Drs Kathy Greenough and Kate Cushing outline the NHS North of Tyne approach to implementing the NICE guideline on familial hypercholesterolaemia

  • FH is common in primary care (prevalence 1 in 500) but is currently under diagnosed
  • The NICE guideline provides comprehensive recommendations on how these patients should be identified and managed in primary and secondary care
  • GPs can identify individuals with possible FH who present with high cholesterol by using current guidelines
  • Practices need to implement a clear strategy to ensure uptake of the NICE guideline by GPs in their daily management of patients with a significant personal or family history of high cholesterol and/or CHD
  • GPs need to be aware of the Simon Broome criteria for a diagnosis of FH (see Box 1)
  • GPs must be aware that CHD risk estimation tools such as those based on the Framingham algorithm cannot be used in people with FH because these individuals are already at a high risk of CHD
  • GPs should offer referral to a specialist lipidologist to all patients with suspected FH in order to confirm the diagnosis, optimise treatment, and identify other family members who may be affected
  • Treatment with lipid-lowering agents is very effective in reducing mortality from ischaemic heart disease
  • Cascade testing using either DNA or LDL-C concentration is used to identify relatives of index individuals with a clinical diagnosis of FH. Age and gender specific LDL-C cut-off charts for diagnosis of first-degree relatives with FH are available in the NICE guideline.

FH=familial hypercholesterolaemia; CHD=coronary heart disease; LDL-C=low density lipoprotein cholesterol

An estimated 4% of the primary care population have hypercholesterolaemia, with a total cholesterol >7.5 mmol/l and/or low density lipoprotein cholesterol (LDL-C) >4.9 mmol/l.1 Approximately 1 in 20 of these individuals will have familial hypercholesterolaemia (FH).1 It is estimated that only a small proportion of individuals affected by FH are identified and treated.

Familial hypercholesterolaemia is a common genetic condition that shows an autosomal dominant pattern of inheritance (half of first-degree relatives and a quarter of second-degree relatives will be affected).1 It is associated with a very high risk of premature coronary heart disease (CHD) if left untreated. Coronary heart disease typically manifests in the fourth decade in men and approximately 10 years later in women; 85% of men with the FH gene will have experienced a myocardial infarction by the age of 60 years.2

The concentration of LDL-C is doubled from birth in people with FH,1,3 but primary prevention consisting of lifestyle changes and treatment with lipid-lowering drugs is highly effective in reducing mortality to population levels or below. Homozygosity (two copies of the FH gene in an individual) is very rare (one per million) and results in a more severe disease with coronary events in childhood.1

Identification of people with FH is important not only because of the risk to the individual but also because of the implications of a diagnosis of FH for the patient’s relatives. As GPs, we are frequently asked to check the cholesterol of a patient who is worried because they have a relative with heart disease or high cholesterol. We are at risk of offering these patients false reassurance if we simply check a random cholesterol level as this can fail to identify many first- or second-degree relatives affected by FH. This article discusses appropriate management based on NICE Clinical Guideline 71 on Identification and management of familial hypercholesterolaemia and also a local guideline developed by NHS North of Tyne, which is based on the NICE guideline.1,4


The Simon Broome criteria are used to make a clinical diagnosis of familial hypercholesterolaemia (see Box 1).5 They are based on:1

  • the characteristic lipid profile in FH
  • a family history of hypercholesterolaemia and/or premature ischaemic heart disease
  • the presence of tendon xanthomata (xanthelasmas and premature corneal arcus may also be present but are not diagnostic).

Use of the Simon Broome criteria results in overestimation and will pick up some people with other forms of hyperlipidaemia in addition to those with FH (e.g. common hypercholesterolaemia and familial combined hyperlipidaemia). In some parts of the UK, genetic testing is available for the three main mutations that have currently been identified as the cause of FH (see Box 1, above). Approximately 80% of individuals with a definite clinical diagnosis of FH will test positive for one of these three mutations.6–8 As more mutations are identified this percentage will increase.

It is important to rule out secondary causes of hypercholesterolaemia, which can occur as a result of hypothyroidism, liver or kidney disease, alcoholism, diabetes, pregnancy, or obesity.1 Some medications can raise cholesterol levels, for example, atypical antipsychotics, corticosteroids, and ciclosporin.9 General practitioners also need to be aware that cardiovascular disease risk assessment tools such as Framingham cannot be used for those individuals with FH since they are already at a significantly increased risk of CHD.1

NHS North of Tyne has produced a local guideline based on the NICE document to help simplify the detection of FH and the management of the patient with high serum lipids.4 This guideline is summarised in an algorithm (see Figure 1, below).4

Box 1: Simon Broome criteria for a diagnosis of FH1

Diagnose a person with definite FH if they have:

  • Cholesterol concentrations as defined in the table below and tendon xanthomas, or evidence of these signs in first- or second- degree relative


  • DNA-based evidence of an LDL-receptor mutation, familial defective apo B-100, or a PCSK9 mutation

Diagnose a person with possible FH if they have cholesterol concentrations as defined in the table below and at least one of the following:

  • Family history of myocardial infarction: aged younger than 50 years in second-degree relative or aged younger than 60 years in first-degree relative
  • Family history of raised total cholesterol: greater than 7.5 mmol/l in adult first- or second-degree relative; or greater than 6.7 mmol/l in child, brother, or sister aged younger than 16 years

Cholesterol levels to be used as diagnostic criteria for the index individual (either pre-treatment, or highest on treatment)

  Total cholesterol
Child/young person
(aged <16 years)
>6.7 >4.0
(aged ?16 years or over)
>7.5 >4.9

FH=familial hypercholesterolaemia; LDL-C=low-density lipoprotein cholesterol
National Institute for Health and Care Excellence (NICE) (2008) CG71. Identification and management of familial hypercholesterolaemia. London: NICE. Reproduced with kind permission. Available at: www.nice.org.uk/CG71

Figure 1: Algorithm for the assessment of severe hypercholesterolaemia4


*Personal history of first-degree relative <60 years with confirmed CHD (i.e. myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention,
and/or definite coronary artery disease on angiography) or second-degree relative <50 years with confirmed CHD, and/or reliable family history of total cholesterol >7.5 mmol
If fasting triglycerides >4.5 mmol/l but less than 10 mmol/l, consider discussion with local adviser
LDL=low density lipoprotein; CHD=coronary heart disease; CVD=cardiovascular disease; HDL=high density lipoprotein

Patients with established cardiovascular disease

People with a personal history of confirmed vascular disease are usually already receiving lipid-lowering treatment. In these patients, the results of the initial lipid profile prior to starting treatment may not be available to the clinician. This will mean that a proportion of patients with FH whose cholesterol levels would have been above the threshold for referral will not have been identified. Clinicians should be aware of this and seek the opinion of a lipid specialist if they have concerns or queries regarding other family members. Secondary causes of hyperlipidaemia still need to be excluded in individuals who have established cardiovascular disease and they should be considered for referral to the lipid clinic using the criteria outlined in Figure 1.

Management of FH

Patients with possible FH who have been identified as having hypercholesterolaemia using the NHS North of Tyne algorithm or the NICE guideline should be referred to the local lipid clinic. Ideally, the clinic will confirm FH or provide an alternative diagnosis; genetic testing may be offered. The patient should then be given lifestyle advice and started on an appropriate lipid-lowering drug. Intensive statin treatment or alternative lipid-lowering drugs will be offered to people with FH, with the aim of lowering LDL-C by 50% or more.1,4 Information about CHD risk should be provided to all patients; and in women of childbearing age, the importance of avoiding statins for 3 months before conception and throughout pregnancy should be discussed.1,4

Cascade testing

People seen in the lipid clinic who are diagnosed with FH should be advised that family members should also be screened.1 In some parts of the country this is undertaken by genetic testing and a referral to the local genetics service may be needed. Such testing may not always be available locally; in which case, first-degree relatives should be advised to visit their own GP and request a fasting lipid profile to be measured. The result of this profile must be interpreted using specific tables devised for diagnosing FH in relatives of an affected person. These tables are available in the NICE guideline.1

It is important to be aware that neither the Simon Broome criteria nor the NHS North of Tyne algorithm for the assessment of hyperlipidaemia can be used to decide whether relatives of a known patient with FH should be referred. First-degree relatives have a 50% pre-test probability of being affected; therefore lower cut-offs of LDL-C apply. The NICE guideline recommends that children with one affected parent are initially assessed by a lipid specialist by the age of 10 years because of the importance of early identification.1

Annual review

All people with FH require an annual review. This can be done in either the lipid clinic or in primary care and should include:1,4

  • fasting lipid profile; comparison with the previous level of LDL-C and an evaluation of its reduction from baseline
  • current drug treatment, concordance, and any problems with side-effects
  • dietetic and lifestyle interventions
  • identification of symptoms or signs of cardiovascular disease with appropriate investigation
  • an update of any family history of CHD events.

The GP should refer a patient with known FH back to secondary care if the patient experiences intolerable side-effects while taking lipid-lowering therapies commonly used in primary care or if this treatment does not reduce the patient’s cholesterol to an agreed target. Children with known FH should remain under the care of the lipidologist as should women planning to embark on a pregnancy in the near future.

It is difficult to know exactly how many GP practices have attempted to embrace the NICE guideline on FH but it is speculated that there is still much work to do in this area. For example, practices could undertake an audit of patient notes to identify which individuals have a significant family history of CHD or a very high cholesterol level. These results would help to determine those patients who may have possible FH and would benefit from a referral to the lipid clinic.

NHS North of Tyne guideline

The NHS North of Tyne guideline on FH will help to raise awareness of the condition among local GPs and also encourage collaboration between GPs and secondary care providers with regards to management and cascade testing. The long-term goal is to reduce the burden of CHD in the region but as yet it is too early to know whether this goal has been achieved.


Familial hypercholesterolaemia is a common condition in primary care and evidence suggests it is currently underdiagnosed. General practitioners have a key role in identifying affected individuals using current guidelines. Treatment with lipid-lowering agents is very effective in reducing mortality from CHD. It is important that GPs refer patients identified in primary care to a lipid clinic in order to confirm the diagnosis, optimise treatment, and identify other affected family members.


The authors would like to acknowledge and thank Dr Jane Skinner (Consultant Community Cardiologist, Newcastle upon Tyne Hospital NHS Foundation Trust) who was the guideline coordinator for the Newcastle, North Tyneside, and Northumberland guideline on familial hypercholesterolaemia.

  • To fully implement the NICE guideline, commissioners will need to be able to fund and ensure that local biochemistry laboratories can provide a service for DNA testing
  • Commissioners will also need to ensure adequate access to specialist lipidologist advice and genetic counselling for affected families
  • Locally commissioned CVD prevention schemes should use the Simon Broome criteria to identify patients with FH
  • A targeted screening regimen aimed at individuals with premature onset CVD or with a family history is likely to be more cost effective than a population screening approach
  • Local drug formularies should allow for specialist initiation of high potency statins for individuals with FH
  • Tariff prices for general medical outpatient = £222 (new), £104 (follow up) (code 300)a

CVD=cardiovascular disease; FH=familial hypercholesterolaemia

  1. National Institute for Health and Care Excellence. Identification and management of familial hypercholesterolaemia. London: NICE, 2008. Available at: www.nice.org.uk/guidance/CG71/NICEGuidance/pdf/English
  2. NHS Evidence website. Turnbull C. Familial hypercholesterolaemia. Available at: www.library.nhs.uk/geneticconditions/viewresource.aspx?resID=126542
  3. Leonard J, Whitelaw A, Wolff O et al. Diagnosing familial hypercholesterolaemia in childhood by measuring serum cholesterol. BMJ 1977; 1: 1566–1568.
  4. Skinner J. Newcastle, North Tyneside and Northumberland guidelines on familial hypercholesterolaemia. Clinical Guideline North of Tyne 16. NHS North of Tyne, 2010.
  5. Scientific Steering Committee on behalf of the Simon Broome Register Group. Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ 1991; 303: 893–896.
  6. Graham C, McIlhatton B, Kirk C et al. Genetic screening protocol for familial hypercholesterolemia which includes splicing defects gives an improved mutation detection rate. Atherosclerosis 2005; 182 (2): 331–340.
  7. Heath K, Humphries S, Middleton-Price H, Boxer M. A molecular genetic service for diagnosing individuals with familial hypercholesterolaemia (FH) in the United Kingdom. Eur J Hum Genet 2001; 9 (4): 244–252.
  8. Humphries S, Whittall R, Hubbart C et al. Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J Med Genet 2006; 43 (12): 943–949.
  9. British Medical Association, Royal Pharmaceutical Society. British National Formulary 60. London: BMJ Group, Pharmaceutical Press, 2010.G