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J Am Coll Cardiol, 2002; 39:1175-1181 © 2002 by the American College of Cardiology Foundation |
* University of Leipzig–Heart Center, Department of Cardiology; Leipzig, Germany
Department of Cardiac Surgery, University of Leipzig–Heart Center, Leipzig, Germany
Department of Radiology, University of Leipzig–Heart Center, Leipzig, Germany
Institute of Clinical Chemistry, Leipzig, Germany
|| Institute of Sport Medicine, Leipzig, Germany
Manuscript received September 17, 2001; revised manuscript received December 28, 2001, accepted January 11, 2002.
* Reprint requests and correspondence: Dr. Rainer Hambrecht, Professor of Medicine, Heart Center, University of Leipzig, Strümpellstr. 39, 04289 Leipzig, Germany.
hamr{at}medizin.uni-leipzig.de
OBJECTIVES: We sought to assess the role of insulin-like growth factor-I (IGF-I) in muscle wasting in chronic heart failure (CHF), serum concentrations and local muscular IGF-I expression were determined in patients with severe CHF.
BACKGROUND: Chronic heart failure is associated with progressive muscle atrophy, leading to cardiac cachexia. Skeletal muscle disuse and inflammatory activation with elevated cytokine levels have been implicated; however, the pathomechanism involved remains largely unknown.
METHODS: Serum levels of IGF-I were measured by competitive solid phase immunoassay in 47 patients with severe CHF (left ventricular ejection fraction 
30%) and 15 age-matched healthy subjects (HS). Insulin-like growth factor-I and IGF-I receptor expression were assessed in vastus lateralis biopsies by real-time PCR and Western blot analysis.
RESULTS: Although serum IGF-I was not significantly different (175 ± 10 ng/ml in CHF vs. 170 ± 12 ng/ml in HS, p = NS), local muscle IGF-I mRNA expression was reduced by 52% in CHF (6.7 ± 0.4 vs. 14.0 ± 0.9 arbitrary units in HS, p < 0.001). This was accompanied by an increase in IGF-I receptor mRNA expression (86.8 ± 5.4 in CHF vs. 23.1 ± 1.8 arbitrary units in HS, p < 0.001). Local IGF-I expression was significantly correlated with muscle cross-sectional area (R = 0.75, p = 0.01). Chronic heart failure patients with a body mass index of <25 kg/m2 showed signs of peripheral growth hormone (GH) resistance, as indicated by elevated serum GH, and reduced IGF-I levels.
CONCLUSIONS: In CHF patients, muscle IGF-I expression is considerably reduced in the presence of normal serum IGF-I levels, possibly contributing to early loss of muscle mass. These findings are consistent with a potential role of IGF-I for skeletal muscle atrophy in CHF.
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