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What's the point of genetic testing for FH?


The PHG Foundation recently reported on updated quality standards for familial hypercholesterolaemia (FH) issued by the National Institute for Health and Care Excellence (see previous news).


One reader, herself an FH patient, commented that she did not see the point of genetic testing, since the few therapies (notably healthy lifestyle modifications and statins) are equally useful in patients with high cholesterol whether or not it is the result of inherited mutations. She also questioned the benefit of giving statins to children based on genetic diagnosis of FH. As an expert on the genetics of FH, and one of the people who helped to put together the 2008 NICE Guidelines and the recent Quality Standards for FH, I would like to address some of these issues.


It is indeed right that people with a clinical diagnosis of FH receive the same lifestyle advice and option of statin therapy whether or not we can find an FH mutation by genetic testing. However, people with a mutation causing FH have unfortunately had the very high ‘bad’ LDL-cholesterol from birth and so their arteries have been ‘furring up’ at a much greater rate than in the general population.  Because of this, the evidence strongly suggests that people with FH should start statins early (sometimes even as teenagers) because their risk of developing atherosclerosis and heart disease is so high! 


There is very good evidence from a group in Holland that children with an FH-causing mutation already have evidence of their arteries being furred up by the age of 10, compared to their non-FH brothers and sisters, that this furring up gets worse as they get older if they are not treated, but that it doesn’t get worse if they are given a statin. 


It is based on this evidence that NICE guidance suggests that for children with a diagnosis of FH (and if the child has inherited the family mutation they definitely do have FH), offering statins by the age of 10 should at least be considered, particularly if their LDL cholesterol is extremely high, or one of their relatives has developed heart disease very early. Of course, everybody thinks that when a child with FH is an adult they should be on statins because of their extreme risk.  


One advantage of having a genetic test is that it may persuade a patient’s general practitioner that they have a disorder requiring treatment.  Unfortunately, we still have examples of where the GP will say (often to a young woman) that although their cholesterol is very high they don’t have any other risk factors and so they don’t need to be taking a statin. Having a genetic result really empowers the patient to make sure they do get the right treatment. 


However, the main use of a genetic test is not for the benefit of the patient themselves but for their relatives.  It allows us to determine unambiguously whether any of their children, brothers or sisters have also inherited the family mutation. If they have, they can then be given lifestyle advice and considered for statin treatment. If they haven’t, they can be given the all clear with regard to the very high risk of atherosclerosis and heart disease (although a healthy lifestyle is advisable for everyone).  


It is this ‘cascade testing’ process of finding relatives in the family who didn’t even know they might have a risk of FH that means that the genetic testing is clinically useful.  In Holland, DNA based cascade testing has been carried out for the last ten years and they have found almost 60% of all the FH patients that they would expect based on the prevalence of 1 in 500 people.  Here in the UK, where cascade testing and genetic testing is not being funded, we have found 10% or maybe 15% at most of the FH patients we expect. This means that the other 85% are living in blissful ignorance but at great danger.


Steve Humphries is British Heart Foundation Professor of Cardiovascular Genetics at University College London (UCL).


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