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      Cardiovascular Disease and Risk Factors: The Role of Growth Hormone

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          Abstract

          Clinical studies in patients with acromegaly have shown that growth hormone (GH) exerts both short- and long-term effects on the structure and function of the heart. Moreover, chronic growth hormone deficiency (GHD) has been associated with impaired cardiac performance, low heart rate and impaired left ventricular systolic function. Exercise capacity in patients with GHD is significantly reduced and in some severely affected individuals, dilated cardiomyopathy and heart failure has been reported. GHD has also been associated with a number of risk factors for cardiovascular disease. Altered lipoprotein metabolism and elevated fibrinogen and plasminogen activator inhibitor-1 activity are associated with GHD, and the risk of hypertension is increased in GH-deficient men. Subcutaneous and intra-abdominal fat mass have also been found to be abnormally high in these patients. These effects may contribute to an increased risk of death from cardiovascular disease. GH is therefore an important factor in the development and function of the cardiovascular system. In this paper, the effects of GH on the physiological mechanisms of the cardiovascular system are discussed, including the effect of GHD on cardiovascular disease risk. We will also discuss the effects of long-term GH replacement therapy in this patient population.

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          Most cited references 33

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          Fibrinogen as a risk factor for stroke and myocardial infarction.

          To study the possible risk factors for cardiovascular disease, we collected data on plasma levels of coagulation factors, blood pressure, serum cholesterol, and smoking in a random sample of 792 men 54 years of age. During 13.5 years of follow-up, myocardial infarction occurred in 92 men, stroke in 37, and death from causes other than myocardial infarction or stroke in 60. The blood pressure, degree of smoking, serum cholesterol, and fibrinogen level measured at the base-line examination proved to be significant risk factors for infarction by univariate analyses during follow-up, and blood pressure and fibrinogen were risk factors for stroke. Fibrinogen and smoking were strongly related to each other. The relation between fibrinogen and infarction, and between fibrinogen and stroke, became weaker when blood pressure, serum cholesterol, and smoking habits were taken into account, but was still significant for stroke. Although causality cannot be inferred from these data, it is possible that the fibrinogen level plays an important part in the development of stroke and myocardial infarction.
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            Premature mortality due to cardiovascular disease in hypopituitarism

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              Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials.

              Patients with hypopituitarism have an increased risk of cardiovascular mortality. GH treatment could modify the cardiovascular risk in adults with GH deficiency, but most published clinical trials involved few patients and the results are variable. We conducted a systematic review of blinded, randomized, placebo-controlled trials of GH treatment in adult patients with GH deficiency published up to August 2003. Thirty-seven trials were identified. We combined the results for effects on lean and fat body mass; body mass index; triglyceride and cholesterol [high-density lipoprotein, low-density lipoprotein (LDL), and total] levels; blood pressure; glycemia; and insulinemia. Overall effect size was used to evaluate significance, and weighted differences between GH and placebo were used to appreciate the size of the effect. GH treatment significantly reduced LDL cholesterol [-0.5 (SD 0.3) mmol/liter], total cholesterol [-0.3 (0.3) mmol/liter], fat mass [-3.1 (3.3) kg], and diastolic blood pressure [-1.8 (3.8) mm Hg] and significantly increased lean body mass [+2.7 (2.6) kg], fasting plasma glucose [+0.2 (0.1) mmol/liter], and insulin [+8.7 (7.0) pmol/liter]. All effect sizes remained significant in trials with low doses and long-duration GH treatment. Thus, GH treatment has beneficial effects on lean and fat body mass, total and LDL cholesterol levels, and diastolic blood pressure but reduces insulin sensitivity. The global cardiovascular benefit remains to be determined in large trials with appropriate clinical endpoints.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                978-3-8055-7866-0
                978-3-318-01177-7
                1663-2818
                1663-2826
                2004
                December 2004
                13 December 2004
                : 62
                : Suppl 4
                : 31-38
                Affiliations
                Sahlgrenska Academy at the University of Göteborg, Göteborg, Sweden
                Article
                80906 Horm Res 2004;62(suppl 4):31–38
                10.1159/000080906
                15591764
                © 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.

                Page count
                Figures: 4, References: 54, Pages: 8
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