CLINICAL STUDY
Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone
Stefan D. Anker, MD, PhD*  ,
Maurizio Volterrani, MD ,
Claus-Dieter Pflaum, MD ,
Christian J. Strasburger, MD,
Karl Josef Osterziel, MD*,
Wolfram Doehner, MD* ,
Michael B. Ranke, MD||,
Philip A. Poole-Wilson, MD, FACC,
Andrea Giustina, MD¶,
Rainer Dietz, MD* and
Andrew J. S. Coats, DM, FACC
* Franz-Volhard-Klinik (Charité, Campus Berlin-Buch) at Max Delbrück Centrum for Molecular Medicine, Charité, Berlin, Germany
Clinical Cardiology, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom
Department of Cardiology, Salvatore Maugeri-Foundation, Gussago, Italy
Medizinische Klinik, Ludwigs Maximilian Universität Munich, Munich; Germany
|| Sektion Pädiatrische Endokrinologie, Kinderklinik, Eberhardt-Karls-Universität, Tübingen, Germany
¶ Endocrine Section, Department of Internal Medicine, University of Brescia, Brescia, Italy
Manuscript received October 13, 2000;
revised manuscript received April 10, 2001,
accepted April 12, 2001.
Reprint requests and correspondence: Dr. Stefan Anker, Clinical Cardiology, National Heart and Lung Institute London, Dovehouse Street, London SW3 6LY, United Kingdom
s.anker{at}ic.ac.uk
OBJECTIVES
We aimed to determine whether growth hormone (GH) resistance is present in patients with chronic heart failure (CHF) and whether it may be linked to the biochemical response to GH treatment.
BACKGROUND
Acquired GH resistance is a feature of severe illness, in particular, cachexia. In patients with CHF, the response to GH therapy appears to be variable.
METHODS
Biochemical markers of the GH-insulin-like growth factor-I (IGF-I) axis were compared in 21 cachectic patients with CHF, 51 noncachectic patients and 26 healthy control subjects. In separate studies, the predictive value of baseline biochemical variables for the IGF-I response to GH treatment was analyzed.
RESULTS
Cachectic patients showed an increase of total GH and immunologically intact GH (p  0.0002) and a decrease of GH-binding protein (BP) (p = 0.005), IGF-BP3 (p = 0.01) and IGF-I (p = 0.06), compared with noncachectic patients. Similar changes were found when the cachectic group was compared with the control group. No differences were found between noncachectic patients and control subjects. Levels of GH-BP correlated with the IGF-I/GH ratio in all subgroups (all p 0.002). Baseline GH-BP levels were related to the increase of IGF-I levels in response to GH treatment in patients with CHF after 24 h (r = 0.83, p = 0.005; n = 9; study 2), 44 days (r = 0.52, p = 0.007; n = 25; study 3) and 96 days (r = 0.54, p = 0.006; n = 24; study 3).
CONCLUSIONS
Most cachectic and some noncachectic patients with CHF show features of acquired GH resistance. The principal predictors of the biochemical features of GH resistance and of the poor biochemical response to short-term and longer-term GH treatment are GH-BP plasma levels. The presence of GH resistance is potentially a major factor determining the response to GH therapy in patients with CHF.
|
Abbreviations and Acronyms
| | BMI | = body mass index | | BP | = binding protein | | CHF | = chronic heart failure | | DEXA | = dual-energy X-ray absorptiometric | | GH | = growth hormone | | IGF-I | = insulin-like growth factor-I | | IRMA | = immunoradiometric assay | | LVEF | = left ventricular ejection fraction | | NYHA | = New York Heart Association | | RIA | = radioimmunoassay | | SC | = standardized coefficient |
|
This article has been cited by other articles:
|
|
|
|
 
A. Cittadini, L. Saldamarco, A. M. Marra, M. Arcopinto, G. Carlomagno, M. Imbriaco, D. Del Forno, C. Vigorito, B. Merola, U. Oliviero, et al.
Growth Hormone Deficiency in Patients with Chronic Heart Failure and Beneficial Effects of Its Correction
J. Clin. Endocrinol. Metab.,
September 1, 2009;
94(9):
3329 - 3336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. H. Lund, J. J. Williams, P. Freda, J. J. LaManca, T. H. LeJemtel, and D. M. Mancini
Ghrelin resistance occurs in severe heart failure and resolves after heart transplantation
Eur J Heart Fail,
August 1, 2009;
11(8):
789 - 794.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. H. Lund, P. Freda, J. J. Williams, J. J. LaManca, T. H. LeJemtel, and D. M. Mancini
Growth hormone resistance in severe heart failure resolves after cardiac transplantation
Eur J Heart Fail,
May 1, 2009;
11(5):
525 - 528.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Sacca
Heart Failure as a Multiple Hormonal Deficiency Syndrome
Circ Heart Fail,
March 1, 2009;
2(2):
151 - 156.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Groban, H. Jobe, M. Lin, T. Houle, D. A. Kitzman, and W. Sonntag
Effects of Short-Term Treadmill Exercise Training or Growth Hormone Supplementation on Diastolic Function and Exercise Tolerance in Old Rats
J. Gerontol. A Biol. Sci. Med. Sci.,
September 1, 2008;
63(9):
911 - 920.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Jorn Schneider, J. Klotsche, B. Saller, S. Bohler, C. Sievers, D. Pittrow, G. Ruf, W. Marz, W. Erwa, A. M Zeiher, et al.
Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients
Eur. J. Endocrinol.,
February 1, 2008;
158(2):
153 - 161.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bruel, T. E.H. Christoffersen, and J. R. Nyengaard
Growth hormone increases the proliferation of existing cardiac myocytes and the total number of cardiac myocytes in the rat heart
Cardiovasc Res,
December 1, 2007;
76(3):
400 - 408.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Doehner, A. C. Bunck, M. Rauchhaus, S. von Haehling, F. M. Brunkhorst, M. Cicoira, C. Tschope, P. Ponikowski, R. A. Claus, and S. D. Anker
Secretory sphingomyelinase is upregulated in chronic heart failure: a second messenger system of immune activation relates to body composition, muscular functional capacity, and peripheral blood flow
Eur. Heart J.,
April 1, 2007;
28(7):
821 - 828.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Ibe, A. Saraste, S. Lindemann, S. Bruder, M. Buerke, H. Darius, K. Pulkki, and L.-M. Voipio-Pulkki
Cardiomyocyte apoptosis is related to left ventricular dysfunction and remodelling in dilated cardiomyopathy, but is not affected by growth hormone treatment
Eur J Heart Fail,
February 1, 2007;
9(2):
160 - 167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. von Haehling, W. Doehner, and S. D Anker
Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure
Cardiovasc Res,
January 15, 2007;
73(2):
298 - 309.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Le Corvoisier, L. Hittinger, P. Chanson, O. Montagne, I. Macquin-Mavier, and P. Maison
Cardiac Effects of Growth Hormone Treatment in Chronic Heart Failure: A Meta-Analysis
J. Clin. Endocrinol. Metab.,
January 1, 2007;
92(1):
180 - 185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. R. Schwarz, P. Jammula, R. Gupta, and S. Rosanio
A Case and Review of Acromegaly-Induced Cardiomyopathy and the Relationship Between Growth Hormone and Heart Failure: Cause or Cure or Neither or Both?
Journal of Cardiovascular Pharmacology and Therapeutics,
December 1, 2006;
11(4):
232 - 244.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. A. Jankowska, B. Biel, J. Majda, A. Szklarska, M. Lopuszanska, M. Medras, S. D. Anker, W. Banasiak, P. A. Poole-Wilson, and P. Ponikowski
Anabolic Deficiency in Men With Chronic Heart Failure: Prevalence and Detrimental Impact on Survival
Circulation,
October 24, 2006;
114(17):
1829 - 1837.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Abe, T. Matsunaga, K. Kameda, H. Tomita, T. Fujiwara, H. Ishizaka, H. Hanada, K. Fukui, I. Fukuda, T. Osanai, et al.
Increased Level of Pericardial Insulin-Like Growth Factor-1 in Patients With Left Ventricular Dysfunction and Advanced Heart Failure
J. Am. Coll. Cardiol.,
October 3, 2006;
48(7):
1387 - 1395.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Toth and D. E. Matthews
Whole-Body Protein Metabolism in Chronic Heart Failure: Relationship to Anabolic and Catabolic Hormones
JPEN J Parenter Enteral Nutr,
May 1, 2006;
30(3):
194 - 201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Groban, N. A. Pailes, C. D. L. Bennett, C. S. Carter, M. C. Chappell, D. W. Kitzman, and W. E. Sonntag
Growth Hormone Replacement Attenuates Diastolic Dysfunction and Cardiac Angiotensin II Expression in Senescent Rats
J. Gerontol. A Biol. Sci. Med. Sci.,
January 1, 2006;
61(1):
28 - 35.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Toth, P. A. Ades, M. M. LeWinter, R. P. Tracy, and A. Tchernof
Skeletal muscle myofibrillar mRNA expression in heart failure: relationship to local and circulating hormones
J Appl Physiol,
January 1, 2006;
100(1):
35 - 41.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Marleau, M. Mulumba, D. Lamontagne, and H. Ong
Cardiac and peripheral actions of growth hormone and its releasing peptides: Relevance for the treatment of cardiomyopathies
Cardiovasc Res,
January 1, 2006;
69(1):
26 - 35.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Huang, X. Zhang, Z.-W. Jiang, B.-Z. Liu, N. Li, and J.-S. Li
Hypoleptinemia in Gastric Cancer Patients: Relation to Body Fat Mass, Insulin, and Growth Hormone
JPEN J Parenter Enteral Nutr,
July 1, 2005;
29(4):
229 - 235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Nagaya, J. Moriya, Y. Yasumura, M. Uematsu, F. Ono, W. Shimizu, K. Ueno, M. Kitakaze, K. Miyatake, and K. Kangawa
Effects of Ghrelin Administration on Left Ventricular Function, Exercise Capacity, and Muscle Wasting in Patients With Chronic Heart Failure
Circulation,
December 14, 2004;
110(24):
3674 - 3679.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. McElhinney, S. D. Colan, A. M. Moran, D. Wypij, M. Lin, J. A. Majzoub, E. C. Crawford, J. M. Bartlett, E. A. McGrath, and J. W. Newburger
Recombinant Human Growth Hormone Treatment for Dilated Cardiomyopathy in Children
Pediatrics,
October 1, 2004;
114(4):
e452 - e458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Dalla Libera, B. Ravara, M. Volterrani, V. Gobbo, M. Della Barbera, A. Angelini, D. D. Betto, E. Germinario, and G. Vescovo
Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure
Am J Physiol Cell Physiol,
January 1, 2004;
286(1):
C138 - C144.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Vasan, L. M. Sullivan, R. B. D'Agostino, R. Roubenoff, T. Harris, D. B. Sawyer, D. Levy, and P. W.F. Wilson
Serum Insulin-like Growth Factor I and Risk for Heart Failure in Elderly Individuals without a Previous Myocardial Infarction: The Framingham Heart Study
Ann Intern Med,
October 21, 2003;
139(8):
642 - 648.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. C. Schulze, J. Kratzsch, A. Linke, N. Schoene, V. Adams, S. Gielen, S. Erbs, S. Moebius-Winkler, and G. Schuler
Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure
Eur J Heart Fail,
January 1, 2003;
5(1):
33 - 40.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Sharma and S.D Anker
From tissue wasting to cachexia: changes in peripheral blood flow and skeletal musculature
Eur. Heart J. Suppl.,
April 1, 2002;
4(suppl_D):
D12 - D17.
[Abstract]
[PDF]
|
|
|
|
