Context

Guidance

In some people, a high cholesterol concentration in the blood is caused by an inherited genetic defect known as familial hypercholesterolaemia (FH). A raised cholesterol concentration in the blood is present from birth and may lead to early development of atherosclerotic disease like coronary heart disease. The disease shows an autosomal dominant pattern of inheritance, being transmitted from generation to generation in such a way that siblings and children of a person with FH have a 50% risk of inheriting FH.

Most people with FH have inherited a defective gene for FH from only 1 parent and are therefore heterozygous. Rarely, a person will inherit a genetic defect from both parents and will have homozygous FH or compound heterozygous FH, which will be collectively termed homozygous FH for the purpose of this guideline.

The prevalence of heterozygous FH in the UK population is estimated to be somewhere between 1 in 250 and 1 in 500, which means that between approximately 130,000 and 260,000 people are affected. The elevated serum cholesterol concentration that characterises heterozygous FH leads to a greater than 50% risk of coronary heart disease in men by the age of 50 years and at least 30% in women by the age of 60 years.

Homozygous FH is rare, with symptoms appearing in childhood, and is associated with early death from coronary heart disease. Homozygous FH has an incidence of approximately 1 case per 1 million.

The guideline will assume that prescribers will use a drug's summary of product characteristics to inform their decisions for individual patients.

In 2017, the areas on case finding, diagnosis and pharmacological monotherapy (statin versus placebo) were updated. Since the original guideline was published in 2008, cascade testing may now be more cost effective, and DNA diagnosis technology has changed greatly. In addition, more evidence has been identified on the use of high-intensity statins, and on the safety profile of statins in children and young people.