Defining Familial Hypercholesterolemia: Understanding Inherited High Cholesterol

Familial hypercholesterolemia (FH) is a genetic condition that disrupts the body’s ability to manage low-density lipoprotein (LDL) cholesterol, often referred to as “bad” cholesterol. The term “familial” in this context is crucial; it defines familial conditions as those passed down through families, meaning FH is inherited. This article will explore what it means to have familial hypercholesterolemia, its causes, and the importance of understanding this inherited risk.

What is Familial Hypercholesterolemia? Defining the Inherited Condition

At its core, familial hypercholesterolemia signifies an inherited disorder affecting how your body processes cholesterol. To Define Familial hypercholesterolemia simply, it’s high cholesterol that runs in families. Individuals with FH are born with a predisposition to elevated LDL cholesterol levels because of genetic defects they inherit. While cholesterol levels naturally tend to increase as we age, those with FH start at a higher baseline, and their LDL levels escalate more significantly over time if left unmanaged.

This persistently high LDL cholesterol is the primary concern in FH. LDL cholesterol contributes to the formation of plaque within the arteries, a process known as atherosclerosis. This plaque buildup narrows and hardens the arteries, dramatically increasing the risk of coronary heart disease. Alarmingly, without treatment, individuals with FH face a risk of developing heart disease that is up to 20 times greater than those without the condition. Understanding the “familial” aspect is the first step in recognizing and addressing this significant health risk.

The Genetic Roots: Causes of Familial Hypercholesterolemia

Familial hypercholesterolemia is, by definition, familial because it stems from genetic mutations passed down from parent to child. The most common cause is a mutation in the gene responsible for the LDL cholesterol receptor. These receptors play a vital role in removing LDL cholesterol from the bloodstream by facilitating its passage into cells for processing or elimination from the body.

When this receptor gene is mutated, it becomes less effective. Consequently, LDL cholesterol is not efficiently removed from the blood, leading to its accumulation. While mutations in the LDL receptor gene are the most prevalent cause, FH can also arise from mutations in other genes involved in cholesterol metabolism. These include the PCSK9 gene and the gene for Apolipoprotein B (APOB). Inheriting specific mutations in any of these genes can result in the development of familial hypercholesterolemia, underscoring the defined familial nature of the condition.

Prevalence: How Common is Familial Hypercholesterolemia?

Familial hypercholesterolemia is more common than many people realize. It’s estimated that approximately 1 in 200 adults carries the genetic mutation for FH. When considering children as well, FH affects roughly 1.3 million individuals in the United States alone. Despite its relatively high prevalence, a significant challenge is that only about 10% of those with FH are aware they have it. This lack of awareness highlights the importance of understanding what it means to define familial hypercholesterolemia and recognizing the need for screening, especially within families with a history of high cholesterol or early heart disease. The positive aspect is that FH is a treatable condition, and early diagnosis can significantly improve outcomes.

Types of Familial Hypercholesterolemia: Heterozygous and Homozygous

Within the definition of familial hypercholesterolemia, there are two primary types, categorized by the genetic inheritance pattern and severity:

Heterozygous FH (HeFH): This is the more common form of FH. Heterozygous means that an individual inherits the mutated gene from only one parent. In HeFH, while the LDL receptors are impaired, they still have some functionality. However, this is often insufficient to maintain healthy cholesterol levels. LDL cholesterol levels in individuals with HeFH can be significantly elevated, sometimes exceeding 190 milligrams per deciliter (mg/dL) of blood in severe cases. If left untreated, individuals with HeFH may 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. Homozygous signifies inheriting the mutated gene from both parents. In HoFH, the LDL receptors are severely deficient or almost completely absent in function. This leads to dramatically high LDL cholesterol levels, often reaching 400 mg/dL of blood or even higher. If HoFH is not detected and aggressively treated early in life, individuals can develop heart disease in childhood, sometimes even as young as 2 or 3 years old. Understanding the distinction between these types is crucial for appropriate diagnosis and management strategies, further emphasizing the importance of accurately defining familial hypercholesterolemia.

Diagnosing Familial Hypercholesterolemia: Identifying the Inherited Risk

Diagnosing familial hypercholesterolemia involves a multi-faceted approach. Because it is defined familial, family history plays a crucial role. Diagnosis typically includes:

Physical Exam and Lab Results: A routine physical exam combined with blood tests to measure cholesterol levels, particularly LDL cholesterol, is the initial step. Consistently high LDL levels, especially in younger individuals or those with a family history, raise suspicion for FH.
Personal and Family History: A detailed personal and family medical history is essential. Doctors will inquire about a family history of high cholesterol, early heart attacks, or other cardiovascular diseases. This familial pattern is a key indicator of potential FH.
Molecular Diagnosis or Genetic Testing: Genetic testing can definitively confirm the diagnosis of FH by identifying specific gene mutations. While not always necessary for initial diagnosis, genetic testing is increasingly utilized, especially when the diagnosis is uncertain, or to facilitate cascade screening within families.
Physical Symptoms: While many individuals with FH are asymptomatic, some may develop physical signs of cholesterol deposits. These can include:
- Tendon Xanthomas: Cholesterol deposits in tendons, most commonly the Achilles tendon, but also tendons in the hands and elbows.
- Xanthelasmas: Cholesterol deposits in the skin around the eyes.
- Corneal Arcus: A whitish ring around the outer edge of the cornea (more common in HoFH).

Cascade Screening: Extending Diagnosis within Families

Cascade screening is a critical strategy for identifying FH within families. Because FH is defined familial, once one individual is diagnosed, it’s essential to screen their close relatives – parents, siblings, and children. Cascade screening involves systematically testing family members to determine if they also carry the same genetic mutation. This proactive approach is crucial for early detection and intervention, allowing for timely management of cholesterol levels and reducing the risk of cardiovascular disease in affected family members.

Treating Familial Hypercholesterolemia: Managing Inherited High Cholesterol

Despite being underdiagnosed and undertreated, familial hypercholesterolemia is a manageable condition. Early diagnosis and treatment are paramount for a positive prognosis. For individuals with HoFH, or suspected HoFH, treatment should commence as early as possible to prevent severe and potentially life-threatening cardiovascular complications in childhood.

It’s important to emphasize that lifestyle modifications alone, such as diet and exercise, are usually insufficient to adequately treat FH. While these lifestyle changes are beneficial for overall health and can complement medical treatment, medications are typically necessary to achieve significant LDL cholesterol reduction, often by at least 50%.

Common treatment approaches include:

Statin Medications: Statins are the cornerstone of FH treatment. They work by reducing cholesterol production in the liver and increasing the liver’s ability to remove LDL cholesterol from the blood.
Ezetimibe: This medication works by reducing the absorption of cholesterol in the small intestine and is often used in combination with statins to further lower LDL cholesterol levels.
LDL Apheresis: For individuals with extremely high LDL cholesterol, particularly those with HoFH, LDL apheresis may be necessary. This procedure is similar to dialysis and involves filtering blood to remove LDL cholesterol. It is typically performed every few weeks.
Bile Acid Sequestrants: Medications like cholestyramine or colesevelam can be used to reduce cholesterol absorption in the intestines, leading to lower blood cholesterol levels.
PCSK9 Inhibitors: These are injectable medications that represent a newer class of lipid-lowering drugs. PCSK9 inhibitors block the PCSK9 protein, which in turn increases the number of LDL receptors on liver cells, enhancing LDL cholesterol removal from the blood.

If you have been diagnosed with FH, consulting with a healthcare professional to develop an individualized treatment plan is crucial. Furthermore, discussing FH with family members to encourage screening and potential treatment is a vital step in managing this defined familial condition across generations.