What is Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is a common life-threatening genetic condition that causes high cholesterol. Untreated, FH leads to early heart attacks and heart disease.*People with FH have a high amount of low density lipoprotein (LDL) or “bad cholesterol” due to a mutation in one of the genes that controls the way cholesterol is cleared by the body. As a result, cholesterol accumulates in the bloodstream and can ultimately build up in the walls of the arteries. Cholesterol build up in the artery wall is called hardening of the arteries, or atherosclerosis, and can lead to problems such as heart attacks and strokes in young adults and even children.

FH is inherited and passed down through families. When one individual with FH is diagnosed, it is important that all family members are screened for FH.

Treatment should begin early. Although lifestyle and diet are important factors to staying heart healthy, for individuals with FH, that is not enough

Cholesterol is vital for life. It is a fatty substance produced and used by the liver. It is necessary for production of hormones and bile acids (they aid in digesting food. Importantly, cholesterol is an integral component of the membranes (outside surfaces) of every cell in the body. The liver gets cholesterol by making it, by recycling bile, or from small particles transported in the bloodstream called lipoproteins.

Two kinds of lipoproteins carry cholesterol throughout your body:

Low-density lipoproteins (LDL) – Sometimes called “bad cholesterol,” it can lead to a buildup in your arteries. The higher the LDL number, the greater the risk of cholesterol depositing in your arteries. This can lead to a heart attack or stroke.

High-density lipoproteins (HDL)- Known as “good cholesterol,” it carries cholesterol from other parts of your body back to your liver. Having high HDL may be a biomarker for protection against heart disease.

Like many other genetic conditions, FH is inherited. Each child of a person with FH has a 50% chance of inheriting the disorder so it is essential to screen parents, siblings and children of a person diagnosed with FH to find others who may have inherited the genes.

At present, most people with FH have variants in one of three genes: LDLR gene, APOB gene, and PCSK9 gene. To date, there are over 2,000 known variants for FH.

How many mutations you inherit affects the type of FH you may have.

One Inherited Mutation – Called Heterozygous Familial Hypercholesterolemia (HeFH), one abnormal mutation is passed down to a child, typically from one parent.

Two Inherited Mutations - When the mutation for HeFH is passed on from both parents to their children this can result in Homozygous Familial Hypercholesterolemia (HoFH), the more rare and severe form of FH.

FH is one of the most common life-threatening family disorders found in 1 in 250 people of all races and ethnicities.

FH is vastly underdiagnosed – only 10% of individuals born with FH know they have it and are diagnosed today. This is due to low public awareness, the failure to link very high cholesterol with a genetic cause, and that many individuals with FH also show no visible symptoms and therefore are not receiving the care they need.

The good news is that FH can be diagnosed with a simple blood test and a reported family history of early cardiovascular disease. Genetic testing can be used to confirm the presence of FH.

And with early and regular treatment, individuals with FH can live longer, healthier lives.

References

Duell, PB, et al. Longitudinal low density lipoprotein cholesterol goal achievement and cardiovascular outcomes among adult patients with familial hypercholesterolemia

Atherosclerosis 2019 https://doi.org/10.1016/j.atherosclerosis.2019.08.007

deGoma, EM, et al. Treatment Gaps in Adults with Heterozygous Familial Hypercholesterolemia in the United States: Data from the CASCADE FH Registry

Circulation: Cardiovascular Genetics 2016 https://doi.org/10.1161/CIRCGENETICS.116.001381

Nordestgaard, B. and Benn, M. Genetic testing for familial hypercholesterolaemia is essential in individuals with high LDL cholesterol: who does it in the world?. European Heart Journal, 38(20), pp.1580-1583.

Foody JM. Familial Hypercholesterolemia: An Under-recognized but Significant Concern in Cardiology Practice. Clin. Cardiol. 2013;37(2):124.

Page reviewed by: Michael Shapiro DO