Pure or familial hypercholesterolemia is a condition in which a genetic anomaly causes high cholesterol levels.
According to the Familial Hypercholesterolemia Foundation, an estimated 1 in 250 people worldwide have pure or familial hypercholesterolemia. However, many people with the condition do not know they have it and do not receive a diagnosis.
Familial hypercholesterolemia (FH) is not the result of lifestyle choices or diet. Similarly, it is not connected to high cholesterol levels or eating high fat foods. However, it does increase a person's risk of heart disease.
In this article, we look at the causes and symptoms of pure hypercholesterolemia and how to manage the condition.
Parents pass FH on to a child because of a genetic mutation in one of three possible genes.
One gene contains instructions for producing a protein called LDL receptor (LDLR), which removes low-density lipoprotein (LDL), or "bad" cholesterol, from the bloodstream.
However, people with FH have a change in this gene that prevents them from producing LDLR. As a result, harmful LDL builds up in the bloodstream and deposits in the blood vessels.
Alterations in the APOB and PCSK9 genes are also responsible for pushing up LDL cholesterol levels.
More than 2,000 different alterations can occur in these three genes.
The liver is responsible for producing high-density lipoprotein (HDL) cholesterol, which helps a person preserve healthy cell walls.
However, the liver of a person with FH cannot recycle cholesterol or regulate cholesterol levels. As a result, cholesterol builds up in the bloodstream and increases the risk of heart disease.
Two forms of FH exist:
- Heterozygous familial hypercholesterolemia (HeFH): This occurs when a person inherits the gene for FH from one parent.
- Homozygous familial hypercholesterolemia (HoFH): This form of the condition occurs when a person inherits FH from both parents. HoFH is rarer than HeFH, according to the Familial Hypercholesterolemia Foundation.
The HoFH form of the condition often results in more severe symptoms than the HeFH form.
The primary risk factor for developing FH is having one or both parents with a history of the condition.
If a person has FH or a parent with the condition, they should also seek testing for the rest of their family.
A parent with FH has a 50% chance of passing the condition on to a child. Genetic counselors can help an individual examine their risk more closely.
Older relatives might also have FH without being aware. According to the FH Foundation, only 10% of all people born with the condition know that they have it.
People of certain ethnicities have a higher risk of developing FH. These include:
- Ashkenazi Jews
- French Canadians
- South African Afrikaners
In other types of high cholesterol, a person experiences the effects later in life as the impact of lifestyle and dietary choices starts to take hold. However, FH occurs from birth, and high cholesterol does not often present many symptoms in its early stages.
A blood test will usually show levels of LDL in the blood. Doctors would consider levels of 190 milligrams per deciliter (mg/dl) or higher in adults and 160 mg/dl or higher in children to be excessive.
Although symptoms rarely occur, some people with FH may experience:
- chest pain
- small bumps on the skin, typically on the hands, elbows, and knees or around the eyes
- xanthomas, which are waxy cholesterol deposits in the skin or tendons
- small, yellow deposits of cholesterol that build up under the eyes or around the eyelids
When a person inherits the mutated genes that cause FH from both parents, they are more likely to develop xanthomas at an early age and even in infancy.
People need a small amount of cholesterol in their body to maintain healthy cell function and produce hormones. However, excessive cholesterol levels can be harmful to overall health and increase the risk of certain complications.
If a deposit of cholesterol breaks off, it can lodge itself in the arteries around the heart, causing a heart attack.
According to the National Human Genome Research Institute, men with FH tend to have heart attacks early in life, when they are in their 40s and 50s. An estimated 85% of men with the condition will have a heart attack by 60 years of age.
Women with the condition also have an increased risk for heart attack, most commonly from 50–60 years of age.
If a person inherits mutated genes for FH from both parents, their risk of heart attack and death before 30 years of age substantially increases.
As well as a raised risk of narrowing arteries, a person with FH may also experience aortic stenosis. This condition causes the opening of the aortic valve to constrict.
The role of the aortic valve is to open to allow the heart to pump oxygenated blood through the body. As a result, aortic stenosis is a serious health concern for a person with FH.
Doctors will diagnose FH by finding out about the person's symptoms and asking about any family history of the condition. A doctor may note any cholesterol deposits that have built up in the body, especially on or around the eyes.
A doctor is likely to suggest blood tests to establish an individual's total cholesterol levels. Levels higher than 300 mg/dl in adults or 250 mg/dl in children will be cause for further investigation.
Genetic testing can help a doctor identify the mutation that indicates the presence of FH.
A doctor may also order tests to determine the overall impact that FH has had on a person's health. These could include a cardiac stress test or an echocardiogram.
Treating FH often depends on the severity of symptoms and how high cholesterol levels are in each case. Almost all people with the condition will need to take a prescription medication to reduce their overall cholesterol levels.
Statins, such as atorvastatin, are the most common medications for FH, as these bring down cholesterol levels.
Doctors will sometimes prescribe additional medications that help a person lower cholesterol, such as:
- bile acid sequestrant resins
- nicotinic acid, or niacin
People with severely high cholesterol levels may also need to undergo a procedure called LDL-apheresis. This process involves the removal of excess cholesterol from the blood, which a doctor will do on a weekly or twice-weekly basis.
In very rare and extremely severe cases, a person may require a liver transplant.
Lifestyle changes can also help to moderate cholesterol levels. Examples of healthful lifestyle measures include:
- Controlling other risk factors: Reducing the risk of other conditions that increase cholesterol, such as high blood pressure and diabetes, can help reduce the impact of FH.
- Managing the diet: People with FH should eat at least 10–20 grams of soluble fiber a day. They should also try to reduce or eliminate their intake of saturated and trans fats, usually by making sure that these are less than 30% of their total daily calories.
- Exercising regularly: A person with FH should be as physically active as possible. The American Heart Association (AHA) recommend 150 minutes of moderate-to-intense exercise every week.
- Quitting smoking: For people who have FH, smoking can cause a further restriction in their arteries. Stopping smoking is vital for preserving blood flow and oxygen supply.
Researchers are conducting clinical trials and studies regarding medications in a new class of drugs called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.
LDLRs control the amount of LDL cholesterol circulating in the body, but these receptors do not function correctly in someone with FH. The available medications help to put more receptors on the surface of the liver to remove LDL from the bloodstream. The body processes LDL cholesterol more efficiently as a result.
The Food and Drug Administration (FDA) have approved evolocumab (Repatha) and Praluent, both PCSK9 inhibitor medication, to treat people who have heterozygous FH.
Doctors will typically only prescribe evolocumab if symptoms do not improve after statin therapy, according to the American Pharmacists Association.
Doctors administer evolocumab one to two times a month. However, the drug costs an estimated $14,100 per year for a person who receives an injection of the medication every 2 weeks, and doctors reserve it for those who do not respond well to the first-line therapy (statins).
FH is a genetic condition that causes excessive cholesterol levels in the blood and increases the risk of heart attack and stroke.
Most people inherit the mutated gene that causes FH from one parent. If a person inherits it from both, they have a high risk of developing severe complications.
Doctors can detect FH from an early age with lipid screening and genetic testing. However, if the tests indicate signs of FH, the whole family may wish to undergo screening, as others may have inherited FH and could pass it on to their children.
Several medications, such as statins, can help a person reduce their cholesterol levels. Managing lifestyle choices and diet can also lessen the risk of complications, such as heart attack.
Can I prevent FH if only one parent has the mutated gene?
There is no way to prevent FH. If a parent has the mutated gene, you can still get HeFH. Therefore, early genetic and lipid screening for children of people with known FH is sensible.Dr. Payal Kohli, MD, FACC Answers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.