Familial Hypercholesterolemia (FH)

Overview

Familial hypercholesterolemia, often shortened to FH, is an inherited disorder that causes very high levels of low-density lipoprotein (LDL) cholesterol, the so-called "bad" cholesterol, from birth. It is caused by changes in genes that control how the body clears LDL cholesterol from the blood. As a result, cholesterol builds up to high levels for the person's entire life, beginning in childhood.

Because the cholesterol level is high from such an early age, FH greatly increases the risk of developing heart disease and having a heart attack at a younger-than-usual age. Many people with FH do not know they have it until a heart problem occurs, because high cholesterol itself causes no symptoms. The condition runs strongly in families, so identifying one person with FH should prompt testing of close relatives. The encouraging news is that FH is treatable: with early diagnosis and lifelong cholesterol-lowering treatment, the risk of heart disease can be greatly reduced.

Symptoms

High cholesterol itself causes no symptoms, so many people with FH feel completely well until heart disease develops. Some physical signs can appear, especially when cholesterol has been very high for a long time.

• Usually no symptoms from the high cholesterol itself
• Fatty deposits under the skin, such as raised lumps on the tendons (for example over the knuckles or the back of the ankle)
• Yellowish cholesterol deposits around the eyelids
• A pale or grayish ring around the colored part of the eye, especially when seen at a young age
• Chest pain or heart attack as a first sign of heart disease, sometimes at a young age

Because the condition is often silent, a high cholesterol result on a blood test, or a family history of early heart disease, may be the only clue before complications occur.

Causes

Familial hypercholesterolemia is caused by inherited changes (mutations) in genes that control how the body removes LDL cholesterol from the blood.

• Genetic mutations: changes in genes responsible for clearing LDL cholesterol mean the body cannot remove it efficiently, so it builds up.
• Inheritance pattern: FH is usually passed down in an autosomal dominant pattern, so a child of an affected parent has about a 50 percent chance of inheriting it.

People who inherit one altered gene have the common form of FH. Rarely, a person inherits an altered gene from both parents, causing a far more severe form with extremely high cholesterol and very early heart disease. Unlike ordinary high cholesterol, FH is not primarily caused by diet or lifestyle, although these still matter.

Risk Factors

The main risk factor for FH is having an affected family member, since it is inherited. Additional factors raise the heart-disease risk for someone who has it.

• A parent or close relative with FH or very high cholesterol
• A family history of early heart disease or heart attacks
• Inheriting the altered gene (the underlying cause)
• Added risk from smoking, high blood pressure, diabetes, and inactivity, which further increase heart risk in people with FH

Diagnosis

FH is diagnosed based on cholesterol levels, physical signs, family history, and sometimes genetic testing.

• Cholesterol blood test: very high LDL cholesterol, especially at a young age, raises suspicion of FH.
• Physical examination: checking for cholesterol deposits on tendons, around the eyes, or in the eyes.
• Family history: a pattern of high cholesterol or early heart disease in relatives.
• Genetic testing: can confirm the diagnosis and is useful for testing family members.

An important part of diagnosis is cascade screening, in which relatives of a diagnosed person are tested, since FH is often passed through families and frequently goes unrecognized.

Treatment

FH is treated by lowering cholesterol as much as possible and reducing overall heart-disease risk, usually for life. Because cholesterol has been high since birth, treatment is started early and continued long term.

• Statins: the cornerstone of treatment, these medicines substantially lower LDL cholesterol.
• Additional cholesterol-lowering medicines: other drugs may be added when statins alone are not enough, including newer injectable therapies for stubborn cases.
• Heart-healthy lifestyle: a healthy diet, regular exercise, not smoking, and managing weight support treatment, though lifestyle alone is rarely sufficient in FH.
• Specialized treatments: for the rare severe form, more intensive therapies such as procedures to remove cholesterol from the blood may be needed.

Treatment dramatically reduces the lifetime risk of heart attack, especially when started early.

Prevention and Self-Care

• Take cholesterol-lowering medicines exactly as prescribed, for life
• Follow a heart-healthy diet low in saturated fat
• Stay physically active and maintain a healthy weight
• Do not smoke, as it greatly increases heart risk in FH
• Control blood pressure and blood sugar
• Encourage close relatives to be tested, since early treatment protects them too

When to See a Doctor

See a clinician for cholesterol testing if you have very high cholesterol, a family history of high cholesterol, or relatives who had heart attacks at a young age. Early diagnosis and treatment can prevent heart disease. If a family member is diagnosed with FH, ask about being screened.

Call emergency services right away if you have chest pain or pressure, especially with shortness of breath, sweating, nausea, or pain spreading to the arm, neck, or jaw. These can signal a heart attack, which people with untreated FH are at higher risk of, sometimes at a young age.

Related Topics

Frequently Asked Questions

References

1. National Heart, Lung, and Blood Institute (NHLBI). Familial hypercholesterolemia.
2. Centers for Disease Control and Prevention (CDC). Familial Hypercholesterolemia.
3. MedlinePlus, U.S. National Library of Medicine. Familial hypercholesterolemia.
4. American Heart Association (AHA). Familial hypercholesterolemia (FH).