Cholesterol plays an important role in the body, but high levels of low-density lipoprotein (LDL) cholesterol can increase the risk of cardiovascular diseases. There are various causes of high LDL cholesterol. One possible cause is the genetic condition familial hypercholesterolemia.

This article describes the link between genetics and high cholesterol. It provides an overview of familial hypercholesterolemia (FH), including its symptoms, diagnosis, treatment, and outlook. We also outline some other causes of high cholesterol and list some steps people can take to prevent high cholesterol levels.

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High cholesterol levels can have a genetic cause. The medical term for this is familial hypercholesterolemia (FH).

Estimates suggest that 1 in 250 people have FH. According to the Centers for Disease Control and Prevention (CDC), if one biological parent has FH, their offspring has a 50% chance of having the condition. If both biological parents have FH, their offspring can have a more severe form of the condition, which doctors call “homozygous FH.”

FH also appears to be more prevalent among people of certain ethnicities. According to the American College of Cardiology, the prevalence of the condition among people of different ethnic groups is as follows:

  • Black people: 1 in 211 people
  • white people: 1 in 249 people
  • Mexican Americans: 1 in 414 people
  • other ethnicities: 1 in 343 people

Lipoproteins are proteins that transport cholesterol throughout the body. There are two main types:

  • LDL cholesterol, or “bad cholesterol“: This type can accumulate in the arteries, impairing blood flow and increasing the risk of cardiovascular diseases.
  • HDL cholesterol, or “good cholesterol“: This type absorbs cholesterol and transports it back to the liver, which then removes it from the body. In this way, HDL helps prevent LDL from becoming too high.

FH impairs the body’s ability to clear LDL cholesterol from the blood. The excess cholesterol builds up in the arteries, forming plaques that impair blood flow. In this way, FH significantly increases the risk of cardiovascular diseases, such as heart attack and stroke.

According to the CDC, 60–80% of people who have FH also have a mutation in one of the following three genes:

  • LDLR gene: Provides the instructions for making LDL receptors on the outside of certain cell types. The LDL receptors pick up circulating LDLs in the blood and bring them in for the cell to use.
  • APOB gene: Allows LDLs to attach to LDL receptors, particularly those on liver cells.
  • PCSK9 gene: Regulates the number of LDL receptors, making it important for controlling blood cholesterol levels.

People with FH who do not receive treatment for the condition are 20 times more likely to develop coronary artery disease (CAD). This disease impairs the flow of oxygenated blood to the heart.

According to the National Organization for Rare Disorders, males who do not receive treatment for FH have a 50% risk of having a heart attack by the age of 50 years, while females who do not receive treatment have a 30% risk of having one by the age of 60 years. Additionally, these risks increase for people who smoke or have diabetes.

However, it is important to note that a person who has FH will not necessarily go on to have a heart attack.

FH is not the only cause of high cholesterol. Other leading causes include obesity and type 2 diabetes.

Having obesity can increase the risk of high cholesterol, particularly if a person is carrying excess fat around their middle. Medical professionals refer to this as “central obesity,” and the condition indicates excess fat around the internal organs.

Obesity also increases a person’s risk of developing type 2 diabetes, another risk factor for high cholesterol. Diabetic dyslipidemia is a condition that doctors characterize by increased LDL and decreased HDL.

Type 2 diabetes can occur as a result of a diet lacking in nutritious foods and a lack of physical activity. However, it can also have a genetic component. The more family members who have type 2 diabetes, the higher a person’s chances of developing the condition.

Not everyone with FH experiences symptoms. However, the CDC notes that the following can sometimes be a sign of the condition:

  • bumps or lumps around the knees, knuckles, or elbows
  • swelling or pain in the Achilles tendons
  • yellowing around the eyes
  • a whitish gray half-moon on the outside of the cornea, which is the protective layer of the eye

The above signs are due to the buildup of cholesterol in the relevant parts of the body.

Doctors may consider a diagnosis of FH when the following factors are present:

  • In children:
    • LDL greater than 160 milligrams per deciliter (mg/dl)
    • a family history of FH or premature heart disease
  • In adults:
    • LDL greater than 190 mg/dl
    • a personal or family history of CAD at a younger age than expected
    • physical signs or symptoms

In addition, most people with FH have a family health history of early heart disease or heart attacks.

Both children and adults can experience the above symptoms of FH.

Doctors can also order genetic testing to clarify whether a person has FH. These tests check for variations in one of three genes: LDLR, APOB, and PCSK9. However, the CDC states that other genes likely play a role in FH. As such, a person may receive a diagnosis of FH even if a genetic test for one of these three genes returns a negative result.

The CDC states that people with FH typically need medication to lower their cholesterol to healthy levels. People with FH often need a combination of drugs to regulate their LDL levels. This may include cholesterol-lowering medications called statins and PCSK9 inhibitors.

Dietary and lifestyle modifications for people with FH include:

  • avoiding smoking or vaping, if applicable
  • eating a diet high in fresh fruits, vegetables, and fiber
  • limiting saturated fats, trans fats, salt, and foods with added sugar
  • limiting alcohol consumption
  • taking part in regular exercise
  • maintaining a moderate body weight
  • regularly checking and controlling blood pressure and cholesterol levels

Additionally, people with FH should receive treatment for any accompanying cardiometabolic conditions, such as high blood pressure or type 2 diabetes.

The CDC offers the following recommendations for keeping cholesterol levels in a healthy range and preventing cardiovascular disease:

  • Making nutritious dietary choices: This includes:
    • limiting the intake of saturated and trans fats, sugar, and salt
    • opting for healthy fats from foods such as avocado, nuts, and oily fish
  • Maintaining a moderate weight: Excess body fat slows the body’s ability to clear LDL cholesterol.
  • Engaging in regular physical activity: Regular exercise can help a person maintain a moderate weight.
  • Quitting smoking, if applicable: Smoking damages the blood vessels and leads to hardening and stiffening of the arteries, increasing the risk of cardiovascular disease.
  • Avoiding or limiting alcohol: Alcohol can contribute to raised cholesterol levels.

According to a 2019 study, people with undiagnosed FH may have a life expectancy around 16 years lower than those who have received a diagnosis of FH. The most likely cause of death is a cardiac event due to a buildup of cholesterol in the arteries.

The outlook for a person with FH also depends on the form of the condition they have. People with heterozygous FH inherit an FH genetic mutation from one biological parent. According to the National Organization for Rare Disorders, people with heterozygous FH have around a 10- to 20-fold increased risk of developing CAD.

Individuals with homozygous FH inherit an FH genetic mutation from both biological parents and tend to develop symptoms in childhood. Without treatment, these individuals are at risk of dying before the age of 30 years.

Therefore, it is important that people discuss their cholesterol levels with a doctor. This is especially true for those with a family history of FH and for individuals with other risk factors for high cholesterol.

High cholesterol levels can have various causes. One possible cause is the genetic condition familial hypercholesterolemia. People with this condition have a genetic mutation that impedes their body’s ability to clear cholesterol from the blood. This can lead to cardiovascular disease and an increased risk of heart attacks.

People with FH can make certain dietary and lifestyle modifications to help manage their cholesterol but will also likely need to take cholesterol-lowering medications, such as statins and PCSK9 inhibitors.

A person with concerns about their cholesterol levels should speak with their doctor, particularly if they have a personal or family history of high cholesterol or other risk factors for high cholesterol.