Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy

Osterziel, Karl Josef; Strohm, Oliver; Schuler, Jochen; Friedrich, Matthias G.; Hänlein, Dankward; Willenbrock, Roland; Anker, Stefan D.; Poole‐Wilson, Philip A.; Ranke, Michael B.; Dietz, Rainer

doi:10.1016/s0140-6736(97)11329-0

Cited by 338 publications

(197 citation statements)

References 24 publications

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“…Low IGF-I has been associated with heart failure and therapeutic approaches of GH or IGF-I in this field have been performed, but no clear benefit could be demonstrated in placebo-controlled trials (17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

“…Heart failure has been found to be associated with low IGF-I (13)(14)(15)(16). In some studies on patients with heart failure, positive effects of GH or IGF-I on cardiac function have been found (17,18), whereas these effects could not be reproduced in other studies (19,20). A recent meta-analysis on 12 studies evaluating GH therapy in 195 patients with chronic heart failure has shown some beneficial effects on hemodynamics, but recommended further research with larger trials (21).…”

Section: Introductionmentioning

confidence: 99%

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Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients

Schneider¹,

Klotsche²,

Saller³

et al. 2008

European Journal of Endocrinology

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Objective: We aimed at investigating the association of age-dependent IGF-I SDS with diabetes, dyslipidemia, hypertension, and heart diseases, in a large patient sample. Background: IGF-I has been suggested to be associated with several diseases and a prognostic marker for the development of cardiovascular diseases and risk factors. The findings, though, have been inconsistent possibly due to the methodological factors. Methods: We studied 6773 consecutive primary care patients, aged 18C years, in a cross-sectional, epidemiological study in primary care, Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment study. All patients underwent a standardized clinical diagnostic and laboratory assessment. IGF-I levels were measured with an automated chemiluminescence assay system. We calculated the odds ratios (OR) for diseases in quintiles of IGF-I, and additionally analyzed the association of age-dependent IGF-I SDS with these conditions. Results: After multiple adjustments for confounders, we found increased ORs for coronary artery disease in patients with high IGF-I. Women, but not men, with low IGF-I also showed increased ORs for coronary artery disease. Dyslipidemia was positively associated with IGF-I. Type 2 diabetes showed a curvilinear association with IGF-I SDS. Conclusions: The findings suggest the existence of multiple and complex interactions between IGF-I and several health conditions. The complex nature of disease-and subgroup-specific associations along with the methodological factors can be held responsible for divergent findings in previous studies. European Journal of Endocrinology 158 153-161

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients

Schneider¹,

Klotsche²,

Saller³

et al. 2008

European Journal of Endocrinology

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“…Preliminary results of the administration of GH in cachectic patients seem to determine some clinical improvement and optimization of the treatment 105 ; however, randomized studies are necessary to assess its real effect 106,107 . It must be used with caution in patients at risk for cancer or with arrhythmias.…”

Section: Growth Hormone (Gh)mentioning

confidence: 99%

I Diretriz Latino-Americana para avaliação e conduta na insuficiência cardíaca descompensada

Bocchi¹,

Vilas-Boas²,

Perrone³

et al. 2005

Arq. Bras. Cardiol.

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“…A single intracoronary artery dose of IGF-1 in dogs after I/R reduces cardiomyocyte apoptosis within the ischemic border zone (10), and intramyocardial IGF-1 administration reduces post-MI infarct size and LV dysfunction in rats (11). However, dose-dependent side effects of acute or chronic IGF-1 therapy, which include potentially maladaptive promotion of cardiomyocyte hypertrophy (12), have hampered its clinical usefulness as a therapy. Hence, our findings open a previously unidentified avenue for locally increasing the cardioprotective effects of IGF-1 signaling by inhibiting a protease that regulates its degradation without impacting circulating IGF-1 levels.…”

mentioning

confidence: 99%

IGF-1 degradation by mouse mast cell protease 4 promotes cell death and adverse cardiac remodeling days after a myocardial infarction

Tejada

Tan

Torres

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in postischemic heart disease.insulin-like growth factor-1 | chymase | mouse mast cell protease 4 | ischemia-reperfusion injury | cardioprotection

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Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy

Cited by 338 publications

References 24 publications

Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients

Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients

I Diretriz Latino-Americana para avaliação e conduta na insuficiência cardíaca descompensada

IGF-1 degradation by mouse mast cell protease 4 promotes cell death and adverse cardiac remodeling days after a myocardial infarction

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