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      Reduced Kidney Function Estimated by Cystatin C and Clinical Outcomes in Hypertensive Patients with Coronary Artery Disease: Association with Homocysteine and Other Cardiovascular Risk Factors

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          Abstract

          Aims: To evaluate the association between serum cystatin C and homocysteine concentrations, cardiovascular risk factors and cardiovascular events in hypertensive patients with coronary artery disease (CAD). Methods: 260 patients with hypertension and CAD (mean age 56.9 ± 9.3) were included. During a mean 40-month follow-up the combined end-point of death from all causes, non-fatal myocardial infarction and stroke or coronary revascularization was assessed. Results: Subjects in the highest serum cystatin C quartile (>103.4 nmol/l) as compared with the lowest were older, were characterized by a higher frequency of multivessel CAD, higher levels of homocysteine (13.2 ± 5.2 vs. 11.4 ± 4.2 µmol/l; p < 0.01), fibrinogen and high-sensitivity C-reactive protein and by an increased intima-media thickness. Combined end-point occurred twice as frequently in the 4th quartile of serum cystatin C as compared with the 1st quartile (10.8 vs. 20.3%; p = 0.11). In an univariate analysis, but not in a multivariate model, cystatin C concentration predicted the combined end-point (Exp(B) = 1.096; p < 0.05). Conclusion: In hypertensive patients with CAD, serum cystatin C level was independently associated with the extent of CAD, homocysteine plasma level and traditional vascular risk factors. However, serum cystatin C concentration did not independently predict the combined end-point.

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          Chronic kidney disease: effects on the cardiovascular system.

          Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.
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            Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis

            D. Wald (2002)
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              Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials.

              Plasma total homocysteine (Hcy) has been associated with cardiovascular risk in multiple large-scale epidemiological studies, and it has been considered as an independent risk factor for atherosclerosis. Homocysteine lowering, achieved after the introduction of the folate food fortification programme in North America, was accompanied by an accelerated decline of cardiovascular risk and especially of stroke. Although the initial clinical trials suggested that homocysteine-lowering treatment with folates and B vitamins induces coronary plaque regression, this finding was not confirmed by more recent clinical studies. Under the light of the findings from the recent large randomized clinical trials that failed to document a benefit of Hcy lowering on clinical outcome of patients with atherosclerosis, the role of Hcy as a risk factor and the efficacy of Hcy lowering against atherosclerosis have been questioned. Therefore, better understanding of the mechanisms relating Hcy and Hcy-lowering treatment with vascular function and atherogenesis is crucial, to help us understand why clinical trials failed to show a benefit from Hcy-lowering treatment. Are these therapeutic strategies ineffective because they fail to reduce intracellular Hcy levels and vascular redox state or should Hcy stop being considered as an independent risk factor for atherosclerosis from now on? In this review article, we provide a global approach of the molecular mechanisms relating Hcy with cardiovascular risk and introduce possible mechanistic explanations regarding the inability of clinical trials to detect any clinical benefit from Hcy-lowering treatment in secondary prevention. Finally, we provide clinical recommendations regarding the therapeutic strategies targeting homocysteine in the general population.
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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
                2010
                June 2010
                28 May 2010
                : 33
                : 2
                : 139-148
                Affiliations
                a1st Department of Coronary Artery Disease, bDepartment of Hypertension, and cDepartment of Heart Failure and Transplantation, Institute of Cardiology, d2nd Department of Clinical Radiology, and eDepartment of Pharmacognosy and Molecular Basis of Phythotherapy, Medical University of Warsaw, Warsaw, and fDepartment of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland
                Article
                314812 Kidney Blood Press Res 2010;33:139–148
                10.1159/000314812
                20516698
                3229af54-3e09-41f1-93fe-a6d10c597fa6
                © 2010 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
                : 23 July 2009
                : 03 March 2010
                Page count
                Figures: 2, Tables: 5, References: 30, Pages: 10
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Coronary artery disease,Hypertension,Cystatin C,Homocysteine,Kidney function,Cardiovascular risk factors,Cardiovascular events

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