People who have familial hypercholesterolemia, or FH, have a much higher than normal risk of coronary heart disease.
FH is an inherited defect in how the body recycles LDL (bad) cholesterol. As a consequence, LDL levels in the blood remain very high – in untreated adults, above 190 milligrams per deciliter (mg/dL) of blood.
People with FH are essentially born with high LDL cholesterol. Everyone’s cholesterol levels tend to rise with age. But those with FH have LDL levels that start high and go even higher over time, according to information provided by the American Heart Association.
Just like with noninherited cholesterol issues, this contributes to atherosclerotic plaques, leading to the greater risk of coronary heart disease. Compared to people with average LDL cholesterol levels (less than 130 mg/dL), people with FH have a five times higher risk for coronary heart disease over a 30-year span.
Men with FH get coronary heart disease up to 20 years earlier. Half of men with untreated FH will have a heart attack or angina before they turn 50. For some it will be as early as their 20s. In women, coronary heart disease appears up to 30 years earlier. Thirty percent of untreated women will have a heart attack before they turn 60.
These increased risks are independent of other risk factors, which can make matters worse. The good news is that familial hypercholesterolemia is treatable, with a combination of lifestyle changes and medications.
How common is it?
One in 250 adults (an estimated 834,000 people) have the FH genetic mutation, according to results from the 1999-2012 National Health and Nutrition Examination Survey.
Men and women are affected equally by FH.
Causes of FH
Familial hypercholesterolemia is caused by mutation in the gene for the LDL cholesterol receptor, which is involved in passing LDL from the body. Mutations in other genes can also cause inherited high cholesterol. Those genes include the PCSK9 gene and the gene for Apolipoprotein B.
All these genes are connected with one another. If you inherit a specific type of mutation in any of these three genes, you can develop FH.
Familial hypercholesterolemia can be inherited from one parent (heterozygous FH) or, in rare instances, from both (homozygous FH). People with this rarer form of FH can have very high LDL cholesterol levels. Many may need bypass surgeries before adulthood. Without treatment, people with homozygous FH rarely live into their 20s.
Some people with FH have physical symptoms. Many don’t.
One symptom is cholesterol deposits in the Achilles tendons or the tendons of the hands or elbows. People with FH can also develop cholesterol deposits in unusual places, such as around the eyes.
Familial hypercholesterolemia is often diagnosed based on a combination of physical exam findings and lab results, as well as personal and family history. FH can also be discovered through molecular diagnosis, genetic diagnosis or genetic testing. It’s helpful when genetic testing reveals FH, because it can alert relatives to their risk.
If one person in a family has FH, it’s advisable for all first-degree relatives – parents, siblings, children – to be checked for it. Similarly, if someone in a family has an early heart attack, it’s a good idea for other family members to get tested.
Children with increased risk for FH should be evaluated between the ages of 6 and 12. Children may be started on medication as early as age 8 or 10 if their cholesterol is high enough or if their family history makes it prudent.
If there’s no sign of FH or heightened LDL levels by the time a child becomes a teenager, it’s unlikely that FH will show up later in life.
Treatment of FH
People with FH have an excellent prognosis, provided the condition is identified early and treated appropriately.
Familial hypercholesterolemia can’t be treated by diet and exercise alone. These lifestyle changes can help, but medications are required when LDL cholesterol levels need to be reduced significantly (as much as 50 or 75 percent).
Treatment usually involves a statin drug, and it’s not uncommon for other cholesterol-lowering medications like ezetimibe to be required too. People with extremely high LDL, like those with homozygous familial hypercholesterolemia, may need to undergo a treatment called LDL apheresis. This is a dialysis-like procedure that’s done every few weeks to remove cholesterol from the blood.
Another class of lipid-lowering medications, bile acid sequestrants (such as cholestyramine or colesevelam), may also be used. These drugs reduce the amount of cholesterol absorbed by the intestines. This, in turn, lowers the amount of cholesterol that gets into the bloodstream.
Two newly developed injectable antibodies, known as PCSK9 inhibitors, can also be used to lower cholesterol levels. These medications target and block the PCSK9 protein, which frees up more receptors on the liver to remove LDL cholesterol from blood. Although FDA-approved, PCSK9 inhibitors are a new, somewhat costly treatment option, with limited use.