Effects of weekly LDL-apheresis on metabolic parameters of apolipoprotein B in heterozygous familial hypercholesterolemia

Abstract

Apheresis is a treatment option for patients with severe hypercholesterolemia and coronary artery disease. It is, however, unknown whether such therapy changes kinetic parameters of lipoprotein metabolism, such as apolipoprotein B (apoB) secretion rates, conversion rates, and fractional catabolic rates (FCR). We studied the long-term effect of regular apheresis therapy on metabolic parameters of apoB in five patients with heterozygous familial hypercholesterolemia (FH) using endogenous labeling with D3-leucine, mass spectrometry, and multicompartmental modeling. Patients were studied prior to (study 1) and after 3-6 months of weekly apheresis therapy (study 2). LDL-apoB concentration was 183 +/- 16 mg d-1 prior to apheresis therapy (study 1), 135 %/- 7 mg. dl-1 at the beginning of study 2, and 163 +/- 10 mg . dl-1 at the end of study 2. VLDL-apoB and IDL-apoB were not different between the two studies and did not change during study 2. Separate modeling of the two studies revealed very similar parameters in each patient. In a second step simultaneous modeling of both studies was performed taking the changing pool size as a non-steady-state condition into account. ApoB tracer data of both kinetic studies and the change in pool size could be described with one set of kinetic parameters (VLDL-apoB FCR 4.32 +/- 1.06 d-1, LDL-apoB FCR 0.17 +/- 0.05 d-1, apoB secretion rate 11.9 +/- 3.7 mg . kg-1 . d-1). These parameters are well within the range of those previously published for FH heterozygotes in steady state. We conclude that regular apheresis therapy did not alter kinetic parameters of apoB metabolism in these patients with heterozygous FH in the long term and that the decreased rate of delivery of neutral lipids or apoB to the liver does not regulate plasma apoB metabolism.