Familial hypercholesterolemia (FH) is disorder of cholesterol processing that causes very high levels of LDL cholesterol, often called ‘bad cholesterol.’ These high cholesterol levels lead to plaque build up in the coronary arteries which dramatically increases the risk of coronary heart disease at an early age. Individuals with FH may also have cholesterol deposits around the cornea of the eye, in the skin around the eyes and between the fingers, or along tendons.
The common form of FH, also called heterozygous FH (HeFH), is caused by a single genetic variant in one of several genes. There is a more severe form of FH called homozygous FH (HoFH) which is caused by the presence of two genetic variants; either two copies of the same variant or two different variants in the same gene.
FH is estimated to affect 1/200-500 individuals. The more severe HoFH affects about 1/160,000-1,000,000.
High cholesterol levels do not typically make an individual feel any different and individuals with FH often have no symptoms at all. If a person does not know they have FH, the first clue may be a heart attack. The warning signs of a heart attack include:
FH is caused by genetic variants that alter the way the body processes cholesterol. Several different sets of clinical criteria exist that raise the suspicion for FH. Clinically, FH is highly likely in an adult with LDL levels above 190mg/dL (160mg/dL in children), premature coronary artery disease, and/or cholesterol deposits with a family history of FH. Distinguishing between HeFH and HoFH requires genetic testing.
Genetic testing can help establish a diagnosis of FH and distinguish from other non-genetic causes of high cholesterol. Genetic testing is currently the only way to distinguish HeFH and HoFH.
Genetic testing is also very important for family members. Once an individual has an established genetic cause of FH, family members can be tested to see whether or not they have also inherited the genetic variant and the risk for premature coronary artery disease. This is very important for family members since earlier initiation of aggressive lipid management leads to better risk reduction.
All individuals with FH are at increased risk for coronary heart disease. The primary treatment involves medication therapy, often requiring a combination of multiple medications. Diet and lifestyle modifications are also recommended including avoiding smoking, high fat intake, excessive cholesterol intake, sedentary lifestyle, obesity, hypertension, and diabetes. In very severe cases, liver transplant may be considered.
Treatment is based on LDL levels and extent of built-up cholesterol. Individuals with genetically confirmed FH may require earlier, more aggressive treatments. Certain medications may be prescribed based on which gene carries the FH causing variant.
Your physician will assist you in identifying and arranging for the appropriate genetic test(s). If you have specific questions or concerns about the testing, your physician may refer you to a genetic counselor to discuss further. Once you are ready to proceed with genetic testing, you will need to submit either a blood or saliva sample.