Homozygous Familial Hypercholesterolemia
| Autor: | Koh Ono, Hitoshi Shimano, Hiroyuki Daida, Shinji Yokoyama, Kota Matsuki, Mariko Harada-Shiba, Hayato Tada, Toshio Hayashi, Sachiko Okazaki, Atsushi Nohara, Tetsuo Minamino, Masatsune Ogura, Mika Hori, Kazushige Dobashi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Homozygous Familial Hypercholesterolemia medicine.medical_specialty PCSK9 inhibitor Review Familial hypercholesterolemia Insurance Coverage Public healthcare Family studies Lipoprotein apheresis Japan Early Medical Intervention Internal medicine Internal Medicine medicine Humans PCSK9 Inhibitors LDL-Receptor Related Proteins Lipid Regulating Agents business.industry Biochemistry (medical) LDL receptor activity Cholesterol LDL Prognosis medicine.disease Family study Heart Disease Risk Factors Genetic diagnosis Blood Component Removal Aortic Supra-valvular stenosis Cutaneous and Tendon Xanthoma lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine business MTP inhibitor Insurance coverage |
| Zdroj: | Journal of Atherosclerosis and Thrombosis |
| ISSN: | 1880-3873 1340-3478 |
| DOI: | 10.5551/jat.rv17050 |
| Popis: | Familial hypercholesterolemia (FH) is an inherited disorder with retarded clearance of plasma LDL caused by mutations of the genes involved in the LDL receptor-mediated pathway and most of them exhibit autosomal dominant inheritance. Homozygotes of FH (HoFH) may have plasma LDL-C levels, which are at least twice as high as those of heterozygous FH (HeFH) and therefore four times higher than normal levels. Prevalence of HoFH had been estimated as 1 in 1,000,000 before but more recent genetic analysis surveys predict 1 in 170,000 to 300,000. Since LDL receptor activity is severely impaired, HoFH patients do not or very poorly respond to medications to enhance activity, such as statins, and have a poorer prognosis compared to HeFH. HoFH should therefore be clinically distinguished from HeFH. Thorough family studies and genetic analysis are recommended for their accurate diagnosis. Fatal cardiovascular complications could develop even in the first decade of life for HoFH, so aggressive lipid-lowering therapy should be initiated as early as possible. Direct removal of plasma LDL by lipoprotein apheresis has been the principal measure for these patients. However, this treatment alone may not achieve stable LDL-C target levels and combination with drugs should be considered. The lipid-lowering effects of statins and PCSK9 inhibitors substantially vary depending on the remaining LDL receptor activity of individual patients. On the other hand, the action an MTP inhibitor is independent of LDL receptor activity, and it is effective in most HoFH cases. This review summarizes the key clinical issues of HoFH as well as insurance coverage available under the Japanese public healthcare system. |
| Databáze: | OpenAIRE |
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