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Activity of GH/IGF-I axis in patients with dilated cardiomyopathy
Insights
Patients with dilated cardiomyopathy (DCM) have lower insulin-like growth factor-I (IGF-I) levels. However, their hearts show normal sensitivity to growth hormone (GH), indicating subtle GH/IGF-I axis alterations in DCM.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play roles in cardiac function.
- Previous studies suggest potential benefits of recombinant human GH (rhGH) in dilated cardiomyopathy (DCM).
- The activity of the GH/IGF-I axis in DCM has not been thoroughly investigated.
Purpose of the Study:
- To assess the activity of the GH/IGF-I axis in patients with DCM.
- To compare GH and IGF-I levels and responses between DCM patients and healthy controls.
- To investigate potential correlations between GH/IGF-I axis activity and cardiac function parameters in DCM.
Main Methods:
- Studied 39 DCM patients and 42 age-matched controls.
- Measured basal IGF-I levels and IGF-I response after 4 days of low-dose rhGH administration.
- Assessed acute GH response to GHRH and hexarelin (HEX), and measured mean GH concentration (mGHc) over 10 hours.
Main Results:
- DCM patients had significantly lower basal IGF-I levels compared to controls.
- IGF-I levels after low-dose rhGH were lower in DCM but normalized with higher doses.
- GH response to GHRH was reduced in DCM, while response to HEX and mGHc were similar to controls.
Conclusions:
- DCM patients exhibit reduced basal IGF-I levels but preserved peripheral GH sensitivity.
- Somatotroph responsiveness to GHRH is diminished in DCM, suggesting subtle GH/IGF-I axis alterations.
- These findings highlight specific dysregulations within the GH/IGF-I axis in dilated cardiomyopathy.
Objective:
There is evidence showing that GH and IGF-I have specific receptors in the heart and that these hormones are able to promote cardiac remodelling and inotropism. It has been reported that patients with dilated cardiomyopathy (DCM) benefit from treatment with rhGH showing a striking increase in cardiac contractility. However, until now, the activity of GH/IGF-I axis in DCM has never been clearly assessed.
Patients:
To clarify this point, we enrolled 39 patients with idiopathic or post-ischaemic DCM (36 M/3 F; age (mean +/- S.D.) 55.3 +/- 9.0 years; BMI: 25.3 +/- 3.2 kg/m2; New York Heart Association class (NYHA) I/2, II/19, III/15, IV/3) and 42 age-matched controls (CS, 38 M/4 F; age 56.0 +/- 7.8 years; BMI: 24.9 +/- 1.5 kg/m2). DCM patients were characterized by a left-ventricular diastolic diameter of 73.8 +/- 8.3 mm, a shortening fraction of 15.9 +/- 6.4% and a left ventricular ejection fraction of 25.1 +/- 8.7%. In all subjects clinical and biochemical indices of renal and hepatic function as well as nutritional parameters were in the normal range.
Measurements:
In both groups we studied: a) IGF-I levels in basal conditions and after administration of low rhGH doses for 4 days (5.0 or 10.0 mu/kg/day x 4 days); b) the acute GH-response to GHRH (1.0 mu/kg i.v.) or hexarelin (HEX, 2.0 mu/kg i.v.), a peptidyl GH secretagogue (GHRP); c) mean GH concentration (mGHc) over 10 h sampling (every 20 min) from 2200 h to 0800 h.
Results:
Basal IGF-I levels in DCM were lower (P = 0.000039) than in CS (135.2 +/- 46.8 vs. 193.7 +/- 63.7 mu/l), whereas, basal IGFBP-3 and GHBP2 levels in DCM and CS were similar (2.5 +/- 1.3 vs. 2.6 +/- 0.5 mg/l and 25.3 +/- 3.6 vs. 28.3 +/- 5.0%; P = 0.95 and P = 0.085, respectively). After 4 days of 5.0 mu/kg/day rhGH administration, IGF-I levels in DCM (215.4 +/- 82.0 mu/l; P = 0.0023 vs. baseline) remained lower (P = 0.027) than those in CS (280.0 +/- 80.7 mu/l; P = 0.000080 vs. baseline). After 10.0 mu/kg/day for 4 days, IGF-I levels in DCM (297.2 +/- 109.2 mu/l; P = 0.0033 vs. baseline) were similar (P = 0.76) to those in CS (310.9 +/- 81.7 mu/l; P = 0.000060 vs. baseline). The GH response to GHRH in DCM was lower (P = 0.0022) than that in CS (hAUC0-120: 192.0 +/- 177.3 vs. 345.3 +/- 191.1 mu/l/h) whereas that to HEX in DCM and CS was similar (611.0 +/- 437.5 vs. 535.4 +/- 302.8 mu/l/h; P = 0.95). Within the DCM group, basal and rhGH-stimulated IGF-levels as wel as the GH response to GHRH or HEX were not different among NYHA classes and did not show any correlation with ECHO parameters. The mGHc in DCM (1.0 +/- 0.5 mu/l) was similar (P = 0.57) to that in CS (0.9 = 0.7 mu/l).
Conclusions:
Our present data demonstrate that in dilated cardiomyopathy patients with severe left ventricular dysfunction basal IGF-I levels are reduced whereas the IGF-I response to low rhGH doses is preserved. These findings suggest a normal peripheral GH sensitivity in dilated cardiomyopathy. On the other hand, though nocturnal mean GH concentration in dilated cardiomyopathy patients is similar to that in normal subjects, the somatotroph responsiveness to GHRH, but not that to hexarelin, is reduced. Thus, subtle alterations in the activity of GH/IGF-I axis are present in dilated cardiomyopathy.