Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
Heart Failure
Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure ― Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) ―
Masaaki KonishiNicole EbnerJochen SpringerJoerg C. SchefoldWolfram DoehnerThomas Bernd DschietzigStefan D. AnkerStephan von Haehling
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2017 Volume 81 Issue 1 Pages 52-61


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.

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