Association between inflammation and skeletal muscle proteolysis, skeletal mass and strength in elderly heart failure patients and their prognostic implications

• Published in: BMC cardiovascular disorders Vol. 20; no. 1; pp. 228 - 9
• Main Authors: Koshikawa, Masayuki, Harada, Masahide, Noyama, Shunsuke, Kiyono, Ken, Motoike, Yuji, Nomura, Yoshihiro, Nishimura, Asuka, Izawa, Hideo, Watanabe, Eiichi, Ozaki, Yukio
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.05.2020; BioMed Central; BMC
• Subjects: Age; Angina pectoris; Blood pressure; Brain natriuretic peptide; C-reactive protein; Complications and side effects; Congestive heart failure; Correlation analysis; Creatinine; Cytokines; Elderly; Enzymes; Frailty; Geriatrics; Health aspects; Heart failure; Hospitalization; Immunoassay; Inflammation; Interleukin 6; Medical prognosis; Mortality; Musculoskeletal system; Older people; Patients; Physiological aspects; Population studies; Prognosis; Proteins; Proteolysis; Sarcopenia; Skeletal muscle; Survival analysis; Urine; Japan; Sarcopenia; Frailty; Elderly; Mortality
• ISSN: 1471-2261; 1471-2261
• DOI: 10.1186/s12872-020-01514-0

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. We 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. Compared 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). This 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.