play key roles in its pathogenesis. In a few experimental models, antioxidant properties of carvedilol have been documented. The aim of this study was to analyze and compare the effects of carvedilol and metoprolol on the development of CIN in patients undergoing coronary angiography. Methods: One hundred patients currently taking metoprolol and 100 patients currently taking carvedilol were enrolled into the study. Venous blood samples were obtained before and 48 h after contrast administration. Cystatin C and malondialdehyde values were examined and compared. CIN was defined as a creatinine increase of at least 25% or 0.5 mg/dl from the baseline value. Results: Seven patients in the carvedilol group (7%) and 22 patients in the metoprolol group (22%) developed CIN (p = 0.003). In the metoprolol group, the median cystatin C concentration increased significantly from 978 to 1,086 ng/ml (p = 0.001) 48 h after radiocontrast administration. In the carvedilol group, the median cystatin C concentration did not change significantly (1,143 vs. 1,068 ng/ml; p = 0.94). In the metoprolol group, the mean malondialdehyde concentration increased significantly from 7.09 ± 1.48 to 8.38 ± 2.6 nmol/l (p < 0.001). In the carvedilol group, the mean serum malondialdehyde concentration did not change significantly (7.44 ± 1.21 vs. 7.56 ± 1.11 nmol/l; p = 0.59). Conclusion: When compared to metoprolol, carvedilol might decrease oxidative stress and subsequent development of CIN.

Attenuated Heart Rate Recovery in Mercury-Exposed Individuals

minute after exercise for protocols that stop exercise abruptly [2– 4] . Since the authors did not use a post-exercise cool down protocol, HRR1 ≤ 18 beats/min should have been assumed to be abnormal in this case. Thus, their definition of abnormal HRR1 as <12 beats/min is not correct. It would be informative to know how many subjects had abnormal HRR1 in each group in this regard. Finally, the authors defined heart rate reserve as the change in heart rate from rest to peak exercise during exercise. However, heart rate reserve is actually the difference between the attainable heart rate at peak exercise (220 – age in years) and resting heart rate [2, 5] . Meanwhile, the heart rate reserve is calculated as a percentage as: (peak heart rate – resting heart rate in beats per min)/ ([220 – age in years] – [resting heart rate in beats per min]) × 100 [2, 5] . Heart rate reserve as a percentage is also considered to indicate the chronotropic response. A heart rate reserve below 80% is considered to be evidence of an impaired chronotropic response, which is a powerful indicator of mortality [3] . Therefore, it would be interesting to know if there was any difference between the mercury-exposed group and control subjects in terms of heart rate reserve in percentages. Dear Editor, We read with great enthusiasm the article by Yilmaz et al. [1] that investigated the heart rate recovery (HRR) of mercury-exposed individuals. They reported that HRR at the first (HRR1), second, and third minute were attenuated in mercury-exposed patients when compared to normal subjects. Interestingly, there were no significant correlations between blood, urine, or hair mercury levels and heart rate recovery at these time points. Furthermore, the duration of mercury exposure was not associated with HRR. Collectively, these findings suggest that, when toxic enough, mercury might lead to long-lasting or even permanent damage to the autonomic nervous system. HRR1 was purely vagal, meanwhile HRR at 2 and 3 min were under the control of both parasympathetic and sympathetic systems [2, 3] . Thus, mercury-induced damage is likely to be a double-edged sword to the autonomic nervous system. Is there any explanation to this in the authors’ perspectives? Are there any cut-off values for mercury to be considered toxic? The authors further reported that exercise testing was terminated (cessation of exercise) abruptly with the patient in the standing or sitting positon (with no ‘cool down’ period) or the patient kept walking at a predetermined speed and incline (cool down period). Abnormal HRR1 is usually defined as a heart rate that declines ≤ 12 beats/min in the first minute after exercise for protocols that use a cool down after exercise, or ≤ 18 beats/min in the first Published online: October 5, 2016

Endothelial nitric oxide synthase gene polymorphisms in patients with slow coronary flow

Background and aims The aim of this study was to explore potential associations of the intron 4 variable number of tandem repeats (VNTR) and E298A polymorphisms of the endothelial nitric oxide synthase (eNOS) gene with slow coronary flow (SCF). The association between plasma nitrate and nitrite (NOx) concentrations and eNOS gene polymorphisms was also assessed. Materials and methods The intron 4 VNTR and E298A polymorphisms of the eNOS gene were evaluated in the isolated DNA blood samples obtained from the SCF patient group (n = 30) and healthy group consisted of age- and sex-matched controls (n = 61). Results Plasma NOx level was significantly lower in patients with SCF than in controls. In addition, patients with SCF have significantly lower nitric oxide levels than control subjects within each genotype variants. The allele and genotyped frequencies of the eNOS intron 4 VNTR and E298A polymorphisms were similar between patients with SCF and the controls. Plasma NOx concentrations with respect to the relevant genotypes were found insignificant. Discussion and conclusion Plasma NOx is lower in patients with SCF than in healthy subjects. Our findings may suggest the lack of association between intron 4 VNTR and E298A polymorphisms of the eNOS gene and SCF.

Comparison of application of 2013 ACC/AHA guideline and 2011 European Society of Cardiology guideline for the management of dyslipidemias for primary prevention in a Turkish cohort

Objective: Atherosclerotic cardiovascular disease is a major global cause of death. The common approach in primary prevention of cardiovascular disease is to identify patients at high risk for cardiovascular disease. This article analyzes and compares the application of 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline and the 2011 European Society of Cardiology (ESC) guideline for the management of dyslipidemias for primary prevention in Turkish population. Methods: The study included 833 patients (482 women and 351 men). Risk scores were calculated according to both guidelines and indications for statin treatment were determined according to sex and age group. Variables are presented as mean±SD or median with interquartile range for continuous data and as proportions for categorical data. Variables were analyzed by unpaired t-test, Mann-Whitney U test, chi-square or Fischer’s exact test as appropriate. Results: The ACC/AHA would suggest statin treatment in 415 patients out of 833 (49.5%), while ESC would recommend statin for 193 patients out of 833 (23.1%) (p<0.001). Statins would be recommended for 40.4% of women and 62.6% of men for primary prevention by the ACC/AHA, while this figure was 12% for women and 38.4% for men according to the ESC guideline (p<0.001 for both). Conclusion: When compared to the ESC guideline, the ACC/AHA guideline suggests augmented statin treatment for primary prevention in Turkish population.