Familial Hypercholesterolemia

Is Testing Right for Me? I Have My Test Results

Familial Hypercholesterolemia

  • Author: Denise Needham, MS, CGC
  • Reviewer: Trisha Brown, MS, CGC
  • Last updated: 2011-11-28

What Is Familial Hypercholesterolemia?

Cholesterol is a waxy substance that is part of the fat your body stores for energy. Your body needs some cholesterol, but having too much greatly increases your risk for heart disease, stroke, diabetes, and other diseases. There are two main kinds of cholesterol. High-density lipoprotein (HDL) is usually called "the good cholesterol" and low density lipoprotein (LDL) is "the bad cholesterol".

People have high LDL when they have more than about 130mg/dL of LDL cholesterol in their blood. Lifestyle changes, and sometimes drug therapies, are recommended for people with high LDL to lower their risk of heart disease.

People who have very high LDL — usually over 190mg/dL— are much more likely to have an inherited condition called familial hypercholesterolemia, or FH. Without treatment, people with FH develop heart disease, often at an early age. They have a very high risk for heart attacks and strokes, also at earlier ages. People with FH usually can't control their cholesterol levels with diet alone. They often need high doses of cholesterol-lowering drugs combined with other therapies.

  • About 1 in 3 adults in the U.S. has high LDL cholesterol levels.
  • About 1 in 500 people in the U.S. has very high LDL cholesterol levels because of familial hypercholesterolemia.

The FDA-approved prescribing information for the common cholesterol-lowering drug, atorvastatin (Lipitor®, Caduet®), specifically talks about the use and dosage of this drug for adults and children with FH. This highlights the importance of accurately diagnosing FH: to make the best treatment decisions possible.

FH and Heart Disease

If you have high LDL, the extra cholesterol can build up and stick to the inside of your arteries. This is called "plaque". Plaque buildup can block blood flow to the heart or other parts of the body. When a blockage gets serious enough, it can cause a heart attack or stroke.

When FH isn't diagnosed and treated early, there is a much higher risk of heart disease — especially at an unusually young age. A man with FH has a 50 times higher risk of having a heart attack before he is 40 than a man without FH. A woman with FH has 125 times the risk. Even children with FH can have plaque buildup in their arteries. Early diagnosis and treatment are key to preventing the development of heart disease at an early age.

Next: Who Is At Risk For Familial Hypercholesterolemia?

Why are you considering genetic testing?

I have signs of FH (usually total cholesterol over 290mg/dL or LDL cholesterol over 190mg/dL). No one in my family has had FH genetic testing before.

I have a family member who had genetic testing that found an FH gene mutation.

I don't have very high cholesterol (or I don't know my cholesterol levels), but my family history has signs of FH. No one has had genetic testing yet.

None of these

People with signs of familial hypercholesterolemia (FH) can consider genetic testing. The National Lipid Association Expert Panel on Familial Hypercholesterolemia says that genetic testing may be useful when the diagnosis is not clear. They also say that finding an FH mutation may help motivate people to follow the treatment needed for FH.

The first person in a family to have FH gene testing has sequencing of the LDLR gene and sometimes, the APOB gene. Sequencing looks at the genes "letter-by-letter" to find any changes. The laboratory may also look to see if large parts of the gene are extra or missing. (This is called duplication/deletion analysis). About 9% of LDLR gene mutations are deletions that sequencing won't find.

This kind of testing is expensive and time-consuming, but needed to find as many mutations as possible. Complete genetic testing will find a mutation that explains FH about 85% of the time.

  • When testing finds a mutation, this confirms that you have FH. You have a high chance for heart disease and need strong treatment to lower your cholesterol. This information can help you and your doctor plan the best testing and treatment for you.
    Family members who want to know about their risk can now have genetic testing for just the mutation you have. This kind of testing costs less and is more accurate than FH gene sequencing. For every person diagnosed with FH by genetic testing, 2 to 3 other relatives will learn they have FH. Only about half of these relatives are already being treated to lower their cholesterol, but almost all people with FH must be treated to prevent early heart disease.
  • When testing doesn't find a mutation, the results don't rule out FH. Genetic testing will not find a mutation in about 15% of people with FH. You could have a mutation the tests couldn't find. You probably still need extra heart disease testing and treatment for high cholesterol.
    FH genetic testing won't be useful for your family members, unless another relative has more convincing signs of FH. Given your medical history, your family members probably need cholesterol and heart disease screening from a young age.

Having a family member with an FH mutation means you have a higher chance for high cholesterol and early heart disease. Your risk depends on how closely you are related to this person. You should review your family history with your doctor.

The typical guidelines doctors use to decide who has high cholesterol and how they should be treated don't work for people with FH. Lifestyle changes — like diet and exercise — are rarely enough to control cholesterol levels. Certain drugs are better at lowering cholesterol and preventing or shrinking plaque buildup in people with FH. People with FH often need higher doses than usual of these drugs or combinations of drugs to get their cholesterol under control. The earlier treatment begins, the less damage is done and the lower the risk is for heart disease. In some cases, even children as young as 10 years old might be treated.

Once an FH gene mutation is found in the family, you and other relatives can have testing for just that one mutation. Testing for one mutation is less expensive than full FH gene testing, and the results are more accurate. The laboratory will need to know the exact name of your family's mutation. If possible, give the lab a copy of your relative's genetic test results.

  • When testing finds the mutation that runs in your family, you can be sure that you have inherited FH and a risk for early heart disease. You probably need strong treatment to lower your cholesterol. This information can help you and your doctor plan the best testing and treatment for you.
  • When testing doesn't find a mutation, you can be sure that you didn't inherit the mutation that runs in your family. You don't have the very high risk for heart disease from FH. But, this result doesn't mean that you won't get high cholesterol. About 1 in 3 adults in the U.S. has high cholesterol for many reasons other than FH. All adults need regular cholesterol screening and treatment if the levels get too high.

You may not be the best person in your family to have FH testing first. The first person tested should be someone who has had very high cholesterol levels if possible. Most people with FH have high cholesterol by the time they are young adults and sometimes in childhood.

Genetic testing can't find all of the mutations that cause FH. Testing the relative most likely to have FH first tells you if this test will be useful for your family. If a mutation is found in that person, then all other family members can have testing for the one mutation that runs in the family. This is cheaper and more accurate than complete gene testing. If a mutation isn't found in that relative, then testing won't likely be useful for anyone else in the family.

The first person tested will usually have gene sequencing of the LDLR gene and sometimes the APOB gene. Sequencing looks at the genes "letter-by-letter" to find any changes. The laboratory may also look to see if large parts of the gene are extra or missing. (This is called duplication/deletion analysis). About 9% of LDLR gene mutations are deletions that sequencing won't find. This kind of testing is expensive and time-consuming, but needed to find as many mutations as possible. Complete genetic testing will find a mutation that explains FH about 85% of the time.

If it isn't possible to test a relative with signs of FH first, you can still have testing. However, the meaning of your results may not be clear.

  • When testing finds a mutation, you probably inherited FH. You have a high chance for heart disease and need strong treatment to lower your cholesterol. This information can help you and your doctor plan the best testing and treatment for you. Family members who want to know about their risk can now have genetic testing for just the mutation you have.
  • When testing doesn't find a mutation, there are a few possible explanations.
    • The mutation that causes FH in your family can't be found with the test that was done.
    • Your family has a reason for high cholesterol or early heart disease that isn't FH.
    • You didn't inherit the mutation that causes FH in your family.
    Testing a family member with signs of FH is still an option. If a mutation were found in that relative, it would clear up the meaning of your results. Your family members still need to know that they are at increased risk and need early and regular cholesterol screening — no matter what your test results are.

FH genetic testing probably won't be useful for you if you don't have signs of FH, and no one in your family does either.

There are many different causes of high cholesterol. Some are genetic but most aren't. If you or a family member has a medical history that concerns you, talk to your doctor or a genetic counselor.