The association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques assessed by near-infrared spectroscopy

Abstract

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Norwegian Health Association The Liaison Committee for education, research and innovation in Central Norway. Background Lipid content in coronary atheromatous plaques, measured by near-infrared spectroscopy (NIRS), can predict the risk of future coronary events. Biomarkers that reflect lipid content in coronary plaques may therefore improve coronary artery disease (CAD) risk assessment, and lipoprotein subfractions could potentially add value beyond traditional lipid measurements. Purpose We aimed to investigate the association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques in statin-treated patients with stable CAD undergoing percutaneous coronary intervention. Methods 56 patients with stable CAD underwent three vessel imaging with NIRS when feasible. The coronary artery segment with the highest lipid content, defined as the maximum lipid core burden index within any 4mm length across the entire lesion (maxLCBI4mm), was selected as target segment. Lipoprotein subfractions were analyzed in fasting serum samples by nuclear magnetic resonance spectroscopy. Penalized linear regression analyses (lasso) were used to identify the best predictors of maxLCBI4mm. The uncertainty of the lasso estimates was assessed as the percentage of the resampled datasets by bootstrapping. Results Only modest evidence was found for an association with lipoprotein subfractions and maxLCBI4mm. The lipoprotein subfractions with strongest potential as predictors according to the percentage presence in resampled datasets were lipoprotein a (Lp(a)) (reg.coeff = 57.0; 78.1 % presence) and free cholesterol in the smallest high-density lipoprotein (HDL) subfractions (reg.coeff = 36.5; 74.3 % presence). When including established cardiovascular risk factors in the regression model, none of the lipoprotein subfractions was considered potential predictors of maxLCBI4mm. Conclusion In this study, Lp(a) and free cholesterol in the smallest HDL subfractions in serum showed the strongest potential as predictors for lipid content in coronary atheromatous plaques. Although the evidence is modest, our study suggests that measurements lipoprotein subfractions may provide additional information with respect to coronary plaque composition compared to traditional lipid measurements, but not in addition to established risk factors. Future studies are needed to verify our findings, and to investigate the clinical implication of lipoprotein subfractions as meaningful biomarkers for lipid-rich plaques and enhanced risk prediction in CAD.