Improving the detection of familial hypercholesterolaemia

Abstract

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder of low-density lipoprotein (LDL) catabolism, which if untreated causes lifelong elevated LDL-cholesterol (LDL-c), accelerated atherosclerosis and premature cardiovascular disease. Recent evidence suggests the prevalence of heterozygous FH is ∼1:220, making FH the most common autosomal dominant condition. Lowering LDL-c with statin and lifestyle therapy reduces the risk of cardiovascular events. Furthermore, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lower LDL-c in addition to statin therapy, and early outcome data suggest improved vascular outcomes with these agents in FH patients in addition to statins. However, the vast majority of people with FH still remain undiagnosed. The onus is on clinicians to identify kindreds with FH, as PCSK9 inhibitors, although expensive, are funded for patients with FH in Australia. Multiple strategies for detecting FH have been proposed. The detection of index cases can be achieved through applying electronic screening tools to general practice databases, universal screening of children during immunisation, and targeted screening of patients with premature cardiovascular disease. Advances in genomic technology have decreased costs of genetic testing, improved the understanding of the pathogenesis of FH and facilitated cascade screening. However, awareness of FH amongst clinicians and the general public still requires optimisation. This review outlines recent advances in FH detection, including emerging strategies and challenges for the next decade.

Keywords: Familial hypercholesterolaemia; detection; diagnosis; dyslipidaemia; genetic testing; screening.