Sebahattin Sari

Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.

Serum Sclerostin and Adverse Outcomes in Nondialyzed Chronic Kidney Disease Patients

BACKGROUND The chronic kidney disease (CKD)-mineral and bone disorder (MBD) syndrome is an important contributor to the CKD-associated cardiovascular disease and high mortality rates. Sclerostin, a protein synthesized in osteocytes, is a potent downregulator of bone metabolism and a novel candidate for the bone-vascular axis in CKD patients. We tested whether serum sclerostin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. METHODS Serum sclerostin was obtained from 173 CKD (stage 3-5) and 47 control patients, and its concentration was correlated with estimated glomerular filtration rate and to mineral and vascular abnormalities that are present in the CKD evolution. All-cause mortality and CVEs were also analyzed in relation to serum sclerostin values. RESULTS Patients with CKD showed higher sclerostin levels (median 63.5 pmol/L vs 52 pmol/L, P < .001) than controls, with values progressively higher across the CKD stages. In univariate analysis, serum sclerostin concentrations were correlated with gender, estimated glomerular filtration rate, flow-mediated dilatation, and endothelium-independent vasodilatation as markers of endothelial dysfunction and with different serum CKD-MBD-associated parameters. However, in multivariate analysis, only gender, fibroblast growth factor-23, phosphate, flow-mediated dilatation, and cholesterol remained significantly associated with sclerostin levels. During the observational period, there were 19 deaths and 50 CVEs. In survival analysis, different sclerostin levels were associated with all-cause mortality and CVEs in these patients. CONCLUSIONS This is the first study that shows that serum sclerostin values are associated, even after multiple adjustments, with fatal and nonfatal CVEs in a nondialyzed CKD population.

Nonalcoholic fatty liver disease is an independent risk factor for atherosclerosis in young adult men

INTRODUCTION The possible cause of accelerated atherosclerosis in NAFLD may be the relationship with the MetS and its components. Our primary goal was to evaluate the relationship between NAFLD and subclinical atherosclerosis in adult male patients between 20 and 40 years of age. Moreover, we aimed to investigate the changes in this association according to the presence or absence of MetS. METHOD Sixty-one male patients with biopsy-proven NAFLD and 41 healthy male volunteers were enrolled. In order to exclude any interference of confounding factors, we studied a specifically selected group with no additional cardiovascular risk. PWV, CIMT and FMD levels were measured in all patients and controls. RESULTS The levels of cf-PWV were significantly higher in SS and NASH patients compared to the control group (P < 0.001); no significant difference was found between SS and NASH patients (P > 0.05). We found significantly decreased FMD levels in patients with SS and NASH compared with control subjects (P < 0.001). Subjects with NASH had significantly greater CIMT measurements than the SS and controls (P = 0.026, P < 0.001, respectively). Although, NAFLD patients with MetS had increased cf-PWV and CIMT and reduced FMD compared to healthy subjects (P < 0.05), no significant difference existed between NAFLD with Mets and NAFLD without MetS in terms of cf-PWV, CIMT and FMD (P > 0.05) CONCLUSION: The present study showed that the presence of NAFLD leads to increased risk of endothelial dysfunction and atherosclerosis in adult male patients, independent of MetS.

Normal Anatomical Features and Variations of the Vertebrobasilar Circulation and Its Branches: An Analysis with 64-Detector Row CT and 3T MR Angiographies

Purpose. To determine the normal anatomical features and variations of the vertebrobasilar circulation and its branches in patients who underwent multidetector computed tomography (CT) or magnetic resonance (MR) angiographies of the brain. Methods. 135 patients (male, 83 and female, 52; mean age, 50.1 years) who underwent CT (n = 71) or MR (n = 64) angiographies of the vertebrobasilar vasculature for various reasons were analyzed retrospectively. The right and left distal vertebral arteries (VAs), posterior inferior cerebellar arteries (PICAs), anterior inferior cerebellar arteries (AICAs), superior cerebellar arteries (SCAs), posterior cerebral arteries (PCAs), and posterior communicating arteries (PCoAs) were analyzed individually. Results. In 24.4% of the cases (33/135) right PICA, in 19.3% of the cases (26/135) left PICA, in 17.8% of the cases (24/135) right AICA, and in 18.5% of the cases (25/135) left AICA were absent. In cases without PICA or AICA, there was a statistically significant, moderately or well-developed AICA or PICA on the same side, respectively (P < 0.001). The most common variation was isolated absence of right PICA and was seen in 17.8% of the cases. Conclusions. The anatomic features of the branches of the vertebrobasilar circulation may be different from well-known normal anatomy. CT and MR angiographies allow a precise and detailed evaluation of vertebrobasilar circulation.

The Relationship between IL-10 Levels and Cardiovascular Events in Patients with CKD

BACKGROUND AND OBJECTIVES Cardiovascular disease is the leading cause of death in patients with CKD. IL-10 is considered an antiatherosclerotic cytokine. However, previous studies have failed to observe an association between IL-10 and cardiovascular disease in CKD. This study aimed to evaluate whether serum IL-10 levels were associated with the risk of cardiovascular events in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Four hundred three patients with stages 1-5 CKD were followed for a mean of 38 (range=2-42) months for fatal and nonfatal cardiovascular events. IL-10 and IL-6 were measured at baseline together with surrogates of endothelial function (flow-mediated dilatation) and proinflammatory markers (high-sensitivity C-reactive protein and pentraxin-3). The association between IL-10 and flow-mediated dilatation through linear regression analyses was evaluated. The association between IL-10 and the risk of cardiovascular events was assessed with Cox regression analysis. RESULTS IL-10, IL-6, high-sensitivity C-reactive protein, and pentraxin-3 levels were higher among participants with lower eGFR. Both fatal (25 of 200 versus 6 of 203 patients) and combined fatal and nonfatal (106 of 200 versus 23 of 203 patients) cardiovascular events were more common in patients with IL-10 concentration above the median. Flow-mediated dilatation was significantly lower in patients with higher serum IL-10 levels, but IL-10 was not associated with flow-mediated dilatation in multivariate analysis. Kaplan-Meier survival curves showed that patients with IL-10 below the median value (<21.5 pg/ml) had higher cumulative survival compared with patients who had IL-10 levels above the median value (log-rank test, P<0.001). CONCLUSIONS IL-10 levels increase along with the reduction of kidney function. Higher serum IL-10 levels were associated with the risk of cardiovascular events during follow-up. We speculate that higher IL-10 levels in this context signify an overall proinflammatory milieu.

MRI diagnosis of dural sinus—Cortical venous thrombosis: Immediate post-contrast 3D GRE T1-weighted imaging versus unenhanced MR venography and conventional MR sequences

OBJECTIVE Primary aim is to compare the diagnostic value of contrast-enhanced 3D GRE T1-weighted sequences with unenhanced MR venography and conventional magnetic resonance imaging (MRI), in detection of dural venous sinus (DVS) and cortical venous thrombosis; secondary aim is to determine the relationship between DVS thrombosis/site and gender, age, infarction or hemorrhage. METHODS We retrospectively reviewed conventional MR images, unenhanced MR venography and immediate post-contrast 3D GRE T1-weighted MR images in 30 patients (17 male and 13 female, 21-70 years old, mean age 40.1) with clinically suspected DVS thrombosis. MR examinations had been performed with 1.5T or 3T MR Scanners. DVSs were evaluated in 10 sub-segments, including cortical veins. Each set of MR images were examined separately, blinded to the final diagnosis. Associated findings were also noted and sensitivity, specificity and accuracy of each MRI technique were calculated. RESULTS Final diagnosis of cortical venous and/or dural sinus thrombosis was established in 24 (80%) of 30 cases and 67 (22.3%) out of 300 segments. For detection of the thrombotic segment, sensitivity, specificity, and accuracy were 83.6%, 95.3%, and 92.7% by conventional MR sequences, 89.6%, 91.8%, and 91.3% by unenhanced MR venography, and 92.5%, 100%, and 98.3% by contrast-enhanced 3D GRE T1-weighted sequence, respectively. Infarction and hemorrhage were more frequent in cases with cortical venous thrombosis, while gender and age had no significant relation with DVS thrombosis or its site. Conventional MR sequences and unenhanced MR venography were helpful due to additional information they provided in some cases with isolated cortical venous thrombosis, with hyperintense thrombus material and with associated hemorrhage or infarction. CONCLUSION Contrast-enhanced 3D GRE T1-weighted MRI is the most accurate imaging method for the detection of DVS and/or cortical venous thrombosis. Infarction and hemorrhage were more frequent in cases with cortical venous thrombosis.

Bronchial arteries: normal anatomy, variation and radiologic evaluation.

We have read the recent article by Osiro et al. [5] with a great interest. They reviewed the anatomy, variation and pathophysiology of the bronchial arteries in humans, considering the recent advances in imaging techniques. But, we need to clarify a few topics not to lead misunderstandings in radiologists, anatomists and clinicians. Firstly, coronary artery–bronchial artery communications are not uncommon as mentioned by the authors. On the other hand, the authors stated the case represented by Battal et al. [1] as an aberrant bronchial artery originating from coronary artery fistula. Indeed, in this case, neither there was a fistula between coronary and bronchial arteries, nor a coronary artery originating from that fistula. In this case, in contrast to previously reported coronary–bronchial arterial fistulas, the right bronchial artery was originating as an aberrant branch from the right coronary artery with normal origin and course. Moreover, there was no other origin for right bronchial artery in contrast to fistulas. Therefore, it was determined as an aberrant right bronchial artery originating from right coronary artery instead of a fistula between coronary and bronchial arteries. Secondly, although Cauldwell et al. [3] reported that type 1 bronchial arteries (one right, two left bronchial arteries) were the most common one, subsequent conventional and multidetector computed tomography (MDCT) angiographic studies reported that type 2 and 3 bronchial arteries were more frequently encountered. In a recent and comprehensive study based on anatomy and variations of bronchial arteries in MDCT angiography performed by Battal et al. [2], the most common type of bronchial artery pattern was revealed as one on each side, followed by two bronchial arteries on the right side and one bronchial artery on the left side. The majority of the right bronchial arteries (45.4 %) were originating from aorta as an intercostobronchial trunk. The number and mean diameter of the right bronchial arteries were significantly higher than the left bronchial arteries. There were more bronchial arteries in males probably due to larger volume of tissue supplied by the bronchial arteries [2]. Third, the authors reported that the mean diameter of the normal bronchial arteries was 1.5 mm at the origin and those with larger than 2 mm were abnormal and prone to rupture. But, Battal et al. [2] reported that the diameters of the normal bronchial arteries and intercosto-bronchial trunks might be up to 3 and 5 mm, respectively. In another study performed by Morita et al. [4], the mean diameters of bronchial arteries, right bronchial arteries, left bronchial arteries, and common bronchial trunks were reported as 1.98, 2.05, 1.69, and 2.38 mm, respectively. Finally, the authors claimed that with recent advances magnetic resonance (MR) angiography could demonstrate the anatomy, course and pathology of the bronchial arteries as computed tomography (CT) angiography. Even recent MR imaging systems with high magnetic field strengths, sophisticated coils and fast sequences cannot adequately demonstrate fine calibrated bronchial arteries within highly mobile thoracic structures such as heart and lungs. We still believe that CT angiography is superior to MR angiography in demonstrating bronchial arteries.

HRCT findings of pulmonary sarcoidosis; relation to pulmonary function tests

BackgroundChest-X-ray has several limitations in detecting the extent of pulmonary disease in sarcoidosis. It might not reflect the degree of pulmonary involvement in patients with sarcoidosis when compared to computed tomography of the thorax. We aimed to investigate the HRCT findings of pulmonary sarcoidosis and to find out the existence of possible relations between HRCT findings and PFTs. In addition, we aimed to investigate the accordance between HRCT findings and conventional chest-X-ray staging of pulmonary sarcoidosis.Method45 patients with sarcoidosis with a mean age 29.7+/− 8.4 years were evaluated. Six of them were female and 39 were male. The type, distribution and extent of the parameters on HRCT/CTs were evaluated and scored. Chest-X-rays were evaluated for the stage of pulmonary sarcoidosis. Correlations were investigated between HRCT/CT parameter scores, Chest X-Ray stages and pulmonary function parameters.ResultsNodule, micronodule, ground glass opacity and consolidation were the most common HRCT findings. There were significant correlations between pulmonary function parameters, HRCT pattern scores, and chest-X-ray stages. A significant correlation between chest-x-ray score and total HRCT score was found.ConclusionsPulmonary sarcoidosis patients might have various pulmonary parenchymal changes on HRCT. Thorax HRCT was superior to chest-X-ray in detecting pulmonary parenchymal abnormalities. The degree of pulmonary involvement might be closely related to the loss of pulmonary function measured by PFTs. Chest-X-ray is considered to have a role in the evaluation of pulmonary sarcoidosis.

Endothelial function in patients with familial Mediterranean fever-related amyloidosis and association with cardiovascular events

OBJECTIVES Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. METHODS We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessed and ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. RESULTS Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Cardiovascular events (n = 54) were registered during 3 years of follow-up. Increased ADMA levels and lower FMD were observed in patients with cardiovascular risk in both groups, but especially in individuals with amyloidosis. CONCLUSION Patients with FMF-related amyloidosis have increased CVD event risk, probably related to the high ADMA levels, elevated inflammatory markers and decreased FMD measures observed in these patients.

Soluble TWEAK plasma levels increase after renal transplantation and associate with the improvement of endothelial function

Soluble TWEAK (sTWEAK) and asymmetric dimethyl arginine (ADMA) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). We tested the hypothesis that the improvement in endothelial function observed after renal transplantation is directly linked to the normalization of both sTWEAK and ADMA.