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Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
Published on: January 28, 2021
Comparison of two low-density lipoprotein apheresis systems in patients with homozygous familial hypercholesterolemia
Jean-Philippe Drouin-Chartier1, André J Tremblay1, Jean Bergeron2
1Institute of Nutrition and Functional Foods, Laval University, Quebec City, Québec, Canada.
Insights
Dextran sulfate adsorption (DS) LDL apheresis (LA) significantly reduced lipids and inflammatory markers more effectively than heparin-induced extracorporeal LDL precipitation (HELP) in homozygous familial hypercholesterolemia (HoFH) patients. HELP showed greater reductions in apoB, HDL-C, and PCSK9 for the same filtered plasma volume.
Area of Science:
- Cardiovascular Medicine
- Medical Technology
Background:
- Low-density lipoprotein (LDL) apheresis (LA) is crucial for managing homozygous familial hypercholesterolemia (HoFH).
- Comparing different LA systems is essential for optimizing HoFH treatment.
Purpose of the Study:
- To compare the efficacy of two LDL apheresis systems: heparin-induced extracorporeal LDL precipitation (HELP) and dextran sulfate adsorption (DS).
- To evaluate the reduction of lipids, inflammatory markers, and adhesion molecules in HoFH patients using HELP versus DS.
Main Methods:
- A single-sequence study involving 9 genetically defined HoFH subjects.
- Each subject underwent both HELP and DS apheresis, serving as their own control.
- Fasting blood samples were collected pre- and post-apheresis for analysis.
Main Results:
- DS demonstrated significantly greater reductions in total cholesterol, LDL-C, C-reactive protein (CRP), and TNF-α compared to HELP.
- No significant differences were observed between DS and HELP in reducing PCSK9, lipoprotein(a), E-selectin, ICAM-1, and VCAM-1.
- For a filtered plasma volume of 3,000 mL, HELP achieved greater reductions in apoB, HDL-C, and PCSK9 than DS.
Conclusions:
- Both HELP and DS apheresis systems are effective in reducing plasma lipids and inflammatory markers in HoFH.
- DS achieved superior reductions in lipid levels and inflammatory markers, likely due to its ability to process a larger plasma volume.
- The choice of apheresis system may influence the extent of lipid and inflammatory marker reduction in HoFH patients.
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.
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