Clinical Studies
Tumor Necrosis Factor and Steroid Metabolism in Chronic Heart Failure: Possible Relation to Muscle Wasting

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Abstract

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.

Abbreviations

BMI
body mass index
DHEA
dehydroepiandrosterone
NYHA
New York Heart Association
sTNFR
soluble tumor necrosis factor receptor
TNF
tumor necrosis factor
co2
carbon dioxide production
e
ventilation
o2
oxygen consumption

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Dr. Clark is supported in part by a fellowship from the Robert Luff Foundation and Dr. Coats by the Viscount Royston Trust, London, England, United Kingdom.

1

Dr. Anker is a Research Fellow of the European Society of Cardiology, Rotterdam, The Netherlands.