Elevated circulating unsaturated fatty acids: A novel metabolic feature of coronary artery disease without traditional risk factors

Coronary artery disease (CAD) remains a major cause of global mortality. While established risk factors are targets of effective preventive interventions, a substantial proportion of CAD patients exhibit no conventional risk factors. To investigate potential metabolomic biomarkers of residual risk in such individuals, we conducted untargeted metabolomic profiling of serum from CAD patients lacking traditional risk factors using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Comparative analysis with non-CAD controls revealed significant alterations in metabolite levels, with 43 metabolites elevated and 46 reduced in CAD patients. Notably, we observed a marked upregulation of circulating unsaturated fatty acids (UFAs) which reflects dysregulated unsaturated fatty acid biosynthesis. Pathway analysis further indicated enrichment in biosynthetic pathways of unsaturated fatty acids, implicating a potential role of dysregulated UFA metabolism in CAD pathogenesis. These altered fatty acids may act as potential biomarkers and residual risk factors for predicting CAD in individuals without conventional risk factors. Collectively, our study identifies elevated circulating UFAs as a novel metabolic signature in this patient subgroup, which may serve as a potential predictive indicator for noninvasive risk stratification and targeted prevention. To our knowledge, this is one of the initial metabolomic studies to identify UFA dysregulation in CAD patients without conventional risk factors, and the clinical utility requires further validation in larger multi-center cohorts.