title: Diagnosis and treatment of familial hypercholesterolaemia.
abstract: Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder, associated with elevated levels of low-density lipoprotein-cholesterol (LDL-C), which can lead to premature cardiovascular disease. Early diagnosis of FH is important to prevent morbidity and mortality. Familial hypercholesterolaemia is usually diagnosed using clinical characteristics, such as family history, and cholesterol levels; however, genetic testing may provide a definite diagnosis of FH by detecting a pathological mutation. Current guidelines highlight the importance of reducing LDL-C levels in patients with FH. Statins are the current standard treatment for the majority of these patients, and have been shown to be effective in reducing the incidence of cardiovascular heart disease in patients with FH. Nevertheless, many FH patients do not achieve their target LDL-C levels; as such, new treatment options are required to decrease LDL-C levels beyond those currently achieved. There are currently several new classes of pharmacotherapy under investigation to control LDL-C levels. These include agents which modify LDL-C production, such as inhibitors of apolipoprotein B, or those which affect LDL-C catabolism, such as inhibition of pro-protein convertase subtilisin/kexin 9, a protein which is responsible for the degradation of the LDL receptor. Therapies which raise high-density lipoprotein cholesterol are also being evaluated. In this article, we consider the diagnosis of FH and the goals of therapy and review the current and potential future treatment options for patients with FH.
authors: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room F4-159.2, 1105 AZ Amsterdam, The Netherlands.
authors: G Kees
authors: GK
authors: Hovingh
authors: Michael H
authors: MH
authors: Davidson
authors: John J P
authors: JJ
authors: Kastelein
authors: Anne M
authors: AM
authors: O'Connor
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use; D053299:Apolipoprotein B-100 / Q000037:antagonists & inhibitors / Q000235:genetics; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000187:drug effects / Q000378:metabolism; D042241:Early Diagnosis; D005820:Genetic Testing; D015316:Genetic Therapy / Q000379:methods; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008074:Lipoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D008078:Cholesterol, LDL; D008074:Lipoproteins; D011973:Receptors, LDL; C030104:lipoprotein cholesterol; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases