Comparison of two low‐density lipoprotein apheresis systems in patients with homozygous familial hypercholesterolemia

Abstract

Low-density lipoprotein (LDL) apheresis (LA) is a reliable method to decrease LDL-C concentrations and remains the gold standard therapy in homozygous familial hypercholesterolemia (HoFH). The objective of this study was to compare the efficacy of two LA systems [heparin-induced extracorporeal LDL precipitation (HELP) vs. dextran sulfate adsorption (DS) on the reduction of lipids, inflammatory markers, and adhesion molecules in a sample of genetically defined HoFH subjects (n = 9)]. Fasting blood samples were collected before and after LA. All subjects served as their own control and were first treated with the HELP system then with DS in this single sequence study. Compared with HELP, DS led to significantly greater reductions in total cholesterol (-63.3% vs. -59.9%; P = 0.05), LDL-C (-70.5% vs. -63.0%; P = 0.02), CRP (-75.3% vs. -48.8%; P < 0.0001), and TNF-α (-23.7% vs. +14.7%; P = 0.003). Reductions in the plasma levels of PCSK9 (-45.3% vs. -63.4%; P = 0.31), lipoprotein (a) (-70.6% vs. -65.0%; P = 0.30), E-selectin (-16.6% vs. -18.3%; P = 0.65), ICAM-1 (-4.0 vs. 5.6%; P = 0.56), and VCAM-1 (8.3% vs. -1.8%; P = 0.08) were not different between the two systems. For the same volume of filtered plasma (3,000 mL), however, HELP led to greater reductions in plasma apoB (-63.1% vs. -58.3%; P = 0.04), HDL-C (-20.6% vs. -6.5%; P = 0.003), and PCSK9 (-63.4% vs. -28.5%; P = 0.02) levels. These results suggest that both LA systems are effective in reducing plasma lipids and inflammatory markers in HoFH. Compared with HELP, greater reductions in lipid levels and inflammatory markers were achieved with DS, most likely because this method allows for a larger plasma volume to be filtered. J. Clin. Apheresis 31:359-367, 2016. © 2015 Wiley Periodicals, Inc.

Impact of lipoprotein apheresis with dextran‐sulfate adsorption on the expression of genes involved in cardiovascular health in the blood of patients with homozygous familial hypercholesterolemia

“…Alternatively, it could not be excluded that the upregulation of these genes reflect acute endothelial activation, since gene expression assessment using peripheral blood is a valid marker of endothelium homeostasis . This hypothesis is also concordant with a previous observation that elevations in plasma concentrations of interleukin‐6, a cytokine that can be secreted from endothelial cells, were reported following LA with DSA in HoFH patients …”

“…9 This hypothesis is also concordant with a previous observation that elevations in plasma concentrations of interleukin-6, a cytokine that can be secreted from endothelial cells, were reported following LA with DSA in HoFH patients. 10,11 In the present study, it remains uncertain whether the upregulation in the expression of EGR1, EGR3, BCL3, and MMP9 was related to the DSA system or to the LA treatment per se. This effect was unlikely attributable to dextransulfate, as whole blood cells and plasma are separated in the LA system prior to the adsorption step.…”

Differential associations between plasma concentrations of insulin and glucose and intestinal expression of key genes involved in chylomicron metabolism

“…Blood samples were collected after a 12-h fast from an antecubital vein in tubes containing disodium EDTA and benzamidine (0.03%) (3). Blood lipids were measured using enzymatic methods and ultracentrifugation as previously described (8). Glucose levels were measured using colorimetry, and insulin levels were dosed using electrochemiluminescence (Roche Diagnostics, Indianapolis, IN).…”

Plasma PCSK9 correlates with apoB-48-containing triglyceride-rich lipoprotein production in men with insulin resistance

“…Fasting blood samples were collected after a 12 h fast prior to the beginning of the kinetic study in tubes containing disodium EDTA and benzamidine (0.03%) (33). Blood lipids were measured using enzymatic methods and ultracentrifugation as previously described (34). Glucose levels were measured using colorimetry, and insulin levels were examined using electrochemiluminescence (Roche Diagnostics, Indianapolis, IN).…”