Summary about Disease
Familial hypercholesterolemia (FH) is a genetic disorder that causes high levels of low-density lipoprotein (LDL) cholesterol (often called "bad" cholesterol) in the blood. This elevated LDL-C increases the risk of early-onset cardiovascular disease, including heart attacks and strokes. FH is caused by mutations in genes that control how the body processes cholesterol.
Symptoms
Many people with FH have no noticeable symptoms until they develop cardiovascular problems. Potential symptoms include:
Xanthomas: Fatty deposits under the skin, often around tendons (especially in the Achilles tendon, elbows, and hands) or on the eyelids (xanthelasma).
Arcus cornealis: A white or gray ring around the cornea of the eye, especially if present before age 45.
Chest pain (angina): Due to narrowed arteries in the heart.
Other symptoms of heart disease: Shortness of breath, fatigue.
Symptoms of stroke: Sudden numbness or weakness, difficulty speaking, vision changes.
Causes
FH is primarily caused by genetic mutations that affect the way the body handles LDL cholesterol. These mutations often occur in genes such as:
LDLR (most common): Codes for the LDL receptor, which removes LDL cholesterol from the blood.
APOB: Codes for apolipoprotein B, a protein component of LDL.
PCSK9: Codes for proprotein convertase subtilisin/kexin type 9, a protein that regulates LDL receptors.
LDLRAP1: Codes for LDL receptor adaptor protein 1, important for LDL receptor function. FH is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is needed to cause the disorder. In rare cases, a person may inherit two copies of the mutated gene (homozygous FH), leading to much higher cholesterol levels and more severe cardiovascular disease at a younger age.
Medicine Used
Medications used to treat FH typically include:
Statins: (e.g., atorvastatin, rosuvastatin, simvastatin) These drugs block an enzyme in the liver that helps produce cholesterol, thus lowering LDL levels.
Ezetimibe: This medication reduces the absorption of cholesterol in the small intestine.
PCSK9 inhibitors: (e.g., evolocumab, alirocumab) These injectable medications block the PCSK9 protein, allowing more LDL receptors to be available on liver cells to remove LDL cholesterol from the blood.
Bempedoic acid: This medication lowers LDL cholesterol by inhibiting an enzyme involved in cholesterol synthesis.
Lomitapide and mipomersen: Used for homozygous FH; these are more specialized medications that affect the production of lipoproteins.
Lipid apheresis: A procedure to filter LDL cholesterol out of the blood; used in severe cases, particularly homozygous FH.
Is Communicable
No, familial hypercholesterolemia is not communicable. It is a genetic disorder that is inherited and cannot be spread from person to person.
Precautions
People with FH should take the following precautions:
Follow a healthy lifestyle: This includes a heart-healthy diet low in saturated and trans fats, regular exercise, and maintaining a healthy weight.
Take medications as prescribed: Adhere strictly to the medication regimen prescribed by a doctor.
Monitor cholesterol levels regularly: Get regular blood tests to monitor cholesterol levels and adjust treatment as needed.
Avoid smoking: Smoking increases the risk of cardiovascular disease.
Manage other risk factors: Control high blood pressure, diabetes, and obesity.
Inform family members: Because FH is genetic, family members should be screened for high cholesterol and genetic testing considered.
Consult a cardiologist: Regular checkups with a cardiologist are important, especially for those with a family history of early heart disease.
How long does an outbreak last?
FH is not an "outbreak" disease. It is a chronic, lifelong condition that, without treatment, leads to continuous elevation of LDL cholesterol from birth. The duration of symptoms related to cardiovascular disease depends on the severity of the condition and the effectiveness of treatment.
How is it diagnosed?
FH is typically diagnosed through:
Blood tests: Measuring LDL cholesterol levels (high LDL cholesterol is a key indicator).
Family history: Evaluating the presence of early heart disease or high cholesterol in family members.
Physical exam: Looking for signs like xanthomas or arcus cornealis.
Genetic testing: Identifying mutations in genes associated with FH (e.g., LDLR, *APOB*, *PCSK9*). Genetic testing can confirm the diagnosis and help identify family members who may be at risk.
Diagnostic criteria: Several sets of diagnostic criteria exist that incorporate LDL-C levels, family history, and clinical findings to determine the likelihood of FH.
Timeline of Symptoms
The timeline of symptoms can vary significantly among individuals with FH.
Childhood/Adolescence: Some children with heterozygous FH may have elevated cholesterol levels detectable in childhood, although symptoms are rare. Homozygous FH presents with very high cholesterol and symptoms may appear in early childhood.
Young Adulthood: Xanthomas and arcus cornealis may begin to appear in some individuals. Cholesterol levels are typically elevated.
Adulthood: Without treatment, symptoms related to cardiovascular disease, such as chest pain (angina), heart attack, or stroke, may occur, often earlier than in the general population (e.g., before age 55 in men and 65 in women). It's important to note that many individuals with FH remain asymptomatic until they experience a cardiovascular event.
Important Considerations
Early diagnosis and treatment are crucial: Starting cholesterol-lowering therapy early in life can significantly reduce the risk of heart disease.
Cascade screening: Testing family members of individuals diagnosed with FH is essential to identify others who may be affected.
Lifestyle modifications are important but often not enough: While a healthy lifestyle is beneficial, most people with FH will require medication to lower their cholesterol to target levels.
Adherence to treatment is key: Consistent use of prescribed medications is vital for managing cholesterol levels and preventing cardiovascular events.
Personalized treatment: The optimal treatment plan may vary depending on the specific genetic mutation, cholesterol levels, other risk factors, and individual response to medications.
Homozygous FH is a severe form: Individuals with homozygous FH require intensive treatment, often including lipid apheresis, due to very high cholesterol levels and a very high risk of early cardiovascular disease.
Pregnancy: Women with FH should discuss their treatment plan with their doctor before becoming pregnant, as some cholesterol-lowering medications are not safe during pregnancy.