Screening infants to identify inherited heart disease

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Inherited heart disease can be successfully detected within families by screening one-to-two-year-old children at the time of their routine vaccinations, according to a clinical study led by researchers at Queen Mary University of London (QMUL) that involved over 10,000 children.

The researchers from QMUL’s Wolfson Institute of Preventive Medicine estimate that, with effective treatment, the screening strategy could prevent about 600 heart attacks in people under the age of 40, each year in England and Wales, if the programme was rolled out by public health agencies.

Familial hypercholesterolaemia (FH) is a genetic disorder characterised by high cholesterol levels and is the main inherited cause of early heart disease. Without preventive medication young FH adults have about a 10-fold increased risk of a heart attack before the age of 40.

In the largest study to date of cholesterol and FH mutations in children, the prevalence of FH mutations in children was found to be about one in 270, nearly double that previously reported (one in 500).

Because of the inherited nature of the disorder every child identified with the disorder will have one parent also affected. This offers the opportunity of screening two generations at the same time – so-called child-parent screening.

Lead researcher Professor David Wald said: “This is the first demonstration that child-parent screening works on a large scale. It’s the only screening method that stands a reasonable chance of covering the whole population and identifying those at highest risk of an early heart attack.

“Now that we’ve demonstrated this as being effective across England, the next step is for public health agencies to consider offering this routinely at the time of childhood vaccination to test all children aged one to two years.”

The study, funded by the Medical Research Council, involved screening at 92 general practices across England – 10,059 children were tested for high cholesterol and FH genetic mutations and 40 were found to be FH positive.

Once an FH positive child was found, the parents were then contacted for screening, revealing an additional FH positive parent. Overall, one person at high risk of early heart attack was identified for every 125 people tested.

The child-parent screening strategy identifies children and their parents together so that early preventive action can be taken. Medication, including statins, can be started immediately in the parents and in children as teenagers, and advice can be given on sensible diets and avoidance of smoking.

Wald added: “This is an example of an effective screening strategy being combined with routine vaccination, which has clear advantages. No extra clinic visits are needed and uptake is high because parents are already focussed on the future health of their children and the family as a whole. The one-stop service requires no new clinical infrastructure and is simple and inexpensive to implement.”

The researchers say that GPs and parents welcomed the screening opportunity, with 84% of families accepting it.

Background: Child–parent screening for familial hypercholesterolemia has been proposed to identify persons at high risk for inherited premature cardiovascular disease. We assessed the efficacy and feasibility of such screening in primary care practice.
Methods: We obtained capillary blood samples to measure cholesterol levels and to test for familial hypercholesterolemia mutations in 10,095 children 1 to 2 years of age during routine immunization visits. Children were considered to have positive screening results for familial hypercholesterolemia if their cholesterol level was elevated and they had either a familial hypercholesterolemia mutation or a repeat elevated cholesterol level 3 months later. A parent of each child with a positive screening result for familial hypercholesterolemia was considered to have a positive screening result for familial hypercholesterolemia if he or she had the same mutation as the child or, if no mutations were identified, had the higher cholesterol level of the two parents.
Results: The use of a prespecified cholesterol cutoff value of 1.53 multiples of the median (MoM, corresponding to a percentile of 99.2) identified 28 children who had positive screening results for familial hypercholesterolemia (0.3% of the 10,095 children; 95% confidence interval [CI], 0.2 to 0.4), including 20 with a familial hypercholesterolemia mutation and 8 with a repeat cholesterol level of at least 1.53 MoM. A total of 17 children who had a cholesterol level of less than 1.53 MoM also had a familial hypercholesterolemia mutation. The overall mutation prevalence was 1 in 273 children (37 in 10,095; 95% CI, 1 in 198 to 1 in 388). The use of an initial cholesterol cutoff value of 1.35 MoM (95th percentile) plus a mutation, or two cholesterol values of at least 1.50 MoM (99th percentile), identified 40 children who had positive screening results for familial hypercholesterolemia (0.4% of the 10,095 children, including 32 children who had a familial hypercholesterolemia mutation and 8 who did not have the mutation) and 40 parents who had positive screening results for familial hypercholesterolemia.
Conclusions: Child–parent screening was feasible in primary care practices at routine child immunization visits. For every 1000 children screened, 8 persons (4 children and 4 parents) were identified as having positive screening results for familial hypercholesterolemia and were consequently at high risk for cardiovascular disease. (Funded by the Medical Research Council.)

David S Wald, Jonathan P Bestwick, Joan K Morris, Ken Whyte, Lucy Jenkins, Nicholas J Wald

Queen Mary University of London material
New England Journal of Medicine abstract

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