Familial Hypercholesterolaemia

Familial Hypercholesterolaemia (FH) is an inherited condition that leads to levels of cholesterol that are higher than that of the general population, sometimes double or even three or four times.

FH affects around 1 in 250 people – but the prevalence may vary across Europe. FH is a genetic condition caused by a ‘spelling mistake’ in our DNA – the genetic material with all the instructions needed to ‘build’ humans.

• The spelling mistake can happen in any one of three genes (genes are small parcels of DNA that code for specific proteins in the body)
• We sometimes refer to this spelling mistake as an altered, faulty or mutated gene.
• FH is passed from one generation to another through inheriting this altered gene.
• FH is a “dominant” disorder – this means that if you have inherited the gene you will have the condition
• If one parent has FH there is a 1 in 2 (50%) chance that each of their children would inherit it.
• FH is not the result of an unhealthy diet or lifestyle

Identifying FH as early in life as possible is vital.  This means that treatment and support can be offered from an early age.

“Familial” means “family” and “hyper – cholesterol – aemia” means “high cholesterol in the blood”. The type of cholesterol that is increased in FH is low density lipoprotein-cholesterol (LDL-cholesterol). LDL-cholesterol is the main carrier of cholesterol around the body.

FH is linked to an increased risk of early cardiovascular disease, in particular coronary heart disease (CHD). The risk of FH causing early heart disease varies from family to family and from person to person within the family. It is influenced by a number of lifestyle and medical risk factors including LDL-cholesterol levels, other inherited factors, diet, smoking, blood pressure, physical activity and gender.

Women who have FH are affected by cardiovascular disease approximately 5–10 years later than men with the same condition and similar risk factors. But with early diagnosis and appropriate treatment the risk of early cardiovascular disease can be reduced considerably in both men and women.

Identifying FH as early in life as possible is vital.  This means that treatment and support can be offered from an early age. As shown in the video clip from Professor Wiegman of the Netherlands, it is very important that children – and adults – with FH don’t start smoking. Smoking causes damage to the arteries, an integral step in the development of heart and circulatory disease. In this way it has a big impact on the future risk of heart disease.

What is good and bad cholesterol?

Because cholesterol is a kind of fat, it cannot mix directly with the blood. It is therefore carried in the blood stream inside lipoproteins (“lipo – proteins”). These are small packages made up of fat (lipid) on the inside and proteins on the outside. There are two main kinds of lipoprotein that carry cholesterol throughout the body – these are low density lipoprotein (LDL) and high density lipoprotein (HDL).

The cholesterol that is carried by LDL is sometimes called “bad cholesterol”. LDL takes cholesterol to the cells, where it is needed. But if there is too much, more than the cells need, this LDL cholesterol can become trapped in the walls of damaged arteries. Over time these fatty deposits (plaques) can start to build up and over time can restrict blood flow to the heart muscle, brains, arms, legs and vital organs.  A heart attack happens when one of the arteries supplying the heart muscle becomes blocked, starving a part of the heart of oxygen and nutrients.

People who have FH have higher levels of LDL cholesterol because they cannot easily remove the LDL from their blood. The organ responsible for the removal of the LDL is the liver. People with FH have fewer functioning LDL receptors in the liver. It is these LDL receptors that normally remove LDL cholesterol from the blood.

The cholesterol carried by HDL is sometimes referred to as “good cholesterol”. This is because HDL carries excess cholesterol back to the liver where it can be broken down and removed from the body.

Treatment for FH therefore focuses on lowering LDL cholesterol (bad cholesterol) and maintaining healthy levels of HDL cholesterol (good cholesterol).

How are people with FH identified?

The way in which people are identified can vary from country to country

• Most countries use an agreed set of medical criteria. These are usually based on LDL cholesterol levels, patterns of early heart disease or raised cholesterol in close family members and a physical examination
• Today it is also possible to diagnose FH through genetic testing – This involves looking for spelling mistakes (gene alterations) on the LDL, ApoB and PCSK9 genes. This process is not available everywhere because it can be very costly. It can take up to three months to get the results from a genetic test.

Cascade Testing

• Once a diagnosis of FH has been made, it is normal for doctors and nurses to consider and talk to other close family members who also might have FH
• This is called cascade testing. Close family (brothers, sisters, children, mother, father) are asked to have a cholesterol test and be assessed to see if they too have FH
• If a genetic diagnosis has already been made in a close family member, then it is much easier, cheaper and quicker to search for that same ‘spelling mistake’ – the same gene alterations.

Types of Familial Hypercholesterolaemia

As we have two copies of each gene, one from each of our parents, it is possible to inherit an altered gene from either our mother or our father, and in some rare cases from both parents. There are three types of FH. These are determined by the number of altered genes we inherit and the way they are inherited