Effect of low-density lipoprotein apheresis on kinetics of apolipoprotein B in heterozygous familial hypercholesterolemia

The acute reduction of low-density lipoprotein (LDL) cholesterol obtained b y LDL-apheresis allows the role of the high level of circulating LDL on lip oprotein metabolism in heterozygous familial hypercholesterolemia (heterozy gous FH) to he addressed. We studied apolipoprotein B (apoB) kinetics in fi ve heterozygous FH patients before and the day after an apheresis treatment using endogenous labeling with [H-2(3)]leucine. Compared with younger cont rol subjects, heterozygous FH patients before apheresis showed a significan t 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 heterozygo us FH patients (18.9 +/- 7.0 vs. 9.9 +/- 4.2 mg/kg.day; P < 0.05). The mode ling of postapheresis apoB kinetics was performed using a nonsteady state c ondition, taking into account the changing pool size of very low density li poprotein (VLDL), intermediate density lipoprotein, and LDL apoB. The posta pheresis kinetic parameters did not show statistical differences compared w ith preapheresis parameters in heterozygous FH patients; however, a trend f or 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-apheresi s is able to stimulate LDL receptor activity and VLDL production in heteroz ygous FH.