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    Association between Red Blood Cell Distribution Width and Coronary Artery Calcification in Patients Undergoing 64-Multidetector Computed Tomography
    (Korean Soc Cardiology, 2015) Gurel, Ozgul Malcok; Demircelik, Muhammed Bora; Bilgic, Mukadder Ayse; Yilmaz, Hakki; Yilmaz, Omer Caglar; Cakmak, Muzaffer; Eryonucu, Beyhan
    Background and Objectives: The red blood cell distribution width (RDW) has been found to be associated with cardiovascular morbidity and mortality. The objective of this study was to determine whether the RDW measures are associated with the coronary artery calcification score (CACS) in patients who did not present with obvious coronary heart disease (CHD). Subjects and Methods: A total of 527 consecutive patients with a low to intermediate risk for CHD but without obvious disease were enrolled in this study. The study subjects underwent coronary computerized tomography angiography and CACS was calculated. The patients were divided into two groups based on CACS: Group I (CACS <= 100) and Group II (CACS>100). The two groups were compared in terms of classic CHD risk factors and haematological parameters, particularly the RDW. Results: Group I patients were younger than Group II patients. The Framingham risk score (FRS) in patients of Group II was significantly higher than that in patients of Group I. Group II patients had significantly elevated levels of haemoglobin, RDW, neutrophil count, and neutrophil/lymphocyte ratio compared with Group I patients. CACS was correlated with age, RDW, and ejection fraction. In the multivariate analysis, age, RDW, and FRS were independent predictors of CACS. Using the receiver-operating characteristic curve analysis, a RDW value of 13.05% was identified as the best cut-off for predicting the severity of CACS (>100) (area under the curve=0.706). Conclusion: We found that the RDW is an independent predictor of the CACS, suggesting that it might be a useful marker for predicting CAD.
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    Association of ambulatory arterial stiffness index with sEPCR in newly diagnosed hypertensive patients
    (Taylor & Francis Ltd, 2015) Yilmaz, Hakki; Cakmak, Muzaffer; Inan, Osman; Darcin, Tahir; Aktas, Aynur; Gurel, Ozgul Malcok; Bilgic, Mukadder Ayse
    Aim: Increased arterial stiffness is strongly associated with cardiovascular diseases, while thrombotic events are more common than hemorrhagic events in hypertensive patients. Markers of a hypercoagulable state may also predict future cardiovascular events in hypertensive patients. Here, we speculated that increased arterial stiffness might lead to the development of a hypercoagulable state that can play a role in the thrombotic complications of hypertension. Soluble endothelial protein C receptor (sEPCR) is one such marker of hypercoagulation. The ambulatory arterial stiffness index (AASI) could be accepted as a non-invasive measure of arterial stiffness. The aim of this study was to investigate association of AASI with levels of sEPCR in newly diagnosed hypertensive patients. Materials and methods: The study included 263 newly diagnosed essential hypertensive patients and 55 healthy normotensive controls. All subjects underwent 24 h ambulatory blood pressure monitoring (ABPM); the AASI was derived from ABPM tracings. Plasma sEPCR was measured by ELISA. Results: Hypertensive patients (n=263) had higher AASI, C-reactive protein (CRP) and sEPCR versus the normotensive healthy group (n=55). Univariate analysis showed that AASI was positively associated with age (r=0.212, p< 0.001) body mass index (r=0.412, p<0.001), pulse pressure (r=0.350, p<0.001), plasma sEPCR (r=0.894, p<0.001), 24-h heart rate (r=0.176, p=0.001) and inversely related to high-density lipoprotein (HDL) (r=-0.293, p<0.001). Multivariate analyses revealed that sEPCR and HDL are independently correlated to AASI. Conclusion: We suggest that increased AASI is associated with elevated sEPCR. It might be responsible for subsequent thrombotic events in newly diagnosed hypertensive patients.
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    CA 125 levels and left ventricular function in patients with end-stage renal disease on maintenance hemodialysis
    (Taylor & Francis Ltd, 2014) Yilmaz, Hakki; Gurel, Ozgul Malcok; Celik, Huseyin Tugrul; Sahiner, Enes; Yildirim, Mehmet Erol; Bilgic, Mukadder Ayse; Bavbek, Nuket
    Purpose: The aim of this study was to analyze associations between serum cancer antigen 125 (CA 125) levels and left ventricular (LV) function in patients with end-stage renal disease on maintenance hemodialysis (HD). Methods: CA 125 levels, pro-brain natriuretic peptide (pro-BNP) and biochemical parameters were measured, and echocardiography was performed for 110 patients and 47 healthy controls. Results: The mean CA 125 level in patients, 38.78 +/- 35.48 U/mL, was significantly higher than that found in healthy controls (9.20 +/- 4.55 U/mL; p = 0.003). Patients with elevated CA 125 levels (n = 40) had significantly lower levels of albumin and reduced relative wall thickness, LV ejection fraction (EF) and fractional shortening but significantly higher levels of pro-BNP and a greater left ventricular end-diastolic diameter (LVEDd) and -systolic diameter (LVESd). CA 125 levels were positively correlated with pro-BNP (r = 0.596, p<0.05) and C-reactive protein (CRP) levels (r = 0.439, p<0.05), as well as LVEDd (r = 0.599, p<0.001), LVESd (r = 0.750, p<0.001) and LV mass index (r = 0.378, p<0.05). In contrast, serum CA 125 levels were negatively correlated with albumin (r = -0.513, p<0.05) and hemoglobin (r = -0.475, p<0.05) as well as the EF (r = -0.878, p<0.0001). A depressed EF (beta = -1.121, p<0.0001) and increased CRP levels (beta = 0.247, p = 0.035) were independent predictors of high CA 125 levels in the whole group in the multivariate-model. Conclusions: Our study is the first to demonstrate an association between serum CA 125 levels and LV systolic dysfunction via inflammation in patients on maintenance HD.
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    Can Serum Gdf-15 be Associated with Functional Iron Deficiency in Hemodialysis Patients?
    (Springer India, 2016) Yilmaz, Hakki; Cakmak, Muzaffer; Darcin, Tahir; Inan, Osman; Bilgic, Mukadder Ayse; Bavbek, Nuket; Akcay, Ali
    Functional iron deficiency (FID) incidence is gradually increasing in hemodialysis (HD) patients. Recently, high levels of GDF-15 supressed the iron regulatory protein hepcidin and GDF-15 expression increased in iron-deficient patients. The relationship between FID, GDF-15, and hepcidin is currently unknown. The present study aimed to evaluate the association between GDF-15, hepcidin, and FID in chronic HD patients. Serum GDF-15 and hepcidin concentrations were measured in 105 HD patients and 40 controls. FID is defined as serum ferritin > 800 ng/mL, TSAT < 25 %, Hb levels < 11 g/dL, and reticulocyte haemoglobin content (CHr) < 29 pg. Serum GDF-15 and hepcidin levels were increased significantly in HD patients with FID, compared to HD patients without anemia and controls. GDF-15 correlated with ferritin, hepcidin, and CRP in the entire cohort. GDF-15 was related to ferritin and CRP in HD patients with FID. GDF-15 is better diagnostic marker than hepcidin for detection of FID [AUC = 0.982 (0.013) versus AUC = 0.921 (0.027); P = 0.0324]. GDF-15 appears to be a promising tool for detection of FID. High levels of ferritin and CRP correlated with GDF-15. Our results support GDF-15 as a new mediator of FID via hepcidin, chronic inflammation, or unknown pathways.
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    Is Kidney Injury Molecule 1 a Valuable Tool for the Early Diagnosis of Contrast-Induced Nephropathy?
    (Bmj Publishing Group, 2015) Akdeniz, Derya; Celik, Huseyin Tugrul; Kazanci, Fatmanur; Yilmaz, Hakki; Yalcin, Serkan; Bilgic, Mukadder Ayse; Ruzgaresen, Nuket
    Aim/Scope Contrast-induced nephropathy (CIN) is a common complication of diagnostic/therapeutic procedures. Serum creatinine levels are sensitive but often lead to diagnostic delays in acute kidney injury and potential misclassification of actual injury status. Kidney injury molecule (KIM-1) is a novel early marker of acute kidney injury. The aim of our study was to evaluate the KIM-1 levels in patients with CIN. We performed a single-center, nested case-control study. Materials and Methods Three thousand two hundred patients who had undergone coronary angiography were included in the study. Thirty-two patients were diagnosed with CIN. Twenty patients who had undergone coronary angiography but did not have CIN were evaluated as a control group (n = 20). The diagnosis of CIN was performed according to the KDIGO 2012 Acute Kidney Injury Guideline criteria. Urinary KIM-1 levels were measured by enzyme-linked immunosorbent assay before as well as on the 6th and 48th hours of contrast exposure. Serum creatinine levels were measured before as well as on the 24th and 48th hours after angiographic procedure. Results We demonstrated that KIM-1 levels increased in the patients with CIN significantly on the sixth hour when compared with the baseline (P < 0.01; median levels, 0.27 and 0.70 mg/dL) but not in the controls (P = 0.107). The precontrast and 48th-hour KIM-1 levels were median ones and were also significantly different (P = 0.001, the median levels were 0.27 and 0.60 mg/dL, respectively). Conclusions Because creatinine is a sensitive but a late marker of CIN, KIM-1 may be used for early diagnosis and early initiation of treatment and may reduce risk for morbidity.
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    Relationship between late arteriovenous fistula (AVF) stenosis and neutrophil-lymphocyte ratio (NLR) in chronic hemodialysis patients
    (Taylor & Francis Ltd, 2014) Yilmaz, Hakki; Bozkurt, Alper; Cakmak, Muzaffer; Celik, Huseyin Tugrul; Bilgic, Mukadder Ayse; Bavbek, Nuket; Akcay, Ali
    Objectives: Primary cause of late arteriovenous fistula (AVF) dysfunction is venous stenosis as result of neointimal hyperplasia. The mechanism of AVF stenosis is not exactly understood. But inflammation is a contributing factor for development of AVF stenosis. Neutrophil-lymphocyte ratio (NLR) reflects systemic inflammation, and it was investigated in many diseases. The aim of this study was to investigate the relationship between NLR and AVF stenosis in chronic hemodialysis patients. Materials and methods: Of 593 patients applied to the department of interventional radiology between January 2011 and November 2012, a total of 108 patients meeting the appropriate criteria were included in this study. All patients were assessed with Color Doppler ultrasonography and then digital subtraction angiography was used for the patients with abnormal results. Sixty-four patients were classified as patients with AVF stenosis (group 1) and 44 patients without AVF stenosis (group 2). Routine biochemical and complete blood count values measured six months ago were recorded for all patients. Results: Mean NLR (3.47 +/- 0.46 vs. 2.27 +/- 0.22; p < 0.001) was higher in group 1 compared to group 2, whereas high-density lipoprotein (HDL; 31.8 +/- 12.6 mg/dL vs. 51.5 +/- 11.9 mg/dL; p < 0.001) was lower in group 1. NLR level was correlated with degree of AVF stenosis (r = 0.625; p < 0.01). Receiver operating characteristic curve analysis showed that NLR (optimal-cut-off = 2.70) was a useful parameter in prediction of AVF stenosis (AUC = 0.893, sensitivity = 98.4% and specificity = 75%; p < 0.001). NLR level and HDL530 mg/dL in logistic regression analysis are independent predictors of AVF stenosis. Conclusions: For hemodialysis patients with increased level of NLR and decreased level of HDL, regular monitoring with regard to the development of AVF stenosis may be beneficial. Our study suggests that the mechanism of AVF stenosis might have similarities to that of atherosclerosis.
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    Relationship of late arteriovenous fistula stenosis with soluble E-selectin and soluble EPCR in chronic hemodialysis patients with arteriovenous fistula
    (Springer, 2015) Bilgic, Mukadder Ayse; Yilmaz, Hakki; Bozkurt, Alper; Celik, Huseyin Tugrul; Bilgic, Ismail Celal; Gurel, Ozgul Malcok; Kirbas, Ismail
    Vascular access dysfunction caused by stenosis is a major complication for hemodialysis (HD) patients. However, physiopathology of late arteriovenous fistula (AVF) stenosis is still under investigation. The aim of the present study was to evaluate the association between plasma soluble EPCR (sEPCR) with serum soluble E-selectin (sE-selectin) concentration and late AVF stenosis in HD patients. Plasma sEPCR and serum sE-selectin concentrations were measured in 94 HD patients. Using these data, we studied the association of sEPCR and sE-selectin with the presence and degree of AVF stenosis using ultrasonography and fistulogram. Fifty-one patients have AVF stenosis, and the others (n = 43) have patent AVF. The degree of AVF stenosis was correlated with serum sE-selectin levels (r = 0.351, p = 0.01), but not sEPCR (r = 0.075, p = 0.702). The median level of sE-selectin was statistically higher in the group of AVF stenosis than in the group of patent AVF [463.2 pg/ml (275.4-671.4) vs. 162.5 pg/ml (96.7-285.3), p = 0.001]. Increased sE-selectin levels [OR (OR) = 6.356, p = 0.015] and high levels of LDL (OR = 4.321, p = 0.044) were independent predictors of late AVF stenosis in the multivariate model. sE-selectin and the LDL were the most important predictors of late AVF stenosis. In addition, sE-selectin correlated with the degree of AVF stenosis. We suggested that atherosclerosis might be contributing factor for development of late AVF stenosis.
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    Serum galectin-3 levels were associated with proteinuria in patients with Familial Mediterranean Fever
    (Springer, 2015) Yilmaz, Hakki; Inan, Osman; Darcin, Tahir; Bilgic, Mukadder Ayse; Akcay, Ali
    The most common and pernicious complication of Familial Mediterranean fever (FMF) is renal amyloidosis, usually affecting the kidneys, leading to end-stage renal failure. FMF-related renal amyloidosis needed to be diagnosed early. Optimal colchicine dose is effective in preventing and reversing renal amyloidosis. Galectin-3, profibrotic mediator, has regulatory functions in inflammation, fibrosis and tumorigenesis. Galectin-3 is a strong prognostic marker for heart failure. Galectin-3 plays role in diabetic nephropathy and chronic kidney disease. The aim of the study is to investigate whether galectin-3 is related to proteinuria and amyloidosis in FMF. Seventy-five FMF patients who have no exclusion criteria and healthy controls (n = 36) were included. Serum galectin-3 was measured and morning spot urine was collected for determination of the protein/creatinine ratio (PCR). Serum Galectin-3 levels were significantly higher in FMF patients than the control group [969.66 (3825) pg/mL vs. 238 (921) pg/mL, respectively; P < 0.001]. We classified into two groups: Group1 (n = 48) had FMF patients with proteniuria, Group2 (n = 27) had FMF patients without proteinuria. Group1 had higher levels of galectin-3 than Group2 [1106(3812) pg/mL vs. 867.3(1433) pg/mL, P < 0.001]. Galectin-3 levels were correlated with PCR in whole group and FMF group (r = 0.785, P < 0.001 and r = 0.803, P < 0.001). In ROC curve, best cutoff value = 581.50 pg/mL was used to detect proteinuria (sensitivity = 91.7 %, specificity = 71.4 %, AUC = 0.879) and optimal cutoff value = 1458.00 pg/mL was an indicator of nephrotic-range proteinuric (sensitivity = 100 %, specificity = 92.1 %, AUC = 0.983). Galectin-3 is associated with proteinuria and renal amyloidosis in FMF. Galectin-3 may play role in pathogenesis of amyloidosis.