What is familial hypercholesterolemia?

Familial hypercholesterolemia (FH) is an inherited condition that results in high levels of low-density lipoprotein (LDL) cholesterol. This also results in high total cholesterol as well.

Cholesterol is a waxy substance found in your cells that can be dangerous when it builds up on artery walls. High cholesterol can cause atherosclerosis and increase your risk of heart attack and stroke.

As the most common form of inherited high cholesterol, FH affects about 1 in every 500 people. Some studies have found that it runs as high as 1 in every 250 people in certain European populations.

FH is generally more severe than cases of nongenetic hypercholesterolemia. People who have the familial version will generally have much higher cholesterol levels, as well as heart disease at a much younger age.

FH is also known as type 2 hyperlipoproteinemia.

What are the signs and symptoms of familial hypercholesterolemia?

High cholesterol often has no symptoms. The damage may be done before you notice anything is wrong. Some of the signs and symptoms are:

  • chest pain with activity
  • xanthomas, which are fatty deposits often found in tendons and on the elbows, buttocks, and knees
  • cholesterol deposits around the eyelids (Xanthomas that occur around the eyes are known as xanthelasmas.)
  • gray-white cholesterol deposits around the corneas, also known as corneal arcus

Blood tests for someone with FS will reveal that their total cholesterol, LDL cholesterol level, or both are well above the recommended healthy level.

What causes familial hypercholesterolemia?

There are currently three known FH genes. Each is located on a different chromosome. In most cases, the condition results from inheriting one of the genes or pairs of genes. Researchers believe particular combinations of genetic material lead to the problem in some cases.

Who is at risk for familial hypercholesterolemia?

FH is more common among certain ethnic or racial groups, such as those of French Canadian, Finnish, Lebanese, and Dutch descent. However, anyone who has a close family member with the disease is at risk.

How is familial hypercholesterolemia diagnosed?

Physical exam

Your doctor will conduct a physical exam. The exam helps identify any types of fatty deposits or lesions that have developed as a result of the elevated lipoproteins. Your doctor will also ask about your personal and family medical history.

Blood tests

Your doctor will also order blood tests. The blood tests are used to determine your cholesterol levels, and the results may indicate that you have high levels of total cholesterol and LDL cholesterol.

There are three main sets of criteria for diagnosing FH: the Simon Broome criteria, the Dutch Lipid Clinic Network criteria and the MEDPED criteria.

With the Simon Broome criteria:

  • total cholesterol will be more than:
    • 260 milligrams per deciliter (mg/dL) in children under 16 years old
    • 290 mg/dL in adults

OR

  • LDL cholesterol will be more than:
    • 155 mg/dL in children
    • 190 mg/dL in adults

The Dutch Lipid Clinic Network criteria gives a score to levels of elevated cholesterol starting at LDL greater than 155 mg/dL.

The MEDPED criteria provides cutoffs for total cholesterol based on family history and age.

Your doctor will typically also test your triglycerides, which are made up of fatty acids. Triglyceride levels tend to be normal in people with this genetic condition. Normal results are below 150 mg/dL.

Family history and other tests

Knowing if any family members are affected by heart disease is an important step in identifying an individual’s personal risk for FH.

Other blood tests may include specialized cholesterol and lipid tests, along with genetic tests that establish whether you have any of the known defective genes.

Identifying those with FH through genetic testing has allowed for early treatment. This has led to a decrease in death due to heart disease at a young age and helped identify other family members at risk for the condition.

Heart tests that include ultrasounds and a stress test may also be recommended.

How is familial hypercholesterolemia treated?

Like ordinary high cholesterol, FH is treated with diet. But unlike other forms of high cholesterol, treating with medication is also a must. A combination of both is needed to reduce cholesterol successfully and delay the onset of heart disease, heart attack, and other complications.

Your doctor will usually ask you to modify your diet and increase exercise along with prescribing medication. If you smoke, quitting smoking is also a critical part of treatment.

Lifestyle changes

If you have FH, your doctor will recommend a diet that focuses on lowering unhealthy fat intake and other less healthful foods. You’ll likely be encouraged to:

  • increase lean proteins such as soy, chicken, and fish
  • decrease red meat and pork
  • use olive oil or canola oil rather than lard or butter
  • switch from full-fat dairy to low-fat dairy products
  • add more fruits, vegetables, and nuts into your diet
  • limit sweetened drinks and soda
  • limit alcohol to no more than one drink per day for women and two drinks per day for men

Diet and exercise are important to maintaining a healthy weight, which can help lower cholesterol levels. Not smoking and getting regular, restful sleep is also important.

Drug therapy

The current treatment guidelines include medications along with lifestyle changes to reduce your cholesterol. This includes starting medications as early as ages 8 to 10 in children.

Statins are the most common drugs used to reduce LDL cholesterol. Examples of statins include:

  • simvastatin (Zocor)
  • lovastatin (Mevacor, Altoprev)
  • atorvastatin (Lipitor)
  • fluvastatin (Lescol)
  • rosuvastatin (Crestor)

Other drugs that lower cholesterol include:

  • bile acid-sequestering resins
  • ezetimibe (Zetia)
  • nicotinic acid
  • fibrates

What are the complications of FH?

Possible complications of FH include:

  • a heart attack at an early age
  • severe heart disease
  • long term atherosclerosis
  • a stroke
  • death due to heart disease at a young age

What is the long-term outlook for FH?

The outlook depends on whether or not you make lifestyle modifications and take your prescribed medications. These changes can significantly reduce heart disease and prevent a heart attack. Early diagnosis and proper treatment can lead to a normal life expectancy.

According to the American Heart Association, untreated people with FH who inherit the mutated gene from both parents, the most rare form, are at greatest risk for heart attack and death before age 30.

Half of men with FH who aren’t treated will develop heart disease by age 50; 3 out of 10 women with FH who aren’t treated will develop heart disease by the time they reach 60. Over a 30-year span, people with FH who go without treatment are five times more likely to develop heart disease than those with LDL cholesterol in the healthy range.

Early diagnosis and treatment is the best way to live a life not shortened by heart disease.

Can I prevent familial hypercholesterolemia?

Because FH is genetic, the best chance of preventing it is to seek genetic counseling before conceiving. Based on your family history, a genetic counselor may be able to identify whether you or your partner are at risk for the gene mutations of FH. Having the condition doesn’t guarantee your children will also have it, but it is important to know your risks and the risk to future children. If you already have the disease, the key to living longer is early diagnosis and treatment of your cholesterol levels.