Plasma kynurenines and prognosis in patients with heart failure.

Autor: Lund A; Department of Clinical Science, University of Bergen, Bergen, Norway., Nordrehaug JE; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Cardiology, Stavanger University Hospital, Stavanger, Norway., Slettom G; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway., Solvang SH; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway., Pedersen EK; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway., Midttun Ø; Bevital AS, Bergen, Norway., Ulvik A; Bevital AS, Bergen, Norway., Ueland PM; Department of Clinical Science, University of Bergen, Bergen, Norway.; Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway., Nygård O; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway., Giil LM; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Jan 10; Vol. 15 (1), pp. e0227365. Date of Electronic Publication: 2020 Jan 10 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0227365
Abstrakt: 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.
Competing Interests: One or more of the authors are employed by a commercial company, Bevital AS. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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