Metabolomic correlates of coronary atherosclerosis, cardiovascular risk, both or neither. Results of the 2 × 2 phenotypic CAPIRE study

on behalf of the CAPIRE Investigators

Research output: Contribution to journalArticlepeer-review


Background: Traditional cardiovascular risk factors (RFs) and coronary artery disease (CAD) do not always run parallel. We investigated functional-metabolic correlations of CAD, RFs, or neither in the CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation) 2 × 2 phenotypic observational study. Methods: Two hundred and fortyone subjects were included based on RF burden, presence/absence of CAD (assessed by computed tomography angiography), age and sex. Participants displayed one of four phenotypes: CAD with ≥3 RFs, no-CAD with ≥3 RFs, CAD with ≤1 RF and no-CAD with ≤1 RF. Metabolites were identified by gas chromatography–mass spectrometry and pathways by metabolite set enrichment analysis. Results: Characteristic patterns and specific pathways emerged for each phenotypic group: amino sugars for CAD/high-RF; urea cycle for no-CAD/high-RF; glutathione for CAD/low-RF; glycine and serine for no-CAD/low-RF. Presence of CAD correlated with ammonia recycling; absence of CAD with the transfer of acetyl groups into mitochondria; high-risk profile with alanine metabolism (all p < 0.05). The comparative case-control analyses showed a statistically significant difference for the two pathways of phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism in the CAD/Low-RF vs NoCAD/Low-RF comparison. Conclusions: The present 2 × 2 observational study identified specific metabolic pathways for each of the four phenotypes, providing novel functional insights, particularly on CAD with low RF profiles and on the absence of CAD despite high-risk factor profiles.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalInternational Journal of Cardiology
Publication statusPublished - Aug 1 2021


  • Cardiovascular risk factors
  • Coronary atherosclerosis
  • Gas chromatography–mass spectrometry
  • Metabolomics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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