High Cholesterol — Silent killer Familial Hypercholesterolemia

Does High Cholesterol Run in Your Family?

You eat a healthy diet, exercise daily, and yet your cholesterol is still very high? This could indicate a hereditary predisposition. Take a look around your family: Are there any relatives with high cholesterol levels or cardiovascular disease at a young age? If so, you and your children could also be affected.

A genetic test can provide certainty. And the earlier countermeasures are taken, the better the chances of preventing serious vascular disease.

Cholesterol is Vital

We need cholesterol above all for the assembly of cell envelopes. In the blood, most cholesterol is found as LDL cholesterol. In this form, cholesterol is transported to the body’s cells, which absorb it via special binding sites — LDL receptors. If too much LDL cholesterol is produced or too little is absorbed into the cells, the excess cholesterol can be deposited in the blood vessel walls. Therefore, LDL is simplified called “bad” cholesterol. These deposits reduce blood flow. If they occur in the coronary arteries, they can cause a heart attack. If they occur in the cerebral arteries, a stroke can be the result.

The Power of Genes

High LDL cholesterol can have various causes. We often think of eating too much fatty food. In many cases, however, high LDL cholesterol is hereditary. This is referred to as “familial hypercholesterolemia”. This means that due to genetic factors (“familial”) there is too much (“hyper”) cholesterol in the blood.

Actually, familial hypercholesterolemia (FH) is one of the most common genetic diseases. It´s dangerous feature: Elevated cholesterol blood level is present from childhood, damages the blood vessels early and goes unrecognized for a long time. It leads to an early onset of coronary heart disease, heart attack or stroke.

Nine out of ten men affected by familial hypercholesterolemia (FH) develop symptomatic coronary heart disease by the age of 60.
On average, FH patients lose 15 to 21 years of life!

Genetic Testing for Familial Hypercholesterolemia

Various mutations — permanent and hereditary changes in the genetic information of the organism — can be responsible for the increased cholesterol levels. The LDL receptor gene, the apolipoprotein B-100 gene, and the PCSK9 gene are usually affected. We explain for you these various genetic changes.

Mutation in the LDL receptor gene

In up to 90 % of cases, the cause of familial hypercholesterolemia is a mutation in the LDL receptor gene (LDL-R for short). LDL-R are located on cells in the liver and have the task of absorbing LDL cholesterol from the blood in the human body. However, a genetic defect in the LDL-R gene means that there are fewer functional LDL receptors on the liver cells. As a result, the LDL cholesterol level in the blood rises two to threefold. Among other things, this leads to the pathological storage of fats in the walls of the blood vessels, and thus in atherosclerosis.

Mutation in the apolipoprotein B-100 gene

Genetic defects in the apolipoprotein B-100 gene can also be the cause of familial hypercholesterolemia. In a healthy state, apolipoprotein B ensures that LDL cholesterol from the blood can bind to LDL receptors in the liver cells: The LDL cholesterol is taken up into the liver cells and broken down, and the receptor returns to the cell surface. However, the mutation in the apolipoprotein B-100 gene disrupts the binding between LDL cholesterol and the LDL receptor: the LDL cholesterol can no longer bind as strongly to the receptor and is therefore, LDL is removed from the blood more slowly. This results in an increased LDL cholesterol level.

Mutation in the PCSK9 gene

In this rare mutation, genetic changes in the PCSK9 gene with the complicated name “proprotein convertase subtilisin/kexin type 9” cause familial hypercholesterolemia. The PCSK9 enzyme is responsible for degrading LDL receptors after they have bound LDL cholesterol. A mutation in the PCSK9 gene can increase the activity of the enzyme and lead to increased degradation of the LDL receptors, and thus to an increased LDL cholesterol level.

All of the genetic causes mentioned above are inherited in an autosomal dominant manner. This means that an altered gene inherited from one of the two parents is enough to cause familial hypercholesterolemia (Read more about autosomal inheritance in our Blog Cord Blood Banking | TheKnowHow). Statistically spoken, FH mutation carrying parents pass on the altered gene to every second of their children. The clinical signs do not differ between these three known genetic causes of FH.

People with familial hypercholesterolemia usually have only one mutated gene. This is referred to as “heterogeneous”. In genetic reports, doctors will refer to it as HeFH, which stands for Heterogeneous Familial Hypercholesterolemia. Two carriers who are unaware of their genetic signature may have children together. In this instance, statistically, one out of every four children may inherit both mutated genes from their parents. This constellation is known as “homogeneous”, or HoFH. This causes excessively high LDL cholesterol levels in the blood, which can lead to heart attacks and strokes as early as childhood.

Unfortunately, the diagnosis rate of FH is very low, FH patients are underdiagnosed and often receive insufficient or late treatment. However, early and effective treatment can virtually eliminate the cardiovascular risk associated with FH.

Not rare, But Little Known

Although familial hypercholesterolemia is one of the most common hereditary diseases, it is little known. In the global population, around one in 300 people have inherited familial hypercholesterolemia from either their father or mother.

In the MENA region, the Gulf FH registry estimated the prevalence of FH (the current frequency of the disease in a population) in Saudi Arabia, Oman, United Arab Emirates, Kuwait, and Bahrain to be 1:112, and very similar in Qatar with 1:125. For Tunisia, prevalence is estimated to be 1:165, and for Lebanon 1:85. These data indicate that the MENA region has a much higher prevalence of HeFH than most of the rest of the world — contributing to the higher prevalence of cardiovascular disease.

Familial hypercholesterolemia should be considered if …

§ the concentration of LDL cholesterol is above 190 mg/dl and your doctor has no further explanation;

§ LDL cholesterol is above 140 mg/dl in children;

§ tendon xanthomas (yellowish deposits of cholesterol), for example in the Achilles heel or in the tendons of the knee or fingers;

§ xanthelasma (yellowish deposits of cholesterol in the skin, mainly around the eyelids);

§ there is a known family history of high cholesterol levels and/or

§ first-degree relatives suffered a heart attack or sudden cardiac death before the age of 60 and second-degree relatives before the age of 50.

Hereditary factors that increase LDL cholesterol can be examined using special genetic tests. These tests can be carried out at an early age and allow early, individualized therapy.

What treatments for Familial Hypercholesterolemia?

LDL cholesterol can only be lowered to a limited extent through lifestyle if you have a genetic predisposition. People with FH can eat a plant-based and low-fat diet and still not be able to lower their blood cholesterol levels. Even the positive effect of, for example, not smoking or more intensive exercise cannot be seen in the LDL cholesterol.

It is often a long and frustrating journey for those affected before the genetic cause is considered and discovered.

Those affected should realize that they are not to blame for their high cholesterol.

Nevertheless, a healthy lifestyle with more exercise and healthy eating habits is of course very important — if only for heart health and general well-being. It serves as the basis for FH therapy. However, anyone suffering from familial hypercholesterolemia requires more extensive therapy. In order to reduce the cholesterol level of FH patients to a healthy level, additional medication is therefore normally required.

The most common treatment for FH is treatment with statins. Statin drugs block an enzyme that produces cholesterol in the liver and increase the body’s ability to remove cholesterol from the blood. Other treatment options include drugs that prevent the absorption of cholesterol from the intestine into the bloodstream, ezetimibe, or drugs that block the PCSK9 enzyme. This can also reduce the amount of LDL cholesterol in the blood of FH patients.

Family Talk — And Talk to Your Doctor!

Early genetic diagnosis and consistent therapy can normalize the risk of atherosclerosis in heterozygous patients to the level of the general population. — and thus also the increased risk of cardiovascular disease.

Seize your chance! Protect your family!