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

Abstract

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.

Plasma kynurenines and prognosis in patients with heart failure

“…Kyn levels in our study were higher in heart failure compared to both control groups. This is in line with previous findings [10]. Adding to prior studies, we found higher HK and QA, and the ratios KTR and HK/XA were also elevated in patients with heart failure.…”

“…The levels of the metabolite Kyn were increased in heart failure compared to controls [10]. In the same study, Kyn was associated with increased mortality, but other mKP were not measured [10]. CAD is frequent in patients with heart failure, and mKP have been hypothesized as a driver of CAD itself [8].…”

“…In patients with stable angina pectoris and coronary artery disease (CAD), mKP predicted incident myocardial infarction [9]. The levels of the metabolite Kyn were increased in heart failure compared to controls [10]. In the same study, Kyn was associated with increased mortality, but other mKP were not measured [10].…”

Metabolomic profiling of patients with high gradient aortic stenosis undergoing transcatheter aortic valve replacement

“…One of the most significantly altered metabolites in this group is kynurenine, a metabolite of the L-tryptophan pathway. Kynurenine has been recently reported to be significantly elevated in patients with coronary artery disease [43] and was suggested to predict cardiovascular prognosis [44]. We demonstrate a strong correlation between kynurenine and GFR and creatinine pre-TAVR as well as between kynurenine and GFR and BNP post-TAVR and, therefore, assume that kynurenine levels are a good indicator not only in AS but also in cardiovascular diseases.…”

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

“…All these results indicate that early activation of KP after cardiac arrest is an independent predictor of survival [99]. Patients with heart failure have higher plasma Kyn level [100]. High incidence of heart calcification on the endometrium proximal to the right ventricle was reported in female IDO-deficient BALB/c mice [101].…”