Threonine in Coronary Artery Disease: Insights From Metabolic Syndrome Amino Acid Profiling

Background:Metabolic syndrome (MeS) amplifies cardiovascular risk, but molecular markers that distinguish between MeS and coronary artery disease (CAD) remain limited.The aim of this study was to determine whether targeted amino acid profiling can identify CAD-specific signals independent of MeS and suggest translational biomarkers for risk stratification. Material/Methods:In a prospective single-center cohort, we quantified 48 serum amino acids by liquid chromatography-tandem mass spectrometry in 65 fasting adults undergoing planned evaluation for chronic coronary syndrome.Quality control comprised blanks, reference sera, internal standards, and retention-time monitoring.Coronary artery disease was adjudicated angiographically in a reference hemodynamic center.Participants were grouped by metabolic syndrome (n=25) versus controls (n=40) and further stratified by CAD status.Group differences were assessed nonparametrically (2-sided a=0.05). Results:The MeS group exhibited a distinct signature versus controls, with lower histidine, ethanolamine, and tryptophan, and higher cystine and proline (all P0.03).The CAD prevalence was 60% in MeS versus 35% in controls (P=0.051).Across MeS strata, threonine was associated most robustly with CAD: concentrations were higher in angiography-confirmed CAD irrespective of MeS, with significant pairwise differences among noMeS+noCAD, MeS+noCAD, noMeS+CAD, and MeS+CAD groups (P=0.03-0.048).Other MeS-linked amino acids were not consistently associated with CAD.Multivariable adjustment was not performed due to the limited sample size. Conclusions:Targeted amino-acid profiling revealed redox-and immune-linked perturbations in MeS and identified threonine as a potential exploratory signal of CAD independent of MeS in our exploratory, limited-sample-size study.If validated, threonine may refine CAD risk stratification beyond traditional risk factors and MeS-related metabolic changes and inform mechanistic studies of amino-acid metabolism in atherogenesis.