Abstract
AIMS: Tryptophan catabolism is implicated in the progression of cardiovascular disease. We sought to investigate the prognostic value of tryptophan catabolism-related features in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: A prospective cohort of 4071 patients (mean age: 60.7 years; 69.1 % men) with AMI between February 2017 and June 2019 was included and followed up for a median of 5.6 years (IQR 5.1-6.2). There were 666 all-cause deaths, 365 cardiovascular deaths, and 559 HF events. Plasma levels of tryptophan-related metabolites were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS), and were repeatedly determined in 1044 patients after discharge. Tryptophan, kynurenine, indole-3-propionic acid, and indole-3-lactic acid were screened to construct tryptophan metabolites combination (TMC) score using coefficients from predictive models for MACE. Patients were divided into 3 groups by TMC tertiles. Patients with higher TMC score were older, more likely to be male and have hypertension. Compared to those with TMC tertile 1, patients in TMC tertile 3 had significant associations with the risk of all-cause death (HR: 1.90; 95 %CI: 1.54-2.34), cardiovascular death (HR: 2.32; 95 %CI: 1.71-3.15) and incident HF (HR: 1.77; 95 %CI: 1.40-2.24). The incremental prognostic value of TMC score over the Grace score was measured by the likelihood ratio, C-statistic, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) for prediction, discrimination, and reclassification of outcomes. CONCLUSIONS: In this hospital-based AMI cohort, the TMC score was significantly associated with all-cause mortality, cardiovascular mortality, and incident HF, and improved risk stratification beyond established clinical risk factors. The TMC score provided a novel tool for assessment of Trp catabolism dysfunction and outcomes risk.