Myocardial infarction (MI) is one of the leading causes of death worldwide, and knowing the early warning signs of MI is lifesaving. To expand our knowledge of MI, we analyzed plasma metabolites in MI and non-MI
chest pain cases to identify markers for alerting about MI occurrence based on metabolomics. A total of 230 volunteers were recruited, consisting of 146
chest pain patients admitted with suspected MI (85 MIs and 61 non-MI
chest pain cases) and 84 control individuals. Non-MI cardiac
chest pain cases include
unstable angina (UA),
myocarditis,
valvular heart diseases, etc. The blood samples of all suspected MI cases were collected not longer than 6 h since the onset of
chest pain. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry were applied to identify and quantify the plasma metabolites. Multivariate statistical analysis was utilized to analyze the data, and principal component analysis showed MI could be clearly distinguished from non-MI
chest pain cases (including UA and other cases) in the scores plot of metabolomic data, better than that based on the data constructed with medical history and clinical biochemical parameters. Pathway analysis highlighted an upregulated
methionine metabolism and downregulated
arginine biosynthesis in MI cases. Receiver operating characteristic curve (ROC) and adjusted odds ratio (OR) were calculated to evaluate potential markers for the diagnosis and prediction ability of MI (MI vs. non-MI cases). Finally, gene expression profiles from the Gene Expression Omnibus (GEO) database were briefly discussed to study differential metabolites' connection with plasma transcriptomics.
Deoxyuridine (dU),
homoserine, and
methionine scored highly in ROC analysis (AUC > 0.91), sensitivity (>80%), and specificity (>94%), and they were correlated to LDH and AST (p < 0.05). OR values suggested, after adjusting for gender, age,
lipid levels, smoking, type II diabetes, and
hypertension history, that high levels of dU of positive logOR = 3.01,
methionine of logOR = 3.48, and
homoserine of logOR = 1.61 and low levels of
isopentenyl diphosphate (
IDP) of negative logOR = -5.15,
uracil of logOR = -2.38, and
arginine of logOR = -0.82 were independent risk factors of MI. Our study highlighted that metabolites belonging to
pyrimidine,
methionine, and
arginine metabolism are deeply influenced in MI plasma samples. dU,
homoserine, and
methionine are potential markers to recognize MI cases from other cardiac
chest pain cases after the onset of
chest pains. Individuals with high plasma abundance of dU,
homoserine, or
methionine have increased risk of MI, too.