Pregnancy and child

Study recommends screening toddlers for heart disease risk

"Toddlers should be screened for an inherited form of heart disease … experts suggest," BBC News reports.

A new study looked at the feasibility of screening for familial hypercholesterolaemia (FH), an inherited condition that affects around 1 to 2 in every 250 people in the UK. It can cause abnormally high cholesterol levels.

It doesn't usually cause any noticeable symptoms, but people with FH aged between 20 and 40 are 100 times more likely to have a heart attack than other people their age.

UK researchers tested 10,095 one-year-olds to explore the feasibility of screening for FH. They tested the toddlers at the same time they had routine vaccinations at the age of one.

Researchers found 28 children with FH. The parents of children with FH were then also tested.

The study found not all children with an FH mutation had high cholesterol, however, and some with high cholesterol did not have a known FH mutation.

This means FH mutation testing alone would not be a useful screening test, so the researchers suggest testing cholesterol levels first.

The approach used in the study does have the added benefit of identifying parents with FH who didn't realise the condition ran in their family.

Once FH is diagnosed, it is relatively straightforward to treat through making lifestyle changes and taking drugs known to reduce cholesterol, mainly statins.

This research will help inform the UK's National Screening Committee when considering whether the benefits of screening for FH outweigh the harms.

Where did the story come from?

The study was carried out by researchers from Queen Mary University of London and Great Ormond Street Hospital, and was funded by the UK Medical Research Council. 

It was published in the peer-reviewed New England Journal of Medicine.

The UK media focused on figures indicating that 600 heart attacks a year could be prevented by the screening strategy. These figures, which were not quoted in the study, seem to have been an estimate made by reporters.

There's some confusion over other figures, with different news reports citing different results. That's because the researchers investigated two different cut-off points for high cholesterol.

The cut-off actually used in the study identified 28 children (0.3%), while the researchers say that if they'd used a lower cut off, it would have identified 40 children, or 0.4%.

The researchers concluded that for every 1,000 children screened, four children and then four adults would be diagnosed with FH.

What kind of research was this?

This was a real-world trial of a screening strategy to see whether it was feasible, and how effective it would be at identifying people with FH.

It can't really tell us how many heart attacks might be prevented by screening. This is because it only looked at the number of people identified by the screening test, not at what happened to them afterwards or what would have happened if they'd not been identified.

What did the research involve?

Researchers asked parents bringing their children for vaccination at 92 GP surgeries in the UK if they'd like their children to be screened for high cholesterol as well.

If parents agreed, the children had a small blood sample taken, which was tested for both cholesterol levels and known FH genetic mutations.

Children with high cholesterol and an FH mutation were classed as having FH, and their parents were then tested. Children with high cholesterol and no known FH mutation had a second cholesterol test.

Rather than using a standard cholesterol level as used to test adults, researchers used a measure called multiple of median.

This looks at the average (median) cholesterol score of the children – the researchers then identified children whose score was 1.53 times the average.

This method was used because the estimated optimal cholesterol levels in children are not as well established as in adults.

The researchers searched for common genetic mutations using a quick identification test first, then used more advanced genetic sequencing if children had high cholesterol but no common mutation.

Children were identified as having FH if they had high cholesterol and an FH mutation, or two tests showing high cholesterol.

The parents of these children were then tested, and the parent thought to have FH was offered treatment with statins.

Children who had an FH mutation but low cholesterol were not identified as having FH as the condition only causes problems when people have high cholesterol.

And those who had high cholesterol on two tests but no known FH mutation were assumed to have a mutation that has not yet been identified. 

What were the basic results?

Of the 13,000 children whose parents were invited to take part in the study, 11,010 (84%) agreed to take part.

However, 892 blood tests couldn't be used and 23 results were found to have been wrongly recorded, so the researchers based their research on the 10,095 remaining results.

With the cut-off of cholesterol 1.53 times the median score, the researchers found:

  • 28 children with FH (0.3%, 95% confidence interval [CI] 0.2 to 0.4)
  • 20 children with a known FH mutation
  • 17 children with an FH mutation, but cholesterol lower than the 1.53 times average score
  • 28 parents of children with FH were identified as also having FH, 25 of whom started treatment to lower cholesterol

The researchers then re-ran the figures to see what would have happened if they'd used a lower cut-off cholesterol level of 1.35 times median score, and only tested for FH mutation in those with cholesterol above that level.

They calculated that they would have found 40 children, 32 of them with an FH mutation, and 40 parents.

The study suggests 3 to 4 in 1,000 people have FH.

How did the researchers interpret the results?

The researchers said screening children – and subsequently parents – at the same time as vaccinating children in GP surgeries was "a simple, practical and effective way of screening the population to identify and prevent a relatively common inherited cause of cardiovascular disease".

They say it's better to think of FH as "a marker that indicates an increased risk" of heart disease, as not everyone with FH mutations has high cholesterol, and not everyone with high cholesterol has heart disease.


There's little doubt that FH is a cause of early unexpected heart attacks, and many people who have the condition are unaware of it.

At present, people are only screened for FH after a close relative, such as a parent or sibling, has a heart attack at a young age (cascade screening).

This study suggests far more people would be diagnosed if one-year-olds were screened routinely during vaccinations and the parents of children identified as having FH were then tested.

However, before introducing a screening test, it's important to be sure it has more benefits than harms.

We don't know from the results of this study what the long-term outcome of screening would be – for example, whether it will definitely reduce the number of heart attacks.

Is the cost to the NHS of screening tens of thousands more people every year outweighed by the possible reduction in heart attacks?

The test could also cause problems. If a one-year-old is identified as having FH, it's an extra cause of worry for parents at an age when the child is not likely to see any ill effects and is too young for treatment.

Is that extra worry justified by being able to offer treatment later in life, which may or may not reduce their chances of a heart attack?

Importantly, we also need to know how accurate the test is. In the study, FH was defined as cholesterol 1.5 or 1.3 times that of the average. But what does that actually mean in practical terms?

We don't know whether the children in the study with cholesterol 1.3 times that of others their age will grow up to have heart disease.

The researchers acknowledge that by defining FH as having a certain cholesterol level, they are making a self-sustaining argument. If a condition is defined as being the same as a test result, then how do we challenge the accuracy of the test?

This study doesn't answer these difficult questions. But they need to be considered by the UK's National Screening Committee before any new screening programme can be introduced.

At present, guidance (PDF, 124kb) from the National Institute for Health and Care Excellence (NICE) recommends only screening if someone has one or more close relatives that have had a heart attack at an early age. 

If you're worried about FH, talk to your GP to see if you're eligible for cholesterol testing and tests for FH mutations.  

NHS Attribution