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      HMG-CoA Reductase Inhibitors: Is the Endothelium the Main Target?

      , ,

      Cardiology

      S. Karger AG

      Statins, Atherosclerosis, Endothelium-derived factors

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          Abstract

          Endothelial dysfunction is an early event in atherosclerosis and could be considered a response to the injury induced by major risk factors. There is evidence that endothelial dysfunction is intimately involved in the onset and the progression of cardiovascular disease through abnormalities in the production, release or degradation of endothelium-derived factors, mainly nitric oxide and endothelin 1. Several reports have shown that drugs of the statin class could have multiple beneficial effects related to endothelium-mediated vasoactive, antithrombotic, antiproliferative and anti-inflammatory actions. Thus, the question arises of whether endothelial cells are the main target of statin therapy, in the setting of both hypercholesterolemia and normocholesterolemia. Experimental and clinical studies are reported that could support this hypothesis.

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          Most cited references 7

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          Statins do more than just lower cholesterol.

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            Cardiopulmonary exercise testing for prognosis in chronic heart failure: continuous and independent prognostic value from VE/VCO(2)slope and peak VO(2).

            Chronic heart failure carries a poor prognosis. Cardiopulmonary exercise testing is useful in predicting survival. We set out to establish the prognostic value of peak VO(2)and VE/VCO(2)slope across a range of threshold values. Three hundred and three consecutive patients with stable chronic heart failure underwent cardiopulmonary exercise testing between 1992 and 1996. Their age was 59+/-11 years (mean+/-SD), peak VO(2)17. 8+/- 6.6 ml. kg(-1)min(-1), VE/VCO(2)slope 37+/-12. At the end of follow-up in January 1999, 91 patients had died (after a median of 7 months, interquartile range 3-16 months). The median follow-up for the survivors was 47 months (interquartile range 37-57 months). The areas under the receiver-operating characteristic curves for predicting mortality at 2 years were 0.77 for both peak VO(2)and VE/VCO(2)slope. With peak VO(2)and VE/VCO(2)slope viewed as continuous variables in the Cox proportional-hazards model, they were both highly significant prognostic indicators, both in univariate analysis and bivariate analysis (P<0.001 for VE/VCO(2)slope, P<0.003 for peak VO(2)). Lower peak VO(2)implies poorer prognosis across a range of values from 10 to 20 ml. kg(-1)min(-1), without a unique threshold. Gradations of elevation of the VE/VCO(2)slope also carry prognostic information over a wide range (30-55). The two parameters are comparable in terms of prognostic power, and contribute complementary prognostic information. Copyright 2000 The European Society of Cardiology.
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              Low-density lipoprotein-independent effects of statins.

              Statins have pleiotropic properties that complement their cholesterol-lowering effects. These properties may partly account for their established benefit in the prevention of coronary artery disease beyond the reduction of LDL-cholesterol levels. The most widely recognized properties are reviewed here. They include: (i) nitric oxide-mediated improvement of endothelial dysfunction and upregulation of endothelin-1 expression; (ii) antioxidant effects; (iii) anti-inflammatory properties; (iv) inhibition of cell proliferation with anticarcinogenic actions in animals; (v) stabilization of atherosclerotic plaques; (vi) anticoagulant effects; and (vii) inhibition of graft rejection after heart and kidney transplantation. As advances are made in our knowledge, new properties are steadily being uncovered. Pleiotropic effects are currently being given consideration when instituting combination therapy for patients at high cardiovascular risk. Some pleiotropic effects are negative, and may account for occasional untoward drug interactions. For many of these new properties, the clinical relevance has not been established. The challenge for the future will be to design and carry out appropriate clinical trials to establish their relative importance in the prevention of coronary artery disease.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2001
                May 2001
                25 May 2001
                : 95
                : 1
                : 9-13
                Affiliations
                Department of Internal Medicine, Cardioangiology and Hepatology, Bologna University, S. Orsola-Malpighi Hospital, Bologna, Italy
                Article
                47336 Cardiology 2001;95:9–13
                10.1159/000047336
                11385185
                © 2001 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.

                Page count
                Tables: 1, References: 64, Pages: 5
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