Abstract 4366409: Linking variability of leukocyte lipid metabolism to circulating lipids, lipoprotein composition and cardiovascular risk in the Finnish adult population

Background: Interindividual differences for outcomes of lipid-lowering therapy are well known. Here we aimed to characterize how alterations in cellular lipid uptake, storage and utilization pathways may contribute to different treatment outcomes. Methods: We performed an observational case-control biobank study quantifying leukocyte low-density lipoprotein (LDL) uptake and lipid storage with an automated multiplexed analysis pipeline for 133 statin recipients and 135 control subjects from the FINRISK 2012 cohort study. Individual cellular readouts as well as their combinations, which we called lipid trafficking scores, were then correlated to blood lipid values and health outcomes of the study participants. Results: Of individuals receiving high-intensity statin therapy those with lower lipid trafficking scores displayed higher circulating concentrations of several pro-atherogenic lipoproteins and had higher odds for myocardial infarction and stroke when compared to the rest of the subjects with equivalent treatment. Most subjects with a poor lipid trafficking score did not reach low-density lipoprotein cholesterol (LDL-C) target levels on statin monotherapy. Combining lipid trafficking score with a polygenic risk score for LDL-C strengthened the association with a pro-atherogenic lipoprotein profile. Conclusions: Our results indicate that quantification of cellular lipid trafficking can aid in treatment selection and risk assessment in dyslipidemia.