Plasma kynurenines and prognosis in patients with heart failure


Autoři: Anders Lund aff001;  Jan Erik Nordrehaug aff001;  Grete Slettom aff001;  Stein-Erik Hafstad Solvang aff001;  Eva Kristine Ringdal Pedersen aff001;  Øivind Midttun aff005;  Arve Ulvik aff005;  Per Magne Ueland aff001;  Ottar Nygård aff001;  Lasse Melvaer Giil aff001
Působiště autorů: Department of Clinical Science, University of Bergen, Bergen, Norway aff001;  Department of Cardiology, Stavanger University Hospital, Stavanger, Norway aff002;  Department of Heart Disease, Haukeland University Hospital, Bergen, Norway aff003;  Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway aff004;  Bevital AS, Bergen, Norway aff005;  Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway aff006
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227365

Souhrn

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.

Klíčová slova:

Angiography – Coronary heart disease – Death rates – Diabetes mellitus – Heart failure – Metabolites – Myocardial infarction – Tryptophan


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