Epidemiological, molecular and clinical aspects of familial hypercholesterolaemia: a narrative review

Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism, characterised by highly elevated low-density lipoprotein cholesterol (LDL-C) from birth, leading to adverse cardiovascular effects at an early age. The prevalence of heterozygous FH is 1:200–250, while that of homozygous FH is 1:100,000–160,000 individuals. Patients with homozygous FH may have cholesterol levels of 25 mmol/L and develop cardiovascular diseases (CVDs) in their early twenties. In contrast, patients with heterozygous FH may have cholesterol levels of 5.2–10.4 mmol/L, with CVD manifesting around the age of 40 to 50 years. Familial hypercholesterolaemia is usually caused by inherited mutations in the APOB , LDLR and PCSK9 genes, and can be detected by routine lipid testing. Early recognition and aggressive management to lower the LDL-C level help to delay or prevent coronary atherosclerosis. This review summarises the epidemiology, genetic basis, screening and treatment options available for the management of FH.