Rapid Responses to:

EDITORIALS: Ned Calonge and Janelle Guirguis-Blake Screening for familial hypercholesterolaemia BMJ 2007; 335: 573-574 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Screening for familial hypercholesterolaemia: a public health opportunity

David S Wald, Jon P Bestwick, Nicholas J Wald   (26 September 2007)

Screening for familial hypercholesterolaemia: a public health opportunity 26 September 2007
David S Wald, Consultant Cardiologist and Senior Lecturer Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, London EC1M 6BQ, Jon P Bestwick, Nicholas J Wald Send response to journal: Re: Screening for familial hypercholesterolaemia: a public health opportunity	Calonge and Guirguis-Blake in their editorial1 are, we believe, too negative about our screening proposal for familial hypercholesterolaemia,2 for the following reasons: 1. They incorrectly state that we proposed that people with cholesterol levels greater than the 95th centile would be screen positive (ie a false-positive rate of 5%). In fact we proposed a false-positive rate 1/50th of this (0.1%).2 It is the potential to achieve a high detection rate with such a low false-positive rate that makes screening a practical possibility. 2. Our paper showed the wide discrimination in cholesterol values between affected and unaffected children between 1 and 9 years of age. It is this new observation and the high screening performance that follows from it that underpins our proposal. 3. It is recognised that early treatment with statins will prevent the adverse effects of familial hypercholesterolaemia.3 There is no reason to present new evidence on this as implied by the editorial. 4. Cascade testing without identifying all, or nearly all, affected families would not be sufficiently effective. A “general sweep” in the population is required to identify affected individuals before cascade testing could take over from testing everyone.4 5. The editorial states that various expert groups, such as the US Preventative Service Task Force argue against population screening,5 but offer no better alternative. Our proposed child-parent screening proposal offers a simple solution that could later be converted to a cascade testing approach which they advocate. The child-screening strategy we propose meets the main criteria necessary for a worthwhile screening test. Familial hypercholesterolaemia is a serious disorder with a known prevalence and natural history. Nearly all cases could be identified with a very low false positive rate in children aged 1 to 9 years and an effective and safe preventive treatment is available that can avert the serious medical consequences of the disorder. The screening test is simple and safe and while the precise costs of screening need to be determined, there is no reason why it should be expensive, based as it is on a simple cholesterol test. Confirmatory DNA testing would increase the cost and miss about 20% of cases,6 so cholesterol testing alone may be preferred. The acceptability of the approach needs to be established, but with appropriate information and presentation, it is likely that most people would welcome a simple and safe means of reducing a high risk of early heart disease in children and their parents. There is therefore no rational reason for rejecting the proposed method of screening. It is a potentially important public health opportunity, recognising that before recommending such screening on a routine basis a feasibility project is needed. References 1. Calonge N, Guirguis-Blake J Screening for familial hypercholesterolaemia BMJ 2007;335:573-574 2. Wald DS, Bestwick JP, Wald NJ. Child-parent screening for familial hypercholesterolaemia: screening strategy based on a meta-analysis. BMJ 2007 335:599 3. Scientific Steering Committee on behalf of the Simon Broome Familial Hyperlipidemia Register Group. Mortality in treated heterozygous familial hypercholesterolemia: implications for patient management. Atherosclerosis 1999;142:105-12 4. Morris JK, law MR, Wald NJ. is cascade testing a sensible method of screening a population for autosomal recessive disorders? Am J Med Genet 2004;128A:271-5 5. US Preventive Services Task Force. Screening for lipid disorders in children: US Preventive Services Task Force recommendation statement. Pediatrics 2007;120:e215-9 6. Humphries S E, Cranston T, Allen M et al. Mutational analysis in UK patients with a clinical diagnosis of familial hypercholesterolaemia; relationship with plasma lipid traits, heart disease risk and utility in relative tracing. J Mol Med 2006;84:203-214 Competing interests: None declared