Friday September 14 2007
A blood test can detect familial hypercholesterolaemia
Children as young as 15 months should have their cholesterol tested, multiple news sources reported today. Cholesterol levels should be checked to determine whether they have a genetic condition that leads to high cholesterol levels. The condition, familial hypercholesterolaemia (FH), is estimated to affect around 110,000 people in Britain, and apparently goes undetected in 90% of them. The news reports added that adults aged 20-39 with the disease are 100 times more likely to die from coronary heart disease than people without it.
These reports are based on a study, which has collated the findings from all the available studies on FH to determine the best target age to screen for the disease.
Due to the expense of setting up a population-screening programme, many factors are taken into account before it is approved. These include consideration of the number of people affected by the condition and whether its early detection will make a significant difference. Screening for FH is a subject of debate at the moment because sufferers are usually detected through chance or opportunistic testing. ‘Cascade screening’, where the relatives of those who have it are also tested in a cascade pattern is one suggested method. This latest study contributes another potential screening strategy for careful consideration.
Where did the story come from?
Dr David Wald and his colleagues from Wolfson Institute of Preventive Medicine at Barts and the London School of Medicine and Dentistry carried out the research. Their study, which was published in the British Medical Journal, received no external funding.
What kind of scientific study was this?
This was a systematic review and meta-analysis investigating at what age the differences in cholesterol levels between people with and without the genetic disorder familial hypercholesterolaemia are greatest. The researchers’ theory is that this knowledge would help to determine at what age it would be best to screen the population for FH.
Scientific literature published up to May 2006 was researched for studies that looked at cholesterol levels in people with and without FH. They only included studies that enrolled at least 10 people, who were not taking lipid-lowering medications.
They separated people into six age groups from newborn to 60 and over, and compared the distribution of cholesterol levels for people with the genetic disorder FH (the cases) to those without (the controls) for each age group. They then looked at what would happen if they used different levels of cholesterol for diagnosing FH (called diagnostic thresholds) in each age group. Using these thresholds, they looked at what percentage of people would be correctly detected as having FH and the number of people who were incorrectly diagnosed.
They specified that the amount of incorrect diagnoses had to be 1% or less and identified the diagnostic threshold that gave them this result. They then looked at how many FH cases would be correctly detected using this threshold. The aim was to find which age group provided the highest levels of detection while also having the lowest rate of incorrect diagnoses.
What were the results of the study?
The researchers included 13 studies in their analysis, with a combined total of 1907 people with FH and 16,211 people without. They found that the greatest differences in cholesterol levels between those with FH and those without occurred in children aged 1 to 9 years old. The result of this was that 88% of children with the condition would be identifiable but the figure dropped to 31% for newborn babies and just 5% for those aged 60 or older.
What interpretations did the researchers draw from these results?
The researchers concluded that screening for FH using blood cholesterol levels is most effective when performed in children between the ages of 1 and 9 years old. FH is a genetic disorder passed from parent to child which means that once an affected child is identified, their parents could also be screened. Treatment can then be offered to the affected parent.
What does the NHS Knowledge Service make of this study?
The study was well-designed and reliable. It provides important information that may help to target a specific age group for cholesterol screening in the general populace. However, any screening strategy is dependent on the population to be screened, and how common the condition is in that population. We need further studies in different populations to test the diagnostic thresholds that were determined for this study before we can draw firm conclusions about their effectiveness in different settings.
Setting up a population-screening programme is expensive, and before such a programme is put in place there are many factors to be considered. The authors of the study report that this method of screening would fulfil eight of the 10 criteria for a good screening programme, but its actual cost effectiveness and the availability of adequate facilities to perform the screening still need to be investigated. It should also be noted that this screening programme is aimed to detect people with FH. High cholesterol is also a problem for many people who do not have this disease, but they would not be detected using this screening programme.
It is also important to remember that the risk of coronary heart disease is not based on cholesterol alone, and is often an accumulation of several risk factors. If you are a young, non-diabetic, non-smoker, of healthy weight and with low blood pressure, your heart disease risk is likely to be at the lower end of the scale in spite of a raised cholesterol level. Therefore newspaper reports that the detection of raised cholesterol in young children ‘would leave a Sword of Damocles hanging over [them]’ is not necessarily the case.
Sir Muir Gray adds…
All children born in the UK are at high risk of vascular disease because, compared with children in other countries, British children will grow into a high-risk population.
It is already possible to identify people at very very high risk of heart disease caused by familial hypercholesterolaemia by contacting the relatives of all people who have a heart attack under the age of 50. This is not routinely done at present.