Is High Cholesterol Genetic?
Inherited high cholesterol is called familial hypercholesterolemia
Medically reviewed by Richard N. Fogoros, MD
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 harmfully high cholesterol 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.
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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 several 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.
Related: Familial Hypercholesterolemia Test
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 the healing ability of skin and tissue.
Causes and Risk Factors
FH arises when genes associated with producing receptors that clear LDL cholesterol from the bloodstream are mutated. Faulty copies of four genes, LDLR, LDLRAP1, APOB, or PCSK9, can cause the condition, with most arising due to LDLR mutation.
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 an aggressive, multifaceted approach. All people with homozygous FH should be under the care of a lipid specialist, if at all possible.
Medications are a primary treatment for FH. Lifestyle changes can also help but are not sufficient in themselves. The key is timely detection and prompt management.
Medications
Aggressive medical treatment with statins to lower LDL cholesterol is needed for all people with heterozygous FH, and those with homozygous FH need care directed by a lipid specialist. 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. Adults are treated with high-intensity statin therapy, such as with Lipitor (atorvastatin) or Crestor (rosuvastatin). Children are started on the lowest recommended dose and it is increased as tolerated.
Selective cholesterol absorption inhibitor: Zetia (ezetimibe) may be added in addition to statins to help reduce LDL cholesterol if not controlled by statins alone.
PCSK9 inhibitors like Praluent (alirocumab), Repatha (evolocumab), and Leqvio (inclisiran) may be prescribed if further control of cholesterol is still needed.
LDL Apheresis
In difficult cases of FH, especially homogenous FH or heterogenous FH that is resistant to drug treatment, a nonsurgical procedure called LDL apheresis may be attempted. Plasma is separated from whole blood in small amounts and run through a machine that removes the LDL. The blood and plasma are then returned to the body by IV access.
Lifestyle Changes
On their own, lifestyle changes are not enough to reverse high cholesterol in FH, but they can have an effect on outcomes and quality of life. 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 and medications and lifestyle changes. Notably, such care will significantly reduce the chance of severe complications, like heart attack.
The outlook is less favorable 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.
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 to talk to your doctor about getting tested. Certainly seek help if you feel any symptoms in your chest, limbs, or head.
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.
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?
Taking cholesterol-lowering drugs, such as statins, is essential to manage the condition. Lifestyle measures are not sufficient in themselves. In severe cases of HoFH, pharmaceutical therapies may be supplemented with apheresis or liver transplant to normalize levels.
Read the original article on Verywell Health.
