Abstract
BackgroundInflammation and skeletal muscle wasting often coexist in elderly populations, but few studies have examined their relationship in elderly heart failure (HF) patients. This study examined the relationship between inflammation and increased skeletal muscle proteolysis, reduced skeletal mass and strength, and their prognostic implications in elderly HF patients (> 65 years) using a random forest approach.MethodsWe prospectively enrolled consecutive elderly HF patients (n = 78) and age- and sex-matched control subjects (n = 83). We measured the interleukin (IL)-6, C-reactive protein (CRP), and B-type natriuretic peptide (BNP) levels, lower limb muscle mass and strength, and 6-min walk distance. The amount of muscle proteolysis was determined by urinary 3-methylhystidine, normalized by creatinine (3-MH/Cr). The composite endpoint was defined as all-cause death or hospitalizations due to worsening HF.ResultsCompared to controls, elderly HF patients had a significantly higher IL-6, CRP, BNP, and 3-MH/Cr, and exhibited a reduced lower limb muscle mass and strength. A correlation analysis demonstrated significant positive correlations between the inflammatory cytokine levels and 3-MH/Cr and BNP, and negative correlations with the lower limb muscle mass and strength, and 6-min walk distance. During a median follow-up of 2.4-years, 24 patients reached the endpoint. A random forest model revealed that inflammatory cytokines, skeletal muscle wasting, and the BNP had greater effects on the risk prediction. The algorithm achieved an area under the receiver operating characteristic curve of 0.887 (95% CI, 0.772–1.000).ConclusionThis study provided evidence of the association between inflammation and increased skeletal muscle proteolysis, reduced skeletal mass and strength, and their prognostic roles in elderly HF patients.
Highlights
Inflammation and skeletal muscle wasting often coexist in elderly populations, but few studies have examined their relationship in elderly heart failure (HF) patients
We investigated the prognostic role of the inflammatory cytokine levels and skeletal muscle wasting using a random forest approach, one of the machine learning techniques widely used in various scientific fields [9]
In this study we investigated the associations between the inflammatory cytokines and skeletal muscle proteolysis, muscle mass, and strength in elderly HF patients
Summary
Inflammation and skeletal muscle wasting often coexist in elderly populations, but few studies have examined their relationship in elderly heart failure (HF) patients. This study examined the relationship between inflammation and increased skeletal muscle proteolysis, reduced skeletal mass and strength, and their prognostic implications in elderly HF patients (> 65 years) using a random forest approach. Examination of muscle biopsies obtained from patients with HF demonstrated fiber atrophy and increased numbers of inflammatory cells [8]. These findings were associated with elevated levels of the inflammatory cytokines, suggesting a potentially shared pathogenesis of skeletal muscle atrophy in elderly HF and aged people and implicate systemic and/ or local inflammation as a potential causative mechanism of skeletal muscle wasting
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