Lipoprotein apheresis and new therapies for severe familial hypercholesterolemia in adults and children.
Familial hypercholesterolemia (FH), the most common and severe monogenic form of hypercholesterolemia, is an autosomal co-dominant disease characterized by an increased plasma low density lipoprotein (LDL)-cholesterol concentration and premature coronary heart disease (CHD). The clinical phenotype depends on the gene involved and severity of mutation (or mutations) present. Patients with homozygous or compound heterozygous FH have severe hypercholesterolemia (LDL-cholesterol >13 mmol/L) due to a gene dosing effect and without treatment have accelerated atherosclerotic CHD from birth, and frequently die of CHD before age 30. Cholesterol-lowering therapies have been shown to reduce both mortality and major adverse cardiovascular events in individuals with FH. Lipoprotein apheresis concomitant with lipid-lowering therapy is the treatment of choice for homozygous FH. This article describes the rationale and role of lipoprotein apheresis in the treatment of severe FH and outlines the recent advances in new pharmacotherapies for this condition.
Lipid Disorders Clinic, Department of Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia.
Michael M
MM
Page
Lipid Disorders Clinic, Department of Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia; School of Medicine & Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Damon A
DA
Bell
Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia; School of Medicine & Pharmacology, University of Western Australia, Perth, Western Australia, Australia; School of Pathology & Laboratory Medicine, University of Western Australia, Perth, Western Australia, Australia.
Amanda J
AJ
Hooper
Lipid Disorders Clinic, Department of Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia; School of Medicine & Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Gerald F
GF
Watts
Lipid Disorders Clinic, Department of Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia; School of Medicine & Pharmacology, University of Western Australia, Perth, Western Australia, Australia. Electronic address: john.burnett@health.wa.gov.au.
John R
JR
Burnett
D000328:Adult; D001781:Blood Component Removal / Q000009:adverse effects / Q000379:methods*; D002648:Child; D000075202:Contraindications; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D008074:Lipoproteins / Q000097:blood / Q000302:isolation & purification*; D008403:Mass Screening; D012720:Severity of Illness Index
D008074:Lipoproteins
antisense oligonucleotides; apheresis; apolipoprotein B; cholesteryl ester transfer protein inhibitors; familial hypercholesterolemia; gene therapy; liver transplantation; low density lipoprotein cholesterol; microsomal triglyceride transfer protein inhibitors; proprotein convertase subtilisin/kexin type 9 inhibitors