Familial hypercholesterolaemia
Familial hypercholesterolaemia is a dominantly inherited condition that affects more than 100 000 people in Australia and accelerates atherosclerotic cardiovascular disease (ASCVD) by 20 to 40 years. However, it is commonly underdiagnosed and undertreatedBenn, 2012Nordestgaard, 2013Watts, 2021.
Familial hypercholesterolaemia should be suspected in patients with any of the following features:
- severely elevated low-density lipoprotein cholesterol (LDL-C)
- tendon xanthomata
- a strong family history of premature cardiovascular events (ie cardiovascular events occurring in males younger than 55 years or females younger than 60 years).
Approximately 50% of family members are affected, so identification by family cascade screening is important.
Diagnosis requires exclusion of secondary causes of hypercholesterolaemia (eg nephrotic syndrome, severe cholestasis, hypothyroidism) together with clinical evaluation using the Dutch Lipid Clinic Network Score1 (see online calculator). Cases of possible familial hypercholesterolaemia should be reviewed regularly (every 2 years) to identify additional features, especially evidence of the development of ASCVD. Ideally, refer all patients with familial hypercholesterolaemia or probable familial hypercholesterolaemia for review by a lipid specialist.
The usual principles of lipid-modifying therapy apply to the management of familial hypercholesterolaemia, but combination therapy and additional monitoring is usually required. Lipid-modifying therapy should usually be started at the time of diagnosis, rather than according to the calculated absolute ASCVD risk or waiting for patients to become symptomatic. The age at which to start treatment in children has not been determined, but statin therapy is often started by the age of 10 years in those with heterozygous familial hypercholesterolaemia, and by the age of 2 years in those with homozygous familial hypercholesterolaemia. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor should be added if treatment targets are not achieved with maximally tolerated dose of statins, ezetimibe and diet. Specialised treatments (including lipoprotein apheresis) may be required in some patientsWatts, 2021.
Detailed information on management is available in the Familial Hypercholesterolaemia Australasia Network consensus model of care.