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

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.