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Meta-Analysis
. 2007 Sep 22;335(7620):599.
doi: 10.1136/bmj.39300.616076.55. Epub 2007 Sep 13.

Child-parent screening for familial hypercholesterolaemia: screening strategy based on a meta-analysis

David S Wald  1 , Jonathan P Bestwick, Nicholas J Wald
Affiliations
Meta-Analysis

Child-parent screening for familial hypercholesterolaemia: screening strategy based on a meta-analysis

David S Wald et al. BMJ. .

Abstract

Objective: To develop a population screening strategy for familial hypercholesterolaemia.

Design: Meta-analysis of published data on total and low density lipoprotein (LDL) cholesterol in people with and without familial hypercholesterolaemia according to age. Thirteen studies reporting on 1907 cases and 16 221 controls were used in the analysis. Included studies had at least 10 cases and controls with data on the distribution of cholesterol in affected and unaffected individuals.

Main outcome measures: Detection rates (sensitivity) for specified false positive rates (0.1%, 0.5%, and 1%) in newborns and in age groups 1-9, 10-19, 20-39, 40-59, and > or =60 years.

Results: Serum cholesterol concentration discriminated best between people with and without familial hypercholesterolaemia at ages 1-9, when the detection rates with total cholesterol were 88%, 94%, and 96% for false positive rates of 0.1%, 0.5%, and 1%. The results were similar with LDL cholesterol. Screening newborns was much less effective. Once an affected child is identified, measurement of cholesterol would detect about 96% of parents with the disorder, using the simple rule that the parent with the higher serum cholesterol concentration is the affected parent.

Conclusions: The proposed strategy of screening children and parents for familial hypercholesterolaemia could have considerable impact in preventing the medical consequences of this disorder in two generations simultaneously.

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Conflict of interest statement

Competing interests: DW has filed a patent application (GB 2414186A) for a medical device that combines medicinal injection and blood sampling.

Figures

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Fig 1 Plots of detection rates against false positive rates for total and LDL cholesterol concentrations according to age in years
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Fig 2 Estimated detection rate for a 0.1% false positive rate for total and LDL cholesterol according to studies in children aged 1-9 years
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Fig 3Relative frequency distributions of total and LDL cholesterol in children aged 1-9 with and without familial hypercholesterolaemia, showing detection rates (DR) and likelihood ratios for cholesterol cut offs set to yield false positive rates (FPR) of 0.1%, 0.5%, and 1%
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Fig 4 Top: distributions of LDL cholesterol (MoMs) in individuals aged 20-39 with and without familial hypercholesterolaemia; bottom: distribution of ratio of all possible pairs of affected and unaffected individuals with familial hypercholesterolaemia (shaded area (4%) indicates proportion of differences <1 (affected less than unaffected) and represents proportion of parents who would be misclassified if parent with higher cholesterol concentration was assumed to have disorder)
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Fig 5 Effect of screening children without and with DNA diagnosis
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Fig 6 Flow diagrams to illustrate the effect of screening parents of affected children without and with DNA diagnosis
See this image and copyright information in PMC

Comment in

References

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