Abstract
BackgroundSystemic immune inflammation is a key mediator in the progression of coronary artery disease (CAD), concerning various metabolic and lipid changes. In this study, the relationship between the inflammatory index and metabolic profile in patients with CAD was investigated to provide deep insights into metabolic disturbances related to inflammation.MethodsWidely 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.ResultsMultiple metabolites and lipid species were linearly associated with the seven inflammatory markers [false discovery rate (FDR) <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 (P < 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 (area under the curve: 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 (P < 0.05).ConclusionsThis 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.
Highlights
Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide [1], and its common underlying pathology is atherosclerosis
Compared with chronic inflammatory markers, systemic immune-inflammatory indices were more important for increased atherosclerosis risk
The results revealed 45 and 46 metabolites significantly associated with general systemic immuneinflammation index (SII) and neutrophil–lymphocyte ratio (NLR) states, and 32 and 26 metabolites were significantly associated with chronic INFLA and hs-CRP states, A
Summary
Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide [1], and its common underlying pathology is atherosclerosis. Numerous circulating inflammatory markers have been proposed, including high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen (FIB), which are important for increased risks in patients with CAD [4, 5]. Their elevated levels indicate chronic low-grade inflammation, which, in turn, is associated with many metabolic disturbances [6] and aggravates atherogenesis [7]. CRP and FIB are acute-phase reactants induced by inflammatory cytokines and exert proinflammatory effects on the vascular endothelium to promote thrombotic states [8, 9] Another accessible inflammatory marker, WBC, is an independent predictor of hospitalization for heart failure, acute myocardial infarction, and all-cause death in patients with CAD [10]. The relationship between the inflammatory index and metabolic profile in patients with CAD was investigated to provide deep insights into metabolic disturbances related to inflammation
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