High-resolution metabolomics study revealing l-homocysteine sulfinic acid, cysteic acid, and carnitine as novel biomarkers for high acute myocardial infarction risk

BACKGROUND: Identifying changes in serum metabolites before the occurrence of acute myocardial infarction (AMI) is an important approach for finding novel biomarkers of AMI. METHODS: In this prospective cohort study, serum samples obtained from patients at risk of AMI (n = 112) and non-risk controls (n = 89) were tested using high-resolution metabolomics (HRM). Partial least-squares discriminant analysis (PLS-DA), along with univariate analysis using a false discovery rate (FDR) of q = 0.05 were performed to discriminate metabolic profiles and to determine significantly different metabolites between healthy control and AMI risk groups. RESULTS: PLS-DA significantly separated the AMI risk sera from control sera. The metabolites associated with amino acid biosynthesis, 2-oxocarboxylic acid, tryptophan, and amino sugar and nucleotide sugar metabolism pathways were mainly elevated in patients at risk of AMI. Further validation and quantification by MS/MS showed that tryptophan, carnitine, L-homocysteine sulfinic acid (L-HCSA), and cysteic acid (CA) were upregulated, while L-cysteine and L-cysteine sulfinic acid (L-CSA) were downregulated, specifically among AMI risk sera. Additionally, these discriminant metabolic profiles were not related to hypertension, smoking or alcoholism. CONCLUSION: In conclusion, detecting upregulated L-HCSA and CA along with carnitine among patients at risk for AMI could serve as promising non-invasive biomarkers for early AMI detection.restrictio