Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting

Department of Cardiac Medicine, National Heart and Lung Institute, London, England.

OBJECTIVES: We sought to assess the possible relations between clinical severity of chronic heart failure and catabolic factors, specifically tumor necrosis factor (TNF), soluble TNF receptors 1 and 2 (sTNFR-1 and sTNFR-2), cortisol, testosterone and dehydroepiandrosterone (DHEA). BACKGROUND: Chronic heart failure is associated with loss of muscle bulk that may be related to alteration of the balance between catabolism and anabolism. METHODS: Sixty-three patients (average age +/- SD 60.4 +/- 11.3 years) with stable chronic heart failure and 20 control subjects aged 52.8 +/- 11.4 years were studied. We measured body mass index (BMI) and obtained maximal incremental exercise testing with metabolic gas exchange measurements and measurements of venous levels of TNF, sTNFR-1 and sTNFR-2, cortisol and DHEA. RESULTS: There was no difference in total TNF-alpha levels between patients and control subjects (9.76 +/- 8.59 vs. 6.84 +/- 2.7 pg/ml). sTNFR-1 (128.9 +/- 84.5 vs. 63.6 +/- 23.3 pg/ml, p < 0.003) and sTNFR-2 (250.1 +/- 109.5 vs. 187.9 +/- 92.2 pg/ml, p = 0.03) were higher in patients. DHEA was lower in patients (9.88 +/- 6.94 vs. 15.64 +/- 8.33 nmol/liter, p = 0.004). The ratio of log cortisol to log DHEA correlated with log TNF level (r = 0.50, p < 0.001 for the patients alone; r = 0.48, p < 0.001 for the group as a whole). Peak oxygen consumption correlated with both sTNFR-1 and sTNFR-2 (r = -0.51, p < 0.001 and r = -0.39, p < 0.001, respectively). There was a negative correlation between BMI and TNF levels (r = -0.43, p < 0.001 for the patients) and the cortisol/DHEA ratio (r = -0.32, p = 0.01 for the patients). CONCLUSIONS: There is an increase in TNF and its soluble receptors in chronic heart failure. This increase is associated with a rise in the cortisol/DHEA (catabolic/anabolic) ratio. These changes correlate with BMI and clinical severity of heart failure, suggesting a possible etiologic link.

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