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Evidence statementsEvidence into recommendations
A single retrospective study(Gray, J., Jaiyeola, A., Whiting, M. et al, 2008) in approximately 12,000 individuals in one GP practice demonstrated that electronic note searching identified 402 records that upon case note review found 2 previously unidentified individuals with definite FH and 4 previously unidentified individuals with probable FH [2+]

No evidence using secondary care registers was identified.

A report(Umans-Eckenhausen, M. A., Defesche, J. C., Sijbrands, E. J. et al, 2001) of the first 5-years of a national screening programme based in the Netherlands using a computerised register of pedigrees found that in relatives of probands with a positive DNA diagnosis 2039 out of 5442 were identified as having the same FH mutation as their proband. On average, 20 1st and 2nd degree relatives were tested per proband in whom the diagnosis of FH was confirmed in 8 (37%). At the time of identification of the mutation, 667 of these adults with FH (39%) received some form of lipid-lowering treatment; 1 year later, this had increased to 93%. [2+]

A Health Technology Assessment report(Marks, D., Wonderling, D., Thorogood, M. et al, 2000) which compared modelling of cascade testing of lipid measurements of 1st degree relatives vs population screening concluded that cascade testing is an efficient and cost effective means of case finding for FH [1+]

Two cost-effectiveness studies (Marks, D., Thorogood, M., Neil, H. A. et al, 2003b), (Marks, D., Wonderling, D., Thorogood, M. et al, 2002) concluded that family tracing is the cost-effective compared to no tracing or universal screening.

Two cost-effectiveness studies (Wonderling, D., Umans-Eckenhausen, M. A., Marks, D. et al, 2004), (Marang-van de Mheen, P. J., ten Asbroek, A. H., Bonneux, L. et al, 2002) also found that genetic based method (DNA) is cost-effective compared to no screening

An economic analysis done for the guideline also found that the most cost-effective method for cascade testing is using DNA testing plus cascading from both DFH and PFH mutation negative index cases compared to the Cholesterol method. The model results are stable in sensitivity analysis.

A retrospective study(Bhatnagar, D., Morgan, J., Siddiq, S. et al, 2000) of cascade testing using lipid measurements in two specialized hospital clinics identified 285 1st degree relatives from 259 probands with definite FH. 200 relatives were tested of whom 121 (60%) were found to have FH, demonstrating the feasibility of cascade testing using direct contact by a clinic nurse. [2+]

A prospective study(Marks, D., Thorogood, M., Neil, S. M. et al, 2006) using cascade testing of lipid measurements from a specialized hospital clinic covering a defined geographical area identified 227 eligible adult index cases who had 1075 1st degree relatives. Using indirect contact via the probands 23% of adult relatives who lived within the catchment area were tested of whom 29% had lipid concentrations indicative of FH. 97% of children/young people under 18 years, where the parents were directly approached were tested, of whom 32% had lipid concentrations indicative of FH [2+]
Primary care registers

There is currently no evidence that note searching in primary care is effective..

The GDG considered the results of a single GP based study that undertook electronic note searching. Because of the high proportion of expected cases already identified in this particular practice the results may not be generalisable to the primary care in general.

Primary care has a key role in the diagnosis and identification of individuals with FH and the NICE guidelines on cardiovascular risk modification can only increase the importance of this role. It is therefore necessary to identify the most effective way of finding individuals with FH in a primary care setting and a research recommendation was developed on the use of primary care records for case finding.

Secondary care registers/records

No evidence was identified and a research recommendation was drafted.

Cascade testing

A nationwide strategy of cascade testing is feasible and would result in an improvement in identification of people with FH (with associated higher rates of treatment).

Two studies showed the feasibility of cascade testing in the UK, and also showed the value of approaching relatives directly. The average age of diagnosis is reduced using this strategy.

Overall, the evidence supported the use of a nationwide strategy of cascade testing as this would not then be limited by geographical boundaries. The evidence supported a direct approach to relatives.

A nationwide, proactive, systematic approach to cascade testing is recommended but will need to be evaluated.

From: 4, Identification strategies

Cover of Identification and Management of Familial Hypercholesterolaemia (FH)
Identification and Management of Familial Hypercholesterolaemia (FH) [Internet].
NICE Clinical Guidelines, No. 71.
National Collaborating Centre for Primary Care (UK).
Copyright © 2008, Royal College of General Practitioners.

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