Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure　― Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF)

• Published in: Circulation Journal Vol. 81; no. 1; pp. 52 - 61
• Main Authors: Konishi, Masaaki, Ebner, Nicole, Springer, Jochen, Schefold, Joerg C., Doehner, Wolfram, Dschietzig, Thomas Bernd, Anker, Stefan D., Haehling, Stephan von
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 01-01-2017
• Subjects: Age Factors; Aged; Body Mass Index; Disease-Free Survival; Exercise; Female; Heart failure; Heart Failure - blood; Heart Failure - mortality; Humans; Kidney - metabolism; Kynurenine; Kynurenine - blood; Liver - metabolism; Male; Middle Aged; Risk Factors; Sex Factors; Skeletal muscle; Survival Rate
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.CJ-16-0791

Background:Kynurenine is a circulating metabolite from the essential amino acid tryptophan. Accelerated degradation of kynurenine in skeletal muscle has been reported to provide an anti-inflammatory effect. The aim of this study was to investigate the association between blood kynurenine and muscle mass/function in patients with heart failure (HF), in whom diseased muscle mass/function plays a pathophysiological role.Methods and Results:Plasma kynurenine was assessed in 249 patients with HF (67±11 years, 21% women) and in 45 controls from the SICA-HF study. Kynurenine was higher in 173 HF patients with reduced ejection fraction (EF) and in 76 patients with preserved EF than controls (3.5±1.5, 3.4±1.3, and 2.4±1.1 μmol/L, P<0.001). In HF patients, kynurenine had an inverse association with handgrip strength (r=–0.26, P<0.01), peak oxygen consumption (r=–0.29, P<0.01), 6-min walk distance (r=–0.23, P<0.01), and had a positive association with kidney and liver function parameters. No correlation was observed between kynurenine and lean mass. On multivariable linear regression analysis, a significant association was noted between kynurenine and peak oxygen consumption even after adjustment for age, gender, BMI, and hemoglobin (β=–0.23, P<0.001). Patients with higher kynurenine were at higher risk of death (adjusted HR, 1.46 per 1 μmol/L, P<0.01).Conclusions:In stable HF patients, plasma kynurenine was inversely correlated with muscle strength and functional capacity as well as with liver and kidney function.