An individual who suffers from familial hypercholesterolemia (FH) has a genetic condition that affects the body's cholesterol metabolism. The body needs cholesterol to make hormones and build cell membranes, but too much cholesterol can cause problems, particularly in the heart and blood vessels.
FH patients have very high levels of low-density lipoprotein (LDL), also referred to as "bad" cholesterol. By building up in the arteries, LDL cholesterol can narrow them and reduce blood flow. This can lead to atherosclerosis, which is the thickening and hardening of the arteries. There are many complications associated with atherosclerosis, including heart disease, stroke, and heart attack.
The disease is inherited, which means it is passed down from both parents. In the most common form of FH, heterozygous FH occurs when one copy of the gene is inherited. The most severe form is homozygous FH, which is very rare and more severe. Homozygous FH can cause symptoms in childhood and may be fatal if left untreated.
This disease is caused by a mutation or change in a gene that controls cholesterol levels in the body. These genes encode proteins that remove excess LDL cholesterol from the bloodstream. The most common gene that is affected is the LDL receptor gene, which makes a protein that binds to cholesterol and takes it to the liver for disposal. The apolipoprotein B gene, which makes a protein that is part of the LDL cholesterol particle, and the PCSK9 gene, which makes a protein that regulates the LDL receptor, can also cause FH.
As a result, when these genes are mutated, the LDL receptor or the LDL cholesterol particle does not function properly, resulting in high levels of LDL cholesterol and an increased risk of atherosclerosis.
FH does not cause any symptoms by itself, but it can lead to symptoms of heart disease and other complications due to atherosclerosis. These symptoms may include:
A feeling of pressure, tightness, or squeezing in the chest, which may spread to the arms, neck, jaw, or back. Angina occurs when there is insufficient blood flow to the heart muscle.
The heart attack is a sudden and severe chest pain accompanied by shortness of breath, sweating, nausea, vomiting, or fainting. The heart attack occurs when a blood clot blocks the flow of blood to a part of the heart muscle, causing damage or death.
Symptoms of a stroke include weakness, numbness, paralysis, vision problems, speech problems, confusion, or loss of consciousness.
In peripheral artery disease, the arteries providing blood to the legs, feet, arms, and hands narrow, causing pain, cramping, numbness, tingling, or cold sensations in the affected limbs, especially when exercising.
There is a condition called an aortic aneurysm, which is a bulging of the wall of the aorta, the artery that carries blood from the heart to the rest of the body. This condition can cause chest or back pain, shortness of breath, or rupture, which can be fatal.
Xanthomas are deposits of cholesterol under the skin, commonly found on the tendons of the hands, elbows, knees, feet, or ankles. They may appear yellow, firm, or rubbery.
Xanthelasmas, which are deposits of cholesterol on the eyelids, usually near the inner corners. They may appear as yellowish, flat, or slightly raised patches.
Corneal arcus, which is a gray or white ring around the edge of the cornea, the clear front part of the eye. It does not affect vision, but it may indicate high cholesterol levels.
FH is diagnosed based on the following criteria:
A blood test that measures the levels of total cholesterol, LDL cholesterol, HDL cholesterol, also called "good" cholesterol, and triglycerides, another type of fat in the blood. As well as having high LDL cholesterol levels, FH patients may also have high HDL cholesterol levels and high triglycerides. LDL cholesterol levels are usually above 190 mg/dL for adults and 160 mg/dL for children.
Physical examination to look for signs of atherosclerosis, such as heart murmurs, reduced pulses, or bruits, which are abnormal sounds heard over the arteries. An examination may also be conducted to detect signs of cholesterol deposits, such as xanthomas, xanthelasmas, or corneal arcus.
Close relatives, such as parents, siblings, or grandparents, who have early heart disease or high cholesterol levels. The condition is inherited autosomally dominantly, which means that one copy of the mutated gene is all that is required to have the condition. As a result, each child of a person with FH has 50% chances of inheriting it.
Identifying the specific mutation or change in the gene that causes FH. This test can confirm the diagnosis and help identify family members who may also be affected.
The main goal of treatment for FH is to lower the LDL cholesterol levels and reduce the risk of atherosclerosis and heart disease. Treatment may include:
It is important to change your lifestyle habits, such as eating a healthy diet that is low in saturated fat, trans fat, and cholesterol, and high in fiber, fruits, and vegetables; exercising regularly; maintaining a healthy weight; quitting smoking; and limiting alcohol consumption.
Medications, such as statins, which block the production of cholesterol in the liver; bile acid sequestrants, which bind to bile acids and prevent them from being reabsorbed into the blood; cholesterol absorption inhibitors, which reduce the amount of cholesterol absorbed from the intestines; niacin, which lowers LDL cholesterol and triglycerides and raises HDL cholesterol; fibrates, which lower triglycerides and raise HDL cholesterol; and PCSK9 inhibitors, which increase the number of LDL receptors on the liver and enhance the removal of LDL cholesterol from the blood. These medications may be used alone or in combination, depending on the severity of the condition and the response to treatment.
In lipoprotein apheresis, harmful substances such as LDL cholesterol and other harmful substances are removed from the blood. This procedure is usually reserved for people with homozygous FH or heterozygous FH who have high LDL cholesterol levels or who do not respond well to medications. LDL cholesterol levels can be reduced by 50% to 80% with lipoprotein apheresis performed once every one to two weeks.
A liver transplant is a surgery to replace a diseased liver with a healthy one from a donor and is only considered for people with homozygous FH who have severe liver damage or have not responded to other treatments.
FH cannot be prevented, as it is a genetic condition that is present from birth. However, people with FH can take steps to prevent or delay the complications of the condition, such as:
Getting regular check-ups and blood tests to monitor the cholesterol levels and the heart and blood vessel health.
Taking the prescribed medications as directed and following the recommended lifestyle changes.
Informing the family members about the condition and encouraging them to get tested and treated if they have it.
Seeking medical attention promptly if any symptoms of heart disease or other complications occur.
