Plasma Kynurenine Predicts Severity and Complications of Heart Failure and Associates with Established Biochemical and Clinical Markers of Disease

• Main Authors: Thomas Bernd Dschietzig (Author), Karl-Heinz Kellner (Author), Katrin Sasse (Author), Felix Boschann (Author), Robert Klüsener (Author), Jana Ruppert (Author), Franz Paul Armbruster (Author), Dragic Bankovic (Author), Andreas Meinitzer (Author), Veselin Mitrovic (Author), Christoph Melzer (Author)
• Format: Book
• Published: Karger Publishers, 2019-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Background: Kynurenine, a metabolite of the L-tryptophan pathway, plays a pivotal role in neuro-inflammation, cancer immunology, and cardiovascular inflammation, and has been shown to predict cardiovascular events. Objectives: It was our objective to increase the body of data regarding the value of kynurenine as a biomarker in chronic heart failure (CHF). Methods: We investigated the predictive value of plasma kynurenine in a CHF cohort (CHF, n = 114); in a second cohort of defibrillator carriers with CHF (AICD, n = 156), we determined clinical and biochemical determinants of the marker which was measured by enzyme immunoassay. Results: In the CHF cohort, both kynurenine and NT-proBNP increased with NYHA class. Univariate binary logistic regression showed kynurenine to predict death within a 6-month follow-up (OR 1.43, 95% CI 1.03-2.00, p = 0.033) whereas NT-proBNP did not contribute significantly. Kynurenine, like NT-proBNP, was able to discriminate at a 30% threshold of left ventricular ejection fraction (LVEF; AUC-ROC, both 0.74). Kynurenine correlated inversely with LVEF (ϱ = -0.394), glomerular filtration fraction (GFR; ϱ = -0.615), and peak VO2 (ϱ = -0.626). Moreover, there was a strong correlation of kynurenine with NT-proBNP (ϱ = 0.615). In the AICD cohort, multiple linear regression analysis demonstrated highly significant associations of kynurenine with GFR, hsCRP, and tryptophan, as well as a significant impact of age. Conclusions: This work speaks in favor of kynurenine being a new and valuable biomarker of CHF, with particular attention placed on its ability to predict mortality and reflect exercise capacity.

Item Description

1420-4096
1423-0143
10.1159/000501483