Clinical Management of Familial Hypercholesterolemia: New Insights from International Guidelines and Recent Studies

This review article assesses the clinical features, diagnosis and management of familial hypercholesterolemia (FH). FH is mostly an autosomally dominantly inherited with an incidence of 1 in 250. Tendon xanthomata are pathognomonic. Untreated FH is associated with 100-200 fold increase in risk of cardiovascular disease (CVD). FH is diagnosed by screening for elevated low density lipoprotein cholesterol (LDL-C) and confirmed by DNA techniques. Once index cases have been identified cascade family screening should occur. FH is primarily treated with high dose statin therapy. This reduces progression of surrogate markers of coronary arterial disease and registry studies show a 70% long-term decrease in CVD mortality. The justification for other lipidlowering therapies e.g., ezetimibe relies on the high population attributable risk of LDL-C in FH. Novel therapies with greater LDL-C reducing actions such as proprotein convertase subtilisin kexin-9 inhibitors show promise in FH Children with FH should be identified through cascade screening but drug treatment is dependent on LDL-C and family history. They should be managed in specialist paediatric units or in family clinics. Cases of homozygous FH are rare. This orphan condition should be managed in specialist centers with a combination of drug therapy, apheresis and liver transplantation. Novel therapies for the treatment of homozygous FH such as mipomersen and lomitapide are gradually coming into use FH is a common underdiagnosed condition. Current, let alone future, therapies are extremely effective in reducing both LDL-C and CVD events in patients with FH. Identification and treatment of FH should be a feature of preventative CVD medicine programmes.