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      Coronary Artery Calcification Progression Is Associated with Arterial Stiffness and Cardiac Repolarization Deterioration in Hemodialysis Patients

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          Abstract

          Background/Aims: Evidence suggests that vascular calcification (VC) portends poor cardiovascular (CV) prognosis in patients undergoing maintenance dialysis (CKD-5). Nonetheless, how VC might predispose to CV mortality still remains to be clarified. Herein, we report on the association between coronary artery calcification (CAC) progression and changes in cardiac repolarization as well as arterial stiffness. Methods: 132 patients new to dialysis were identified. Demographic and clinical characteristics were collected at study entry and during the 12-month follow-up. CAC, 12-lead ECG and pulse wave velocity (PWV) were assessed at baseline and study completion. Uni- and multivariable analyses were applied to detect factors associated with worsening of cardiac repolarization (QTd) and arterial stiffness (PWV). Results: Uni- and multivariable analyses revealed that CAC progression was associated with a significant increase in both QTd and PWV. Every 20-unit increase in the CAC score corresponded to a significant 23% (95% CI 1.12–1.27; p < 0.001) and 32% (95% CI 1.09–1.37; p < 0.01) increase in the risk of experiencing a 1-m/s increase in PWV and 1 ms in QTd, respectively. Conclusion: VC is a marker of vasculopathy and appears to be associated with cardiac repolarization and arterial stiffness abnormalities in CKD-5 patients.

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          Coronary calcium as a predictor of coronary events in four racial or ethnic groups.

          In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected. Copyright 2008 Massachusetts Medical Society.
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            Phosphate regulation of vascular smooth muscle cell calcification.

            Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMCs cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (>1.4 mmol/L) showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs also enhanced the expression of the osteoblastic differentiation markers osteocalcin and Cbfa-1. The effects of elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. The full text of this article is available at http://www.circresaha.org.
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              Arterial stiffening and vascular calcifications in end-stage renal disease.

              Epidemiological studies have identified aortic stiffness as an independent predictor of cardiovascular mortality in end-stage renal disease (ESRD) patients. In these patients, aortic pulse wave velocity (PWV) was associated with mediacalcosis, but the influence of arterial calcifications on the viscoelastic properties of large arteries was not well characterized. The purpose of the present study was to analyse the influence of arterial calcifications on arterial stiffness in stable haemodialysed patients. We studied 120 stable ESRD patients on haemodialysis. All patients underwent B-mode ultrasonography of common carotid artery (CCA), aorta, and femoral arteries to determine CCA distensibility, the elastic incremental modulus (Einc), and the presence of vascular calcifications. All patients underwent measurement of aortic PWV and echocardiogram. The presence of calcifications was analysed semiquantitatively as a score (0 to 4) according to the number of arterial sites with calcifications. Our observations indicate that arterial and aortic stiffness is significantly influenced by the presence and extent of arterial calcifications. The extent of arterial calcifications is in part responsible for increased left ventricular afterload, and is inversely correlated with stroke volume. The influence of calcifications is independent of the role of ageing and blood pressure. Arterial calcifications density increases with age, duration of haemodialysis, the fibrinogen level, and the prescribed dose of calcium-based phosphate binders. The results of this study showed that the presence of vascular calcifications in ESRD patients was associated with increased stiffness of large capacity, elastic-type arteries, like the aorta and CCA. The extent of arterial calcifications increased with the use of calcium-based phosphate-binders.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2011
                May 2011
                18 April 2011
                : 34
                : 3
                : 180-187
                Affiliations
                aUO di Nefrologia e bUO di Diagnostica per Immagini, PO ‘A Landolfi’, Solofra, cCattedra di Nefrologia, Università Federico II, Napoli, e dUOC di Nefrologia, Dialisi ed Ipertensione, Policlinico S. Orsola-Malpighi, Azienda Ospedaliero-Universitaria, Bologna, Italia
                Author notes
                *Biagio Di Iorio, UO di Nefrologia, PO ‘A Landolfi’, Via Melito, snc, IT–83029 Solofra (Italy), E-Mail br.diiorio@gmail.com
                Article
                325656 Kidney Blood Press Res 2011;34:180–187
                10.1159/000325656
                21502766
                dedd6eb2-e62c-4701-8dda-c7a0633c8508
                © 2011 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
                : 19 October 2010
                : 10 February 2011
                Page count
                Figures: 3, Tables: 5, Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Coronary artery calcification,Progressor,QT dispersion
                Cardiovascular Medicine, Nephrology
                Coronary artery calcification, Progressor, QT dispersion

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