2022 Edition 1
clinical initiatives, research and current updates in treatment
Familial Hypercholesterolaemia: An under-diagnosed and under-treated high-risk disease Sarah Steinke, Pharmacy Practice Unit Familial hypercholesterolaemia (FH) is one of the most common inherited disorders. FH is a high-risk condition, characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels, predisposing individuals to atherosclerotic cardiovascular disease (ASCVD).1 FH is an autosomal dominant genetic disorder caused by a mutation in the gene which codes for the receptors for LDL-C.2 The heterozygote form has an estimated prevalence of 1 in 250.3 Untreated, FH-associated elevated LDL-C results in a greater than 50% risk of ASCVD in men by the age of 50 years and at least 30% of women by the age of 60 years.4 Currently, greater than 90% of Australia’s estimated 100,000 FH cases remain undetected, one in five of whom are children.5-7
Early identification and intervention of patients with FH is crucial because preventive strategies can lower the absolute lifetime cardiovascular risk and screening can detect affected relatives. However, recent evidence in Australia has found that patients are detected late in life, have a high burden of ASCVD, multiple risk factors, and do not achieve guideline-recommended LDL-C targets (box 1).8 Furthermore, genetic and cascade testing are under-utilised, posing hurdles in the prevention of FHrelated cardiovascular events.8
Diagnosis and Screening FH is usually diagnosed using clinical characteristics, such as family history, cholesterol deposits under the skin (xanthomas) and in the cornea (corneal arcus), significantly elevated LDL-C levels, and early-onset ASCVD;
however, genetic testing may provide a definite diagnosis of FH by detecting a pathological mutation.7 There are currently three accepted tools for FH diagnosis,7 with the Dutch Lipid Clinic Network Score (DLCNS) the most widely used in Australia.9 Australian and international guidelines recommend at-risk individuals be genetic tested to confirm the diagnosis.8,9 Where a pathogenic mutation is identified, systematic cascade testing of close relatives who carry a 50% risk of the disorder is a cost-effective approach to diagnose new cases of FH, particularly in younger family members.8,9 Box 1 summarises recommendations and therapeutic targets, based on moderate levels of evidence and class of recommendation, for managing FH.7
Box 1. LDL-C treatment targets for the management of FH Adults 1. LDL-C targets can be divided as follows: o LDL-C <2.5 mmol/L (absence of ASCVD or other major ASCVD risk factors) o LDL-C <1.8 mmol/L (imaging evidence of ASCVD alone or other major ASCVD risk factors) o LDL-C <1.4 mmol/L (presence of clinical ASCVD). Children ¬ ¬
For children with FH aged 8–10 years on a suitable diet, an LDL-C treatment target <4.0 mmol/L or a 30–40% reduction in LDL-C may be acceptable. In children aged >10 years who are maintained on a suitable diet, an LDL-C treatment target <3.5 mmol/L or a 50% reduction in LDL-C may be acceptable.
Current Treatment Options There is strong evidence for patients with FH to be actively treated with cholesterol-lowering medication, diet, and lifestyle modification from an early age.10 Other risk factors, such as obesity, smoking, diabetes mellitus, inactive
lifestyle, and hypertension, should also be addressed.7 HMG-CoA reductase inhibitors (or statins) remain the mainstay of treatment and represent first-line therapy for lowering LDL-C in both adult and paediatric patients with FH.11,12
Their efficacy in reducing cardiovascular morbidity and mortality is well established. However, a large proportion of patients at high risk do not reach the recommended target concentration of LDL-C.12 Continued on page 2