Early Childhood Screening for Familial Hypercholesterolemia May Reduce Later CVD

Larry Hand

October 27, 2016

LONDON, UK — Screening for familial hypercholesterolemia (FH) during early childhood vaccination visits in primary care could routinely identify children and parents who are at risk of cardiovascular disease, according to new research[1].

The study was published in the October 27, 2016 issue of the New England Journal of Medicine.

"Child-parent screening for FH is an effective, feasible, and acceptable method of population screening. This, for the first time, provides the potential to identify nearly all children and their parents at the highest risk of an inherited premature ischemic heart disease event so preventive treatment can be started early," Dr David S Wald (Barts and the London School of Medicine and Dentistry, UK) told heartwire from Medscape.

"Childhood vaccination is an ideal opportunity to screen because parents are motivated and uptake is high," he said.

Wald and colleagues analyzed results of capillary blood tests of 10,095 children 1 to 2 years old taken at 92 UK general medical practices between March 2012 and March 2015 during routine immunization visits. They also tested parents of children who tested positive for FH.

Using a prespecified cutoff value of 1.53 multiples of the median (MoM), they identified 28 children (0.3%) with positive screening results for FH, including 20 children with an FH mutation and eight children who had high cholesterol levels on repeat visits 3 months later. They identified 17 additional children with cholesterol levels below the cutoff value who had FH mutations.

Using the cutoff value of 1.35 MoM plus a mutation, or two cholesterol values of 1.50 MoM or more, they identified 40 children (0.4%) with positive screening results, as well as 40 parents who had positive results.

For every 1000 children screened, they identified eight individuals (four children and four parents) as positive for FH.

Asked if the new results required rethinking current practices, Wald replied, "Yes, because the current method of screening, so-called cascade testing, has been shown to miss large numbers of affected individuals so is an inadequate method of population screening. Child-parent screening overcomes this limitation.

"We also need to rethink whether heterozygous FH is really a disorder, because about a third of children in whom we found an FH mutation (and their parents with the same mutation) did not have high cholesterol. There must be other factors besides the FH mutation that determine a person's cholesterol and therefore their future risk of ischemic heart disease," he said.

He continued, "This means that FH is better regarded as a risk factor for a premature ischemic heart disease event, rather than a disorder in its own right, in the same way as a BRCA gene mutation is a risk factor for breast cancer rather than the disorder. Screening for FH, therefore, should start with the cholesterol level rather than the FH mutation, although both are necessary to identify those at highest risk of inherited ischaemic heart disease.

"This research provides the evidence to allow public-health agencies to consider offering child-parent screening routinely at the time of childhood vaccination," he concluded.

In an accompanying editorial[2], Dr Brian W McCrindle (Hospital for Sick Children, Toronto, ON) and Dr Samuel S Gidding (Nemours Cardiac Center, Wilmington, DE) write that the study by Wald and colleagues "identifies additional cases and cases at a younger age, when treatment has greater benefits."

The study "provides a critical evaluation of an efficient and effective screening and identification strategy that appropriately targets children. This strategy affords the greatest opportunity for the prevention of atherosclerosis and achievement of a low lifetime risk of cardiovascular disease," they write.

The Medical Research Council funded this research. Wald reported being a founder and shareholder in Polypill Ltd. Disclosures for the coauthors are listed on the journal website. Gidding reported being an unpaid member of the scientific advisory board and publications committee of the FH Foundation. McCrindle reported relevant relationships with Aegerion, Amgen, Daiichi Sankyo, Bristol-Myers Squibb, Janssen, Merck, and Cellaegis Devices outside the submitted work.

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