Activity of GH/IGF‐I axis in patients with dilated cardiomyopathy

Broglio, Fabio; Fubini, A; Morello, Mara; Arvat, Emanuela; Aimaretti, Gianluca; Gianotti, Laura; Boghen, Muny F.; Deghenghi, Romano; Mangiardi, L; Ghigo, Ezio

doi:10.1046/j.1365-2265.1999.00696.x

Cited by 67 publications

(53 citation statements)

References 76 publications

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“…Thus, IGF-I has been found to be positively associated with progression of coronary artery stenosis and restenosis (8,9) and coronary artery disease (12). 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).…”

Section: Introductionmentioning

confidence: 90%

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: Introductionmentioning

confidence: 90%

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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“…17) Several studies have looked at GH secretion in patients with heart failure and reported that subtle alterations in the activity of GH/IGF-I axis were present in DCM. [18][19][20] Thus, since the alterations in GH/IGF-I axis which may occur as a result of octreotide therapy are already present in these patients, and GH excess and deficiency alone were a cause of heart failure, 21) it is more reasonable to search for indirect, rather than direct, effects in the results achieved through octreotide therapy in patients with ischemic or idiopathic DCM.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Octreotide in Dilated Cardiomyopathy: An Open-label Trial in 12 Patients

et al. 2004

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SUMMARYOctreotide, a somatostatin analogue, has been found effective in the treatment of acromegalic cardiomyopathy. We investigated whether intermittent octreotide therapy had beneficial effects in patients with ischemic or idiopathic dilated cardiomyopathy, which are refractory to conventional therapy.Twelve patients with ischemic or idiopathic dilated cardiomyopathy were enrolled in the study. In addition to conventional treatment, octreotide (first 50 µg and then 25 µg three times per day for 4 days) was administered and repeated after 1, 2, and 3 months. The patients were evaluated 3 times, before and immediately after the first treatment and after 3 months of treatment, using echocardiography, exercise stress testing, ambulatory ECG, right ventricular catheterization, cardiac enzymes, and the Minnesota living with heart failure questionnaire for quality of life.There were no significant changes in parameters after the first treatment. However, after 3 months of treatment, there were significant improvements in the left ventricular ejection fraction, left ventricular posterior wall thickness, hemodynamics, exercise capacity, and quality of life. Additionally, ischemic burden and the number of ventricular premature beats also decreased slightly.Intermittent octreotide therapy led to significant improvements in patients with ischemic and idiopathic dilated cardiomyopathy refractory to conventional treatment. We believe that this therapy should be attempted as an adjunctive therapy in these patients, and that in this respect, randomized, double-blind, clinical, and large-scale studies are required before regular usage is undertaken. (Jpn Heart J 2004; 45: 613-621)

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“…Recently it was shown that basal IGF-I levels are reduced in dilated cardiomyopathy patients with severe left ventricular dysfunction (104) and that serum IGF-I levels are negatively correlated with the severity of the cardiomyopathy (105). IGF-I improves cardiac contractility, cardiac output, stroke volume and ejection fraction by the human heart in the short and long term (91).…”

Section: Diabetic Cardiomyopathymentioning

confidence: 99%

The role of IGF-I in the development of cardiovascular disease in type 2 diabetes mellitus: is prevention possible?

Janssen

Lamberts

2002

European Journal of Endocrinology

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The incidence of peripheral, cerebro-and cardiovascular disease (CVD) in patients with type 2 diabetes mellitus is approximately twice as high as in the non-diabetic population. Conventional cardiovascular risk factors such as plasma lipids, lipoproteins and hypertension only partially explain this excessive risk of developing atherosclerosis and CVD. Meta-analysis of studies performed in nondiabetic populations indicates that the risk of CVD increases continuously with glucose levels above 4.2 mmol/l. The glucose hypothesis suggests that treatment which normalizes glucose levels prevents or delays the long-term complications of diabetes mellitus. However, the outcome of the UK Prospective Diabetes Study demonstrates that glucose control does not completely prevent CVD. In healthy subjects, serum IGF-I levels peak in early adulthood, after which they gradually decrease with increasing age. Several observations suggest that there is a premature and progressive agerelated decline in serum IGF-I bioactivity in type 2 diabetics, which eventually results in a (relative) IGF-I deficiency. In type 2 diabetics, close relationships have been demonstrated between glycaemic control and serum IGF-I levels, with worse control being associated with lower IGF-I levels. Several studies (in non-diabetics) suggest that lowered circulating IGF-I levels account for a poor outcome of CVD. We previously observed in a population-based study that a genetically determined lowered IGF-I expression increases the risk of myocardial infarction with type 2 diabetes. This genetic approach overcomes the problem that cross-sectional studies cannot distinguish whether changes in IGF-I levels are a cause or a consequence of a disease. IGF-I is an important metabolic regulatory hormone. In addition, IGF-I suppresses myocardial apoptosis and improves myocardial function in various models of experimental cardiomyopathy. Compared with other growth factors, the 'survival' effect of IGF-I on myocardium seems rather unique. Therefore, we hypothesize that the premature and progressive decline in serum IGF-I bioactivity in ageing patients with type 2 diabetics is an important pathophysiological abnormality. It contributes not only to elevated glucose and lipid levels, but also to the progression and the poor outcome of CVD. If this hypothesis is proven to be right, treatment with IGF-I as an adjunct to insulin offers great potential and might not only improve metabolic control but also reduce the incidence and prevalence of CVD in type 2 diabetes patients. However, there is as yet no experimental evidence that long-term (replacement) treatment with IGF-I prevents, delays or reduces CVD in type 2 diabetes patients. Clinical trials are necessary to prove that long-term IGF-I treatment, preferably in the form of a bettertolerated IGF-I/IGF-binding protein-3 complex, improves the overall cardiovascular risk in type 2 diabetes.

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Activity of GH/IGF‐I axis in patients with dilated cardiomyopathy

Cited by 67 publications

References 76 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

The Effects of Octreotide in Dilated Cardiomyopathy: An Open-label Trial in 12 Patients

The role of IGF-I in the development of cardiovascular disease in type 2 diabetes mellitus: is prevention possible?

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