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      High Prevalence of Aortic Valve Alterations in Haemodialysis Patients Is Associated with Signs of Chronic Inflammation

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          Abstract

          Aims: Cardiovascular morbidity is high in chronic haemodialysis patients. Previous studies showed a relation between uraemia-associated inflammation and cardiovascular mortality. This study intends to relate chronic inflammation to ultrasonographic markers of atherosclerotic cardiac or vascular alterations. Methods: Complete echocardiographic status and sonography of the common carotid arteries with measurement of intima media thickness (IMT) was performed in 55 stable chronic haemodialysis patients and 15 patients with arterial hypertension and normal renal function (controls). C-reactive protein (CRP) was determined monthly. The number of cardiovascular events after initiation of haemodialysis treatment was recorded by analysis of the patient’s files. Results: Aortic valve sclerosis was found in 19 dialysis patients (34%) and 1 control (6%), haemodynamically relevant stenosis in additional 14 patients (25%) and 1 control. Carotid IMT thickening was frequent in both dialysis patients (38%) and controls (20%). Aortic stenosis was associated with chronically elevated CRP levels while aortic sclerosis and thickening of the carotid wall were not. Eleven patients had cardiovascular events in their history, tightly associated with chronically elevated CRP levels. Conclusions: Chronic inflammation in dialysis patients is associated with aortic valve stenosis and high prevalence of cardiovascular events but not with thickening of the carotid wall. This suggests pathogenetic differences between destructive vascular disease and arterial wall thickening.

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          Endotoxin and immune activation in chronic heart failure: a prospective cohort study.

          Immune activation in patients with chronic heart failure may be secondary to endotoxin (lipopolysaccharide) action. We investigated the hypothesis that altered gut permeability with bacterial translocation and endotoxaemia would be increased in patients with oedema secondary to congestive heart failure. We compared 20 patients who had chronic heart failure with recent-onset peripheral oedema (mean age 64 years [SD 10], New York Heart Association [NYHA] class 3.3 [0.7]), 20 stable non-oedematous patients with chronic heart failure (mean age 63 years [19], NYHA class 2.6 [0.7]), and 14 healthy volunteers (mean age 55 years [16]). Biochemical markers of endotoxaemia, inflammation, and immune activation were measured. Ten patients were studied within 1 week of complete resolution of oedema. Five patients survived longer than 6 months and were restudied again after remaining free of oedema for more than 3 months. Mean endotoxin concentrations were higher in oedematous patients with chronic heart failure than in stable patients with chronic heart failure (0.74 [SD 0.45] vs 0.37 EU/mL [0.23], p=0.0009) and controls (0.46 EU/mL [0.21], p=0.02). Oedematous patients had the highest concentrations of several cytokines. After short-term diuretic treatment, endotoxin concentrations decreased from 0.84 EU/mL [0.49] to 0.45 EU/mL [0.21], p<0.05) but cytokines remained raised. After freedom of oedema for more than 3 months after oedema resolved, endotoxin concentrations remained unchanged from the previous visit (0.49 EU/mL [0.06], p=0.45). Raised concentrations of endotoxin and cytokines are found in patients with chronic heart failure during acute oedematous exacerbation. Intensified diuretic treatment can normalise endotoxin concentrations. Our preliminary findings suggest that endotoxin may trigger immune activation in patients with chronic heart failure during oedematous episodes.
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            Prognostic implications of intima-media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris.

            Ultrasonographic assessments of intima-media thickness and plaques in the carotid artery are widely used as surrogate markers for coronary atherosclerosis, but prospective evaluations are scarce and appear to be lacking in patients with coronary artery disease. Ultrasonographic evaluations of femoral vascular changes have not been studied prospectively. In the Angina Prognosis Study in Stockholm (APSIS), 809 patients with stable angina pectoris were studied prospectively during double-blind treatment with verapamil or metoprolol. Ultrasonographic assessments of intima-media thickness, lumen diameter and plaques in the carotid and femoral arteries were evaluated in a subgroup of 558 patients (182 females) with a mean age of 60 +/-7 years, and related to the risk of cardiovascular death (n = 18) or non-fatal myocardial infarction (n = 26), or revascularization (n = 70) during follow-up (median 3.0 years). Univariate Cox regression analyses showed that carotid intima-media thickness and plaques were related to the risk of cardiovascular death or myocardial infarction. Femoral intima-media thickness was related to cardiovascular death or myocardial infarction, as well as to revascularization, whereas femoral plaques were only related to the latter. After adjustment for age, sex, smoking, previous cardiovascular disease and lipid status, carotid intima-media thickness failed to predict any cardiovascular event, whereas carotid plaques tended (P = 0.056) to predict the risk of cardiovascular death or myocardial infarction. Femoral intima-media thickness (P < 0.01) and plaques (P < 0.05) were also related to the risk of revascularization after adjustments. Carotid and femoral vascular changes were differently related to cardiovascular events. Carotid intima-media thickness was a weak predictor of events, whereas femoral intima-media thickness predicted revascularization. Plaques in the carotid artery were related to cardiovascular death or non-fatal myocardial infarction, whereas plaques in the femoral artery were related to revascularization. Evaluations of plaques provided better prediction than assessments of intima-media thickness in patients with stable angina. Copyright 2001 The European Society of Cardiology.
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              Adhesion molecules in nonrheumatic aortic valve disease: endothelial expression, serum levels and effects of valve replacement.

              We studied the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial selectin (E-selectin) on aortic valve endothelium in patients undergoing valve replacement. We also assessed the relation between serum levels and endothelial expression and also the changes in serum levels following surgery. Nonrheumatic aortic valve disease is believed to be a degenerative condition. Increased tissue and soluble adhesion molecule levels are described in inflammatory conditions. Aortic valves from 22 surgical (16 bicuspid, 6 tricuspid) and 6 autopsy (4 normal, 2 thickened) cases were studied by immunohistochemistry. Soluble adhesion molecules were measured in peripheral blood preoperatively, and at 6 and 18 months postoperatively, and compared with controls. The majority of the surgically removed tricuspid and bicuspid valves expressed adhesion molecules (E-selectin, 75% and 100%; ICAM-1, 75% and 80%; VCAM-1, 69% and 60%, respectively). The normal postmortem valves did not express these, while the diseased ones did. Endothelial expression of E-selectin correlated strongly with serum levels (r = 0.695, p = 0.004). Soluble E-selectin levels were significantly higher at baseline compared with controls (p = 0.017) and fell significantly at 18 months postoperatively (p = 0.005). Adhesion molecule expression on diseased valves supports an inflammatory component in "degenerative" aortic valve disease. The diseased valves may be the main source of elevated soluble E-selectin in this condition as blood levels correlate with endothelial expression and blood levels fall at 18 months postoperatively.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2004
                February 2004
                17 November 2004
                : 96
                : 2
                : c48-c55
                Affiliations
                Medical Department IV, University Homburg/Saar, Homburg/Saar, Germany
                Article
                76399 Nephron Clin Pract 2004;96:c48–c55
                10.1159/000076399
                14988598
                b380b99d-967e-49a1-bbfc-7a6bb160dc2f
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 20 May 2003
                : 20 October 2003
                Page count
                Figures: 2, Tables: 4, References: 20, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Carotid artery,Atherosclerosis,C-reactive protein,Aortic valve stenosis,Ultrasonography,Kidney failure, chronic,Haemodialysis

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