Lloydspharmacy.com Health - Familial hypercholesterolaemia (FH)

Reviewed by Dr Neal Uren, consultant cardiologist and Dr Dan Rutherford, GP

What is familial hypercholesterolaemia?

Cholesterol is one of the body's fats. High cholesterol levels are usually caused by poor diet and lifestyle combined with the way an individual produces cholesterol in their liver.

But for 1 in 500 of the population, a specific genetic defect causes high cholesterol levels in the blood.

People with inherited or familial hypercholesterolaemia (FH) have a lack of low-density lipoprotein receptors that remove cholesterol from the blood.

These people have high cholesterol levels from birth and this leads to an early development of hardening of the arteries and vascular diseases.

Siblings and children of a person with FH have a 50 per cent risk of getting the defect. The disease does not skip generations. This means that children and grandchildren of family members who don't have the defect are not at risk from FH.

What causes FH?

Term watch

High-density lipoproteins (HDL) mop up excess cholesterol and return it to the liver for reprocessing.

HDL is often called good cholesterol and raised amounts give protection against heart disease.

Low-density lipoproteins (LDL) transport cholesterol from the liver to elsewhere in the body.

LDL is known as bad cholesterol because it deposits cholesterol in the lining of your arteries.

The more LDL you have, the more likely you are to develop heart disease.

On all cells of the body, and mainly in the liver, there is a receptor that allows low-density lipoprotein (LDL) cholesterol to be cleared from the bloodstream.

People with FH have a defect in the gene of this LDL-cholesterol receptor. This causes LDL cholesterol to accumulate in the blood and ultimately in the walls of your arteries.

Of all the different cholesterol particles in your circulation, LDL cholesterol is the most likely to contribute to fatty deposits in your arteries. Hard, narrow arteries can restrict blood flow around your body and to vital organs such as your heart.

The genetic basis for the LDL-cholesterol receptor has been well researched and today we know of more than 300 different gene defects that lead to FH.

What are the symptoms of FH?

You can't feel whether you have high cholesterol levels in the same way that you can a headache, but the following can indicate FH.

Cholesterol deposits over tendons, eg the Achilles tendon, or in the skin around the eyes. These look like whitish streaks on the skin.
A family history of raised cholesterol and premature coronary artery disease.
Symptoms of cardiovascular disease, such as chest pain which develops as a result of the narrowing of the arteries (atherosclerosis).

The development of atherosclerosis begins in childhood and can be compared to calcium deposits in a water pipe. Gradually, the opening gets smaller and smaller, the inner surface becomes more irregular and blood can no longer flow freely through.

If it becomes so narrow that the blood supply stops, the tissue dies.

This means that if a blood clot is situated in one of the vessels of the heart (the coronary arteries), the area of the heart muscle supplied by that vessel is injured irreversibly (heart attack). Scar tissue forms and the heart is left weakened.

What else affects the cholesterol level?

Both hereditary and environmental factors affect the cholesterol level.

We know that diet is a major factor, with diets that are high in saturated fat (cakes, pastry, meat, dairy products) raising cholesterol levels.

The cholesterol level in northern European countries is higher than in southern Europe and much higher than in Asia.

Raised blood cholesterol can also be a feature of the following diseases:

hypothyroidism (underactive thyroid gland)
kidney diseases
diabetes
alcohol abuse.

What can I do myself?

While high cholesterol is the most important risk factor in developing arterial disease, other factors also have an influence on this process. It is therefore important to establish a sensible lifestyle in childhood and continue this into adulthood.

A diet low in cholesterol and fat and rich in wholemeal bread, fruits, vegetables, small amounts of lean meat, fish and olive oil is generally recommended.
Moderate consumption of red wine reduces the damaging effects of LDL cholesterol (bad cholesterol) and increases HDL cholesterol (good cholesterol). However this is not appropriate for children or teenagers.
It is very important to stop smoking. Smoking significantly increases the risk of a serious heart condition in patients with very high cholesterol levels.
An active lifestyle and physical exercise strengthen the heart and reduce the risk of cardiovascular disease.

How does the doctor make the diagnosis?

After a 12-hour fast in which only water is consumed, a blood sample is taken to determine the level of:

LDL cholesterol
HDL cholesterol
triglyceride
total cholesterol in the blood.

Test levels are adjusted to take into account age, weight, diabetes, kidney diseases and decreased metabolism.

It should be noted that the cholesterol count rises during pregnancy and drops significantly for at least three months after a heart attack. This could lead to a misdiagnosis in mild cases of high cholesterol, but not with respect to FH.

The results suggest FH if LDL cholesterol levels are raised to a very high level.

If both LDL cholesterol and triglycerides are raised, you may have familial combined hyperlipidaemia, which is another genetic condition. Triglyceride is another fat found in the blood.

The doctor can make a rough estimate of the extent of cardiovascular disease by checking the pulse, the blood pressure, listening to the heart and large arteries, checking kidney function with a blood test and arranging an exercise stress test.

How is FH treated?

FH is mostly treated with medicines and diet. Treatment with genetic manipulation is still at the experimental stage.

Medicine is always necessary in combination with lifestyle changes because it is difficult to normalise cholesterol levels by dietary changes alone.

Statins (eg Simvastatin, Atorvastatin, Rosuvastatin) are the first choice for medicines. These reduce the production of LDL cholesterol by the liver, which decreases LDL cholesterol blood levels by up to 50 per cent. They can be given in a wide range of strengths and doses and are generally well tolerated, although a small percentage of patients report muscle pain and stiffness on taking them that settles once they have been stopped..
Ezetrol (Ezetimibe) is a modern non-statin medication given once daily. It's a cholesterol absorption inhibitor and is an effective treatment if lipid levels remain high despite statin treatment or if there are unacceptable side effects from taking a statin. It can be given in combination with a statin, sometimes in a once-daily combination drug.
Other medicines used are anion exchange resins (also known as bile acid sequestrants eg Questran) and fibrates (eg Bezalip mono and Modalim). The former increase the excretion of LDL-cholesterol by preventing its reabsorption from the intestine.

A combined treatment with statins, anion exchange resins and diet will reduce the total cholesterol level in the blood by 30 to 40 per cent and the LDL cholesterol by a greater amount.

Children and adults should be referred to a specialist lipid clinic.

Future prospects

The progress of FH varies greatly. However, in a particular family it tends to follow a similar pattern.
The risk of a fatal heart attack before the age of 40 is significantly higher in those with FH than among the general population.
Research shows that 50 per cent of men and 40 per cent of women with FH have had a blood clot in the coronary arteries before the age of 60.
About one third of patients with FH show no symptoms until sudden cardiac death.

Based on a text by Annebirth Bo Hansen, PhD, specialist

Last updated 03.07.2008