Familial Hypercholesterolemia
Conditions
Brief summary
Familial hypercholesterolemia (FH) is an autosomal codominant single-gene disorder caused by mutations in the LDL receptor gene that disrupt the normal clearance of LDL particles from the plasma compartment. Heterozygous patients present a 2- to 3-fold raise in plasma LDL-cholesterol (C) concentrations, tendinous xanthomatosis and premature atherosclerotic coronary heart disease (CHD), usually occurring between the age of 35 and 55 years. Since the mid-1970s, LDL-C has been removed from the blood of patients using plasmapheresis, and this technique has been shown to improve the life expectancy of FH homozygotes. LDL apheresis selectively removes LDL particles but not immunoglobulins and other beneficial proteins, thereby overcoming a potential drawback of the traditional plasmapheresis method. LDL-C is effectively reduced by more than 60% immediately after LDL apheresis, although LDL levels rebound rapidly. Dextran sulfate adsorption is a commonly apheresis technique used in familial hypercholesterolemia patients. In this apheresis plasma is separated from red blood cells and passed over columns of cellulose beads containing dextran sulfate which binds apolipoprotein B (apoB) by a highly selective electrostatic binding mechanism. Since LDL, very-low density lipoprotein (VLDL), and Lipoprotein (a) all contain apoB, dextran sulfate adsorption apheresis selectively reduces these lipoproteins while having little effect on the non-apoB containing HDL particles. In clinical practice, LDL apheresis reduces the rate of future cardiovascular events and has been postulated to have additional effects on potentially pro-atherogenic factors. Some proteins have been identified with adhesive characteristics to lipoproteins, rheological, immunological and inflammation relevant proteins16-19 that influence microcirculation as well as the inflammatory response. However, no studies have yet to investigate the impact of LDL apheresis on the expression of different genes involved in cardiovascular disease. The main objective of the present research project is to investigate the impact of the LDL apheresis dextran sulfate adsorption system on the messenger ribonucleic acid (mRNA) expression of genes involved in cardiovascular disease using microarrays analysis in 9 FH homozygotes.
Interventions
OTHERPre-lipid apheresis
Blood samples will be taken just before the start of the lipid apheresis treatment.
OTHERPost-lipid apheresis
Blood samples will be taken following the lipid apheresis treatment.
Sponsors
Laval University
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Homozygotes for familial hypercholesterolemia who receive lipid apheresis * Aged between 18-60 years
Exclusion criteria
* Smokers (\> 1 cigarette/day) * Subjects with a previous history of cardiovascular disease * Subjects with type 2 diabetes * Subjects with a monogenic dyslipidemia that it is not homozygote for familial hypercholesterolemia * Subjects with endocrine or gastrointestinal disorders * History of alcohol or drug abuse within the past 2 years * Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in mRNA expression of genes involved in cardiovascular disease using microarrays analysis. | Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h) |
Secondary
| Measure | Time frame |
|---|---|
| Change in serum levels of C-reactive protein | Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h) |
Other
| Measure | Time frame |
|---|---|
| Change in serum levels of vascular cell adhesion molecule | Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h) |
Countries
Canada
Outcome results
None listed