Is High Cholesterol Genetic?

Inherited High Cholesterol Is Called Familial Hypercholesterolemia

There are many causes of high cholesterol—everything from diet, activity levels, and medications—but among the more concerning of these is genetics. Approximately one in 250 people have an inherited form of this condition called familial hypercholesterolemia (FH), meaning they’re genetically predisposed to develop unhealthy high levels.

FH specifically refers to excessively elevated levels of low-density lipoprotein (LDL) or “bad” cholesterol due to a genetic mutation, and what’s alarming is that it’s associated with earlier onset of coronary artery disease (CAD), increasing the risk of heart attack and stroke. Making this issue even more critical, only about 10% to 20% of those with the condition know they have it.

It’s important to have a sense of what FH is, how it presents, and how it can be managed.

Doctor checking blood pressure of women patient lying in a hospital bed


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What Is Familial Hypercholesterolemia?

As mentioned, FH arises due to an inherited mutation of a specific gene; this hinders the body’s ability to manufacture receptors to clear LDL from your blood. There are actually two types of FH, depending on whether the genetic abnormality was inherited from one or both parents. Here’s a quick breakdown:

  • Heterozygous FH: This more common type of FH occurs when one parent carries the faulty gene, and the other doesn’t. In these cases, people display high LDL from birth on, with levels climbing to especially dangerous levels in adults.
  • Homozygous FH: When both parents carry the faulty gene, this type of FH arises. It causes even more severe LDL levels from birth on, as no LDL receptors are present. As such, homozygous FH is associated with significantly earlier onset of serious heart problems and other issues.

If high cholesterol runs in your family, you should have your levels checked more regularly.

Causes of High Cholesterol

In addition to genetics, high cholesterol arises due to several factors:

  • Diet: Certain foods, especially those high in trans and saturated fats (as in fatty meats, dairy, and processed foods), elevate cholesterol levels.
  • Level of activity: Those who do not get enough exercise or physical activity are at risk for high cholesterol.
  • Weight status: Being overweight (a body mass index (BMI) of 25 to 29.9) or obese (BMI greater than 30) are significant risk factors for high cholesterol.
  • Lifestyle factors: Smoking tobacco and consuming alcohol are directly linked with higher levels of cholesterol.
  • Medications: Certain medications, including certain steroids, antiviral medications, beta-blockers, immunosuppressants, and diuretics, among others, can cause levels to rise.
  • Other diseases: Higher cholesterol can also be caused by other diseases or health conditions, including chronic kidney disease, human immunodeficiency virus (HIV/AIDS), hepatitis C, and pregnancy, among others.

Signs and Symptoms

So how can you tell if you have high cholesterol? And how can you tell if high levels are due to FH? A big issue, unfortunately, is that you often can’t without testing. High cholesterol is often asymptomatic, which is a major reason why it often goes undetected. Over time, it can lead to restrictions or blockages of coronary and other arteries in the body, respectively. This can lead to:

  • Angina (chest pains or discomfort)
  • Fatigue,
  • Irregular heartbeat
  • Shortness of breath
  • Cramping or pain in the limbs, especially when walking
  • Slurred speech
  • Drooping on one side of the face
  • Weakness or numbness in the limbs

There are also a couple symptoms of high cholesterol that are particularly associated with FH:

  • Xanthoma: Excess levels of LDL cholesterol can cause nodules to form in clusters around the hands, elbows, feet, and other parts of the body. In children and infants particularly, these are signs of FH.
  • Achilles tendon xanthoma: When a xanthoma develops in the Achilles tendon on the back of the foot, it can cause serious damage. Tendonitis, an inflammation of the tendon, as well as rupture can occur.
  • Corneal arcus: Cholesterol deposits can also form around the cornea, the transparent portion that covers the front of the eye. This causes gray, white, or yellowish rings to form around both corneas.

Complications

The real danger of FH is that it can lead to a host of very serious conditions. When you have high cholesterol—especially high levels of LDL—a plaque can form in the arteries. Over time, this build-up causes them to narrow, harden, and stiffen—a condition called atherosclerosis. This reduces blood flow, which can cause:

  • Heart attack: If FH is untreated, the risk of fatal or nonfatal heart attack rises 50% in men younger than 50, and 30% in women under 60. This dangerous condition is often the result of coronary artery disease (CAD).      
  • Heart disease: Aside from CAD, heart failure can also occur, which is when insufficient amounts of blood reach the rest of the body. In addition, arrhythmia—irregular heartbeat—can occur.  
  • Stroke: Interruptions in blood flow to the brain associated with high cholesterol greatly increase the chance of developing a stroke, in which clots cause brain cells to die. This potentially fatal condition severely impacts neurological function.  
  • Peripheral vascular diseases: Interrupted blood flow in the limbs causes peripheral artery disease (PAD), leading to numbing, cramping, and pain when walking. These conditions can also affect skin and tissues in the limbs to heal.

Causes and Risk Factors

FH arises when genes associated with producing receptors that clear LDL cholesterol from the bloodstreams are mutated. Faulty copies of four genes—LDLR, LDLRAP1, APOB, or PCSK9—can cause the condition, with most arising due to LDLR mutation. Your chances of developing FH are 50% if one parent has it, and 100% if both do.

Heterogenous FH, by far the most common type, arises when a faulty gene from an affected parent is paired with a healthy counterpart from the other. Only about half of the receptors that clear out LDL are present in these cases. When both parents carry the variant, homogenous FH arises, in which these receptors are entirely absent.

Globally, FH is one of the most common genetic disorders seen; however, exact estimates of prevalence are difficult because the condition often goes undetected. That said, certain populations have been found to have higher rates of inherited high cholesterol:

  • Lebanese Christians
  • Afrikaners in South Africa
  • French Canadians
  • Ashkenazi Jews

Diagnosis

Diagnosis of FH involves a combination of physical examination of symptoms, and, most conclusively, lab tests. Critical among the latter is the lipoprotein profile, sometime called a lipid panel, which measures levels of LDL, HDL (good cholesterol), and triglyceride (another type), while also providing a total score.

Doctors suspect FH in the following cases:

  • High total cholesterol: In children, scores above 250 milligrams/deciliter (mg/dL) prompt concern, with this figure rising to 300 mg/dL in adults.
  • High LDL: Levels of bad (LDL) cholesterol above 200 mg/dL in adults, and 150 mg/dL in children, can be signs of FH.
  • Physical symptoms: Those with xanthoma, corneal arcus, and Achilles tendon xanthoma will be suspected for FH.
  • Family history: Having an immediate relative with high cholesterol or early heart disease (onset younger than 55 for a father or brother, and 65 for a sister or mother) will warrant additional examination.   

In suspected cases, while several sets of criteria (such as MEDPED) are effective at catching cases, only genetic testing can conclusively determine the presence of FH. They will show which specific genes are abnormal, with mutations in LDLR, APOB, and PCSK9 genes seen in 70% to 80% of these cases.

Treatment

Because of its nature, taking on FH can be difficult, and it often involves a multifaceted approach. Medications can certainly take on this condition, but lifestyle changes can help a great deal. The key is timely detection and prompt management.

Medications

Diagnosis of FH usually means being put on prescription medication, with the primary goal of lower LDL cholesterol levels. For high cholesterol, you most often see the following classes of drugs prescribed:

  • Statins reduce the amount of cholesterol produced by the liver and may also be taken for heart attack and stroke. Lipitor (atorvastatin), Lescol (fluvastatin), and Mevacor (lovastatin) are among the most commonly prescribed of these.   
  • Bile acid sequestrants affect liver function, hindering its digestive function, which burns up cholesterol. Also called “resins,” this class of drug includes Questran (cholestyramine) and Colestid (colestipol), among others.
  • Fibrates lower triglyceride levels and raise HDL to reduce the impact of LDL cholesterol. For FH, you may be prescribed fenofibrate, which is sold as Antara, Tricor, or Fenoglide.
  • Other classes of drugs often indicated are PCSK9 inhibitors (alirocumab and evolocumab), selective cholesterol absorption inhibitors [Zetia (ezemtimibe); ACL inhibitors (Nexletol (bempedoic acid)], omega 3 fatty acids, and niacin.   

LDL Apheresis

In difficult cases of FH, especially homogenous FH or heterogenous FH that’s resistant to drug treatment, a nonsurgical procedure called LDL apheresis may be attempted. The plasma of the blood is separated from the rest and run through a machine that removes the LDL. This is then combined with the rest.

Lifestyle Changes

While on their own, lifestyle changes may not be enough to reverse high cholesterol in FH, they can have a huge impact on outcomes. A recommended approach might include:

  • Steering clear of tobacco: Among the many negative aspects of smoking is elevated cholesterol levels; quitting can help bring them down.   
  • Adjusting diet: Steer clear of foods high in trans or saturated fats, like red meat or fried foods. Cut out sugars, whole milk products, and emphasize heart-healthy foods: fruits and vegetables, fish, poultry, and whole grains.
  • Getting exercise: Being more active can certainly help bring down cholesterol levels. If you aren’t active, aim for about 150 minutes a week, or about 30 minutes a day, five of the seven days. Even low impact activities like brisk walks or cycling can help.
  • Losing weight: If you’re overweight or obese, you’ll want to see about means of losing weight. Even modest losses of 10% of body weight can positively impact cholesterol levels. Talk to your doctor about how to safely and sustainability achieve your target weight.
  • Maintaining emotional health: Stress and anger can also cause cholesterol levels to climb. Adopting means to take on these negative emotions, like meditation or yoga, can also help.
  • Managing other conditions: Diabetes mellitus, which affects blood sugar, is another cause of high cholesterol, as is hypertension (high blood pressure). Getting the right treatment for these conditions will also help lower your cholesterol.      

Prognosis

If caught early and treated appropriately, most cases of heterogenous FH can be effectively managed. This is why it’s important to carefully follow doctor’s orders about lifestyle changes and medications. Notably, such care will significantly reduce the chance of severe complications, like heart attack.

The outlook is considerably worse for homogenous FH. This form is notoriously resistant to treatment, and it’s associated with onset of early heart attack (under 55 in men, and under 65 in women). Careful monitoring and more aggressive treatment is necessary in these cases.

FAQs

What is genetic high cholesterol?

Clinically referred to as familial hypercholesteremia (FH), genetic high cholesterol is high cholesterol that runs in families. Specifically, this causes elevated levels of LDL cholesterol (the "bad" kind), which is linked with an increased risk of developing coronary artery disease.

As an autosomal dominant disorder, parents with FH have a 50% chance of passing it to their children. The most common type is heterozygous FH (HeFH), which is when only one of your parents is carrying the gene variant that causes the condition. When both parents have it, in cases of homozygous FH (HoFH), two faulty variants are inherited. The latter is the more severe form.

How do you know if your high cholesterol is genetic?

If you're found to have high cholesterol, your doctor will ask whether there's any family history of the condition. If there is, this can be a first clue that your case is FH. The only way to conclusively know, however, is through genetic testing and counseling. Doctors look for mutations of the genes LDLR, LDLRAP1, APOB, or PCSK9, which help regulate cholesterol levels.

However, in about 20% to 30% of FH cases, standard genetic testing is unable to find the faulty gene. As such, negative results do not necessarily rule out a diagnosis.

What percentage of high cholesterol is genetic?

While about one in three Americans has high cholesterol, only about one in 200 adults has FH. Counting children, it affects an estimated 1.3 million Americans; however, about 90% of cases are undiagnosed. A vast majority of high cholesterol cases are due to other factors, such as diet and lifestyle.

Can you lower cholesterol if it’s genetic?

While high cholesterol can be tougher to take on if it's due to FH, it can be managed. Making lifestyle changes such as adopting a cholesterol-lowering diet and increasing physical activity is the first step in lowering cholesterol.

Since FH cases are often resistant to these approaches, taking cholesterol-lowering drugs, such as statins or bile acid sequestrants, can further manage the condition. In severe cases of HoFH, pharmaceutical therapies may be supplemented with apheresis or liver transplant to normalize levels.

A Word From Verywell

While inherited high cholesterol can be difficult and dangerous, it’s important not to forget that it can be handled through a combination of medicine and lifestyle changes. Managed proactively and caught early, outcomes improve dramatically.

If you have any concerns about your cholesterol, or you know that FH runs in your family, don’t hesitate in talking to your doctor about getting tested. Certainly seek help if you feel any symptoms in your chest, limbs, or head.

A confirmed case is not the end of the world; it’s merely the beginning of the road to recovery. So long as you’re engaged in that process—and have help along the way—you’ll be able to take control of your cholesterol levels.    

 

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10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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