Abstract

Background: Low-density lipoprotein (LDL) apheresis via dextran-sulfate-cellulose absorption lowers LDL cholesterol (LDL-C) levels (>60%) by removing apoB containing lipoproteins due to their positive charge. Although HDL is negatively charged LDL apheresis also causes small but significant reductions in HDL-C levels (10-15%). LDL particle number (LDL-P) has been associated more strongly with clinical atherosclerotic outcomes than LDL-C; however, the impact of LDL apheresis on lipoprotein particle concentrations as determined by nuclear magnetic resonance (NMR) has not been reported. Objective: To determine the effects of LDL apheresis on lipoprotein particle concentrations and to compare changes in lipoprotein particle concentrations to conventional serum lipid levels. Methods: Comprehensive NMR lipoprotein analysis was performed on serum obtained from five subjects prior to and following three occasions of LDL apheresis performed at two-week intervals. Three subjects had homozygous familial hypercholesterolemia (FH) and two had coronary artery disease (CAD) and mixed dyslipidemia with LDL-C > 200 mg/dL (one subject had pre-treatment triglyceride (TG) levels > 400 mg/d) prior to and following LDL apheresis Results: Mean LDL-P concentration was 2957+1024 nmol/L, HDL particle number (HDL-P) was 27+9 μ mol/L and TG was 224+208 mg/dL. LDL apheresis treatment reduced LDL-P by 67% (p < 0.0001) and decreased TG (43%, p = 0.153) to a lesser extent. All reductions were significant in subjects with pre-treatment TG levels < 400 mg/dL. The mean HDL-P increased slightly with treatment (29+7 mg/dL, p = 0.533), but the effect was not significant. There were no treatment-dependent changes in the size distribution of LDL particles, whereas HDL particle size shifted toward an increase in medium HDL-P in FH subjects. Conclusion: This is the first report on the effects of LDL apheresis on serum concentrations of lipoprotein particles as determined by NMR. LDL apheresis promoted dramatic reductions in both LDL-C and LDL-P, whereas HDL-P was unchanged to slightly increased despite a significant decrease in HDL-C.

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