Background

Familial hypercholesterolaemia (FH) is a common inherited disorder of lipid metabolism (1) causing high levels of low-density-lipoprotein cholesterol (LDL-C) which frequently lead to early coronary heart disease (CHD). Roughly half of men with FH, if untreated, will have developed clinically evident CHD by the age of 55 years, while affected women from the same families typically develop CHD about 9 years later than their affected male relatives. A significant reduction in the morbidity and mortality of the disease can be achieved through changes in lifestyle and the use of statins to lower cholesterol (2), but currently the vast majority of affected individuals in the UK remain undiagnosed (probably 85% of the predicted 100,000 cases). Effective management of FH requires specialist input, and GPs may not recognise that patients with FH need particularly aggressive lipid-lowering treatment to reduce this single major heart disease risk factor. Testing the families of known cases of FH (cascade testing) can identify those with FH and modelling indicates this will be cost-effective (3), but to date, resources have not been available to implement systematic family tracing. Currently, three genes (LDLR, APOB, PCSK9) have been identified where mutations have been found that cause the disorder (4).

Following the genetics White Paper Our inheritance, our future: realising the potential of genetics in the NHS, the DH funded a pilot project of systematic cascade testing for FH, using LDL-C measures to diagnose relatives (The DH FH Cascade Testing Audit Project). The pilot was run at five locations in England to assess the feasibility of implementing a genetic service
in a mainstream healthcare setting (Lipid Clinics), and the resulting recommendations are reported here.

Main Recommendations
Cascade testing, using specially-trained nurses integrated in Lipid Clinics (a secondary referral outpatient setting), is feasible, desirable, cost-effective and acceptable to patients and clinicians. For effective implementation the following are required:

A. Infrastructure
An integrated national infrastructure of Lipid Clinics should be developed, so that relatives, wherever they live, have access to the service. A national patient register, using suitable software, is required.

B. Diagnosis of FH
DNA testing should underpin FH cascade testing, as the use of cholesterol (LDL-C) measurements for the diagnosis of FH gives poor sensitivity and specificity. Two laboratories should be identified to do this testing.

C. Children
Specialist services must be developed for the management of young people with FH. Childfriendly
environments, preferably integrated in family clinics, will be required.

D. Improve awareness of FH in Primary Care
Education and incentives are needed for primary care teams, to ensure patients with FH are identified and offered appropriate care.