Plasma kynurenines and prognosis in patients with heart failure

Abstract

Background Metabolites of the kynurenine pathway (mKP) relate to important aspects of heart failure pathophysiology, such as inflammation, energy-homeostasis, apoptosis, and oxidative stress. We aimed to investigate whether mKP predict mortality in patients with heart failure. Methods The study included 202 patients with heart failure (73.8% with coronary artery disease (CAD)), propensity score matched to 384 controls without heart disease, and 807 controls with CAD (71%). All underwent coronary angiography and ventriculography at baseline. Plasma mKP, pyridoxal 5'phosphate (PLP) and CRP were measured at baseline. Case-control differences were assessed by logistic regression and survival by Cox regression, adjusted for age, gender, smoking, diabetes, ejection fraction, PLP, eGFR and CRP. Effect measures are reported per standard deviation increments. Results Higher plasma levels of kynurenine, 3-hydroxykynurenine (HK), quinolinic acid (QA), the kynurenine-tryptophan-ratio (KTR) and the ratio of HK to xanthurenic acid (HK/XA) were detected in heart failure compared to both control groups. The mortality rate per 1000 person-years was 55.5 in patients with heart failure, 14.6 in controls without heart disease and 22.2 in CAD controls. QA [HR 1.80, p = 0.013], HK [HR 1.77, p = 0.005], HK/XA [HR 1.67, p < 0.001] and KTR [HR 1.55, p = 0.009] were associated with increased mortality in patients with heart failure, while XA [HR 0.68-0.80, p = 0.013-0.037] were associated with lower mortality in all groups. HK and HK/XA had weak associations with increased mortality in CAD-controls.

HPLC‐QTOF/MS‐based metabolomics to explore the molecular mechanisms of Yiqi Fumai Lyophilized Injection in heart failure mice

“…In addition, the levels of quinolinic acid, uric acid, and creatine were significantly reduced by YQFM in comparison with CHF model group mice. Quinolinic acid is one of the metabolites of the kynurenine pathway related to essential aspects of heart failure and increased levels of quinolinic acid have been shown to be correlated with heart failure [35]. Uric acid, the endproduct of purine metabolismis, is considered as an independent risk factor for congestive heart failure [36].…”

Indoleamine 2,3 dioxygenase (IDO) level as a marker for significant coronary artery disease

“…We also excluded non-cardiac cause that known to elevated inflammatory biomarkers. Our study protocol was written in 2016 before the information of elevated IDO activity in heart failure setting [ 22 , 23 ] and metabolic syndrome setting [ 24 ]. We included 66 patients with heart failure and 134 patients with diabetes mellitus to our study.…”

Physical Exercise as Kynurenine Pathway Modulator in Chronic Diseases: Implications for Immune and Energy Homeostasis

“…However, solely the preclinical animal model by Agudelo et al 22 provided substantial evidence indicating that exercise-induced KYN pathway modulations can directly impact chronic diseases. As KYN pathway metabolites and ratios represent prognostic or progression biomarkers in many different chronic diseases, [65][66][67] exercise-induced KYN pathway modulations may represent a global underlying mechanism that, at least in part, is involved in the well-described benefits of exercise in a broad range of medical conditions. 64…”