Prognostic value of liver damage assessed by direct bilirubin and skeletal muscle weakness in patients with heart failure

Abstract

Abstract Background Patients with heart failure (HF) have a high prevalence of liver function abnormalities such as bilirubin abnormalities. However, the relationship between abnormalities of direct bilirubin (DB), a fraction of total bilirubin, and dynapenia are unclear, and the effect of the coexistence of both on the prognosis of patients with HF remains unclear. Purpose This study investigated the association between total/direct bilirubin and dynapenia, a muscle weakness syndrome. Moreover, we considered the effect of the combination of high DB and dynapenia on increased mortality. Methods In this retrospective cohort study, we reviewed patients with HF for whom we assessed total bilirubin, DB, handgrip strength, and leg strength at discharge, which were further evaluated to determine the presence of dynapenia. Dynapenia was defined by the lower handgrip strength and leg strength. Low handgrip strength was defined as <26 kg for males and <18 kg for females, and low leg strength assessed by the maximal quadriceps isometric strength was defined as <45% body mass (%BM) for males and <35% BM for females. Multiple linear and multivariate logistic regression analyses were used to examine the association between DB with muscle weakness and dynapenia. In addition, we examined the prognostic value of comorbid DB abnormalities (≥0.5) and dynapenia. The endpoint was all-cause mortality. Results Among 853 inpatients enrolled, high DB was identified in 147 and dynapenia in 377 (44.2%) patients. Multiple regression analysis showed that high DB was independently associated with decreased grip and leg strengths (grip strength, P=0.027; leg strength, P=0.002). Furthermore, after adjusting for covariates, the high DB group (odds ratio: 1.800, 95% confidence interval [CI]: 1.203–2.695, P=0.004) was significantly associated with dynapenia compared to the low DB group. During the follow-up period, 189 patients died (median, 1.77 years; interquartile range, 0.64–3.81 years). The risk of death was significantly higher in the high DB/dynapenia group than in the low DB group, even after adjusting for the severity of HF (hazard ratio: 2.610, 95% CI: 1.680–4.051, P<0.001). Conclusions High DB is associated with muscle weakness in patients with HF and affects patient prognosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was partially supported by JSPS KAKENHI.