Study of Child-Parent Screening for Familial Hypercholesterolaemia
Lead Research Organisation:
Queen Mary University of London
Department Name: Wolfson Institute
Abstract
Familial hypercholesterolaemia (FH) is an inherited condition that causes high blood cholesterol levels from birth and an extremely high risk of heart attack at a young age ? about one hundred times the usual risk before age 40. There are about 115,000 people with FH in the UK, but only about 15,000 have been identified, leaving about 100,000 children and adults undiagnosed and without life-saving cholesterol lowering treatment. This project aims to test a new screening strategy (child-parent screening), which for the first time, has the potential to systematically identify and treat nearly all cases of FH in the population.
Research published in 2007 showed that a cholesterol test undertaken between the age of 1 and 9 would identify about 90% of all FH cases, with only about 1 per 1000 unaffected children falsely classified as positive. Screening children when they attend for immunization at 1 to 2 years of age by combining a blood test and immunization in a single procedure has been shown to be a feasible and acceptable method of implementing this screening method.
Each identified child has at least one affected parent (FH is inherited from parent to child) so screening children provides a means of identifying (and consequently treating) affected adults and children who have a high risk of a heart attack, before the onset of disease. There is now a need to test the accuracy and cost-effectiveness of child-parent screening in practice.
This award, if granted, would fund the screening, blood collection and data analysis in 10,000 children from 76 UK General Practices over a 3 year period. The immediate value of the results would be the formal scientific evaluation of this screening approach and the quantitative assessment of the measurements needed in screening. The longer term goal is the provision of a universal screening policy capable of identifying nearly all families with FH in the population and providing the opportunity to start treatment that could prevent about 800 deaths in young people each year.
Research published in 2007 showed that a cholesterol test undertaken between the age of 1 and 9 would identify about 90% of all FH cases, with only about 1 per 1000 unaffected children falsely classified as positive. Screening children when they attend for immunization at 1 to 2 years of age by combining a blood test and immunization in a single procedure has been shown to be a feasible and acceptable method of implementing this screening method.
Each identified child has at least one affected parent (FH is inherited from parent to child) so screening children provides a means of identifying (and consequently treating) affected adults and children who have a high risk of a heart attack, before the onset of disease. There is now a need to test the accuracy and cost-effectiveness of child-parent screening in practice.
This award, if granted, would fund the screening, blood collection and data analysis in 10,000 children from 76 UK General Practices over a 3 year period. The immediate value of the results would be the formal scientific evaluation of this screening approach and the quantitative assessment of the measurements needed in screening. The longer term goal is the provision of a universal screening policy capable of identifying nearly all families with FH in the population and providing the opportunity to start treatment that could prevent about 800 deaths in young people each year.
Technical Summary
A common cause of ischaemic cardiovascular disease in young adult life is the autosomal dominant inherited disorder Familial Hypercholesterolaemia (FH). There are about 100,000 undiagnosed people with FH in the UK population. Identifying affected individuals before the onset of disease is important because statin therapy, which lowers blood cholesterol levels, substantially reduces the risk of heart disease and stroke.
A recent meta-analysis of observational studies has shown that a cholesterol measurement in children aged 1 to 9 identified about 90% of affected individuals with only about one per thousand unaffecteds falsely classified as positive. Screening newborns or adults was much less effective. The acceptability of screening children when they attend for routine immunization at 1 to 2 years of age has been demonstrated in a General Practice feasibility study. Each affected child will have one affected parent, identifiable as the one with the higher cholesterol, so screening children provides a means of identifying and treating both child and parent in a systematic manner. This has been called child-parent screening. There is now a need to test the predicted accuracy of child-parent screening in practice with a view to specifying an effective primary care based population screening policy.
We propose a study of child-parent screening in 76 UK General Practices, administered through the MRC General Practice Research Framework using DNA analysis on all the children screened (10,000) as the confirmatory test. The results of the study will determine the screen positive rate based on total cholesterol, the detection rate and false positive rate based on DNA analysis and the cost-effectiveness and acceptability of a national screening programme in Britain. This will provide independent scientific evidence on the accuracy of child-parent screening and determine what modifications, if any, to the screening protocol are needed. The study will last three years and cost approximately #833,000.
A recent meta-analysis of observational studies has shown that a cholesterol measurement in children aged 1 to 9 identified about 90% of affected individuals with only about one per thousand unaffecteds falsely classified as positive. Screening newborns or adults was much less effective. The acceptability of screening children when they attend for routine immunization at 1 to 2 years of age has been demonstrated in a General Practice feasibility study. Each affected child will have one affected parent, identifiable as the one with the higher cholesterol, so screening children provides a means of identifying and treating both child and parent in a systematic manner. This has been called child-parent screening. There is now a need to test the predicted accuracy of child-parent screening in practice with a view to specifying an effective primary care based population screening policy.
We propose a study of child-parent screening in 76 UK General Practices, administered through the MRC General Practice Research Framework using DNA analysis on all the children screened (10,000) as the confirmatory test. The results of the study will determine the screen positive rate based on total cholesterol, the detection rate and false positive rate based on DNA analysis and the cost-effectiveness and acceptability of a national screening programme in Britain. This will provide independent scientific evidence on the accuracy of child-parent screening and determine what modifications, if any, to the screening protocol are needed. The study will last three years and cost approximately #833,000.