When very high cholesterol runs in the family

Photo: Thinkstock

Fewer than 10% of people who have a genetic condition called familial hypercholesterolemia realize they have it.

Published: April, 2014

More than 600,000 Americans have an inherited condition that can cause heart attacks at an early age.

For most American adults with high cholesterol, the problem stems from eating foods rich in cholesterol and saturated fat. But some have an inherited genetic error that causes cholesterol levels to skyrocket. This often-undetected condition is called familial hypercholesterolemia (FH). If not treated, a person with FH has a 20-fold higher risk of heart attack compared with an unaffected person.

"Familial hypercholesterolemia is a major cause of premature coronary disease," says Dr. Linda Hemphill, an instructor in medicine at Harvard Medical School and director of the LDL Apheresis Unit at Massachusetts General Hospital. Premature coronary disease refers to heart disease that occurs before age 55 in men or before age 65 in women. People with FH can succumb to a heart attack in their 30s or even 20s, says Dr. Hemphill. That fact—and the condition's inherited nature—underscores the importance of diagnosing FH as early as possible.

Faulty receptors

All people have two genes (one from each parent) responsible for making receptors on cell surfaces that clear low-density lipoprotein (LDL, or "bad" cholesterol) from the blood. People who inherit just one copy of the faulty gene have heterozygous FH. Half of their LDL receptors work; the other half don't. Those who inherit two malfunctioning genes (homozygous FH) have no working receptors. With nothing to pull harmful LDL from the bloodstream, the level stays high.

Heterozygous FH, by far the more common form, can cause LDL levels as high as 350 milligrams per deciliter (mg/dL), more than three times higher than is considered ideal. Among the one in a million people with homozygous FH, LDL levels can reach 1,000 mg/dL.

Detecting FH

People often don't realize they have FH because they (and their doctors) assume they simply have hard-to-treat high cholesterol. If your LDL cholesterol level was 190 mg/dL or higher before you started treatment, FH is a definite possibility, says Dr. Hemphill. For children, an LDL of 160 mg/dL suggests FH. Another red flag is premature heart disease or very high cholesterol in an immediate family member (occurring before age 55 in a father or brother, or before age 65 in a mother or sister).

People with FH may also develop small nodules filled with cholesterol over various tendons, especially the Achilles' tendons of the lower leg. These growths are called xanthomas. Cholesterol-filled nodules that form on the eyelids are called xanthelasmas.

Treating FH

For people with FH, the standard advice for anyone with high cholesterol still applies: cut back on foods rich in cholesterol and saturated fat, such as red meat and full-fat dairy products, and eat more vegetables, fruit, whole grains, and fish. Other cholesterol-cutting foods include beans, oats, soy protein, nuts, and foods or supplements containing plant sterols or stanols. Controlling blood pressure, exercising, and not smoking are also essential for protecting the heart and blood vessels.

Cholesterol-lowering statins are the drug of choice, but many people with FH also require additional drugs, including ezetimibe (Zetia), niacin, and colesevelam (WelChol). People with homozygous FH often need LDL apheresis, a dialysis-like procedure to filter LDL out of the bloodstream. Last year, the FDA approved lomitapide (Juxtapid) and mipomersen (Kynamro) for people with homozygous FH to further lower their LDL. Because these drugs may cause serious liver problems, they can be given only under a doctor's close supervision. 

Genetic testing

If you have FH, your family members should be tested. Children of a parent with heterozygous FH have a 50% chance of inheriting the defective gene; it's 100% if a parent has homozygous FH. Most of the time, a cholesterol test can verify the diagnosis, but genetic testing can be helpful for borderline cases. More information is available at the FH Foundation (www.thefhfoundation.org), which aims to boost awareness and improve the diagnosis and treatment of FH.

As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.