Linking biological variation to outcomes of statin treatment in the general population

Interindividual differences for outcomes of lipid-lowering therapy are well known. Alterations in cellular pathways may contribute to the phenomenon. To address this question, we employed an automated multiplexed analysis pipeline to systematically characterize alterations in cellular lipid trafficking in leukocytes from 400 subjects of the FINRISK 2012 Study. Of individuals receiving high-intensity statin therapy those with lower cellular 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. Lipid trafficking scores showed synergy with a polygenic risk score for LDL-C, improving the association with pro-atherogenic lipoprotein profile when combined. Our results suggest that quantification of cellular lipid trafficking can aid in treatment selection and risk assessment in dyslipidemia. Graphical Abstract