Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation.
BACKGROUND
Recent studies of growth hormone supplementation in chronic heart failure have been associated with variable results. Acquired abnormalities of biochemical parameters of the growth hormone insulin-like growth factor I axis have been associated with severe chronic heart failure. There are suggestions of an acquired growth hormone resistance with deficient insulin-like growth factor I in some patients.


OBJECTIVE
Therefore, we set out to investigate the clinical and functional status and the degree of cytokine and neurohormonal alteration of chronic heart failure patients with deficient insulin-like growth factor I responses.


METHODS
Patients with chronic heart failure were divided into two groups according to their insulin-like growth factor I levels (classified according to the manufacturer's assay range in normal controls): low insulin-like growth factor I <104 (n = 20; 89 +/- 9.6 ng/ml), and normal/high >104 ng/ml (n = 32; 169 +/- 52 ng/ml). Between groups there was no difference in age (low versus high: 65.3 +/- 12.1 versus 61.6 +/- 9.1 years, p = 0.21), body mass index, aerobic capacity (peak oxygen consumption: low versus high: 15.5 +/- 5.2 versus 17.3 +/- 6.3 mL/kg/min, p = 0.23), left ventricular ejection fraction, New York Heart Association classification.


RESULTS
During quadriceps strength testing, patients with low insulin-like growth factor I had reduced absolute strength (-24%), and strength per unit area muscle (- 14%) than patients with normal/high insulin-like growth factor I. Leg muscle cross-sectional area was lower in the low insulin-like growth factor I group (-12% and -13% for right and left legs, respectively). These alterations were accompanied by increased levels of growth hormone (+145%), tumor necrosis factor-alpha (+46%), cortisol/ dehydroepiandrosterone ratio (+60%), noradrenaline (+49%) and adrenaline (+136%) (all at least p < 0.05).


CONCLUSIONS
Patients with low insulin-like growth factor I levels show signs of altered body composition, cytokine and neuroendocrine activation, to a greater extent than patients with normal/high levels.
Department of Cardiac Medicine, Royal Brompton Hospital and National Heart and Lung Institute, London, England, United Kingdom.
J
J
Niebauer
C D
CD
Pflaum
A L
AL
Clark
C J
CJ
Strasburger
J
J
Hooper
P A
PA
Poole-Wilson
A J
AJ
Coats
S D
SD
Anker
D000316:Adrenergic alpha-Agonists / Q000097:blood; D000367:Age Factors; D000368:Aged; D019412:Anatomy, Cross-Sectional; D001823:Body Composition / Q000502:physiology*; D015992:Body Mass Index; D016207:Cytokines / Q000097:blood / Q000502:physiology*; D003687:Dehydroepiandrosterone / Q000097:blood; D004351:Drug Resistance; D004734:Energy Metabolism / Q000502:physiology*; D004837:Epinephrine / Q000097:blood; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D019382:Human Growth Hormone / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000627:therapeutic use; D007866:Leg; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009479:Neuropeptides / Q000097:blood / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D016277:Ventricular Function, Left / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D016207:Cytokines; D009479:Neuropeptides; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone; D003687:Dehydroepiandrosterone; D007334:Insulin-Like Growth Factor I; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine