Familial Hypercholesterolaemia

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What Is Familial Hypercholesterolaemia & What Causes It?

FH is one of many genetic disorders that can negatively affect your heart, like some connective tissue disorders. In this instance, your liver cannot effectively remove low-density lipoproteins (LDL) from your blood. This bad cholesterol then stays in the blood and begins to build up in your arteries, making it harder for your heart to function as normal. As the condition is genetic, and therefore present from birth, this build-up begins from childhood.

Higher-than-normal levels of bad cholesterol increase your chance of a range of heart diseases, including heart attacks, and also can affect your life expectancy. When left untreated, the prognosis gets worse as the person ages (with some differences between genders). The condition seems to affect males more severely than females, and It is estimated that 50% of men with FH will have a heart attack by age 50. 

It’s important to note that FH is different to typical ‘high cholesterol’ (also called dyslipidaemia) because it is a genetic condition. Where common dyslipidaemia is generally caused by an unhealthy lifestyle, FH is due to a genetic mutation that affects how your liver processes LDL or bad cholesterol.

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Additionally, FH can vary between individuals, even those in the same family. Therefore, one person may develop progressive heart issues, while another stays stable. Another again may have minor changes that can only be detected by a cardiologist who is experienced with FH.

Several genes have been identified to be associated with FH. These are:

• LDLR (This is the most commonly affected gene.)
• LDLRAP1
• APOB
• PCSK9

The above genes all affect how the body regulates and removes cholesterol, with approximately 60–80% of those with FH having a mutation in at least one of these genes.

Genetic mutations can be passed down from parents (inherited) or occur spontaneously at conception (known as ‘de novo’ mutation). FH is mostly an autosomal dominant disorder. meaning only one member of a gene pair needs to have the mutation for the condition to be present. This means that if a parent has the disorder, there is a 50% chance that they will pass it on to their children. When this occurs, the child has what is known as dominant familial hypercholesterolemia. 

In rare cases, a child may inherit two copies of the same mutation. As a result, they will develop a different type of FH: recessive familial hypercholesterolemia. Recessive FH is more serious as it results in even higher levels of cholesterol and heart attacks are likely to begin in childhood. If both parents have FH, there is a 25% chance their child will have the recessive type of FH.

It is possible for a person to spontaneously develop the genetic mutations that cause FH (heterozygous or homozygous) at conception (this is known as a ‘de novo’ mutation. This can then mean that they have the condition but have no family history of it.

Whether the mutation is inherited or de novo, the child is at risk from birth of developing the disease. Unfortunately, it is not possible to reverse the mutation or completely remove the possibility of the disease developing. The best way to be proactive when working with the possibility of FH is to aim for an early diagnosis. This is vital for improving life expectancy and quality of life.

Genetic testing can be used to determine if a person has FH. This can then allow for quicker diagnosis and treatment before those more serious stages are reached, as well as helping families plan how to minimise passing the condition on to their children.

Do You Have Familial Hypercholesterolaemia Symptoms?

As FH predominantly affects your LDL cholesterol levels, FH symptoms tend to focus on evidence of increased cholesterol.

This can include:

• Accumulation of cholesterol in parts of the body, like bumps or lumps around your knees, knuckles and elbows.
• Thickened tendons, like swollen or painful Achilles tendons.
• Corneal arcus (a whitish-grey half-moon shape on the outside of the cornea and around the iris of the eye).

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However, it is quite common for FH to manifest with no obvious signs or symptoms. This unfortunately means that familial hypercholesterolemia is more prevalent in Australia than most patients and doctors realise. Therefore, it’s important that you pay close attention to your family health history. There may be evidence of FH there.

This can include any instances of a close relative having a:

• Heart attack, particularly a premature heart attack (for males, before age 55; for females, before age 60).
• Premature coronary artery disease.
• High blood cholesterol level at an early age.
• Stroke.
• Peripheral arterial disease.

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Genetic testing can then confirm if you have FH.

How Do You Get a Familial Hypercholesterolaemia Diagnosis?

If you speak with your general practitioner or cardiologist about your concerns, they will likely recommend a blood test and may also conduct a physical examination to look for fatty lumps and deposits of cholesterol.The blood test will allow them to check your levels of blood cholesterol (lipids). Most people with high lipid levels in their blood do not have FH. The risk for FH increases as the lipid levels increase, particularly if you have high LDL type cholesterol. However, there are individuals with FH who only have mildly elevated cholesterol. 

Unlike other genetic health conditions, such as arrhythmogenic right ventricular cardiomyopathy, an ECG and other heart function diagnostic tests are unlikely to be as effective at identifying FH. While an increase in bad cholesterol can affect how your heart beats, there are many heart diseases, such as catecholaminergic polymorphic ventricular tachycardia, which can alter your heart rate. Focusing on blood tests and familial history first will generally help you get a quicker diagnosis of FH without having to rule out other causes.

A genetic test, using a small sample of blood or saliva, is often a crucial step in confirming a familial hypercholesterolaemia diagnosis. 

When investigating genetic testing for FH, choosing a cardiology and genetics service that truly understands the nuances of hereditary heart conditions is integral. They will know how serious the diseases are and how they can vary between people. Similarly, they will be able to choose the most appropriate genetic testing to diagnose the condition, as well as accurately interpret the results. Ultimately, this is a specialised field that requires experts.

How Genetic Testing Can Help Treatment

With the specialised genetic tests available, it’s now possible to know which genes are affected. This information is key to better tailor your familial hypercholesterolaemia treatment and management plans.

Your diagnosis through genetic testing can also go on to fast track those of other family members’, so that they receive treatment sooner too. As FH leads to a build-up of LDL over time, the earlier the diagnosis the better. This means your heart is not put under such a great strain, with early diagnosis having shown to be able to reduce the risk of heart disease by approximately 80%.

Is Familial Hypercholesterolaemia in Your Family?

Along with blood tests, reviewing your family health history is one of the simplest ways to begin gathering evidence for an FH diagnosis. You may even like to begin your conversation with your general practitioner or cardiologist about potentially having FH by explaining why your family’s health history makes you concerned. 

This might include discussing close relatives who have had premature coronary artery disease or heart attacks. It’s relevant to highlight if there have been family members who have had unusually high blood cholesterol levels from an early age or despite a healthy lifestyle, and if any family members have been diagnosed with FH or even severe dyslipidaemia (as FH is frequently misdiagnosed as the more common ‘high cholesterol).

If there have been sudden, premature or unexplained deaths in your family, particularly of otherwise healthy or young people, make a note of these too. While they may indicate FH, they may be evidence of another type of genetic health condition, like Brugada syndrome. Having more information and context for your general practitioner or cardiologist to understand your health is always helpful. 

Then, if you learn you have a genetic health condition, you have made it easier for other affected family members to get diagnosed quickly and receive treatment as soon as possible. By looking after your own health, you help to care for your family too.