Immune activation is associated with reduced skeletal muscle mass and physical function in chronic heart failure
Introduction
Chronic heart failure is characterized by immune activation and increased circulating concentrations of several proinflammatory cytokines [1], [2], [3]. These inflammatory mediators may contribute to the pathophysiology and progression of the disease by altering cardiac structure and function [4], [5]. In addition to their detrimental effects on cardiac muscle, elevated cytokine levels may contribute to the peripheral manifestations of the heart failure syndrome; most notably, skeletal muscle wasting and reduced muscle function. The catabolic effects of cytokines on skeletal muscle have been well-characterized [6], [7]. In addition, recent evidence has shown that, similar to cardiac muscle, cytokines promote contractile dysfunction in skeletal muscle [8], [9]. Despite these detrimental effects, few studies have explored the relationship of inflammatory mediators to muscle mass and function. Thus, our goals in the present study were threefold: (1) to measure and compare aerobic capacity, muscle strength and cytokine levels between heart failure patients and controls; (2) to examine the relationship of circulating cytokines to skeletal muscle mass; and (3) to determine the relationship of cytokine levels to aerobic capacity and skeletal muscle strength measures. To accomplish these objectives, we measured circulating tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), their soluble receptors (sTNF-α RII, IL-6sR) and markers of immune activation (C-reactive protein (CRP)) and related these measures to total and regional skeletal muscle mass, peak aerobic capacity and knee and forearm muscle strength in a cohort of heart failure patients and controls. We hypothesized that heart failure patients would be characterized by decreased aerobic capacity and muscle strength and increased circulating concentrations of inflammatory markers. Moreover, immune activation would be related to reduced muscle mass and physical function.
Section snippets
Subjects
Ten male volunteers with chronic heart failure due to left ventricular systolic dysfunction were recruited from the Heart Failure Clinic of the Cardiology Unit of the University of Vermont (ejection fraction: 32 ± 4% by echocardiography). New York Heart Association (NYHA) functional class averaged 2.5 ± 0.2 with six patients in class II, 3 in class III and 1 in class IV. Heart failure was due to coronary artery disease in seven patients, defined by a history of myocardial infarction and/or
Physical characteristics
Physical characteristics are shown in Table 1. No differences in age, body size, body composition or total or regional muscle mass were observed between groups. Exclusion of the two controls with coronary artery disease did not affect group differences.
Exercise capacity
Differences in peak VO2, expressed on an absolute basis, and relative to either body mass or fat-free mass, are shown in Table 2. Peak VO2 was 36% lower (P < 0.01) in heart failure patients compared to controls. This reduction in exercise capacity
Discussion
Numerous studies suggest a role for immune activation and increased circulating concentrations of proinflammatory cytokines in the pathophysiology and progression of heart failure. Whether inflammatory mediators contribute to the peripheral manifestations of heart failure, such as muscle atrophy and reduced functional capacity, however, is not clear. The present study was undertaken to explore the relationship of circulating inflammatory mediators to skeletal muscle mass and physical function
Acknowledgments
The authors would like to thank all the participants who volunteered their time for this study. This work was supported by grants from the NIH (AM-02125; AG-17494; RR-00109) and American Federation for Aging Research.
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