Original article
Association of adiponectin with peripheral muscle status in elderly patients with heart failure

https://doi.org/10.1016/j.ejim.2013.09.011Get rights and content

Highlights

  • Patients with heart failure demonstrated increased levels of adiponectin.

  • Peripheral muscle mass and strength were decreased in patients with heart failure.

  • Adiponectin was associated with muscle mass and muscle strength in heart failure.

Abstract

Background

Reduced peripheral muscle mass was demonstrated in patients with chronic heart failure (HF). Adipokines may have potent metabolic effects on skeletal muscle. The associations between adipokines, peripheral muscle mass, and muscle function have been poorly investigated in patients with HF.

Methods

We measured markers of fat and bone metabolism (adiponectin, leptin, 25-hydroxy vitamin D, parathyroid hormone, osteoprotegerin, RANKL), N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in 73 non-cachectic, non-diabetic, male patients with chronic HF (age: 68 ± 7 years, New York Heart Association class II/III: 76/26%, left ventricular ejection fraction 29 ± 8%) and 20 healthy controls of similar age. Lean mass as a measure of skeletal muscle mass was measured by dual energy X-ray absorptiometry (DEXA), while muscle strength was assessed by hand grip strength measured by Jamar dynamometer.

Results

Serum levels of adiponectin, parathyroid hormone, osteoprotegerin, RANKL, and NT-pro-BNP were elevated in patients with chronic HF compared to healthy controls (all p < 0.0001), while no difference in serum levels of leptin, testosterone or SHBG was noted. Levels of 25-hydroxy vitamin D were reduced (p = 0.002) in HF group. Peripheral lean mass and hand grip strength were reduced in patients with HF compared to healthy subjects (p = 0.006 and p < 0.0001, respectively). Using backward selection multivariable regression, serum levels of increased adiponectin remained significantly associated with reduced arm lean mass and muscle strength.

Conclusions

Our findings may indicate a cross-sectional metabolic association of increased serum adiponectin with reduced peripheral muscle mass and muscle strength in non-cachectic, non-diabetic, elderly HF patients.

Introduction

The age-related decrease in skeletal muscle mass is associated with a spectrum of consequences including functional limitation, disability, falls and bone fractures, immunodeficiency, and impaired thermoregulation [1], [2]. In healthy ageing, a relationship with increased mortality has been demonstrated as well [3]. Loss of peripheral muscle tissue is a common abnormality even in non-cachectic patients with chronic heart failure (HF), and it may contribute to accelerated pathogenesis of disability [4]. Peripheral muscle mass accounts for > 75% of total body skeletal muscle and is the primary portion of skeletal muscle involved in ambulation and physical activities. The prevalence of chronic HF is increasing, as well [5]. As the number of elderly persons increases with related higher prevalence of chronic HF, new studies are required to understand changes in peripheral muscle mass in elderly patients with chronic HF.

Thanks to the integrative approach considering the whole organism, many new findings about the cross-talk between different body systems in respect to failing heart were discovered including the complex interplay between body compartments (fat, bone and muscle compartment) [6]. Previous studies have shown that in HF, bone and muscle losses are linked [7]. It is often debated whether fat mass or muscle mass is a more important determinant of bone status. Adipose tissue contributes to endocrine signaling via the secretion of bioactive molecules, termed ‘adipokines’ [8]. Adiponectin and leptin are the most abundant adipokines. They are involved in the regulation of whole-body energy metabolism [9] and have similar acute and chronic effects on muscle metabolism [10]. Adiponectin levels exceed those of other adipokines by 100-fold. Since adiponectin receptors are expressed in skeletal muscle, adiponectin exerts potent metabolic effects particularly in skeletal muscle [11]. Interestingly, serum adiponectin, in addition to its beneficial effects on both lipid and glucose metabolism, may play a cardioprotective role in chronic HF due to its favorable effects on myocardial inflammation, hypertrophy, and fibrosis [12]. However, others have suggested its paradoxal role in the pathogenesis of cardiac cachexia [13]. The receptor activator of nuclear factor-kB ligand (RANKL) and its decoy receptor, osteoprotegerin, are members of the TNF-signaling super-family and are the main cytokines regulating bone remodeling. We have recently shown increased serum RANKL levels in HF patients associated with variables of neuroendocrine activation such as N-terminal pro-B-type natriuretic peptide (NT-proBNP) and adiponectin [14].

In this study, we aimed to evaluate association between metabolic markers of fat and bone tissue metabolism with peripheral muscle mass and muscle function in non-cachectic elderly patients with chronic HF.

Section snippets

Study design

We screened 152 males aged 55 years and older with chronic HF due to ischaemic or idiopathic dilated cardiomyopathy. Inclusion criteria were: 1. duration of chronic HF longer than one year; 2. echocardiographically assessed left ventricular ejection fraction < 40%; 3. ischemic or idiopathic dilated cardiomyopathy; 4. New York Heart Association (NYHA) functional class II or III; 5. stable medication regimen within the previous 6 weeks; 6. clinically stable condition with no clinical evidence of

Results

Patients' and control subjects' baseline characteristics are summarized in Table 1. Patients with chronic HF and healthy controls were similar in age and body mass index, while hand grip strength and 6-minute walk distance were lower in the first group. Serum adiponectin, osteoprotegerin, RANKL, parathyroid hormone levels (PTH) were higher in patients with HF than in controls, with comparable levels of serum leptin and high sensitivity C-reactive protein (hs-CRP). Serum vitamin D levels

Discussion

Metabolic markers of fat and bone metabolism were significantly different between non-cachectic, non-diabetic patients with chronic HF and healthy controls. Patients with HF demonstrated increased levels of adiponectin, RANKL, osteoprotegerin, and PTH, while levels of 25(OH)D were decreased. Additionally, peripheral muscle mass was decreased in HF patients more at the expense of reduced leg muscle mass. Bone mineral content was decreased in all body compartments, while there was no difference

Limitations

Although our study is limited by its cross-sectional design and modest sample size, the strength of this study includes a homogeneous study population. It should, however, be noted that the associations obtained in this study apply to the elderly and non-cachectic males with systolic HF and that these associations may not hold true for patients with preserved left ventricular ejection fraction. It is also acknowledged that body composition measurements with DEXA may be affected by tissue

Conclusion

Our findings indicate a cross-sectional metabolic association between serum adiponectin with reduced peripheral muscle mass and muscle strength in non-cachectic, non-diabetic, elderly patients with chronic HF. This result may contribute to the recent hypothesis that serum adiponectin may participate in the development of “heart failure myopathy”, and consequently in the development of disability in these patients.

Learning points

• Patients with HF demonstrated increased levels of serum adiponectin.

• Peripheral muscle mass and strength were decreased in patients with HF.

• Serum adiponectin was inversely associated with muscle mass and muscle strength in elderly patients with HF.

• Serum adiponectin may participate in the development of “HF myopathy”.

Conflict of interests

The authors declare no conflict of interest.

Acknowledgments

This work was supported by Serbian Ministry of Science (grant 175033). Dr von Haehling and Dr Lainscak are supported by the 7th Framework Program (FP7/ 2007–2013) under grant agreement number 241558 of the European Commission (SICA-HF).

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