Familial hypercholesterolemia (FH), often referred to as familial high cholesterol, is a genetic condition that disrupts the body’s ability to manage low-density lipoprotein (LDL) cholesterol, commonly known as “bad” cholesterol. Unlike high cholesterol that develops later in life, individuals with FH are born with elevated LDL levels. These levels, already high at birth, tend to increase further with age, posing significant health risks.
High LDL cholesterol is a primary contributor to plaque buildup in the arteries, a process called atherosclerosis. This buildup drastically increases the risk of coronary heart disease and other cardiovascular issues. Alarmingly, without proper management, individuals with familial high cholesterol face a risk of heart disease that is 20 times higher than those without the condition. Early diagnosis and intervention are therefore critical in mitigating these risks.
What Causes Familial High Cholesterol?
Familial hypercholesterolemia is primarily caused by genetic mutations. The most common cause is a mutation in the gene responsible for the LDL receptor. These receptors play a crucial role in removing LDL cholesterol from the bloodstream by transporting it 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 can also lead to inherited high cholesterol. These include the PCSK9 gene and the apolipoprotein B (APOB) gene. These genes are also involved in cholesterol metabolism and clearance. Inheriting specific mutations in any of these genes can result in the development of familial high cholesterol. Understanding the genetic basis of FH is key to diagnosis and family screening.
How Common is Familial High Cholesterol?
Familial high cholesterol is surprisingly common, affecting approximately 1 in 200 adults globally. In the United States alone, it is estimated that around 1.3 million people, including children, live with FH. Despite its prevalence, a significant challenge is the lack of awareness, with only about 10% of those affected knowing they have the condition. This lack of diagnosis underscores the importance of increased screening and awareness campaigns. The positive aspect is that familial high cholesterol is a treatable condition. With timely diagnosis and appropriate management through medication and lifestyle adjustments, individuals with FH can lead healthy lives and significantly reduce their risk of heart disease.
Types of Familial High Cholesterol
There are two main types of familial high cholesterol, differing in severity and inheritance patterns:
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Heterozygous Familial Hypercholesterolemia (HeFH): This is the more prevalent form of FH. Heterozygous FH is inherited from only one parent. Individuals with HeFH have one copy of the mutated gene. In severe cases of HeFH, LDL cholesterol levels can reach extremely high levels, exceeding 190 milligrams per deciliter (mg/dL) of blood. Without treatment, individuals with HeFH may develop heart disease at a relatively young age, sometimes as early as 30 years old.
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Homozygous Familial Hypercholesterolemia (HoFH): Homozygous FH is a rare and more severe form of the condition. It occurs when an individual inherits the mutated gene from both parents. As a result, individuals with HoFH have two copies of the mutated gene. LDL cholesterol levels in HoFH can be exceptionally high, often surpassing 400 mg/dL of blood. If Homozygous FH is not diagnosed and treated promptly, it can lead to very early onset heart disease, sometimes developing in the first decade of life, even as young as 2 or 3 years old.
Understanding the type of FH is crucial as it impacts treatment strategies and prognosis.
Diagnosing Familial High Cholesterol
Diagnosing familial high cholesterol involves a combination of clinical evaluation, laboratory tests, and medical history assessment. Both Heterozygous and Homozygous FH can be identified through these methods.
A physical examination is typically the first step. Doctors will assess for physical signs of FH, such as cholesterol deposits in tendons (Achilles, hands, elbows) known as tendon xanthomas, or around the eyes (xanthelasmas) and cornea (corneal arcus), especially in HoFH.
Lab results, specifically lipid panels measuring LDL cholesterol, total cholesterol, HDL cholesterol, and triglycerides, are essential for diagnosis. Persistently high LDL cholesterol levels, particularly from a young age, are a strong indicator of FH.
Personal and family medical history is also critical. A family history of early heart disease or known FH significantly increases the likelihood of the condition.
Molecular diagnosis, including genetic testing, can confirm the diagnosis by identifying specific gene mutations associated with FH. Genetic testing is particularly valuable as it can also help identify at-risk relatives, facilitating cascade screening.
It’s important to note that many individuals with familial high cholesterol may not exhibit obvious physical symptoms, especially in the early stages of Heterozygous FH. This is why routine cholesterol screening and awareness of family history are so important. Children at increased risk should be screened as early as age 2, and all children should have cholesterol checks between 9 and 11 and again between 17 and 21.
Cascade Screening for Familial High Cholesterol
Cascade screening is a systematic approach to identify individuals within a family who may have inherited a genetic condition, like familial hypercholesterolemia. It begins with identifying an individual (the proband) diagnosed with FH. Then, their close relatives – parents, siblings, and children – are screened to determine if they also carry the same genetic mutation.
Cascade screening is particularly important for familial high cholesterol and elevated Lipoprotein(a) [Lp(a)], another genetic lipid disorder, because early detection allows for timely intervention. By identifying family members with FH, healthcare providers can implement strategies to manage their LDL cholesterol levels and significantly reduce their risk of developing cardiovascular disease. This proactive approach can save lives and improve long-term health outcomes within families affected by inherited high cholesterol.
Treating Familial High Cholesterol
Despite being a treatable condition, familial high cholesterol often remains underdiagnosed and undertreated. Early identification and aggressive treatment are crucial, especially for Homozygous FH, where delayed intervention can lead to severe cardiovascular complications in childhood.
Lifestyle changes, including a heart-healthy diet and regular exercise, are beneficial for overall health but are typically insufficient to manage FH on their own. Medications are usually necessary to achieve significant LDL cholesterol reduction, often aiming for at least a 50% decrease.
Common medications for treating familial high cholesterol include:
- Statins: These are the first-line drugs for lowering LDL cholesterol. Statins work by reducing cholesterol production in the liver.
- Ezetimibe: This medication works by reducing the absorption of cholesterol from the small intestine. It is often used in combination with statins.
- Bile Acid Sequestrants: Such as cholestyramine or colesevelam, these drugs bind to bile acids in the intestine, promoting cholesterol removal from the body.
- PCSK9 Inhibitors: These injectable medications are highly effective in lowering LDL cholesterol. They work by blocking the PCSK9 protein, which increases the number of LDL receptors available to remove cholesterol from the blood.
- LDL Apheresis: For individuals with extremely high LDL cholesterol, particularly those with Homozygous FH, LDL apheresis may be necessary. This procedure is similar to dialysis and involves removing LDL cholesterol directly from the blood.
If you have been diagnosed with familial high cholesterol, it is essential to work closely with your healthcare provider to develop a personalized treatment plan. Furthermore, discussing FH with your family members and encouraging them to get screened is a crucial step in managing this inherited condition within families and preventing early heart disease.
Read this article in Spanish: ¿Qué es la hipercolesterolemia familiar? (PDF)
