About this item:

60 Views | 102 Downloads

Author Notes:

aquyyum@emory.edu

The authors would like to acknowledge the Emory Cardiovascular Biobank participants and study coordinators.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This study was funded by the National Heart, Lung, and Blood Institute grant 1P20HL113451-01.

A.M., A.S.T., D.S.D., and J.H.K. have been supported by the Abraham J. & Phyllis Katz Foundation.

A.M. is supported by American Heart Association grant 19POST34400057.

A.Q. is supported by NIH grants 1R61HL138657-02, 1P30DK111024-03S1, 5R01HL095479-08, 3RF1AG051633-01S2, 5R01AG042127-06, 2P01HL086773-08, U54AG062334-01, 1R01HL141205-01, 5P01HL101398-02, 1P20HL113451-01, 5P01HL086773-09 1RF1AG051633-01, R01 NS064162-01, R01 HL89650-01, HL095479-01, 1DP3DK094346-01, 2P01HL086773, and American Heart Association grant 15SFCRN23910003.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • ATHEROTHROMBOTIC RISK STRATIFICATION
  • ISCHEMIC-HEART-DISEASE
  • AMINO-ACID-METABOLISM
  • T-CELL PROLIFERATION
  • C-REACTIVE PROTEIN
  • MASS-SPECTROMETRY
  • MYOCARDIAL-INFARCTION
  • DENDRITIC CELLS
  • TRYPTOPHAN
  • INHIBITION

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

Show all authors Show less authors

Journal Title:

PLOS ONE

Volume:

Volume 15, Number 8

Publisher:

, Pages e0237579-e0237579

Type of Work:

Article | Final Publisher PDF

Abstract:

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

Copyright information:

© 2020 Mehta et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote