Prognostic value of tryptophan catabolism-base scores in acute myocardial infarction patients

(A) Forest plot for association between Trp metabolites and incident MACE. Adjusted for Trp, Kyn, IPA and ILA. 4071 patients with AMI were admitted into the hospital, and 1044 of them went outpatient follow-up. (B) Forest plot for association between Trp metabolites and MACE, adjusted for Trp, Kyn, IPA and ILA. (C) Associations between TMC scores and outcomes. (D) Comparison between two TMC score regression coefficients. • The TMC score was developed to investigate Tryptophan catabolism dysfunction in an AMI cohort. • The TMC score was significantly associated with all-cause mortality, cardiovascular mortality, and incident HF. • The TMC score improved risk stratification beyond established clinical risk factors. 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). 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. 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.