The Kynurenine Metabolite 3-Hydroxykynurenine is Associated With Risk of Heart Failure in Patients With Predominantly Stable Coronary Artery Disease.

Background: Inflammation and immune activation contribute to the development and progression of heart failure (HF). The kynurenine pathway, linking tryptophan metabolism to inflammation, oxidative stress, and cell death by way of its metabolites (kynurenines), has not been studied as a pathway associated with risk for incident HF. Aims: To investigate whether kynurenine metabolites are associated with incident HF in patients with predominantly stable coronary artery disease. Methods: Serum kynurenine metabolites were quantified in 3841 patients who underwent elective coronary angiography for evaluation of chest pain. Fasting was not routine. Patients with established HF at baseline were excluded. The hazard for incident HF was estimated using Cox regression, adjusted for age, gender, current smoking, diabetes, hypertension, previous myocardial infarction, body mass index, glomerular filtration rate, troponin T, left ventricular ejection fraction, and resting heart rate. Results: During follow-up, 221 participants developed HF. Higher serum concentrations of 3-hydroxykynurenine (HK) were associated with increased HF risk (adjusted HR 1.31, 95% CI 1.07-1.46, Conclusion: Higher plasma HK was independently associated with incident HF in patients with predominantly stable coronary artery disease. These findings support a possible link between kynurenine pathway activity and future HF risk, but the underlying mechanisms and clinical implications remain to be established.