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Apheresis technology for prevention and regression of atherosclerosis
A Yamamoto1, M Harada-Shiba, A Kawaguchi
1National Cardiovascular Center Research Institute, Suita, Osaka, Japan. ymmta@juno.dti.ne.jp
Insights
Familial hypercholesterolemia (FH) treatment with LDL-apheresis shows limited success in homozygous patients but improves life expectancy in heterozygous patients with coronary artery disease. Combination therapy may reduce coronary events.
Area of Science:
- Cardiology
- Metabolic Disorders
- Genetics
Background:
- Familial hypercholesterolemia (FH) is a genetic disorder of cholesterol metabolism.
- Deficiency in low-density lipoprotein (LDL) receptors leads to very high LDL-cholesterol levels.
- Homozygous FH is particularly severe, often leading to early coronary artery disease (CAD).
Purpose of the Study:
- To evaluate the effectiveness of LDL-apheresis in treating patients with homozygous and heterozygous FH.
- To assess the impact of adjunctive therapies, such as atorvastatin and probucol, on LDL-apheresis outcomes.
- To review clinical data on LDL-apheresis for FH from multiple institutions.
Main Methods:
- Treatment of 10 homozygous and 28 heterozygous FH patients using LDL-apheresis.
- Administration of high-dose atorvastatin (40 mg/day) to suppress LDL-cholesterol rebound.
- Combination therapy with probucol and LDL-apheresis in some heterozygous patients.
- Review of clinical data from other Japanese institutions.
Main Results:
- Two of 10 homozygous FH patients died of myocardial infarction; others developed aortic valve regurgitation.
- LDL-apheresis extended life expectancy in heterozygous FH patients with pre-existing CAD, especially after interventions like CABG or PTCA.
- High-dose atorvastatin showed limited efficacy in receptor-negative homozygous FH patients but improved HDL-cholesterol and reduced triglycerides.
- Probucol combined with LDL-apheresis reduced coronary events in heterozygous FH patients.
Conclusions:
- LDL-apheresis is a critical treatment for severe FH but has limitations, particularly in homozygous cases.
- Combination therapies, including statins and probucol, may enhance the benefits of LDL-apheresis.
- LDL-apheresis significantly improves outcomes for heterozygous FH patients with established cardiovascular disease.
Abstract:
Familial hypercholesterolemia (FH) is a congenital disorder of cholesterol metabolism, which is due to a deficiency in low-density lipoprotein (LDL) receptors. The homozygous form of FH is especially liable to coronary artery disease (CAD) in youth because of the very high LDL-cholesterol levels. It is resistant to drug therapy, and LDL-apheresis is the only practical way of treatment for these patients. Some patients with heterozygous FH also have high LDL-cholesterol levels that cannot be brought down into the optimum range by any combination drug therapy. We have treated or are treating 10 homozygous and 28 heterozygous FH patients in our hospital or in affiliated hospitals expert in blood purification. Among the 10 homozygous patients, 2 died of myocardial infarction. Only one young female patient is still free of symptoms, and the other patients have been suffering from regurgitation through the aortic valve although they have not experienced myocardial infarction. Rapid rebound of LDL-cholesterol after each apheresis treatment limits the period during which LDL-cholesterol is in the optimum range. The use of atorvastatin at a high dose (40 mg/day) was attempted to suppress this rebound. In contrast with good results in receptor-defective-type patients, receptor-negative-type patients did not show a response in LDL-cholesterol levels to the statin therapy although there was a slight increase in high-density lipoprotein (HDL)-cholesterol with a decrease in very-low-density lipoprotein-triglyceride and -cholesterol. Follow-up study of the patients with heterozygous FH revealed that LDL-apheresis was effective in lengthening the life expectancy of the patients with pre-existing CAD, especially those who had received intervention coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA). It was also shown that the use of probucol in combination with LDL-apheresis was effective in reducing coronary events as shown by the necessity of CABG or PTCA. Clinical data on the effect of LDL-apheresis, recently reported from some other institutions in Japan, will also be reviewed.