Table S10 Widely-targeted metabolomic and lipidomic dataset used in the formal analysis.xlsx

<b>Background</b>Systemic immune inflammation is a key mediator in the progression coronary artery disease (CAD), concerning various metabolic and lipid changes. In this study, the relationship between the inflammatory index and metabolic profiling in patients with CAD was investigated to provide deep insights into metabolic disturbances related to inflammation.<b>Methods</b>Widely targeted plasma metabolomic and lipidomic profiling was performed in 1,234 patients with CAD. Laboratory circulating inflammatory markers were mainly used to define general systemic immune and low-grade inflammatory states. Multivariable-adjusted linear regression was adopted to assess the associations between 860 metabolites and 7 inflammatory markers. Least absolute shrinkage and selection operator (LASSO) logistic-based classifiers and multivariable logistic regression were applied to identify biomarkers of inflammatory states and develop models for discriminating an advanced inflammatory state.<b>Results</b>Multiple metabolites and lipid species were linearly associated with the seven inflammatory markers (<i>FDR</i>&lt;0.05). LASSO and multivariable-adjusted logistic regression analysis identified significant associations between 45 metabolites and systemic immune-inflammation index, 46 metabolites and neutrophil-lymphocyte ratio states, 32 metabolites and low-grade inflammation score, and 26 metabolites and high-sensitivity C-reactive protein states (<i>P</i>&lt;0.05). Glycerophospholipid metabolism and arginine and proline metabolism were determined as key altered metabolic pathways for systemic immune and low-grade inflammatory states. Predictive models based solely on metabolite combinations showed feasibility (AUC: 0.81 to 0.88) for discriminating the four parameters that represent inflammatory states and were successfully validated using a validation cohort. The inflammation-associated metabolite, namely, β-pseudouridine was related to carotid and coronary arteriosclerosis indicators (<i>P</i> &lt;0.05).<b>Conclusions</b>This study provides further information on the relationship between plasma metabolite profiles and inflammatory states represented by various inflammatory markers in CAD. These metabolic markers provide potential insights into pathological changes during CAD progression and may aid in the development of therapeutic targets.