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Treatment of hypercholesterolemia with heparin-induced extracorporeal low-density lipoprotein precipitation (HELP)
R S Lees1, N N Holmes, R W Stadler
1Harvard/MIT Joint Program in Health Sciences and Technology, Cambridge, USA.
Insights
Familial hypercholesterolemia (FH) is a severe genetic disorder. LDL apheresis effectively removes cholesterol, improving outcomes for FH patients unresponsive to other treatments.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Lipidology
Background:
- Familial hypercholesterolemia (FH) causes premature atherosclerotic cardiovascular disease, leading to early disability and death.
- Homozygous FH patients exhibit extremely high plasma cholesterol, xanthomatosis, and often fatal atherosclerosis in youth.
- Previous treatments like ileal bypass and biliary diversion were unsuccessful in improving FH prognosis.
Purpose of the Study:
- To evaluate the efficacy and safety of low-density lipoprotein (LDL) apheresis for severe familial hypercholesterolemia.
- To compare LDL apheresis with other historical and alternative treatments for FH.
Main Methods:
- Direct plasmapheresis for LDL removal was first performed on a homozygous FH patient in 1966.
- Selective LDL apheresis methods were developed, including the HELP (Heparin-mediated Extracorporeal LDL Precipitation) system in 1983.
- The HELP system removes apolipoprotein B-containing lipoproteins, including LDL and lipoprotein (a).
Main Results:
- Direct LDL apheresis was well tolerated and led to rapid xanthoma reduction.
- The HELP method for LDL apheresis is well tolerated with a low incidence of side effects.
- LDL apheresis has been associated with the regression of cardiovascular disease in FH patients.
Conclusions:
- LDL apheresis is a well-tolerated and effective treatment for severe familial hypercholesterolemia.
- The HELP apheresis method demonstrates efficacy in removing atherogenic lipoproteins and improving clinical outcomes.
- LDL apheresis is considered the treatment of choice for severe, life-threatening hypercholesterolemia refractory to diet and medication, surpassing liver transplantation in many cases.
Abstract:
Familial hypercholesterolemia (FH) can cause early disability and death from premature atherosclerotic cardiovascular disease. Patients homozygous for the disease have very high plasma cholesterol, extensive xanthomatosis, and die from atherosclerosis in childhood or early adulthood. Past attempts to improve the prognosis included removal of cholesterol from the circulation by ileal bypass or biliary diversion. Neither treatment was successful. Direct removal by plasmapheresis of low-density lipoprotein (LDL), the primary carrier of cholesterol in plasma, was first performed on an FH homozygous patient in 1966. The treatment was well tolerated and led to rapid diminution of xanthomas. Other experimental treatments included selective LDL apheresis with monoclonal or polyclonal antibody affinity columns. A method for selective LDL apheresis was developed in 1983 by Armstrong, Seidel, and colleagues based on heparin precipitation of LDL at low pH. This method, called HELP, removes all apolipoprotein B-containing lipoproteins including LDL and lipoprotein (a), as well as some fibrinogen. LDL apheresis by HELP is well tolerated; the incidence of side effects is low, and the treatment has been associated with regression of cardiovascular disease. LDL apheresis, rather than liver transplantation, is the treatment of choice for patients with severe, life-threatening hypercholesterolemia which does not respond to diet and drug therapy.