Focus on: Familial hypercholesterolaemia

A FH researcher at work in the lab at University College London

Too much fatty food is a cause of high cholesterol for many of us, but for about 250,000 people in the UK, it’s all in the genes. Sarah Brealey speaks to Professor Steve Humphries, BHF Chair of Cardiovascular Genetics at University College London, to find out more.

Cholesterol plays a vital part in how our body works, but if levels get too high, it increases our risk of heart disease. For most of us, this doesn’t happen until we’re in our 40s, and a common cause is eating too much saturated fat in things like butter, cheese, cakes and pastries.

So there’s a lot we can do to keep the levels under control, and we should all try to have a healthy lifestyle to reduce our risk of heart disease.

But for some people, it’s not just a question of lifestyle and getting older. About one in 250 people has familial hypercholesterolaemia (FH), an inherited condition that means their cholesterol levels are higher than normal from birth. It’s caused by an abnormal gene and, despite it putting people at high risk of early heart disease, most of them don’t even know they have it.

What’s the difference between FH and standard high cholesterol?

Anyone can develop high cholesterol as they age, but FH is a genetic condition, passed on to you by one of your parents. When you have FH, your cholesterol is high from birth, whereas most people’s cholesterol goes up as they get older and they may be 50, 60 or 70 before their cholesterol is considered high enough to increase their risk of heart disease. So it’s not that the cholesterol itself is  any different, but that your risk of heart disease is much higher because you’ve had high cholesterol for so much longer. Someone who is 40 with FH could easily have the heart attack risk of a 70 year old.

What problems can FH cause?

If untreated, about 50 per cent of men and 30 per cent of women with FH will develop coronary heart disease by the time they’re 55

If untreated, about 50 per cent of men and 30 per cent of women with FH will develop coronary heart disease by the time they’re 55.

On average in the UK, one person a day with FH has a heart attack. About a third of people don’t survive their first heart attack, and many who do survive will have damaged hearts.

The good news is that a 2008 study part-funded by the BHF found that people with FH who are diagnosed and treated before they develop heart disease generally live as long as people who don’t have FH. So it’s really important to get diagnosed as early as possible.

How do I know if I have FH?

You may not have any signs, as they only happen when you have FH for a long time, and some people never get any. The classic signs of FH are lumps and bumps around your knuckles or Achilles tendon (caused by cholesterol deposits), yellow cholesterol build-up around the eyes and eyelids, or a pale ring around the iris of your eye. However, you can also get these last two signs for reasons other than FH.

What can I do?

SaladWhether you have FH or not, it’s important that you eat a healthy balanced diet that is low in saturated fat and includes plenty of fresh fruit and vegetables. Keeping fit and active will also help to keep your heart healthy and it’s essential that you don’t smoke.

If you have FH, a healthy lifestyle alone will not be enough to reduce your cholesterol, so you will also need to take medication.

Can I get tested for it?

It is important to identify FH as early in life as possible, so that you can get treatment and support

Yes, you can be tested. The first step is to go to your doctor to have your cholesterol checked. If a close relative has had a heart attack at a young age (before 55 in a man and before 65 in a woman), then it’s important that you do this.

If your doctor considers that you may have FH, he or she should refer you to a specialist for an assessment, which is likely to include gene tests. The specialist will explain which of your relatives should be checked out, too.

I’ve been told I have FH – who else needs to be tested?

First-degree relatives (parents, children, brothers and sisters) of someone with FH should be tested. If a relative who is tested does not have FH, there is no need to test their children. If a relative does have FH, their first-degree relatives should also be tested, and so on.

It is important to identify FH as early in life as possible, so that you can get treatment and support. It is particularly important that children – and adults – with FH don’t start smoking, as this has a big impact on their future risk of heart disease.

Gene puzzle

Familial hyper diagram There are three genes in which we know mutations (a permanent change in the DNA sequence) can cause FH. When we look at those three genes in people with FH, we can find mutations in about 80 per cent of cases. We are now looking at what is going on in the other 20 per cent. It may be that there is another gene to find.

It’s an exciting possibility that, if we find a new gene in which defects cause high cholesterol, we could develop a new drug to treat it. In 2003, scientists found the third gene in which mutations cause FH. Less than ten years later, a drug that targets the protein made by this gene is being trialled and seems to be effective in lowering cholesterol in both FH and non-FH patients. It is hoped that it may be available in two to three years’ time.

What does treatment involve?

FH can be easily and effectively treated with a cholesterol-lowering statin. Usually, a high-intensity statin such as atorvastatin or rosuvastatin is needed to bring it down. Sometimes a different cholesterol-lowering drug called ezetimibe is given as well as a statin. Regular follow-up appointments are important, too. Lifestyle changes (see What can I do, above) can also reduce your risk of heart disease.

How is it inherited?

FH can be easily and effectively treated with a cholesterol-lowering statin

FH is caused by changes in one of three genes. Genes are the DNA instructions that our body uses to tell every cell how things should function.

The genes involved in FH tell the body to produce proteins that are involved in clearing LDL cholesterol – the harmful type of cholesterol – from the bloodstream. So if one of them is faulty, then your body won’t get the correct instructions.

If someone carries a faulty gene – and therefore has FH – then there is a 50:50 chance that they will pass it on to each of their children.

I’ve heard that most people with FH have not been diagnosed – why is that?

There are several reasons, but one problem is that there is no national programme for FH in England, and official guidelines to improve screening and treatment are often not followed. This means that people are having heart attacks that could have been prevented. So it’s important to talk to your doctor if you think FH runs in your family.

There is better news in Scotland and Northern Ireland, which have national screening programmes, and also in Wales where the genetic testing programme has been helped with funding from the BHF.

We’re also funding an audit of FH services across the UK to give us a clearer picture of what’s being done.

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