Preoperative plasma biomarkers associated with atrial fibrillation after coronary artery bypass surgery

J Thorac Cardiovasc Surg. 2021 Sep;162(3):851-863.e3. doi: 10.1016/j.jtcvs.2020.01.079. Epub 2020 Feb 19.

Abstract

Objectives: Postoperative atrial fibrillation (POAF) is a common complication in coronary artery bypass grafting (CABG) procedures. This prospective study aimed to investigate predisposition of proteins and metabolites correlated to POAF after CABG and related cellular pathways.

Methods: Preoperative plasma samples from patients undergoing CABG procedures were prospectively collected. After CABG, the patients were grouped to POAF or sinus rhythm (N = 170; n = 90 in the discovery set and n = 80 in the validation set). The plasma samples were analyzed using proteomics, metabolomics, and bioinformatics to identify the differential proteins and differential metabolites. The correlation between differential proteins and POAF was also investigated by multivariable regression analysis and receiver operator characteristic analysis.

Results: In the POAF(+) group, 29 differential proteins and 61 differential metabolites were identified compared with the POAF(-) group. The analysis of integrated omics revealed that preoperative alteration of peroxisome proliferators-activated receptor α and glutathione metabolism pathways increased the susceptibility of POAF after CABG. There was a correlation between plasma levels of apolipoprotein-C3, phospholipid transfer protein, glutathione peroxidase 3, cholesteryl ester transfer protein, and POAF.

Conclusions: The present study for first time at multi-omics levels explored the mechanism of POAF and validated the results in a new cohort of patients, suggesting preexisting differential proteins and differential metabolites in the plasma of patients prone to POAF after CABG. Dysregulation of peroxisome proliferators-activated receptor α and glutathione metabolism pathways related to metabolic remodeling and redox imbalance-associated electrical remodeling may play a key role in the pathogenesis of POAF. Lower plasma phospholipid transfer protein, apolipoprotein-C3, higher cholesteryl ester transfer protein and glutathione peroxidase 3 levels are linked with POAF. These proteins/metabolites may be developed as biomarkers to predict POAF.

Keywords: atrial fibrillation; coronary artery bypass grafting; coronary artery disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Apolipoprotein C-III / blood
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / etiology*
  • Biomarkers / blood
  • Cholesterol Ester Transfer Proteins / blood
  • Chromatography, High Pressure Liquid
  • Chromatography, Reverse-Phase
  • Coronary Artery Bypass / adverse effects*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / surgery*
  • Enzyme-Linked Immunosorbent Assay
  • Glutathione Peroxidase / blood
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Phospholipid Transfer Proteins / blood
  • Predictive Value of Tests
  • Preoperative Period
  • Prospective Studies
  • Proteome*
  • Proteomics*
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

Substances

  • APOC3 protein, human
  • Apolipoprotein C-III
  • Biomarkers
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • PLTP protein, human
  • Phospholipid Transfer Proteins
  • Proteome
  • GPX3 protein, human
  • Glutathione Peroxidase