Kynurenic Acid Is a Predictive Prognostic Metabolic Marker in ST‐Elevation Myocardial Infarction

<b>Background:</b> The tryptophan/kynurenic acid (KYNA) pathway plays a crucial role by modulating inflammation, oxidative stress, and immune activation. The clinical value of tryptophan metabolites in the KYNA pathway for the early diagnosis and prognosis of STEMI patients, as well as the underlying functional mechanisms, remains to be elucidated. <b>Objectives:</b> This study evaluated the prognostic value of KYNA, a metabolite of the tryptophan pathway, in STEMI patients. <b>Methods:</b> Untargeted metabolomics by ¹H-nuclear magnetic resonance (NMR) analysis was used to examine metabolite changes between 50 control subjects and 50 STEMI patients with an onset time of < 3 h. Furthermore, targeted metabolomic analysis was employed to investigate the association between KYNA and the prognosis of STEMI patients by LC-Q-TOF MS analysis. <b>Results:</b> Fifteen differential metabolites were identified between STEMI patients and control subjects by ¹H-NMR analysis. KYNA as an important metabolite upregulated obviously in the tryptophan pathway was 337.67 nmol/L in STEMI patients (interquartile range: 241.16-500.29 nmol/L). In addition, KYNA was significantly associated with major adverse cardiovascular events (MACEs) (HR: 5.95, 95% CI: 2.03-17.44; <i>p</i> = 0.0012) and all-cause mortality (HR: 7.11, 95% CI: 1.52-33.29; <i>p</i> = 0.013) and showed moderate predictive value for 12-month MACE (area under the curve (AUC) = 0.72, 95% CI: 0.65-0.80) and all-cause mortality (AUC = 0.74, 95% CI: 0.65-0.83). KAT1 expression was upregulated in infiltrating macrophages of thrombus tissue coming from the culprit coronary artery of STEMI patients. KAT1 upregulation was also observed in macrophages located within the peri-infarct myocardium. <b>Conclusions:</b> The KYNA level may correspond to the underlying status of acute myocardial infarction and is a promising biomarker for predicting STEMI progression.