Whole-Body Protein Metabolism in Chronic Heart Failure: Relationship to Anabolic and Catabolic Hormones

Abstract

Background: Patients with chronic heart failure frequently experience profound wasting during the course of the disease, a condition termed cardiac cachexia. Although protein is the primary structural and functional component of most tissues, few studies have examined the effect of heart failure on protein metabolism. Moreover, no study has assessed the relationship of protein turnover to hormonal alterations thought to promote cachexia. Thus, our goal was to determine if whole-body protein metabolism is altered in heart failure patients and to assess the relationship of protein kinetics to circulating levels of anabolic and catabolic hormones. Methods:We measured whole-body protein metabolism using ¹³C-leucine, body composition, and circulating anabolic and catabolic hormone levels in 10 patients with chronic heart failure and 11 elderly controls. Results: No differences in leucine rate of appearance, oxidation, or nonoxidative disposal were noted between heart failure patients and controls. However, in a subgroup of patients characterized by increased resting energy expenditure for their metabolic body size (n = 4; ≥20% above that predicted from fat-free mass), leucine rate of appearance (mean ± SE; 146 ± 6 μmol/min), an index of protein breakdown, tended to be higher compared with patients with normal resting energy expenditure (n = 5; 120 ± 8 μmol/min) and controls (127± 4 μmol/min; p = .06). Alterations in anabolic/catabolic hormone balance did not explain increased protein breakdown in this subgroup, and no correlations were found between hormone levels and protein breakdown in the heart failure group as a whole. In contrast, increased circulating interleukin-6 soluble receptor (r = 0.829; p < .01) and reduced insulin-like growth factor-I (r =–.751; p < .05) levels were related to greater rates of leucine oxidation in heart failure patients. Conclusion: Our results demonstrate that, although increased protein turnover is not a generalized feature of heart failure, there is a subgroup of patients characterized by resting hypermetabolism and increased protein breakdown. Moreover, hormonal alterations related to the heart failure syndrome were related to increased protein oxidation.

This study demonstrates that, although increased protein turnover is not a generalized feature of heart failure, a subgroup of patients exhibit increased protein breakdown and resting hypermetabolism. In addition, protein oxidation was related to reduced concentrations of anabolic and increased concentrations of catabolic hormones.