Identification of a plasma metabolomic signature of thrombotic myocardial infarction that is distinct from non-thrombotic myocardial infarction and stable coronary artery disease

AIMS: Current non-invasive diagnostics for acute myocardial infarction (MI) identify myocardial necrosis rather than the primary cause and therapeutic target—plaque disruption and resultant thrombosis. The aim of this study was to identify changes specific to plaque disruption and pathological thrombosis that are distinct from acute myocardial necrosis. METHODS AND RESULTS: We quantified 1,032 plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic MI, and 15 stable coronary artery disease (CAD) subjects at two acute phase (time of catheterization [T0], six hours [T6]) and one quiescent (>3 months follow-up) time points. A statistical classifier was constructed utilizing baseline (T0) abundances of a parsimonious set of 17 qualifying metabolites. Qualifying metabolites were those that demonstrated a significant change between the quiescent phase and the acute phase and that were distinct from any change seen in non-thrombotic MI or stable CAD subjects. Classifier performance as estimated by 10-fold cross-validation was suggestive of high sensitivity and specificity for differentiating thrombotic from non-thrombotic MI and stable CAD subjects at presentation. Nineteen metabolites demonstrated an intra-subject change from time of acute thrombotic MI presentation to the quiescent state that was distinct from any change measured in both the non-thrombotic MI and stable CAD subjects undergoing cardiac catheterization over the same time course (false discovery rate <5%). CONCLUSIONS: We have identified a candidate metabolic signature that differentiates acute thrombotic MI from quiescent state after MI, from acute non-thrombotic MI, and from stable CAD. Further validation of these metabolites is warranted given their potential as diagnostic biomarkers and novel therapeutic targets for the prevention or treatment of acute MI.