High cholesterol—you’re more than what you eat!

When you’re trying to lower your cholesterol, you’ll probably get lots of advice from friends and family. They mean well, but at times, it can feel like you’re doing everything right and still not seeing the results you expect. This can be frustrating. Before you give up, you should know that for some people changing your diet or exercise isn’t enough. In some families, high cholesterol can begin at a very young age. If this is true in your family, finding out as early as possible may reduce the chance of heart disease or even heart attack for you and your family members.

What is familial hypercholesterolemia?

Familial hypercholesterolemia (FH) is a genetic condition that causes high cholesterol. It is common and can be life-threatening. As many as 1 in 300 to 500 people have FH, but most don’t know it. If not treated, FH leads to early heart disease and heart attacks.

People with FH have a high level of bad cholesterol called “low-density lipoprotein (LDL).” This happens because genetic changes affect how cholesterol is cleared out of the body. As a result, cholesterol builds up in the bloodstream and the walls of the arteries. This buildup is called “plaque” and can lead to problems such as heart disease, heart attacks, and strokes. With FH, this can happen in people of all ages, including young adults and children. Other signs of cholesterol buildup with FH are bumps under the surface of the skin (called “xanthomas”) and white, fatty buildup in the eye (called “corneal arcus”).

What are the genetics behind FH?

Genes are the body’s instruction manuals. We inherit 2 copies of each gene, 1 from each of our parents. FH usually occurs when 1 copy of the gene has a change that prevents the gene from functioning correctly. If you have FH caused by changes in certain genes (called LDLR, APOB, or PCSK9), every child you have has a 50% chance of inheriting FH. This is called “autosomal dominant inheritance”. Less often, FH is caused by changes in the LDLRAP1 gene, when both copies of the gene need to have changes to see symptoms.

Why do genetic testing for FH?

Testing can help you find out whether a gene change that causes FH is causing your high cholesterol so that you and your doctor can consider treatment options. The test uses a blood sample taken from your vein. Your test results can also help your family members. If someone in your family already knows they have a gene change that causes FH, there is a test that only looks for that change.

FH isn’t the only cause of high cholesterol, and genetic testing may not be right for everyone. You may want to consider genetic testing for FH if you or someone in your family:

• Have high LDL (≥190 mg/dL in an untreated adult, or ≥160 mg/dL in an adult with treatment, or ≥160 mg/dL in an untreated child)
• Have early heart disease
• Have fatty deposits under the skin or in the eyes
• Have a genetic change that causes FH

The first step is to talk with your doctor about your personal and family history. You can also speak to a genetic counselor. This will help you decide if testing is right for you.

How is FH treated?

Medication may lower plaque buildup inside the arteries. Prescription medications called “statins” can reduce cholesterol levels; other medications may also be needed. A combination of medication and a healthy lifestyle works best for children and adults with FH. Making healthy choices means:

• Eating fewer fats and more fruits and vegetables
• Getting regular exercise
• Controlling your weight
• Not smoking
• Treating high blood pressure if you have it

What to do next?

When high cholesterol runs in a family, FH genetic testing can give an explanation. Understanding the genetics behind FH can lead to helpful next steps, including starting medications sooner or getting family members screened earlier in life. It can also reduce judgment about high cholesterol levels. Speak to your doctor to decide if genetic testing and/or genetic counseling are right for you.

References

1. Family Heart Foundation. Accessed 8/1/2023. www.familyheart.org
2. Marais AD. Familial hypercholesterolaemia. Clin Biochem Rev. 2004 Feb;25(1):49-68. PMID: 18516203; PMCID: PMC1853359.
3. MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 Jan 1]. Familial Hypercholesterolemia; [cited 2023 Sept 13]; Available from: https://medlineplus.gov/genetics/condition/familial-hypercholesterolemia
4. Soutar, A., Naoumova, R. Mechanisms of Disease: genetic causes of familial hypercholesterolemia. Nat Rev Cardiol 4, 214–225 (2007). https://doi.org/10.1038/ncpcardio0836/