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Effect of Low-Density Lipoprotein Apheresis on Kinetics of Apolipoprotein B in Heterozygous Familial Hypercholesterolemia¹

Centre de Recherche en Nutrition Humaine (C.M., K.O., R.F., P.M., T.M., M.K.) and Clinique d’Endocrinologie, Maladies Métaboliques et Nutrition (B.C., M.K.), Hôtel Dieu, 44093 Nantes Cedex 01, France

Address all correspondence and requests for reprints to: Dr. Michel Krempf, Clinique d’Endocrinologie, Hôtel Dieu, 44093 Nantes Cedex 01, France. E-mail: mkrempf{at}sante.univ-nantes.fr

The acute reduction of low-density lipoprotein (LDL) cholesterol obtained by LDL-apheresis allows the role of the high level of circulating LDL on lipoprotein metabolism in heterozygous familial hypercholesterolemia (heterozygous FH) to be addressed. We studied apolipoprotein B (apoB) kinetics in five heterozygous FH patients before and the day after an apheresis treatment using endogenous labeling with [²H₃]leucine. Compared with younger control subjects, heterozygous FH patients before apheresis showed a significant decrease in the fractional catabolic rate of LDL (0.24 ± 0.08 vs. 0.65 ± 0.22 day^-1; P < 0.01), and LDL production was increased in heterozygous FH patients (18.9 ± 7.0 vs. 9.9 ± 4.2 mg/kg·day; P < 0.05). The modeling of postapheresis apoB kinetics was performed using a nonsteady state condition, taking into account the changing pool size of very low density lipoprotein (VLDL), intermediate density lipoprotein, and LDL apoB. The postapheresis kinetic parameters did not show statistical differences compared with preapheresis parameters in heterozygous FH patients; however, a trend for increases in fractional catabolic rate of LDL (0.24 ± 0.08 vs. 0.35 ± 0.09 day^-1; P = 0.067) and the production of VLDL (13.7 ± 8.3 vs. 21.9 ± 1.6 mg/kg·day; P = 0.076) was observed. These results suggested that the marked decrease in plasma LDL obtained a short time after LDL-apheresis is able to stimulate LDL receptor activity and VLDL production in heterozygous FH.

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