Mayo Clinic | American Hospital

By Mayo Clinic Staff

Overview

Familial hypercholesterolemia is an inherited condition that affects the way the body processes cholesterol. As a result, people with familial hypercholesterolemia have a higher risk of heart disease and a greater risk of early heart attack.

The genetic changes that cause familial hypercholesterolemia are present from birth, but symptoms may not appear until adulthood.

There are two types of familial hypercholesterolemia. Heterozygous familial hypercholesterolemia (HeFH) is the more common type. HeFH is inherited from one parent. Homozygous familial hypercholesterolemia (HoFH) is the rare type. HoFH is inherited from both parents.

People who inherit the condition from both parents usually develop symptoms in childhood. If this rare and more-serious form is not treated, death often occurs before age 20.

Treatments for both types of familial hypercholesterolemia include a variety of medicines and healthy-lifestyle behaviors.

Symptoms

Adults and children who have familial hypercholesterolemia have very high levels of low-density lipoprotein (LDL) cholesterol in their blood. LDL cholesterol is known as "bad" cholesterol because it can build up in the walls of the arteries, making them hard and narrow.

This excess cholesterol is sometimes deposited in certain portions of the skin, some tendons and around the iris of the eyes:

Skin. The most common spots for cholesterol deposits to occur is on the hands, elbows and knees. They also can occur in the skin around the eyes.
Tendons. Cholesterol deposits may thicken the Achilles tendon, along with some tendons in the hands.
Eyes. High cholesterol levels can cause corneal arcus. This is a white or gray ring around the iris of the eye. This happens most commonly in older people, but it can occur in younger people who have familial hypercholesterolemia.

Causes

A gene alteration that's passed down from one or both parents causes familial hypercholesterolemia. People who have this condition are born with it. This gene alteration prevents the body from ridding itself of the type of cholesterol that can build up in the arteries and cause heart disease.

Risk factors

The risk of familial hypercholesterolemia is higher if one or both parents have the gene alteration that causes it. Most people who have the condition receive one affected gene. But in rare cases, a child can get the affected gene from both parents. This can cause a more serious form of the condition.

Familial hypercholesterolemia can happen in any race or ethnic group, but it may be more common in certain populations, including:

Ashkenazi Jews.
Some Lebanese groups.
French Canadians.

Complications

People who have familial hypercholesterolemia have a higher risk of heart disease and death at a younger age. Heart attacks may occur before age 50 in men and age 60 in women. The rare and more serious form of the condition, if not diagnosed or treated, can cause death before age 20.

Diagnosis

A detailed family history is an important key to diagnosing familial hypercholesterolemia. Healthcare professionals will be interested to know if your siblings, parents, aunts, uncles or grandparents ever had high cholesterol levels or heart disease, especially during childhood.

During the physical exam, your healthcare team will usually check for cholesterol deposits that may occur in the skin around the hands, knees, elbows and eyes. Tendons in the heel and hand may be thickened, and a gray or white ring may develop around the iris of the eye.

Cholesterol tests

Your healthcare team will likely order blood tests to check your cholesterol levels. The National Heart, Lung, and Blood Institute recommends that a person's first cholesterol screening should occur between the ages of 9 and 11 and be repeated every five years after that. Earlier or more-frequent screenings may be suggested for families with a history of childhood heart disease.

In the United States, cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter (dL) of blood. In Canada and many European countries, cholesterol levels are measured in millimoles per liter (mmol/L).

Adults who have familial hypercholesterolemia usually have LDL cholesterol levels over 190 mg/dL (4.9 mmol/L) or have cholesterol levels that stay high even when on cholesterol-lowering treatments. Children who have the condition often have LDL cholesterol levels over 160 mg/dL (4.1 mmol/L). In more serious cases, LDL cholesterol levels can be over 500 mg/dL (13 mmol/L).

LDL cholesterol also is known as the "bad" cholesterol because it can build up in the walls of the arteries, making them hard and narrow. This can increase the risk of heart attacks.

Genetic testing

A genetic test can confirm familial hypercholesterolemia, but it's not always necessary. However, a genetic test can help determine whether other family members also may be at risk.

If one parent has familial hypercholesterolemia, each child has a 50% chance of inheriting it. Inheriting the altered gene from both parents can result in a rare and more serious form of the disease.

If you are diagnosed with familial hypercholesterolemia, healthcare professionals usually recommend that your first-degree relatives — such as siblings, parents and children — be checked for the condition. This allows for treatment to begin early, if needed.

Treatment

Familial hypercholesterolemia treatment focuses on reducing the extremely high levels of LDL cholesterol, also called the "bad" cholesterol. This helps lower the risk of heart attack and death.

Medications

Most people with familial hypercholesteremia need to take more than one medicine to control their LDL cholesterol levels. Options include:

Statins. These medicines block a substance the liver needs to make cholesterol. Examples include atorvastatin (Lipitor), fluvastatin (Lescol XL), lovastatin, pitavastatin (Livalo), pravastatin, rosuvastatin (Crestor) and simvastatin (Zocor).
Ezetimibe (Zetia). This medicine limits the absorption of cholesterol contained in the food you eat. If statins don't reduce cholesterol enough, healthcare professionals often suggest adding ezetimibe.
PCSK9 inhibitors. These newer medicines — alirocumab (Praluent), evolocumab (Repatha) and inclisiran (Leqvio) — help the liver absorb more LDL cholesterol, which lowers the amount of cholesterol circulating in the blood. They are injected under the skin every few weeks or months and are very expensive.
Bempedoic acid (Nexletol). This newer oral medicine reduces the production of LDL cholesterol by the liver. It is taken in a fixed daily dose and has been shown to be well tolerated.

Other treatments

People with more-serious familial hypercholesterolemia also may need to periodically have a procedure that filters the excess cholesterol from their blood. Some may need liver transplants.

Self care

Healthy-lifestyle habits also can help reduce the risk of heart disease, and some may lower your cholesterol:

Lose extra pounds. Losing weight can help lower cholesterol.
Eat a heart-healthy diet. Focus on plant-based foods, including fruits, vegetables and whole grains. Limit saturated fats and trans fats.
Exercise regularly. Aim for at least 30 minutes of moderate-intensity exercise five times a week.
Don't smoke. If you smoke, find a way to quit.

Preparing for your appointment

You might start by talking to your family healthcare professional. Your healthcare professional may refer you to a specialist in heart disease, called a cardiologist.

What you can do

You may want to write a list that includes:

Details about your symptoms.
Other medical conditions you've had.
All the medicines, vitamins and supplements you take, including doses.
Your family's medical history, including if your siblings, parents, aunts, uncles or grandparents ever had high cholesterol levels or heart disease, especially during childhood.
Questions you want to ask the care team.