Linking Lipidomics to Vulnerable Coronary Plaques: A PROSPECT II Substudy

Area of Science:

• Cardiovascular Research
• Metabolomics
• Lipidomics

Background:

• Coronary atherosclerosis involves complex metabolic alterations.
• Understanding vulnerable plaque formation is critical for preventing myocardial infarction.
• Lipidomics offers insights into metabolic changes associated with coronary artery disease.

Purpose of the Study:

• To investigate the association between circulating lipid metabolites and imaging-defined features of vulnerable coronary plaque.
• To identify specific lipid species that correlate with high-risk plaque characteristics.
• To explore potential diagnostic and therapeutic targets for coronary atherosclerosis.

Main Methods:

• 877 patients with myocardial infarction underwent 3-vessel coronary artery imaging (near-infrared spectroscopy and intravascular ultrasound).
• Plasma lipid metabolites (424 species) were quantified using mass spectrometry.
• Associations between lipid metabolites and plaque metrics (lipid core burden index, plaque burden) were analyzed and validated in the SCAPIS cohort.

Main Results:

• 156 significant associations (P<0.05) were found between lipid metabolites and coronary plaque characteristics.
• Sphingomyelins showed an inverse association with all plaque metrics, while 1-palmitoyl-2-oleoyl-GPE (a phosphatidylethanolamine) was positively associated.
• After multiple testing correction, 27 lipid species remained significant, with sphingomyelins demonstrating the strongest inverse association with lipid burden.

Conclusions:

• This study first demonstrates a negative association of sphingomyelins and a positive association of 1-palmitoyl-2-oleoyl-GPE with vulnerable coronary plaque features.
• These findings were validated in an independent cohort using coronary computed tomography angiography.
• The identified lipid associations may pave the way for novel diagnostic markers and therapeutic interventions for coronary atherosclerosis.