Overview

What is Familial Hypercholesterolemia?

Familial hypercholesterolemia, or FH, is a genetic disease characterized by a severely high level of low-density lipoprotein, or LDL cholesterol, which is known as the "bad" cholesterol because it can clog your arteries. The value of a healthy person falls below 100 mg/dL, but in someone with familial hypercholesterolemia, levels may reach up to 400 mg/dL.

Unless they receive treatment, this condition usually makes individuals develop coronary artery disease at an early age. It may, in return, bring heart attacks and other cardiovascular problems much sooner compared to individuals who do not have the FH.

What are the symptoms of familial hypercholesterolemia?

Adult and pediatric patients with familial hypercholesterolemia have high levels of low-density lipoprotein (LDL) cholesterol in the blood. Because low-density lipoprotein (LDL) cholesterol can deposit in arteries, making them rigid and narrow, it is called "bad" cholesterol.

At times, this excess cholesterol may deposit in the following locations in the skin, tendons, and near the orbit around the eyeball:

Skin: Cholesterol nodules tend to accumulate in the palms, elbows, and knees. They can also affect the skin around the eyes.
Tendon: The accumulation of cholesterol in the body tends to thicken some of the tendons in the hand, including the Achilles tendon.
Eyes: A white or gray ring around the pupil of the eye, called a corneal arcus and may be due to high cholesterol. It usually affects older adults, although younger patients with familial hypercholesterolemia are also affected.

What causes familial hypercholesterolemia?

Familial hypercholesterolemia is caused by genetic mutations that change how your body manages low-density lipoprotein, or "bad" cholesterol. Here's an even greater look at its genetics:

Inherited mutations: FH is inherited by families. This indicates that one copy of the altered gene, presumably inherited from only one parent, suffices to cause the condition. In rare cases, inheriting two altered copies of the gene-one from each parent-can lead to a more severe disorder.
Genes involved: Many genes contribute to FH. The most frequently involved one is the gene for LDLR, which encodes the instructions to build the LDL cholesterol receptors. Your cells require these receptors to extract LDL from your bloodstream. When they are dysfunctional or less functional, the process fails, and LDL aggregates in the cells.
Other cholesterol-related genes: Mutations in genes such as APOB, PCSK9, and LDLRAP1 may also cause FH. These genes control all aspects of the metabolism and processing of LDL in the body.

This translates to what the mutations mean in terms of cholesterol levels as follows:

Functional Failure: The mutations either failed to produce enough LDL receptors or malfunctioned LDL receptors. In both cases, the cells' ability to clear LDL from the blood is drastically affected.
Accumulation of LDL: The LDL particles can stay in your blood and cause accumulation, which creates plaque deposits in your arterial walls.
Artery constriction: The accumulation of plaque narrows your arteries. This is medically referred to as atherosclerosis. This reduces blood flow in your body and increases your risk of stroke and heart disease.

What are the diagnosis and tests for familial hypercholesterolemia?

The diagnosis of familial hypercholesterolemia (FH) tends to rely on many factors:

Medical history and family history: Your doctor will ask you about your personal and family medical history, especially regarding:

Level of cholesterol.
Family history of heart disease or stroke, particularly if at a young age.
Presence of symptoms like tendon xanthomas or corneal arcus.

Physical examination: Your doctor can look for visible signs at cholesterol deposition sites, including:

Xanthomas: yellowish bumps often appearing around tendons in elbows, knees, and eyelids.
Corneal arcus: A gray or white ring surrounding the pupil of the eye.

Blood tests: A significant test is a lipid panel, in which cholesterol is measured, including:

LDL cholesterol, also known as bad cholesterol.
HDL cholesterol, also known as good cholesterol.
Total cholesterol.
Triglycerides.

Genetic testing: Genetic testing is not generally required for diagnosis, but in cases of a confirmed diagnosis of FH, it can be established by a genetic test that checks for any mutation within your genes responsible for causing an FH mutation. Genetic testing may help with:

Definitive diagnosis of FH: Knowing which gene mutation is present helps confirm the diagnosis.
Cascade screening: If you have an identified mutation in your FH, then your family members can be screened for the same mutation so that others at risk may be identified in due time. Early detection leads to early intervention and treatment.

The way these components come together to form a diagnosis is shown below:

High levels of LDL: LDL cholesterol is typically high in adults with FH above 190 mg/dL, whereas in children, it is predominantly elevated above 160 mg/dL. Very high levels (>400 mg/dL) are suggestive of a more aggressive form.
Family history: The existence of a first-degree relative with high cholesterol or early-onset heart disease puts one under suspicion of having FH.
Physical examination: Xanthomas and corneal arcus are suggestive, though not diagnostic, of the condition. Their absence does not conclusively make a subject free of the condition.
Genetic testing: It is not usually required, but a positive genetic test confirms the existence of FH and can help determine the need for treatment decisions and screening relatives.

What is the treatment for Familial hypercholesterolemia?

Fortunately, familial hypercholesterolemia, or FH, is a treatable condition. Treatment objectives are to greatly reduce the levels of LDL cholesterol and limit the accumulation of plaque within your arteries.

Medications:

Most people with FH will also need additional pharmacologic therapy, aside from lifestyle modifications, to successfully lower their LDL cholesterol levels. There are:

Statins: Statins are a first-line defense for lowering LDL cholesterol and blocking the hepatic pathway involved in cholesterol synthesis. There are several types of statins, and your physician will know what dosage is right for you.
Ezetimibe decreases cholesterol intake from the diet within the intestines. It can be administered with or without statins for a greater fall in LDL levels.
PCSK9 Inhibitors: These are the latest injectable drugs. They work by potentiating the action of your liver to remove much more LDL cholesterol from your bloodstream. They are managed in patients who haven't reached an adequate LDL lowering on statins or when combined with ezetimibe.

Other drugs-

Other drugs, such as Lomitapide or Mipomersen, would be prescribed in the more extreme cases, but again very sparingly in those diagnosed with homozygous FH, a much worse variant of the condition.

How can I lower my risk?

All you can do to reduce your risk, though hereditary diseases such as familial hypercholesterolemia cannot be avoided. You can eat right, start exercising, and take medicines prescribed by your doctor.

Living With

How can I care for myself if I have familial hypercholesterolemia?

The following are ways that will reduce the risk of cardiovascular problems for those who have familial hypercholesterolemia:

Take the prescribed drugs by your doctor.
Take foods low in Trans, saturated, and fatty foods that cause cholesterol.
Take foods containing more unsaturated fat.
Engage in exercises.
Keep off excess weight.

Why Tender Palm Super-Speciality Hospital for Familial Hypercholesterolemia?

Tender Palm Hospital has the most experienced team of Cardiologists, Cardiac Surgeons, and diagnostics with the latest and International standard infection control measures in Lucknow, India. The Cardiac Science Centre team has decades of experience in successfully treating Familial Hypercholesterolemia.