Abstract 344: Comparative Metabolomic Profiling of Thrombotic Myocardial Infarction Reveals a Metabolic Signature Distinct From Non-Thrombotic Myocardial Infarction and Stable Coronary Artery Disease in Human Participants

Abstract

Background: 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. Aim: The aim of this study is to identify change specific to plaque disruption and pathological thrombosis. Methods: We quantified 1,032 plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic MI and 15 stable 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 (T0) abundances of a parsimonious set of metabolites that demonstrated a significant change between quiescent phase and the acute phase that was 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. Results: Nineteen metabolites (Table 1) with an intra-subject fold change from time of acute thrombotic MI presentation to the quiescent state were 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 and from acute non-thrombotic MI and 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.