Understanding Familial Hypercholesterolemia
You’ve probably heard that “bad” cholesterol isn’t good for your heart.
High levels of low-density lipoprotein—known as the “bad” cholesterol—are usually due to older age, a high-fat diet, not exercising enough or being overweight. But some people are born with dangerously high levels of this type of cholesterol. They have what is called familial hypercholesterolemia (FH)
. About 1 out of 250 people have this inherited disorder.
FH happens when there is a harmful change (called a mutation) to one of several genes in the body. Most often, the “defect” is in the LDL-receptor gene that usually helps to find and remove cholesterol in the body. But in people with FH, this gene is either missing or doesn’t work well. Meanwhile, the liver continues to make cholesterol, so LDL levels quickly rise in the blood.
Having such high levels of LDL cholesterol in the blood from such a young age puts people with FH at especially high risk of heart disease—even dying early. Sadly, 90% of people with FH don’t know they have it. As a result, they remain very likely to have a heart attack or die in the prime of their lives, often with no warning.
“The lifetime risk of a cardiovascular event—having a heart attack or stroke—is five to 20 times greater for someone with FH than for the general population,” said James A. Underberg, MD, a cholesterol specialist and clinical assistant professor of medicine at New York University Medical School.
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The good news is that when FH is found and treated early, cholesterol can be lowered. With the right treatment, an individual’s cardiovascular risk can go back down to what would be expected in the general population.
Knowing that you or a loved one has FH early on is key to being able to take steps to treat it and can help prevent potentially life-threatening problems.
FH runs in families. FH occurs when a there is a change in a gene that you are born with that makes the body unable to remove LDL, or "bad" cholesterol, from the blood. If you have FH, each child has a 50% chance of being born with it, too. If both parents have FH, then any children will have FH. However, this is rare.
How is FH different from high cholesterol in most people?
Many people with FH are young and appear otherwise healthy. Yet their arteries may tell a different story. That’s because high levels of “bad” cholesterol have been circulating in their bodies—often unchecked—since they were born. Over time, this can damage the blood vessels and block the heart’s arteries.
“It is very different from high cholesterol in the general population because these people have had many more years of dangerously high cholesterol. Finding and treating FH early is critical,” said Laurence Sperling, MD, FACC, director of preventive cardiology at the Emory University School of Medicine in Atlanta.
For people with FH, high levels of "bad" cholesterol have been circulating in their bodies since they were born.
Because it is underdiagnosed, FH is often first suspected after someone has had a heart attack or stroke at a very early age. Untreated men with FH have a 50% chance of having a cardiac event by 50 years of age, and untreated women have a 30% chance by age 60.
The risk for problems is even higher in people who have other risk factors such as smoking or diabetes.
What are the signs and symptoms?
For many people with FH, a heart attack, stroke or dying suddenly and at a young age may be the first sign.
Other possible signs may include:
angina, or chest pain or discomfort due to cholesterol buildup in the heart’s arteries
peripheral vascular disease, which is when cholesterol builds up in arteries in the legs, which may result in pain upon walking that usually subsides when resting
bumps on your tendons (called xanthomas), around your eyes (called xanthelasma) or on the tops of your hands
a white ring around the upper and lower portions of the cornea in the eye, especially before age 45
carotid artery disease, which is a narrowing of the blood vessels in the neck that carry blood from the heart to the brain
Anyone can have FH, but it seems to be more common in French Canadians, Ashkenazi Jews, South Africans and Christian Lebanese.
How is it confirmed?
A diagnosis of FH is usually based on:
A review of your family history. Your doctor will want to know if a first-degree relative has: FH, very high LDL cholesterol, or has had/died from heart disease at an early age.
A physical exam, to look for any physical signs.
A lipid panel, a blood test that measures cholesterol levels in your blood.
For the most part, LDL cholesterol is considered borderline high when the reading is between 130 and 159 ml/dL and high when it is over 160 ml/dL in adults. But in people with FH, LDL numbers tend to be much higher on average.
Your health care team will also want to rule out other conditions that may affect LDL levels, for example, kidney, liver or thyroid disease or eating disorders.
If you have FH, you may be referred to a preventive cardiologist, endocrinologist or lipidologist—a doctor who specializes in treating high cholesterol or lipid disorders.
What about genetic testing?
Genetic testing is sometimes done, but it’s not always needed. It can be expensive, and it doesn’t pick up all of the genetic mutations that might be responsible for FH. In other words, a genetic test could come back as negative, but the person still has FH.
When should screening begin?
Two types of screening approaches can be used to find FH: universal and cascade. The American Academy of Pediatrics, for example, recommends that all children have their cholesterol levels checked by ages 9 to 11 years old. This universal screening approach can identify children with high LDL cholesterol that are caused by genetics or lifestyle, given the growing number of children who are overweight.
If you have FH, “family tracing” or “cascade screening” with lipid and/or genetic testing can help identify other first-degree family members who might be affected. If there is suspected or confirmed FH in a parent, consider screening children before 9 years old.
How is FH treated?
Early and intensive treatment is needed to lower LDL cholesterol and, in turn, the likelihood of heart attack, stroke or dying early. A reasonable initial approach is to try to cut LDL cholesterol by half. Other recommendations suggest getting LDL to below 100 mg/dL if you have no other heart disease risk factors and under 70 mg/dL if you do. Your health care provider is the best person to advise you on this.
Although a healthy diet, regular exercise, weight loss and not smoking are essential to staying healthy, for many people with FH these changes aren’t enough. Instead, a combination of therapies is often needed.
- Lifestyle changes
eat a diet low in saturated fats, trans fats and cholesterol, while high in soluble fiber, fresh fruits and vegetables
lose weight, if needed
- Lipid-lowering or other medications, including:
“High potency” statins, or statins (which block an enzyme needed to produce cholesterol) given at high doses.
Bile acid sequestrants to help remove cholesterol from the body.
Cholesterol absorption inhibitors, which block cholesterol from being absorbed.
Other medications include PCSK9 inhibitors, and for people with homozygous FH in which both parents have FH, mipomersen and lomitapide are approved options
- Lipoprotein apheresis—a nonsurgical therapy that removes LDL cholesterol from the blood. This is usually an option when medications are not adequate or well tolerated.
- Ongoing monitoring
Keeping tabs on your cholesterol
Talking with your care team
If you have FH, you will need to keep a close eye on your cholesterol. Talk with your health care team about how often you need to get your blood cholesterol checked, and any other steps you can take to stay healthy.
It’s important to prepare for your appointments to make sure any questions you have are answered. Remember to mention any changes in how you feel—especially any chest pain, shortness of breath or concerns about the medications you are taking.
It may help to write down a list of questions ahead of time. Some helpful ones might include:
Can we review the medications I am taking to help lower my cholesterol and how each one works?
How can I best manage side effects?
I have other health conditions. How can I best manage them together?
Will I be taking these medications for the rest of my life?
I’ve heard there is a therapy that removes LDL from the blood. How does it work? Is it safe?
How often should I have my cholesterol checked?
Are there other tests I will need?
Should I see a genetic counselor? If so, who would you recommend?
At what point should I talk with my kids about FH or get them tested?
How is FH treated in children?
If I have FH and want to get pregnant, do my medications need to be adjusted or stopped?
To learn more about cholesterol, visit CardioSmart’s condition center
. You can find out more from:
American Heart Association
National Lipid Association
Foundation of the National Lipid Association
National Heart Lung and Blood Institute
Published: September 2016
Medical Reviewers: Laurence Sperling, MD, FACC, FACP, FAHA; James A. Underberg, MD, MS, FACPM, FACP, FASH, FNLA, FASCP