Familial hypercholesterolemia (FH), sometimes referred to as Familial Hyperlipidemia, is a genetic disorder passed down through families. It disrupts the body’s ability to manage low-density lipoprotein (LDL) cholesterol, often called “bad” cholesterol. Individuals with FH are born with elevated LDL levels, and these levels tend to increase more significantly over time compared to those without the condition. This persistently high LDL cholesterol dramatically increases the risk of developing heart disease.
What Causes Familial Hypercholesterolemia?
The primary cause of familial hypercholesterolemia is a genetic mutation. This mutation most commonly occurs in the gene responsible for the LDL receptor. These receptors play a crucial role in removing LDL cholesterol from the bloodstream by facilitating its uptake into cells for processing or elimination. When this gene is mutated, the receptors become less effective, leading to a buildup of LDL cholesterol in the blood.
Mutations in other genes, such as PCSK9 and Apolipoprotein B genes, can also lead to inherited high cholesterol. Inheriting a specific mutation in any of these genes can result in the development of familial hypercholesterolemia.
How Common is Familial Hypercholesterolemia?
Familial hypercholesterolemia is more common than many people realize. It is estimated that approximately 1 in 200 adults carry the genetic mutation for FH. In the United States alone, about 1.3 million individuals, including children, are affected by FH. Despite its prevalence, it’s concerning that only about 10% of those with FH are aware of their condition. Fortunately, familial hypercholesterolemia is a treatable condition, and with appropriate management, individuals can significantly reduce their risk of heart disease.
Types of Familial Hypercholesterolemia
There are two main types of familial hypercholesterolemia, categorized by the genetic inheritance pattern and severity:
Heterozygous FH (HeFH)
Heterozygous FH is the more common form of the condition. It occurs when an individual inherits the FH genetic mutation from only one parent. In HeFH, LDL cholesterol levels are significantly elevated and can often exceed 190 milligrams per deciliter (mg/dL) of blood. Without treatment, individuals with heterozygous FH can develop heart disease at a relatively young age, sometimes as early as 30 years old.
Homozygous FH (HoFH)
Homozygous FH is a much rarer and more severe form of familial hypercholesterolemia. It arises when an individual inherits the FH genetic mutation from both parents. People with HoFH experience extremely high LDL cholesterol levels, often reaching 400 mg/dL of blood or even higher. If homozygous FH is not diagnosed and treated early in life, individuals can develop heart disease in childhood, sometimes as young as 2 or 3 years old.
Diagnosing Familial Hypercholesterolemia
Diagnosing familial hypercholesterolemia involves a comprehensive approach that includes:
- Physical Exam and Lab Results: A doctor will conduct a physical examination and review blood tests to measure cholesterol levels, particularly LDL cholesterol.
- Personal and Family History: A detailed medical history, including family history of high cholesterol and early heart disease, is crucial for diagnosis.
- Genetic Testing: Molecular diagnosis or genetic testing can confirm the presence of FH by identifying specific gene mutations. Genetic testing is particularly helpful as it can also identify at-risk relatives.
While some individuals with FH may exhibit physical signs like cholesterol deposits in tendons (Achilles, hands, elbows) or around the eyes or cornea (in HoFH), many others do not have any visible symptoms.
Cascade Screening: If one person in a family is diagnosed with FH, it is essential that all immediate family members (parents, siblings, children) undergo cascade screening. This process involves systematically screening relatives to identify others who may have inherited the condition. Furthermore, if someone in a family has experienced an early heart attack, other family members should also be screened for FH. Children with a family history of FH should be screened as early as age 2. For all children, routine cholesterol checks are recommended between ages 9 and 11 and again between ages 17 and 21.
Treating Familial Hypercholesterolemia
Despite being underdiagnosed and undertreated, familial hypercholesterolemia is highly manageable, especially when identified and treated early. Individuals with homozygous FH or suspected HoFH require immediate treatment due to the high risk of early cardiovascular complications.
While lifestyle modifications like diet and exercise are beneficial for overall health, they are not sufficient to manage FH alone. Medications are typically necessary to lower LDL cholesterol levels by at least 50% in individuals with FH.
Common treatment strategies include:
- Statin Medications: Statins are often the first-line medication prescribed to lower LDL cholesterol production in the liver.
- Ezetimibe: This medication works by reducing the absorption of cholesterol in the small intestine and may be used in combination with statins.
- LDL Apheresis: For individuals with extremely high LDL cholesterol, particularly those with HoFH, LDL apheresis may be necessary. This procedure, similar to dialysis, removes LDL cholesterol directly from the blood.
- Bile Acid Sequestrants: Medications like cholestyramine or colesevelam reduce cholesterol absorption in the intestines, thereby lowering bloodstream cholesterol.
- PCSK9 Inhibitors: These injectable medications are a newer class of drugs that significantly lower LDL cholesterol levels by blocking the PCSK9 protein, allowing more LDL receptors to clear cholesterol from the blood.
If you have been diagnosed with familial hypercholesterolemia, it is crucial to consult with your healthcare provider to develop an appropriate treatment plan. Furthermore, discussing FH with your family members is essential so they can also be screened and receive timely treatment if needed. Early diagnosis and management of FH are key to preventing heart disease and ensuring a healthy life.
