Salih Topal

Carotid intima–media thickness in patients with cardiac syndrome X and its association with high circulating levels of asymmetric dimethylarginine

BACKGROUND The cause of myocardial ischemia and chest pain in patients with cardiac syndrome X (CSX) has been explained by mechanisms including endothelial dysfunction. CSX patients have higher levels of asymmetric dimethylarginine (ADMA) and increased mean common carotid intima-media thickness (C-IMT). Accordingly, this study was designed to examine C-IMT with its association serum endothelial function parameters in patients with CSX. METHODS The study population consisted of 30 enrolled consecutive patients with diagnosis of CSX. As a control group, 30 individuals with the complaint of anginal chest pain without any ischemia on myocardial perfusion scintigraphy and with normal coronary angiographies were selected. C-IMT was measured by recording ultrasonographic images of both the left and the right common carotid artery. Plasma levels of L-arginine, ADMA, and nitrate/nitrite (NO(x)) were measured from blood samples. RESULTS Both C-IMT (mm) and carotid atherosclerotic plaques were significantly higher in patients with CSX than in control group. Also, the plasma level of NO(x), L-arginine, and L-arginine/ADMA ratio were lower in patients with CSX than they were in the control group subjects. Plasma ADMA level increased in the CSX patients group. Correlation analysis showed significant positive correlation with C-IMT and plasma ADMA levels and showed significant negative correlation with plasma NO(x) and L-arginine levels. L-arginine/ADMA ratio and C-IMT was also showed significant negative correlation with the same analysis. CONCLUSIONS CSX patients had higher plasma ADMA levels and C-IMT values than the controls, reflecting the presence of subclinical atherosclerosis. These findings suggest that, besides endothelial dysfunction, presence of atherosclerosis may also contribute to the etiopathogenesis of the CSX phenomenon.

The effect of nebivolol treatment on oxidative stress and antioxidant status in patients with cardiac syndrome-x

BackgroundFree radical-mediated oxidative stress has been implicated in the etiopathogenesis of several disorders. The aim of this study was to elucidate the effect of treatment with nebivolol on the metabolic state of oxidative stress, and antioxidant status markers in patients with cardiac syndrome-X (CSX), additionally, to compare with the effect of metoprolol treatment. MethodsThirty patients, 17 female and 13 male, with CSX were enrolled in the study. Nebivolol (5 mg/day) or metoprolol (50 mg/day) was administrated for 12 weeks. Twelve hour fasting blood samples, taken at the initiation and on the third month of therapy, were analyzed for the levels of malondialdehyde (MDA), nitrite+nitrate (NOx), and the activity of myeloperoxidase (MPO), superoxide dismutase (SOD). No patient presented additional risk factors for increased reactive oxygen species levels. ResultsCompared with sixteen control participants, patients with CSX had significantly higher activity of MPO and levels of MDA, but significantly lower SOD activity and levels of NOx before treatment. After treatment, MPO activity and MDA levels were significantly reduced; SOD activity and NOx levels were significantly increased with nebivolol but remained unchanged with metoprolol. ConclusionWe have shown that patients with CSX who taken nebivolol have lower serum MPO activity, levels of MDA and higher serum SOD activity, NOx levels when compared with metoprolol treatment. Exercise stress test parameters were also ameliorated in patients who had taken nebivolol in contrast to metoprolol. Nebivolol treatment may be a novel treatment strategy in cases with CSX in the future.

The Relationship of Serum Erythropoietin Level With Coronary Collateral Grade

BACKGROUND Erythropoietin has been shown to induce neovascularization and protect against ischemic vascular injury. We investigated whether a higher serum erythropoietin (EPO) level is related to better coronary collateral vessel grade. METHODS Ninety-nine patients with stable angina pectoris who have at least 1 coronary stenosis of equal to or greater than 70% at coronary angiography were prospectively enrolled. Serum EPO and vascular endothelial growth factor (VEGF) levels were studied. Coronary collateral degree was graded according to the Rentrop method. Patients with grade 2-3 collateral degree were included in the good collateral group and formed Group I. The patients with grade 0-1 collateral degree were included in the poor collateral group and formed Group II. RESULTS The serum EPO level was significantly higher in the good collateral group (17.3 ± 9.3 mU/mL vs 11.7 ± 5.0 mU/mL; P < 0.001). There was also a positive correlation between serum EPO level and Rentrop score (r = 0.39; P < 0.001). In multivariate analysis, serum EPO level (odds ratio [OR] 1.336; 95% confidence interval [CI], 1.120-1.593; P = 0.001), oxygen saturation (OR 0.638; 95% CI, 0.422-0.963; P = 0.033) and presence of chronic total occlusion (CTO) (OR 26.7; 95% CI, 3.874-184.6; P = 0.001) were independently related to well-developed coronary collaterals. CONCLUSIONS Higher serum EPO level is related to better coronary collateral development. Erythropoietin may have a positive effect on the development of collaterals and may provide a new agent for the treatment strategies to enhance coronary collateral vessel development.

Left Ventricular Hypertrophy and Blood Pressure Control in Automated and Continuous Ambulatory Peritoneal Dialysis Patients

Hypertension, non‐dipper blood pressure (BP) pattern and decrease in daily urine output have been associated with left ventricular hypertrophy (LVH) in peritoneal dialysis (PD) patients. However, there is lack of data regarding the impact of different PD regimens on these factors. We aimed to investigate the impact of circadian rhythm of BP on LVH in end‐stage renal disease patients using automated peritoneal dialysis (APD) or continuous ambulatory peritoneal dialysis (CAPD) modalities. Twenty APD (7 men, 13 women) and 28 CAPD (16 men, 12 women) patients were included into the study. 24‐h ambulatory blood pressure monitoring (ABPM) and transthoracic echocardiography besides routine blood examinations were performed. Two groups were compared with each other for ABPM measurements, BP loads, dipping patterns, left ventricular mass index (LVMI) and daily urine output. Mean systolic and diastolic BP measurements, BP loads, LVMI, residual renal function (RRF) and percentage of non‐dippers were found to be similar for the two groups. There were positive correlations of LVMI with BP measurements and BP loads. LVMI was found to be significantly higher in diastolic non‐dippers compared to dippers (140.4 ± 35.3 vs 114.5 ± 29.7, respectively, P = 0.02). RRF and BP were found to be independent predictors of LVMI. Non‐dipping BP pattern was a frequent finding among all PD patients without an inter‐group difference. Additionally, higher BP measurements, decrease in daily urine output and non‐dipper diastolic BP pattern were associated with LVMI. In order to avoid LVH, besides correction of anemia and volume control, circadian BP variability and diastolic dipping should also be taken into consideration in PD patients.

Gemcitabine-Induced Acute Coronary Syndrome: A Case Report

Objectives: To report a case of metastatic leiomyosarcoma, in which a patient developed chest pain accompanied by acute left bundle-branch block (LBBB) after gemcitabine infusion. Clinical Presentation and Intervention: A 59-year-old woman admitted with bilateral pulmonary nodules had classic risk factors for coronary heart disease and coronary stenosis as demonstrated by previous coronary angiography. She was treated with gemcitabine infusion, and 30 min later she experienced severe chest pain accompanied by acute LBBB confirmed by ECG. We suspected gemcitabine-induced coronary vasospasm exacerbated by the preexisting coronary artery disease as the cause of the acute coronary syndrome. The patient was subsequently treated with antianginal therapy and percutaneous coronary intervention. Her chest pain resolved and LBBB disappeared. She was discharged 2 days later without any further cardiac events. No additional cancer therapy was given and she died 5 months later, due to disease progression. Conclusion: This case showed that chemotherapeutic agents must be administered with intensive cardiac monitoring especially in patients with cardiac disease and well-known risk factors to prevent the development of cardiac complications, despite an agent not being known to be ‘cardiotoxic’.

Incremental effects of serum uric acid levels, autonomic dysfunction, and low-grade inflammation on nocturnal blood pressure in untreated hypertensive patients and normotensive individuals.

OBJECTIVES We aimed to evaluate the associations between nocturnal blood pressure (BP) and serum uric acid (SUA) level, low-grade inflammation, and cardiac autonomic function in untreated dipper and nondipper hypertensive patients and normotensive individuals. STUDY DESIGN The study included 92 consecutive patients (44 men, 48 women; mean age 51.6 ± 9.7 years) who presented for initial evaluation of hypertension. All patients underwent 24-hour Holter monitoring to assess heart rate variability (HRV) and ambulatory BP. Serum high-sensitivity C-reactive protein (hs-CRP) and SUA levels were measured. Due to the non-normal distribution of hs-CRP and microalbuminuria (MAU), they were normalized by logarithmic transformation. RESULTS Of the study group, 60 patients (65.2%) were diagnosed as hypertensive (50% nondippers). In univariate correlation analysis, log(MAU) showed a significant correlation with nocturnal BP (r=0.560, p<0.001). Among HRV parameters, SDNN, SDANN, and triangular index were inversely correlated with log(hs-CRP) (r=-0.356, p=0.001; r=-0.350, p=0.001; r=-0.314, p=0.002, respectively) and nighttime BP (r=-0.286, p=0.006; r=-0.251, p=0.02; r=-0.294, p=0.004, respectively). Log(hs-CRP) was positively correlated with nighttime BP (r=0.302, p=0.003). Serum UA levels were correlated with only nocturnal BP; i.e., nocturnal mean (r=0.260, p=0.01), systolic (r=0.249, p=0.016), and diastolic BP (r=0.249, p=0.017). In multiple linear regression analysis, log(hs-CRP) and age were independent predictors of cardiac autonomic dysfunction, and log(hs-CRP), SUA, and HRV parameters were independent predictors of nocturnal BP measurements. CONCLUSION Our findings suggest the role of low-grade inflammation, uric acid levels, and autonomic dysfunction even in the early stages of hypertension.

Neutrophil gelatinase-associated lipocalin levels in isolated coronary artery ectasia.

BACKGROUND The pathophysiology of coronary artery ectasia (CAE) is still unknown. Inflammation and degradation of connective tissue may have a role in the development of coronary ectasia. In the present study, the authors examined neutrophil gelatinase-associated lipocalin (NGAL) levels in isolated CAE patients. METHODS Thirty-five patients with isolated CAE (25 males; mean age, 59±10 years) and 35 age- and sex-matched healty volunteers (22 males; mean age, 57±11 years) who had been shown to have normal coronary arteries were included in the study. Basal characteristics were recorded. Serum NGAL levels were determined with an enzyme-linked immunosorbent assay kit. RESULTS NGAL levels were significantly higher in the isolated CAE group than in the control group (65.1±13 vs 53.7±19 ng/mL; P=0.006). There were also significant difference in NGAL levels according to the number of ectatic coronary arteries (58.1±13, 70.9±9, and 71.1±11 ng/mL for 1, 2, and 3 arteries, respectively; P=0.015). Level of NGAL was lowest in patients who have only 1 ectatic coronary artery. CONCLUSION Serum NGAL levels increased in patients with isolated CAE, and NGAL may play a crucial role in the development and/or progression of coronary artery ectasia.

Relation between serum monocyte chemoattractant protein-1 and coronary collateral development

BackgroundThe degree of coronary collateral development is not same in every patient with similar degree of coronary stenosis. In animal studies monocyte chemoattractant protein-1 (MCP-1) has been found to be related to collateral vessel development. In this study we investigated whether a higher serum MCP-1 level is related to better coronary collateral vessel development in patients with stable coronary artery disease. MethodEighty-three patients with stable angina pectoris, who have at least one coronary stenosis equal to or greater than 70% at coronary angiography, were prospectively enrolled. Serum MCP-1 and vascular endothelial growth factor (VEGF) levels were studied. Coronary collateral development was graded according to the Rentrop method. Patients with grade 2–3 collateral developments were included in good collateral group and formed group I. The patients with grade 0–1 collateral developments were included in poor collateral group and formed group II. ResultsThe serum MCP-1 level was significantly higher in good collateral group (288±277 pg/ml vs. 132±64 pg/ml; P<0.001). There was also a positive correlation between serum MCP-1 level and Rentrop score (r=0.39, P<0.001). The patients in the good collateral group also had a significantly higher number of coronary arteries with significant stenosis (1.7±0.7 vs. 1.4±0.6, P=0.049), and higher VEGF levels (322±147 pg/ml vs. 225±161 pg/ml, P=0.007). In multivariate analysis, only serum MCP-1 level (P=0.014, odds ratio: 1.01, 95% confidence interval: 1.002–1.019) was independently related to good coronary collateral development. ConclusionHigher serum MCP-1 level is related to better coronary collateral development.

[The relation of serum monocyte chemoattractant protein-1 level with coronary atherosclerotic burden and collateral degree in stable coronary artery disease].

OBJECTIVES We investigated whether serum monocyte chemoattractant protein-1 (MCP-1) level predicted coronary atherosclerotic burden in patients with stable coronary artery disease and its relationship with coronary collateral grade. STUDY DESIGN We prospectively included 196 patients (103 males, 93 females; mean age 59 ± 11 years) who underwent coronary angiography for stable angina pectoris. Serum MCP-1 levels were determined before coronary angiography. Coronary atherosclerotic burden was measured by the Gensini score, and coronary collateral development was assessed by the Rentrop classification. The patients were divided into four groups: those with normal coronary arteries (NCA); those with coronary lesions of <70% luminal obstruction; and those with coronary lesions of ≥ 70% luminal obstruction accompanied by a good or poor collateral grade. RESULTS The mean serum MCP-1 level was higher in patients with coronary lesions compared to patients with NCA (129 ± 130 vs. 102 ± 55 pg/ml, p=0.048). Although there were no significant differences in the MCP-1 levels of patients with NCA, with <70% luminal obstruction, and those with a significant luminal obstruction and a poor collateral grade, patients with significant luminal obstruction and a good collateral grade had significantly higher MCP-1 levels compared to the remaining groups (p=0.016). However, in multivariate regression analysis, MCP-1 level was not independently associated with the Gensini score. CONCLUSION Our findings suggest that serum MCP-1 level is higher in patients with coronary atherosclerosis, without a significant and independent association with coronary atherosclerotic burden. Significantly increased serum MCP-1 levels in patients with a good collateral grade may be an interesting issue of investigation.

The Relationship of Serum Soluble Fas Ligand (sFasL) Level with the Extent of Coronary Artery Disease.

Fas/Fas ligand system contributes to the programmed cell death induced by myocardial ischemia. We investigated whether serum soluble Fas ligand (sFasL) level is independently related with the severity and extent of angiographically assessed coronary artery disease (CAD). We included 169 patients in this study. Two groups were formed based on the existence of a lesion on coronary angiography. First group included patients with normal coronary arteries (NCA; n = 53). Patients with atherosclerotic lesions were included in the second group (n = 116). We used the coronary vessel score (the number of the coronary arteries with a lesion leading to ≥ 50% luminal obstruction) and the Azar score to determine the extent and the severity of CAD. Standard enzyme-linked immunosorbent assay kits were used to measure serum sFasL levels. The serum sFasL level was higher in patients with CAD than in patients with NCA (0.52 ± 0.23 mU/mL vs. 0.45 ± 0.18 mU/mL, p = 0.023). The sFasL level correlated with Azar score (r = 0.231, p = 0.003) and with coronary vessel score (r = 0.269, p < 0.001). In the multivariate analysis, we found that age (beta: 0.188, p = 0.008), gender (beta: 0.317, p < 0.001), diabetes mellitus (DM; beta: 0.195, p = 0.008), and sFasL level (beta: 0.209, p = 0.003) were independently related with Azar score. When we used coronary vessel score as the dependent variable, we found that age (p = 0.020), gender (p < 0.001), DM (p = 0.006), and sFasL level (p = 0.001) were independent predictors. Serum sFasL level is associated with angiographically more severe CAD. Our findings suggest that sFasL level may be a biochemical surrogate of severe coronary atherosclerosis.