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

Area of Science:

• Metabolomics
• Cardiovascular Disease Research
• Biochemistry

Background:

• Traditional cardiovascular risk factors (RFs) do not always correlate with coronary artery disease (CAD).
• The CAPIRE study investigated functional-metabolic correlations in diverse patient phenotypes.
• Understanding these discrepancies is crucial for personalized cardiovascular risk assessment.

Purpose of the Study:

• To identify specific metabolic pathways associated with four distinct phenotypes: CAD with high/low RFs and no-CAD with high/low RFs.
• To explore functional-metabolic correlations in coronary atherosclerosis.
• To uncover novel risk factors and protective mechanisms in cardiovascular disease.

Main Methods:

• Phenotypic classification of 241 subjects into four groups based on CAD presence/absence and RF burden (≥3 RFs vs ≤1 RF).
• Metabolite profiling using gas chromatography-mass spectrometry.
• Metabolite set enrichment analysis to identify associated pathways.

Main Results:

• Distinct metabolic pathways were identified for each phenotype: amino sugars (CAD/high-RF), urea cycle (no-CAD/high-RF), glutathione (CAD/low-RF), and glycine/serine (no-CAD/low-RF).
• CAD presence correlated with ammonia recycling; absence of CAD with mitochondrial acetyl group transfer.
• Significant differences in phenylalanine metabolism pathways were observed between CAD/low-RF and no-CAD/low-RF groups.

Conclusions:

• Specific metabolic pathways are uniquely associated with different combinations of CAD and RF profiles.
• Novel functional insights were gained, particularly for low-RF CAD and asymptomatic high-risk individuals.
• These findings highlight the complex interplay between metabolism and cardiovascular disease, suggesting new avenues for research and potential therapeutic targets.