Familial Hypercholesterolemia

What is familial hypercholesterolemia?

Familial hypercholesterolemia (FH) is a genetic disorder that gives you very high levels of low-density lipoprotein (LDL) cholesterol. LDL is the “bad” cholesterol that can lead to cholesterol plaque buildup in your arteries. This can eventually cause heart attacks, strokes or peripheral artery disease.

A healthy LDL level is less than 100 mg/dL (milligrams per deciliter). People with familial hypercholesterolemia can have an LDL of 160mg/dL or higher.

Without treatment, people who have this disorder are at a higher risk of getting coronary artery disease early. This can lead to heart attacks and other cardiovascular issues at a much younger age than for people who don’t have FH.

While this may sound overwhelming, there is hope. You can treat familial hypercholesterolemia by taking medicines and changing daily habits.

Types of familial hypercholesterolemia

There are two types of FH. The difference between them is in whether one or both biological parents give you the genetic variant (change) that causes FH:

• Heterozygous familial hypercholesterolemia is the type you have if one of your parents gives you the FH variant. This is the more common of the two types.
• Homozygous familial hypercholesterolemia is the type you have if you get the variant from both of your parents. This is rare and more severe than the heterozygous type.

FH is an autosomal dominant genetic disorder, which means it only takes one parent to pass it on.

How common is it?

About 1 in 250 people have a genetic variant for the more common type of familial hypercholesterolemia. Only 1 in 250,000 people have the more severe type.

Most people — 9 out of 10 — who have FH don’t know they have it.

What are the signs and symptoms of familial hypercholesterolemia?

You may not notice symptoms of familial hypercholesterolemia until you have coronary artery disease. But people with FH need treatment much earlier than that because their LDL level starts out high even as newborns.

This condition leads to LDL cholesterol buildup, which can cause familial hypercholesterolemia symptoms like:

• Chest pain
• Heart attack at a younger age
• Stroke
• Calf cramps
• Yellow plaques or xanthomas in the skin of your elbows, fingers, eyelids or Achilles tendon
• Tendonitis

What causes familial hypercholesterolemia?

FH is a genetic disorder you inherit or get from one or both of your biological parents. In most people with this genetic issue, a specific protein (LDL receptor) that gets LDL out of your blood doesn’t work well or there isn’t enough of it.

Although most people with familial hypercholesterolemia will have a variant on one of three specific genes (APOB, LDLR or PCSK9), researchers are still discovering more. If you appear to have familial hypercholesterolemia but test negative for it, you may have gotten it from a genetic variant that researchers haven’t identified yet.

What are the complications?

It’s common for people who have FH to have atherosclerosis, or plaque (atheroma) collecting in their arteries. This can lead to:

• Xanthomas (skin bumps from cholesterol buildup on your Achilles tendon, elbow, knee or hand tendons)
• Xanthelasmas (yellow cholesterol around your eyelids)
• Corneal arcus (white, grey or blue ring around your eye’s cornea)
• Aortic aneurysm (stretched out wall of your largest artery)
• Peripheral artery disease (plaque buildup in arteries in your legs and arms)
• Coronary artery disease (heart attack)
• Aortic stenosis (narrow aortic valve)
• Cerebrovascular disease (stroke)
• Sudden death

Early treatment greatly reduces your risk of these complications.

How is familial hypercholesterolemia diagnosed?

Your healthcare provider can make a familial hypercholesterolemia diagnosis based on:

• Unusually high LDL levels
• A history of coronary artery disease in your family or yourself at a young age
• Symptoms linked to atherosclerosis at a younger age than usual
• Abnormal skin findings like xanthomas or xanthelasmas
• DNA test results

What tests will be done to diagnose this condition?

A provider can use a lipid panel or DNA test to make a familial hypercholesterolemia diagnosis.

A lipid panel blood test measures your cholesterol levels, including your LDL cholesterol. Children with familial hypercholesterolemia can have LDL levels higher than 160 mg/dL. Adults can have LDL of 190 mg/dL or higher. In people with the severe form, homozygous familial hypercholesterolemia, LDL can be higher than 400 mg/dL.

A DNA test can find problems with one of the three genes researchers know can cause FH.

After you get an FH diagnosis, you can expect to see your provider regularly to check on your cardiovascular health.

How is familial hypercholesterolemia treated?

Familial hypercholesterolemia treatment may include one or more medications to reduce your LDL level as low as possible. People with severe FH may need periodic LDL apheresis (blood filtering) or a liver transplant (rarely).

Medications for heterozygous FH

Medicines for this type include:

• Statins
• PCSK9 inhibitors
• Bile acid sequestrants
• Ezetimibe
• Fibrates
• Nicotinic acid
• Bempedoic acid

Medicines for homozygous FH

Medications for this type include:

• Statins
• PCSK9 inhibitors
• Ezetimibe
• Fibrates
• Mipomersen
• Lomitapide
• Evinacumab

Can FH be prevented?

You can’t prevent an inherited disease like familial hypercholesterolemia. But you can help your family get treatment early by letting them know about your diagnosis.

People with FH are at a higher risk of heart disease at a younger age than those without FH. If you have familial hypercholesterolemia, your biological siblings, parents and children should get a test. You can start screening a child at age 2 if they have a high risk of FH.

What can I expect if I have familial hypercholesterolemia?

People with familial hypercholesterolemia have a much higher risk of atherosclerosis, which can cause heart attacks and strokes. Without treatment, people who have FH have 20 times the risk of coronary artery disease compared to someone without the disease. The chances of getting coronary artery disease go up even more if you use tobacco products, have diabetes or other risk factors for cardiovascular disease.

Without early treatment, heart disease can start before age 10 for people who have homozygous FH. People with the heterozygous type may develop heart disease at age 30 without treatment. For either type, this can lead to a heart attack by age 50 or 60 (depending on your sex).

Since FH is a condition you inherit from your parents, it’s a part of your DNA all your life. You’ll need lifelong treatment.

Outlook for this condition

Healthcare providers don’t have a cure for familial hypercholesterolemia. But once you know you have FH, your provider can treat you for it and help you prevent cardiovascular disease. With early treatment for FH, the outlook (prognosis) is excellent.

You can most likely have a normal life expectancy if you know your risk at a younger age and get treatment. Getting treatment for familial hypercholesterolemia cuts down your risk of heart disease by more than half. Without treatment, people with the rare type of FH may not live to be 30.

How do I take care of myself?

If you have familial hypercholesterolemia, you can lower your risk of cardiovascular problems in these ways:

• Take medicines your provider prescribes.
• Get regular physical activity (at least 30 minutes a day or 150 minutes a week).
• Stay at a weight that’s healthy for you.

What can I eat with this condition?

If you have familial hypercholesterolemia, your top goal is to cut down your LDL level. Ways to achieve this — before or in addition to taking medicine — include eating:

• Vegetables, fish, lean poultry and low-fat dairy foods
• More soluble fiber
• Foods that have unsaturated fat
• Foods that are low in cholesterol and saturated and trans fats
• Nuts, legumes, fruit and whole grains

When should I see my healthcare provider?

Regular appointments with your healthcare provider are crucial to make sure your medication is working. Contact your provider if you’re having trouble with side effects from your medicine. They may be able to switch you to a different one.

Get help immediately if you have chest pain, shortness of breath or another symptom of a heart attack or stroke.

What questions should I ask my healthcare provider?

Questions to ask your provider include:

• What type of familial hypercholesterolemia do I have?
• How often do I need to have checkups?
• What’s the best treatment for me?