Familial hypercholesterolemia (FH) is the most common monogenic disorder associated with premature atherosclerotic cardiovascular disease. Early diagnosis and effective treatment can significantly improve prognosis. Recent advances in the field of lipid metabolism have shed light on the molecular defects in FH and new therapeutic options have emerged. A search of PubMed database up to March 2020 was performed for this review using the following keywords: “familial hypercholesterolemia”, “diagnosis”, “management”, “guideline”, “consensus”, “genetics”, “screening”, “lipid lowering agents”.
The prevalence rate of heterozygous FH is approximately 1 in 200 to 250 and FH is underdiagnosed and undertreated in many parts of the world. Diagnostic criteria have been developed to aid the clinical diagnosis of FH. Genetic testing is now available but not widely used. Cascade screening is recommended to identify affected family members and the benefits of early interventions are clear. Treatment strategy and target is currently based on LDL cholesterol levels as the prognosis of FH largely depends on the magnitude of LDL cholesterol lowering that can be achieved by lipid-lowering therapies. Statins with or without ezetimibe are the mainstay of treatment and are cost-effective. Addition of newer medications like PCSK9 inhibitors is able to further lower LDL cholesterol levels substantially but the cost is high. Lipoprotein apheresis is indicated in homozygous FH or severe heterozygous FH patients with inadequate response to cholesterol-lowering therapies. In conclusion, FH is a common treatable genetic disorder and although our understanding of this disease has improved, many challenges still remain for its optimal management.
