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

• Published in: PloS one 2017-04, Vol.12 (4), p.e0175591-e0175591
• Main Authors: DeFilippis, Andrew P, Trainor, Patrick J, Hill, Bradford G, Amraotkar, Alok R, Rai, Shesh N, Hirsch, Glenn A, Rouchka, Eric C, Bhatnagar, Aruni
• Format: Article
• Language: English
• Subjects: Anticoagulants; Bioindicators; Bioinformatics; Biology and Life Sciences; Blood platelets; Cardiac Catheterization - methods; Cardiology; Cardiovascular disease; Care and treatment; Catheterization; Coronary artery; Coronary Artery Disease - blood; Coronary Artery Disease - metabolism; Coronary vessels; Diabetes; Female; Gangrene; Health aspects; Health risk assessment; Heart attack; Heart attacks; Heart diseases; Hormones; Humans; Ischemia; Male; Mass spectrometry; Mass spectroscopy; Medicine; Medicine and Health Sciences; Metabolites; Metabolomics; Metabolomics - methods; Middle Aged; Myocardial infarction; Myocardial Infarction - blood; Myocardial Infarction - metabolism; Myocardium - metabolism; Necrosis; Obesity; Pain; Patient outcomes; Plasma - metabolism; Risk factors; Thromboembolism; Thrombosis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0175591

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. 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