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Familial hypercholesterolemia: A genetic disease in need of early testing

New research shows that familial hypercholesterolemia -- a genetic condition that leads to high LDL cholesterol --  is commonly diagnosed late and patients often don't get adequate treatment. FH can cause aggressive and premature heart disease, including heart attacks, strokes, narrowing heart valves and sudden cardiac death.

Joshua Knowles, MD, PhD, assistant professor of medicine and chief medical advisor for the FH Foundation, is senior author of a new study that characterizes adult FH patients in the United States using data from the new CASCADE FH Registry, a phrase that is trademarked. As reported in Circulation: Cardiovascular Genetics, the study found many flaws in the current treatment of patients with FH. I spoke with Knowles about this silent and deadly disease:

What is familial hypercholesterolemia?

Familial hypercholesterolemia is the medical term given to very high cholesterol that runs in families. We say, 'We never find an individual with FH. We only find families with FH.'

It's caused by genetic mutations that control the body's ability to recycle LDL cholesterol. Your liver makes cholesterol and sends it through the bloodstream. Your body takes what it needs and then sends excess LDL cholesterol back to the liver for recycling.

In FH patients, the liver cannot recycle LDL cholesterol because there are defects in some receptors that pull the cholesterol from the blood. Therefore, the LDL levels remains very high in the blood, which is toxic to the blood vessels over time. If you have FH, your LDL cholesterol levels are two to three times higher than normal and that puts you at a much, much higher risk of early onset coronary disease such as heart attacks.

How is FH diagnosed?

There are over a million people in the U.S. with this disorder, but less than 10 percent have been diagnosed. In the U.S., genetic testing hasn't become standard of care yet, largely due to the cost. So usually FH is diagnosed with a clinical point system based primarily on your personal and family medical history.

If you're not diagnosed and treated, your risk of a heart attack is extremely high. However, if you are diagnosed, you can be treated and live a long and healthy life. So it's a poster child for preventative and personalized medicine.

How is FH treated?

Lifestyle changes -- like improving your diet or exercising -- are almost never enough for FH patients. FH patients need to be treated with medications that lower their LDL cholesterol. For most people with high cholesterol, one drug is sufficient. However, many FH patients require more than one drug.

The most common and important medications for FH are statins, which work by tricking the body into activating the LDL recycling program. Normally for every gene, you have one copy from mom and one copy from dad. In the most common form of FH, you've inherited the mutation from one parent. So you have one receptor in the liver that works well and one that doesn't work at all. The statin drug tricks the body into increasing the levels of the good receptors to compensate for the bad ones -- basically putting the good receptors in overdrive to activate the LDL recycling program.

What do you recommend for patients with a family history of early heart disease?

Really the biggest and best thing is to get your cholesterol tested when you're young, when nothing but the genetic condition causes high cholesterol. If you wait until your 60 years old, it can get trickier to figure out and may be too late. Guidelines from the American Academy of Pediatrics recommend cholesterol screening for children as young as 10 years old for the general population and as young as 2 years old for families with a history of FH. Current research shows that intervening early has a big impact.

What is the CASCADE FH Registry?

To advocate for change, it's really important to have some numbers to back up what we're saying. When we publish on the data, it raises the profile of the condition. We also need a baseline to compare to in the future. The beauty of the new CASCADE FH Registry is that we'll be able to follow patients over time to see if what we are doing is making a difference.

It's not just important for the individual to know whether they have FH. It's also important for the family to know. When you identify one person with FH, the real potential benefit comes with screening the rest of the family so you can identify ticking time bombs before they have problems. This is called cascade screening - hence the name of the registry. We want to prevent people with FH from becoming patients with FH. We want to prevent those heart attacks.

Previously: Big Data to help identify patients at risk of deadline high-cholesterol disorderPrecision health in action -- The hunt for families with a high-cholesterol disorder and Hope for patients with familial hypercholesterolemia
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