Clin Chem. 2026 Oct 15:hvag129. doi: 10.1093/clinchem/hvag129. Online ahead of print.
ABSTRACT
BACKGROUND: Glycoprotein acetylation (GlycA) is a nuclear magnetic resonance-derived biomarker of systemic inflammation. GlycA shows statistical interaction with small HDL particle number (s-HDL-P) in relation to coronary artery disease (CAD). This study examines the confounding effects of GlycA-related glycoproteins, hypertriglyceridemia, and s-HDL-P on CAD risk.
METHODS: Plasma samples from 752 participants in the CATHGEN biorepository were size-fractionated by asymmetric flow field-flow fractionation and analyzed by targeted proteomics and lipidomics. Fraction concentrations were converted to HDL particle number using a volumetric approach based on apolipoprotein A-I (APOA1) concentration, HDL size, and lipoprotein lipid composition. Correlations between GlycA, glycoproteins, total triglyceride (TG), HDL composition and HDL particle number, and their associations with CAD were assessed using multivariate least-squares fit and nominal logistic regression analysis, respectively.
RESULTS: Acute-phase inflammation-related glycoproteins (GlycA-proteins) correlated strongly with GlycA. However, the size-distribution profiles of GlycA-proteins were consistent with circulation as free dimers/trimers, and their lack of overlap with APOA1 profiles suggested no detectable HDL binding. In contrast, apolipoproteins and lipid transfer proteins showed size-profile shifts relative to APOA1 consistent with HDL binding. s-HDL-P showed an inverse association with GlycA, most significantly at low TG levels. In CAD models, significant GlycA × s-HDL-P interaction emerged only when TG was included as a covariate. CAD correlated with lipoprotein lipids, apolipoproteins, and lipid transfer proteins that influence lipoprotein remodeling.
CONCLUSIONS: GlycA-proteins circulate freely without direct HDL binding. The empirical GlycA × s-HDL-P interaction is consistent with indirect coupling between systemic inflammation and altered lipoprotein remodeling associated with CAD risk.
PMID:42879436 | DOI:10.1093/clinchem/hvag129