Familial Hypercholesterolemia

(LifeWire) - Who Is at Risk?

Familial hypercholesterolemia is an inherited condition in which the body is unable to effectively remove low-density lipoprotein cholesterol (LDL-C) from the bloodstream. Although some cholesterol is necessary for your body to function properly, high blood levels of this fatty material, especially the LDL-C type, allow it to accumulate along blood vessel walls. Plaque is a mixture of LDL and other substances that build up along the walls of the arteries, resulting in stiffened, hardened and narrowed arteries (atherosclerosis) that increase the risk of a heart attack or stroke. You may suspect that you have this condition if people in your family have a history of unsuccessful treatment of high LDL levels or a history of heart attacks at an early age.

About 1 in every 500 people has familial hypercholesterolemia. The condition is even more common in people of French-Canadians, Afrikaner or Christian Lebanese descent, striking about 1 in every 250 of these individuals.

Familial hypercholesterolemia is caused by a defect in a gene located on the 19th chromosome. Since familial hypercholesterolemia is a dominant trait, you only have to receive the flawed gene from one of your parents to have the condition. If you have one flawed gene and one normal gene, you are considered to be "heterozygous" for the condition. People who receive a flawed gene from each of their parents are considered to be "homozygous" for the condition. People who are homozygous for familial hypercholesterolemia are likely to have more severe symptoms, with problems occurring at an earlier age, but, fortunately, the homozygous status is relatively rare.

What Are the Symptoms?

People with familial hypercholesterolemia begin to have high LDL-C blood levels in early childhood. Although normal LDL-C levels are considered to be under 200 mg/dL, people with familial hypercholesterolemia often have values that top 250 mg/dL in childhood and greater than 300 mg/dL in adulthood. People with two copies of the defective gene can have cholesterol levels that reach 1,200 mg/dL.

Other symptoms of familial hypercholesterolemia include cholesterol deposition in the skin or along the tendons (called "xanthomas"), on the eyelids (called "xanthelasmas") or ringing around the cornea of the eye (called "corneal arcus"). Men with familial hypercholesterolemia often have heart attacks in their 40s or 50s, whereas women often have heart attacks in their 50s or 60s. By age 60, about 85% of men with familial hypercholesterolemia will have had a heart attack. People who are homozygous for familial hypercholesterolemia may have heart attacks in their 20s or 30s.

How Is the Diagnosis Made?

Diagnosis of familial hypercholesterolemia is usually made clinically when a doctor notes the presence of high LDL-C and xanthomas, coupled with a family history of early heart attacks or early onset or difficult-to-treat LDL-C or coronary artery disease.  Although genetic tests are available, they are not often used in the United States. Early diagnosis is beneficial, so doctors often look for it in children with a family history of premature heart disease.

How Is it Treated?

Treatment of high LDL-C levels should be very aggressive. It's important that people with familial hypercholesterolemia stop smoking, reach and maintain a healthy weight, participate in regular exercise and adhere to a low-fat diet (with fat calories less than 30% of total calories). Lower fat calorie percentages may be recommended for patients with higher LDL-C levels. Other potentially complicating, coexisting conditions (such as high blood pressure or diabetes) should be kept under good control, however, careful attention to these aspects of a healthy lifestyle is usually insufficient to treat familial hypercholesterolemia. Many people with this condition will require one or more medications as well, which may include:

• Statin drugs, such as Lipitor (atorvastatin), Zocor (simvastatin), Mevacor (lovastatin), Pravachol (pravastatin) or Crestor (rosuvastatin), which work by interfering with a liver enzyme required for cholesterol production
• Zetia (ezetimibe), which blocks the absorption of cholesterol in the intestine
• Nicotinic acid drugs (including Niaspan and Niacor), which lower LDL cholesterol, as well as raising blood levels of the "good" cholesterol called "HDL-C"
• Bile acid resins, such as Questran (cholestyramine) and Colestid (colestipol), which bind to bile acids in the intestine after which the entire compound is eliminated in the stool. Since the bile acids contain cholesterol, this results in the elimination of cholesterol from the body.

In severe cases and sometimes in children, a procedure called "LDL apheresis" can be used to cleanse the blood and remove excess LDL-C. People who are homozygous for familial hypercholesterolemia may even require a liver transplant, although this is rare.

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