Beste Ozben

Carotid artery intima-media thickness correlates with oxidative stress in chronic haemodialysis patients with accelerated atherosclerosis

BACKGROUND Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis (HD). Increased oxidative stress might be the major factor leading to high cardiovascular mortality rate in HD patients. The aim of our study was to clarify effects of uraemia and dialysis on oxidative stress parameters and explore the relation between oxidative stress markers and carotid artery intima-media thickness (CIMT) as an indicator of atherosclerosis. METHODS Twenty chronic HD patients, 20 predialytic uraemic patients and 20 healthy subjects were included in the study. Serum thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO) and nitrite/nitrate levels were determined as oxidative stress markers. Serum vitamin E, plasma sulfhydryl (P-SH), erythrocyte glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. RESULTS Both chronic HD and predialytic uraemic patients had enhanced oxidative stress indicated by higher levels of nitrite/nitrate, TBARS and PCO, and lower levels of P-SH, SOD, CAT and GPx compared to controls. HD patients had significantly higher CIMT and nitrite/nitrate while significantly lower P-SH,vitamin E, SOD, CAT and GPx compared to predialytic uraemic patients. There was a significant positive correlation between CIMT and TBARS (r = 0.38, P = 0.003) and nitrite/nitrate levels (r = 0.41, P = 0.001), while there was a significant negative correlation between CIMT and SOD (r = -0.35, P = 0.01), CAT (r = -0.65, P < 0.001) and P-SH levels (r = -0.50, P < 0.001). A linear regression analysis showed that TBARS were still significantly and positively correlated with CIMT (P = 0.001), while CAT and P-SH were significantly and negatively correlated with CIMT (P = 0.002 and P = 0.048, respectively). CONCLUSIONS HD exacerbates oxidative stress and disturbances in antioxidant enzymes in uraemic patients. We propose that serum TBARS and nitrite/nitrate can be used as positive determinants, while erythrocyte SOD, CAT and P-SH may be used as negative determinants of atherosclerosis assessed by CIMT in uraemic and HD patients.

Aspirin resistance in patients with chronic renal failure

BACKGROUND Chronic renal failure (CRF) is associated with increased risk of cardiovascular morbidity and mortality. Aspirin resistance worsens clinical prognosis. The aim of this study was to explore the prevalence of aspirin resistance in CRF. METHODS Two hundred and forty-five CRF patients (115 patients undergoing chronic hemodialysis and 130 patients with stage 3-4 chronic kidney disease [CKD]) and 130 patients with normal renal functions (control group) were consecutively recruited. All subjects were taking aspirin regularly. Aspirin responsiveness was determined by Ultegra Rapid Platelet Function Assay-ASA (VerifyNow Aspirin). Aspirin resistance was defined as aspirin reaction unit (ARU) =550. RESULTS Aspirin resistance was detected in 53 patients undergoing hemodialysis, 32 patients with stage 3-4 CKD and 22 controls. The frequency of aspirin resistance was significantly higher in the CRF group compared with controls (34.7% vs. 16.9%, p<0.001) and in hemodialysis patients (46.1%) compared with stage 3-4 CKD patients (24.6%, p<0.001) and controls (16.9%, p<0.001). Multivariate analysis revealed female sex (odds ratio [OR] = 2.201; 95% confidence interval [95% CI], 1.173-4.129; p=0.014), hemodialysis (OR=3.636; 95%CI, 1.313-10.066; p=0.013) and HDL cholesterol (OR=0.974; 95% CI, 0.950-0.999; p=0.043) as independent predictors of aspirin resistance in this cohort of patients. CONCLUSION Patients with CRF have higher frequency of aspirin resistance. This might further increase the risk of cardiovascular morbidity and mortality in these patients.

Circulating endothelial cell number and markers of endothelial dysfunction in previously preeclamptic women.

OBJECTIVE Patients with preeclampsia (PE) have endothelial dysfunction and an increased future risk of cardiovascular (CV) mortality. The number of circulating endothelial cells (CECs) is markedly increased in conditions associated with a high degree of endothelial cell activation/injury including PE. We hypothesized that the number of CECs continues to be increased in women with a history of PE, reflecting ongoing endothelial cell activation/injury. STUDY DESIGN CECs, flow-mediated vasodilation, levels of adhesion molecules and soluble vascular endothelial growth factor receptor-1 (sVEGFR1), and urine albumin/creatinine ratio were determined in 21 healthy women with ongoing normal pregnancy, 24 healthy currently nonpregnant women with a history of normal pregnancy, a total of 17 women with currently active mild (n = 11) or severe (n = 6) PE without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, and 16 currently nonpregnant women with a history of mild (n = 10) or severe (n = 6) PE. RESULTS Blood samples from women with active preeclampsia had higher CECs (9.9 ± 7.9 cells/mL) than healthy pregnant women (3.0 ± 4.1 cells/mL; P < .001), healthy nonpregnant women with a history of normal pregnancy (3.4 ± 4.0 cells/mL; P < .001), or women with a history of preeclampsia (2.4 ± 2.0 cells/mL; P < .001). The number of CECs were similar between women with a history of preeclampsia and healthy nonpregnant women with a history of normal pregnancy. Patients with active preeclampsia had significantly higher soluble vascular cell adhesion molecule-1, soluble E-selectin, sVEGFR1, and urinary albumin/creatinine ratio than healthy pregnant women. However, soluble vascular cell adhesion molecule-1, soluble E-selectin, urinary albumin/creatinine ratio were similar in women with a history of preeclampsia and healthy nonpregnant women with a history of normal pregnancy. However, women with a history of preeclampsia had higher sVEGFR1 levels than women with a history of normal pregnancy (P < .05). CONCLUSION Markers of endothelial activation, dysfunction, and damage were increased in patients with PE. After the delivery, this activation status is similar to the age-matched nonpregnant women with a history of normal pregnancy. However, sVEGFR-1 levels remain higher in women with a history of preeclampsia compared with women without a history of preeclampsia.

Circulating endothelial cells are elevated in patients with type 1 diabetes mellitus

OBJECTIVE Circulating endothelial cells (CECs) have emerged as vascular damage markers and are increased in type 2 diabetic patients. Since type 1 diabetes is associated with vascular damage, we hypothesized high CEC numbers in this patient population. METHODS Thirty-nine patients with type 1 diabetes and 39 controls were included. CECs were isolated using anti-CD146-coated Dynabeads, stained with Ulex lectin-1, and counted by fluorescence microscopy. Endothelial function was measured as flow-mediated dilation (FMD). Thiobarbituric acid reactive substances (TBARS), total glutathione levels (GSH), and paraoxonase (PON) activity levels were measured as oxidative stress markers. RESULTS Patients with type 1 diabetes mellitus had higher number of CECs (7.46+/-5.37 vs 2.13+/-1.13 cells/ml, P<0.001), lower FMD (7.87+/-2.19 vs 12.06+/-2.34%, P<0.001), higher TBARS (4.94+/-1.20 vs 3.07+/-0.75 nmol/MDA, P<0.001), lower GSH (206.12+/-98.06 vs 353.61+/-68.45 microM, P<0.001), and lower PON activity levels (89.10+/-17.82 vs 127.65+/-29.01 U/l, P<0.001) as compared to controls. There was positive correlation between CEC numbers and HbAlc levels (r=0.49, P=0.002). CECs and fasting glucose levels were not correlated. There was no correlation between the number of CECs and FMD. Furthermore, there were no correlations between the number of CECs and TBARS, GSH and PON activity levels. Multiple regression analysis showed that HbAlc levels (r(2)=0.40, P<0.009) were associated with CEC numbers. CONCLUSION CECs are elevated in patients with type 1 diabetes mellitus reflecting endothelial damage. This increase is dependent on long-term glucose control.

Early detection of left ventricular dysfunction with strain imaging in thalassemia patients.

Iron‐mediated cardiomyopathy is the main cause of death in thalassemia patients. Early detection of cardiac abnormalities is important as aggressive chelation therapy may improve prognosis in these patients. The aim of this study is to evaluate left ventricular (LV) functions by tissue velocity imaging (TVI) and strain imaging (SI) in thalassemia patients without overt heart failure.

The effect of hemodialysis on accelerated atherosclerosis in diabetic patients: correlation of carotid artery intima-media thickness with oxidative stress

OBJECTIVE Both diabetes and hemodialysis (HD) are associated with increased oxidative stress. The aim of this study was to clarify the effect of maintenance HD on oxidative stress parameters in diabetic patients and to explore any relation between carotid artery intima-media thickness (CIMT) and oxidative stress markers. METHODS Twenty Type 2 diabetic patients undergoing chronic maintenance HD, 20 type 2 diabetic patients with normal renal function, and 20 age- and sex-matched healthy subjects were included. Serum thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO), and nitrite/nitrate levels were determined as oxidative stress markers. Serum vitamin E, plasma sulfhydryl (P-SH), erythrocyte glutathione (GSH) levels, and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. RESULTS Both diabetic patient groups had enhanced oxidative stress indicated by higher levels of TBARS, PCO, and nitrate/nitrite and lower activities of SOD, CAT, and GPx compared to controls. Diabetic patients undergoing HD had significantly higher CIMT (P=.001) and higher levels of nitrite/nitrate (P=.05), PCO (P=.03), and GSH (P=.04) but significantly lower levels of P-SH (P<.001), serum vitamin E (P=.04), SOD (P=.02), CAT (P=.001), and GPx (P=.006) compared to diabetic patients with normal renal functions. There were significant negative correlations between CIMT and SOD (r=-0.50, P<.001), CAT (r=-0.41, P=.003), and P-SH levels (r=-0.51, P<.001) and significant positive correlation between CIMT and nitrite/nitrate levels (r=0.41, P=.003) and TBARS (r=0.35, P=.02). Linear regression analysis showed TBARS was significantly and positively correlated with CIMT (P=.04), while SOD and P-SH were significantly and negatively correlated with CIMT (P=.05 and P=.02, respectively). CONCLUSIONS Hemodialysis exacerbates oxidative stress and disturbances in antioxidant enzymes in diabetic patients. Serum nitrite/nitrate and TBARS can be used as positive determinants, while erythrocyte SOD, CAT activities, and P-SH level can be used as negative determinants of atherosclerosis assessed by CIMT in diabetic patients.

P Wave Dispersion Increases during Hemodialysis Sessions

Background/Aims: Atrial fibrillation (AF) is common among hemodialysis (HD) patients and is associated with high mortality. P wave dispersion (PWD) is a noninvasive electrocardiographic marker of paroxysmal AF. Our aim was to evaluate the effect of HD session on PWD. Methods: Twenty-five patients (mean age 63 years, 10 males) with sinus rhythm and undergoing chronic HD treatment were included. Blood samples were drawn and 12-lead electrocardiograms were recorded immediately before HD session, at the 2nd hour during HD and at the end of the HD session. The difference between maximum and minimum P wave durations was calculated as PWD. Results: PWD significantly increased during HD sessions compared with predialysis values (41 ± 12 vs. 21 ± 10 ms, respectively, p < 0.001), then decreased to a value of 24 ± 7 ms at the completion of HD, which was not significantly different from the predialysis values. PWD during HD was significantly correlated with predialysis systolic and diastolic blood pressure (r = 0.42, p = 0.037, and r = 0.59, p = 0.002, respectively) and predialysis serum potassium level (r = 0.44, p = 0.031). Linear regression model revealed that predialysis diastolic blood pressure (p = 0.002), predialysis serum potassium level (p = 0.037) and the amount of ultrafiltration (p = 0.048) were the significant predictors of prolonged PWD during HD. Conclusion: PWD increases significantly during HD sessions. This may increase the risk of AF episodes during HD. High diastolic blood pressure and serum potassium level before HD and ultrafiltration amount may predict prolonged PWD during HD.

Aspirin Resistance in Hypertensive Patients

J Clin Hypertens (Greenwich). 2010;12:714–720. ©2010 Wiley Periodicals, Inc.

Evaluation of Improvement in Exercise Capacity after Pulmonary Endarterectomy in Patients with Chronic Thromboembolic Pulmonary Hypertension: Correlation with Echocardiographic Parameters

BACKGROUND The study evaluates the alterations in exercise capacity of chronic thromboembolic pulmonary hypertension (CTEPH) patients after pulmonary endarterectomy (PEA) and investigates the echocardiographic parameters associated with the degree of functional recovery. METHODS Thirty consecutive patients with the diagnosis of CTEPH (17 males; mean age, 45.9 ± 15.1 years) who had been referred for PEA operation were included in the study. Each patient underwent transthoracic echocardiography and 6-minute walk test (6-MWT) before and 6 months after PEA. RESULTS After PEA, 6-MWT distances significantly increased (242.8 ± 112.8 m vs. 423.6 ± 89.1 m, p < 0.001), whereas systolic pulmonary artery pressures and right ventricular dimensions significantly decreased (86 ± 25.1 mm Hg vs. 41.9 ± 15.6 mm Hg, p < 0.001 and 42.1 ± 10.1 mm vs. 35.3 ± 5.6 mm, p < 0.001, respectively). Magnitude of change in 6-MWT distance (Δ-6-MWT) was found to be correlated with concomitant change in tricuspid annular plane systolic excursion and left ventricular myocardial performance index (r: 0.518, p: 0.004 and r: -0.385, p: 0.043, respectively). Linear regression analysis revealed preoperative 6-MWT distance as an independent negative predictor of delta-6-MWT (beta: -0.89, t: -3.97, p: 0.001). CONCLUSION CTEPH patients with more severely depressed exercise capacity at baseline displayed relatively greater degree of functional recovery after PEA in our study. Improvement in functional capacity was found to be correlated with improvement in parameters reflecting right ventricular functions rather than improvement in pulmonary artery pressure after PEA operation.

Polymorphisms of the angiotensin-converting enzyme and angiotensinogen gene in patients with atrial fibrillation

Activation of the renin–angiotensin system (RAS) is associated with atrial fibrillation (AF). The aim of this study was to investigate the relation between AF and polymorphisms in RAS. One hundred and fifty patients with AF, 100 patients with no documented episode of AF and 100 healthy subjects were consecutively recruited into the study. The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and the M235T, A-20C, and G-6A polymorphisms of the angiotensinogen gene were genotyped. Patients with AF had significantly lower frequency of II genotype of ACE I/D and higher frequency of angiotensinogen M235T polymorphism T allele and TT genotype and G-6A polymorphism G allele and GG genotype compared with the controls. AF patients had significantly larger left atrium, higher left ventricular mass index (LVMI) and higher frequency of significant valvular pathology. ACE I/D polymorphism II genotype, angiotensinogen M235T polymorphism TT genotype and G allele and GG genotype of angiotensinogen G-6A polymorphism were still independently associated with AF when adjusted for left atrium, LVMI and presence of significant valvular pathology. Genetic predisposition might be underlying the prevalence of acquired AF. Patients with a specific genetic variation in the RAS genes may be more liable to develop AF.