Untargeted high-resolution plasma metabolomic profiling predicts outcomes in patients with coronary artery disease

• DOI: 10.1371/journal.pone.0237579
• Publication Date: 2020-08-18T17:50:55Z
• Authors: Anurag Mehta; Chang Liu; Aditi Nayak; Ayman S. Tahhan; Yi-An Ko; Devinder S. Dhindsa; Jeong Hwan Kim; Salim S. Hayek; Laurence S. Sperling; Puja K. Mehta; Yan V. Sun; Karan Uppal; Dean P. Jones; Arshed A. Quyyumi
• Keywords: Metabolome; Profiling (computer programming)

Patients with CAD have substantial residual risk of mortality, and whether hitherto unknown small-molecule metabolites metabolic pathways contribute to this is unclear. We sought determine the predictive value plasma metabolomic profiling in patients CAD.Untargeted high-resolution subjects undergoing coronary angiography was performed using liquid chromatography/mass spectrometry. Metabolic features associated mortality were identified 454 metabolome-wide association studies Mummichog, respectively, validated 322 subjects. A score comprising log-transformed HR estimates that passed LASSO regression created its performance validated. In 776 (66.8 years, 64% male, 17% Black), 433 357 (FDR-adjusted q<0.20); clustered into 21 9 first second cohorts, respectively. Six (urea cycle/amino group, tryptophan, aspartate/asparagine, lysine, tyrosine, carnitine shuttle) common. 7 independently predicted cohort (HR per 1-unit increase 2.14, 95%CI 1.62, 2.83). Adding a model clinical predictors improved discrimination (delta C-statistic 0.039, -0.006, 0.086; Integrated Discrimination Index 0.084, 0.030, 0.151) reclassification (continuous Net Reclassification 23.3%, 7.9%, 38.2%).Differential regulation six involved myocardial energetics systemic inflammation CAD. novel consisting representative highly mortality.