Familial Hypercholesterolemia (FH) is a genetic condition passed down through families. It disrupts the body’s natural process of managing LDL cholesterol, often referred to as “bad” cholesterol. Unlike typical increases in cholesterol that occur with age, individuals with FH are born with elevated LDL levels that progressively worsen over time.
This persistently high LDL cholesterol significantly accelerates the formation of plaque within the arteries, a condition known as atherosclerosis. Consequently, people with FH face a dramatically increased risk of developing coronary heart disease. Alarmingly, if left undiagnosed and untreated, individuals with FH are 20 times more likely to develop heart disease compared to those without the condition.
What Causes Familial Hypercholesterolemia?
The primary cause of familial hypercholesterolemia is a genetic mutation affecting the LDL cholesterol receptor. This receptor plays a crucial role in removing LDL cholesterol from the bloodstream and transporting it into cells for processing or elimination. Mutations in this gene, as well as in other genes like PCSK9 and Apolipoprotein B, can lead to inherited high cholesterol. Inheriting a specific mutation in any of these genes can result in the development of FH.
Prevalence of Familial Hypercholesterolemia
Familial hypercholesterolemia is more common than many realize. It’s estimated that approximately 1 in 200 adults carries the genetic mutation for FH. In the United States alone, around 1.3 million people, including children, are affected by FH. Despite its prevalence, a significant challenge is that only about 10% of those with FH are aware of their condition. Fortunately, with early detection and appropriate management through medication and lifestyle adjustments, FH is a treatable condition.
Types of Familial Hypercholesterolemia: Heterozygous and Homozygous FH
There are two main types of familial hypercholesterolemia, differing in severity and inheritance patterns:
-
Heterozygous FH (HeFH): This is the more common form of FH. It occurs when an individual inherits the genetic mutation from only one parent. Individuals with Heterozygous FH can experience very high LDL cholesterol levels, sometimes exceeding 190 milligrams per deciliter (mg/dL) of blood. Without treatment, heart disease can develop at a relatively young age, sometimes as early as 30 years old in individuals with HeFH.
-
Homozygous FH (HoFH): Homozygous FH is a rarer and more severe form of the condition. It arises when a person inherits the FH genetic mutation from both parents. People with Homozygous FH experience extremely high LDL cholesterol levels, often surpassing 400 mg/dL of blood. If Homozygous FH is not diagnosed and treated promptly, heart disease can manifest very early in life, even in childhood, with some cases appearing as young as 2 or 3 years old. More detailed information can be found on resources dedicated to Homozygous FH.
Diagnosis of Familial Hypercholesterolemia
Diagnosing both Heterozygous and Homozygous FH typically involves a comprehensive approach. This includes a physical examination, a review of lab results, and an assessment of both personal and family medical history. Molecular diagnosis, genetic testing, or genetic diagnosis can also be used to confirm FH. Genetic testing is particularly valuable as it can identify family members who may also be at risk.
While some individuals with FH may exhibit physical signs, many do not experience noticeable symptoms.
One potential physical sign is the presence of cholesterol deposits in tendons, particularly the Achilles tendon and tendons of the hands or elbows. Individuals with Homozygous FH may also develop cholesterol deposits in other areas, such as the skin around the eyes or on the outer edge of the cornea of the eye.
If FH is diagnosed in one family member, it is crucial that all immediate relatives, including parents, siblings, and children, undergo screening for the condition. Similarly, if there is a history of early heart attacks in a family, other family members should consider getting tested for FH.
For children at increased risk of FH, screening is recommended to begin as early as age 2. For all children, routine cholesterol checks are advised between the ages of 9 and 11 and again between ages 17 and 21.
The Importance of Cascade Screening for Genetic Conditions like FH
Cascade screening is a systematic approach to identifying individuals within a family who may be at risk for inheriting genetic conditions such as familial hypercholesterolemia. This process involves screening close relatives of someone already diagnosed with FH to determine if they also carry the same genetic mutation.
For conditions like familial hypercholesterolemia and elevated Lipoprotein(a) [Lp(a)], early detection through cascade screening is vital. It allows for timely intervention to manage LDL cholesterol levels and significantly reduce the risk of developing cardiovascular disease within families.
Further information is available in resources about Cascade screening for FH (PDF) and Cascade Screening in Spanish (PDF).
Treatment Options for Familial Hypercholesterolemia
Despite its treatability, Familial Hypercholesterolemia remains underdiagnosed and undertreated. However, with early identification and appropriate treatment, individuals with FH can have a very positive outlook. For those with Homozygous FH, or suspected Homozygous FH, immediate treatment is crucial. Untreated Homozygous FH can lead to life-threatening cardiovascular complications in childhood.
It’s important to understand that familial hypercholesterolemia cannot be effectively managed through diet and exercise alone. While lifestyle modifications are beneficial, medications are typically necessary to achieve a significant reduction in LDL cholesterol levels, often by at least 50%.
The cornerstone of FH treatment is usually a statin medication. Additional cholesterol-lowering medications, such as ezetimibe, may also be prescribed. For individuals with extremely high LDL cholesterol, particularly those with Homozygous FH, a procedure called LDL apheresis may be required. This procedure, similar to dialysis, is performed regularly to remove cholesterol directly from the blood.
Another class of medications, known as bile acid sequestrants, including cholestyramine or colesevelam, can also be used. These medications work by reducing cholesterol absorption in the intestines, thereby lowering the amount of cholesterol that enters the bloodstream.
Injectable medications called PCSK9 inhibitors represent another effective treatment option. These medications target and block the PCSK9 protein, which in turn increases the number of LDL receptors on liver cells. This leads to more efficient removal of LDL cholesterol from the blood.
If you have been diagnosed with FH, it is essential to consult with your healthcare provider to develop a personalized treatment plan. Furthermore, discussing FH with your family members is crucial to ensure they are also screened and receive appropriate care if needed.
