Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer

Fröhlich, A.-K. et al. (2024) Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer. Clinical Research in Cardiology, (doi: 10.1007/s00392-024-02400-x) (PMID:38587563) (Early Online Publication)

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Abstract

Background Growth hormone (GH) resistance is characterized by high GH levels but low levels of insulin-like growth factor-I (IGF-I) and growth hormone binding protein (GHBP) and, for patients with chronic disease, is associated with the development of cachexia. Objectives We investigated whether GH resistance is associated with changes in left ventricular (LV) mass (cardiac wasting) in patients with cancer. Methods We measured plasma IGF-I, GH, and GHBP in 159 women and 148 men with cancer (83% stage III/IV). Patients were grouped by tertile of echocardiographic LVmass/height2 (women, < 50, 50–61, > 61 g/m2; men, < 60, 60–74, > 74 g/m2) and by presence of wasting syndrome with unintentional weight loss (BMI < 24 kg/m2 and weight loss ≥ 5% in the prior 12 months). Repeat echocardiograms were obtained usually within 3–6 months for 85 patients. Results Patients in the lowest LVmass/height2 tertile had higher plasma GH (median (IQR) for 1st, 2nd, and 3rd tertile women, 1.8 (0.9–4.2), 0.8 (0.2–2.2), 0.5 (0.3–1.6) ng/mL, p = 0.029; men, 2.1 (0.8–3.2), 0.6 (0.1–1.7), 0.7 (0.2–1.9) ng/mL, p = 0.003). Among women, lower LVmass was associated with higher plasma IGF-I (68 (48–116), 72 (48–95), 49 (35–76) ng/mL, p = 0.007), whereas such association did not exist for men. Patients with lower LVmass had lower log IGF-I/GH ratio (women, 1.60 ± 0.09, 2.02 ± 0.09, 1.88 ± 0.09, p = 0.004; men, 1.64 ± 0.09, 2.14 ± 0.11, 2.04 ± 0.11, p = 0.002). GHBP was not associated with LVmass. Patients with wasting syndrome with unintentional weight loss had higher plasma GH and GHBP, lower log IGF-I/GH ratio, and similar IGF-I. Overall, GHBP correlated inversely with log IGF-I/GH ratio (women, r =  − 0.591, p < 0.001; men, r =  − 0.575, p < 0.001). Additionally, higher baseline IGF-I was associated with a decline in LVmass during follow-up (r =  − 0.318, p = 0.003). Conclusion In advanced cancer, reduced LVmass is associated with increased plasma GH and reduced IGF-I/GH ratio, suggesting increasing GH resistance, especially for patients with wasting syndrome with unintentional weight loss. Higher baseline IGF-I was associated with a decrease in relative LVmass during follow-up.

Item Type:Articles
Additional Information:Funding: Open Access funding enabled and organized by Projekt DEAL. This study was partly funded by the German Centre for Cardiovascular Research through research support to Dr Hadzibegovic, DrS. Anker, and Dr M. Anker. TZ is supported by the German Center of Cardiovascular Research (DZHK, FKZ: 81Z0710102).
Keywords:Cancer, Insulin-like growth factor-I, Growth hormone, Echocardiography, Left ventricular mass, Cachexia, Cardiology
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John
Authors: Fröhlich, A.-K., Porthun, J., Talha, K. M., Lena, A., Hadzibegovic, S., Wilkenshoff, U., Sonntag, F., Nikolski, A., Ramer, L. V., Zeller, T., Keller, U., Bullinger, L., Anker, S. D., Haverkamp, W., von Haehling, S., Doehner, W., Rauch, U., Skurk, C., Cleland, J. G.F., Butler, J., Coats, A. J.S., Landmesser, U., Karakas, M., and Anker, M. S.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Clinical Research in Cardiology
Publisher:Springer
ISSN:1861-0684
ISSN (Online):1861-0692
Published Online:08 April 2024
Copyright Holders:Copyright: © 2024 The Authors
First Published:First published in Clinical Research in Cardiology 2024
Publisher Policy:Reproduced under a Creative Commons licence

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