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O026 - LINKING CELLULAR LIPID TRAFFICKING PROFILES OF INDIVIDUALS TO THE OUTCOMES OF CHOLESTEROL-LOWERING THERAPY IN THE GENERAL POPULATION (ID 311)
Abstract
Background and Aims
The outcomes of lipid-lowering therapy (LLT) vary between individuals. Previously we showed that for FH patients cellular lipid trafficking profiles are associated with on-treatment LDL-c levels (Pfisterer et al. CellRep Methods, doi:10.1016/j.crmeth.2022.100166). Here, we investigated how cellular profiles link with LDL-c levels, lipoprotein profiles, polygenic risk scores, and cardiovascular outcomes in the general population.
Methods
We used peripheral blood mononuclear cells (PBMCs) collected by THL Biobank as part of the Finnish population-based FINRISK 2012 study. We obtained samples for 400 subjects, including 200 recipients of LLT with available genetic, drug reimbursement, NMR metabolomic and longitudinal CVD outcome data. Using a multiplexed high-content imaging platform we obtained over 26 readouts for lipid uptake and storage in leukocytes for each sample.
Results
Cellular lipid uptake and storage were highly variable in our population-based study sample, and, in patients receiving either medium- or high-intensity statin monotherapy (n=39), were negatively correlated with serum LDL-cholesterol. Combining lipid uptake and storage readouts into cellular lipid trafficking scores (LTSs) improved this relationship (R=-0.45, p=0.0036). Subsequent combination of LTS with LDL-PRS produced even stronger correlation (R=-0.54, p=0.0004). Subjects in the lowest quintile of the LTS were at lower odds to be at their LDL target level (OR=0.068 CI [0.007,0.63], p=0.013) and at higher odds to experience MI or stroke (OR=30, 95% CI [2.64,339.75] p=0.004) in the 8-year follow-up period as compared to the rest of the group.
Conclusions
Cellular readouts provide novel insight into interindividual variation of LLT outcomes, providing new opportunities for treatment optimization and risk assessment for CVD prevention.