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      GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis

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          Background and Objective:

          The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on cardiovascular risk, both in isolated GH deficien-cy (GHD) and in compensated panhypopituitarism including GH deficit.


          Original articles published from 1991 to 2015 were searched on Medline (Pubmed). Among an overall number of 181 potentially suitable studies, 24 fulfilled the selection criteria and were included in the analysis. Data aggregation was car-ried out through the calculation of the absolute risk reduction. The meta-analysis was then conducted by means of a fixed-effects model, according to the heteroge-neity test (Chi-square statistic).


          Fat-free mass (FFM) increase and fat mass (FM) reduction were found, together with a C-LDL reduction, a wide variation in glycaemia and a neutral effect on glycated haemoglobin (HbA1c) and blood pressure. These effects were valid both for isolated GHD patients and for those with compensated panhypopituitarism. The global out-come D showed a nonsignificant reduction of the overall cardiovascular risk (0.53; 95% C.I. -1.23, 2.85).


          Our meta-analysis shows no signnificatly positive trend in cardiovascular risk after both short and long-term GH supplementation therapy in adult GHD patients. However, a reduction of LDL cholesterol levels has been found. No differences were found between isolated GHD participants and those affected by panhypopituitarism well compensated since at least 3 months.

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          Most cited references 57

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          Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study.

          Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD). We conducted a nested case-control study within a large prospective study on cardiovascular epidemiology (DAN-MONICA). We measured IGF-I and IGFBP-3 in serum from 231 individuals who had a diagnosis of IHD 7.63 years after blood sampling and among 374 control subjects matched for age, sex, and calendar time. At baseline when all individuals were free of disease, subjects in the low IGF-I quartile had significantly higher risk of IHD during the 15-year follow-up period, with a relative risk (RR) of 1.94 (95% CI, 1.03 to 3.66) of IHD compared with the high IGF-I quartile group, when IGFBP-3, body mass index, smoking, menopause, diabetes, and use of antihypertensives were controlled for. Conversely, individuals in the high IGFBP-3 quartile group had an adjusted RR of 2.16 (95% CI, 1.18 to 3.95) of having IHD. Identification of a high-risk population with low IGF-I and high IGFBP-3 levels resulted in markedly higher risk of IHD (RR 4.07; 95% CI, 1.48 to 11.22) compared with the index group. Individuals without IHD but with low circulating IGF-I levels and high IGFBP-3 levels have significantly increased risk of developing IHD during a 15-year follow-up period. Our findings suggest that IGF-I may be involved in the pathogenesis of IHD.
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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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              Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study.

              Several experimental investigations have emphasized the favorable effects of insulin-like growth factor I (IGF-I) on left ventricular remodeling, partly through its antiapoptotic effects. Cross-sectional clinical studies have reported that low serum IGF-I levels in patients with heart failure correlate with cachexia and severity of ventricular dysfunction. It is unclear whether low serum IGF-I is a risk factor for heart failure. To prospectively study the association between serum IGF-I level and the incidence of congestive heart failure. Community-based, prospective cohort study. Framingham, Massachusetts. 717 elderly individuals (mean age, 78.4 years; 67% women) who did not have myocardial infarction and congestive heart failure at baseline. Incidence of a first episode of congestive heart failure on follow-up. During follow-up (mean, 5.2 years), 56 participants (35 women) developed congestive heart failure. In multivariable Cox regression models adjusting for established risk factors at baseline, there was a 27% decrease in risk for heart failure for every 1 standard deviation increment in log IGF-I. Individuals with serum IGF-I level at or above the median value (140 microg/L) had half the risk for heart failure (hazard ratio, 0.49 [95% CI, 0.26 to 0.92]) of those with serum IGF-I levels below the median. These comparisons were maintained in analyses adjusting for the occurrence of a myocardial infarction on follow-up. In our prospective, community-based investigation, serum IGF-I level was inversely related to the risk for congestive heart failure in elderly people without a previous myocardial infarction. Additional investigations are warranted to confirm these findings.

                Author and article information

                Endocr Metab Immune Disord Drug Targets
                Endocr Metab Immune Disord Drug Targets
                Endocrine, Metabolic & Immune Disorders Drug Targets
                Bentham Science Publishers
                December 2017
                December 2017
                : 17
                : 4
                : 285-296
                [1 ]Outpatient Clinic for Endocrinology and Metabolic Diseases, Conversano Hospital, ASL Bari Via De Amicis, 70014, Conversano , Italy;
                [2 ]Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124, , Bari , Italy;
                [3 ]Medical Science Liaison Merck, Serono S.p.A., Rome, , Italy;
                [4 ]Interdisciplinary Department of Medicine-Section of 
Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “A. Moro” , Bari, , Italy;
                [5 ]Cardiology Unit, Cardiothoracic Department, University of Bari, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124, Bari , Italy
                Author notes
                [* ]Address correspondence to this author at the Outpatient Clinic for Endocrinology and Metabolic Diseases, Conversano Hospital, ASL Bari, Via De Amicis, 70014 Conversano, Italy; Tel: +39 080 409 13 68; E-mail: vitogiagulli@ 123456alice.it
                © 2017 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.



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