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      Effect of Low-Dose Atorvastatin on Plasma Concentrations of Adipokines in Patients with Metabolic Syndrome

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          Abstract

          Objective: It has not been conclusively proven whether or not the beneficial effect of statins on the cardiovascular system is mediated through their influence on adipokine secretion. We designed a prospective open-label study to assess the influence of 6 months’ atorvastatin therapy on plasma concentrations of some adipokines in patients with metabolic syndrome. Subjects: 36 adult patients with metabolic syndrome and serum LDL cholesterol >3.5 mmol/l, previously untreated with statins, were included in the study. Measurements: Plasma concentrations of adiponectin, leptin, resistin and insulin were measured before initiation and after 2, 4 and 6 months of atorvastatin therapy (10 mg), and 2 months after treatment cessation. Results: Treatment with atorvastatin was followed by a 35.6% decline in LDL cholesterol. Plasma adiponectin concentration decreased by 20.7% after 2 months; however, after 4 and 6 months, this did not differ significantly from the initial values. There was a negative correlation between the initial plasma concentration of leptin and changes in HDL cholesterol (R = –0.358; p = 0.04). Conclusions: Firstly, the long-term effect of atorvastatin therapy in patients with metabolic syndrome is not mediated by changes in the secretion of adiponectin, leptin and resistin by adipose tissue. Secondly, plasma leptin concentration seems to be a predictor of HDL cholesterol changes during atorvastatin therapy.

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          Effect of pravastatin on outcomes after cardiac transplantation.

          Hypercholesterolemia is common after cardiac transplantation and may contribute to the development of coronary vasculopathy. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to be effective and safe in lowering cholesterol levels after cardiac transplantation. Cell-culture studies using inhibitors of HMG-CoA reductase have suggested an immunosuppressive effect. Early after transplantation, we randomly assigned consecutive patients to receive either pravastatin (47 patients) or no HMG-CoA reductase inhibitor (50 patients). Twelve months after transplantation, the pravastatin group had lower mean (+/- SD) cholesterol levels than the control group (193 +/- 36 vs. 248 +/- 49 mg per deciliter, P < 0.001), less frequent cardiac rejection accompanied by hemodynamic compromise (3 vs. 14 patients, P = 0.005), better survival (94 percent vs. 78 percent, P = 0.025), and a lower incidence of coronary vasculopathy in the transplant as determined by angiography and at autopsy (3 vs. 10 patients, P = 0.049). There was no difference between the two groups in the incidence of mild or moderate episodes of cardiac rejection. In a subgroup of study patients, intracoronary ultrasound measurements at base line and one year after transplantation showed less progression in the pravastatin group in maximal intimal thickness (0.11 +/- 0.09 mm, vs. 0.23 +/- 0.16 mm in the control group; P = 0.002) and in the intimal index (0.05 +/- 0.03 vs. 0.10 +/- 0.10, P = 0.031). In a subgroup of patients, the cytotoxicity of natural killer cells was lower in the pravastatin group than in the control group (9.8 percent vs. 22.2 percent specific lysis, P = 0.014). After cardiac transplantation, pravastatin had beneficial effects on cholesterol levels, the incidence of rejection causing hemodynamic compromise, one-year survival, and the incidence of coronary vasculopathy.
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            Adiponectin as a Biomarker of the Metabolic Syndrome

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              Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes.

              Adiponectin and resistin, two recently discovered adipocyte-secreted hormones, may link obesity with insulin resistance and/or metabolic and cardiovascular risk factors. We performed a cross-sectional study to investigate the association of adiponectin and resistin with inflammatory markers, hyperlipidemia, and vascular reactivity and an interventional study to investigate whether atorvastatin mediates its beneficial effects by altering adiponectin or resistin levels. Associations among vascular reactivity, inflammatory markers, resistin, and adiponectin were assessed cross-sectionally using fasting blood samples obtained from 77 subjects who had diabetes or were at high risk to develop diabetes. The effect of atorvastatin on adiponectin and resistin levels was investigated in a 12-week-long randomized, double-blind, placebo-controlled study. In the cross-sectional study, we confirm prior positive correlations of adiponectin with HDL and negative correlations with BMI, triglycerides, C-reactive protein (CRP), and plasma activator inhibitor (PAI)-1 and report a negative correlation with tissue plasminogen activator. The positive association with HDL and the negative association with PAI-1 remained significant after adjusting for sex and BMI. We also confirm prior findings of a negative correlation of resistin with HDL and report for the first time a positive correlation with CRP. All of these associations remained significant after adjusting for sex and BMI. No associations of adiponectin or resistin with any aspects of vascular reactivity were detected. In the interventional study, atorvastatin decreased lipid and CRP levels, but adiponectin and resistin were not specifically altered. We conclude that adiponectin is significantly associated with inflammatory markers, in part, through an underlying association with obesity, whereas resistin's associations with inflammatory markers appear to be independent of BMI. Lipid profile and inflammatory marker changes produced by atorvastatin cannot be attributed to changes of either adiponectin or resistin. Copyright 2004 American Diabetes Association
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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
                2012
                May 2012
                03 January 2012
                : 35
                : 4
                : 226-232
                Affiliations
                Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland
                Author notes
                *Prof. Dr hab. med. Andrzej Więcek, FRCP (Edin), Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia in Katowice, ul. Francuska 20/24, PL–40-027 Katowice (Poland), Tel. +48 322 552 695, E-Mail awiecek@spskm.katowice.pl
                Article
                332403 Kidney Blood Press Res 2012;35:226–232
                10.1159/000332403
                22223218
                59d7561b-7d05-448d-a78c-22f4574949c5
                © 2012 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
                : 18 March 2010
                : 28 August 2011
                Page count
                Figures: 2, Tables: 2, Pages: 7
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Metabolic syndrome,Obesity,Adiponectin,Statins
                Cardiovascular Medicine, Nephrology
                Metabolic syndrome, Obesity, Adiponectin, Statins

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