Open AccessPlasma kynurenines and prognosis in patients with heart failure
Author(s) -
Anders Lund,
Jan Erik Nordrehaug,
Grete Slettom,
Stein-Erik Hafstad Solvang,
Eva Kristine Ringdal Pedersen,
Øivind Midttun,
Arve Ulvik,
Per Magne Ueland,
Ottar Nygård,
Lasse Melvær Giil
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0227365
Subject(s) - heart failure , ejection fraction , medicine , cardiology , coronary artery disease , kynurenine , quinolinic acid , myocardial infarction , diabetes mellitus , heart disease , endocrinology , gastroenterology , biology , tryptophan , biochemistry , amino acid
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. Conclusion Elevated plasma levels of mKP and metabolite ratios are associated with increased mortality, independent of CAD, in patients with heart failure.