There are several reasons why a patient may present in primary care with high serum lipids. One of the main genetic causes is familial hypercholesterolaemia.
It is important that GPs are able to identify those patients who may be affected by this condition, since treatment is highly effective in reducing the associated risk of premature coronary heart disease.
Genetics
Familial hypercholesterolaemia (FH) is a common, but under-diagnosed, condition.
The incidence is 1 in 500 in Europe. 5% of all myocardial infarctions in over 60 year olds will have FH.
- It is an autosomal dominant inherited disorder causing elevations of total cholesterol and low density lipoprotein (LDL), cholesterol with normal high density lipoprotein (HDL), and triglycerides. It is due to absent or malfunctioning LDL receptors which result in impaired uptake and raised serum levels of LDL. First degree relatives of an affected individual have a 50% likelihood of inheriting the condition.
- It is associated with a grossly elevated risk of premature coronary heart disease. This typically manifests in the fourth decade in men, and approximately 10 years later in women. 85% of heterozygote men have experienced a myocardial infarction by age 60.
- Homozygosity for FH is much less common (1 per million) and results in a more severe disease with coronary events in infancy.
Diagnosis
The clinical diagnosis of FH is based on the characteristic lipid profile, a family history of hypercholesterolaemia, and/or premature ischaemic heart disease and the presence of tendon xanthomata.
Xanthelasmas and premature corneal arcus may also be present, but are not diagnostic.
The major diagnostic features are included in the Simon Broome criteria, the use of which has been endorsed in the Northern region FATS 4 guidelines.
It is important to rule out secondary causes of hypercholesterolaemia due to hypothyroidism, liver or kidney disease, alcoholism, diabetes, pregnancy or obesity.
The Simon Broome criteria are over inclusive and will pick up some people with other forms of hyperlipidaemia in addition to those with FH. Other common causes of hypercholesterolaemia include common hypercholesterolaemia, familial combined hyperlipaemia, and familial defective apolipoprotein B. Although these people should be referred to a lipid clinic for assessment and treatment, the genetics of these other conditions is not straight forward and cascade screening is not indicated.
It is important to refer patients to secondary care for investigation of possible FH rather than simply commencing the individual on a statin. This will enable a firm diagnosis to be made so that cascade screening of other family members can be undertaken, thus ensuring that affected relatives are offered treatment with a statin before ischaemic heart disease has developed. In the Northern region cascade screening is initiated at the lipid clinic, following referral.
In families with definite (or genetically confirmed) heterozygous FH, testing and treatment of children is usually recommended before the age of 10 years. Genetic testing of family members is currently being undertaken in Newcastle as part of a national pilot study and may be used to support family cascade testing in future, as per the Familial Hypercholesterolaemia NICE Guidance.
The guidelines on the next page (based on the Simon Broome criteria) are for use in primary care. They should be used to determine which patients with a raised total or LDL cholesterol, or significant personal or family history of coronary heart disease, would benefit from a referral on to secondary care for further investigation (which may include genetic testing), and consideration of cascade screening of family members.
The guideline should NOT be used to determine whether relatives of an affected individual should be referred to secondary care, since a different set of criteria are applied to relatives of an affected case.
