FH: Understanding, Testing, and Managing Familial Hypercholesterolemia
"Familial Hypercholesterolemia can lead to premature heart disease if left untreated. It is imperative that families with a history of FH get tested and seek early intervention to manage this condition effectively."
--Familial Hypercholesterolemia Foundation
"Genetics loads the gun, but lifestyle pulls the trigger." This saying hits close to home for me. While I don’t have familial hypercholesterolemia (FH), it runs in my family. My mother, uncles, and cousins all live with it, and I vividly remember one of my uncles having a heart attack at just 42 years old. Fortunately, he survived and continues to manage his health today. As a parent, though, I can’t help but worry about my kids potentially inheriting this condition.
FH is not just about high cholesterol from a poor diet—it’s genetic. For years, statins were the primary option for controlling the dangerously high cholesterol levels associated with FH. Thankfully, treatment options have expanded in recent decades. In addition to statins, therapies like PCSK9 inhibitors, ezetimibe, and bempedoic acid offer new ways to manage cholesterol. These advances provide more tailored, effective strategies to reduce cardiovascular risk, giving families like mine hope for better health outcomes.
Understanding FH and its treatments is crucial for those of us with a genetic history of heart disease, especially for our children’s future.
Familial Hypercholesterolemia (FH)
What is FH?
Familial Hypercholesterolemia (FH) is a genetic disorder that results in very high levels of low-density lipoprotein (LDL) cholesterol from birth. This condition is caused by mutations in the genes responsible for removing LDL cholesterol from the blood, leading to dangerously elevated cholesterol levels. While cholesterol itself is essential for cell function, excessive amounts can accumulate in the blood, causing atherosclerosis, which narrows and hardens the arteries. Over time, this can significantly increase the risk of heart disease, particularly premature coronary artery disease, in those with FH.
FH is often inherited in an autosomal dominant pattern, meaning that only one defective gene from a parent is enough to cause the disorder. Approximately 1 in 250 people worldwide has FH, making it one of the most common inherited genetic disorders. Without treatment, individuals with FH are at a much higher risk of cardiovascular events like heart attacks and strokes, often at a much younger age than those without FH.
Symptoms of FH
One of the challenges of diagnosing FH is that it typically doesn’t present clear, outward symptoms until significant damage has already occurred. Some might not even be aware they have the condition until a cardiac event, such as a heart attack, occurs. That said, there are a few clinical signs that can be observed, particularly in more severe cases:
Xanthomas: These are fatty deposits that form under the skin, usually around joints, tendons, or the eyes. These can appear as lumps or patches and are common in individuals with very high cholesterol levels.
Achilles Tendon: Affected individuals might experience stiffness, thickening, or pain in the Achilles tendon, which can lead to discomfort when walking or exercising.
Wrist Extensors: Cholesterol buildup in these tendons can affect grip strength, wrist movement, and overall functionality, making daily activities more challenging.
Corneal Arcus: A whitish or gray ring around the cornea of the eye, often seen in younger individuals with FH.
Angina (Chest Pain): Due to the buildup of cholesterol and plaque in the arteries, people may experience chest pain or discomfort, particularly during physical activity.
Family History of Early Heart Disease: A strong family history of early cardiovascular diseases, particularly heart attacks or strokes before the age of 50, can be a critical clue to the presence of FH.
Given that FH symptoms may be silent until a cardiovascular issue arises, it is essential for people with a family history of heart disease to get tested, even if they do not exhibit physical signs. Early detection can be life-saving.
How to Test for FH
Diagnosing Familial Hypercholesterolemia (FH) typically begins with a thorough evaluation of a patient's medical history, physical exam, and blood tests.
A Lipid Panel: The key test used to identify FH is a lipid panel that measures total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), Lipoprotein(a), and triglycerides. Elevated LDL cholesterol levels, particularly over 190 mg/dL, are often a strong indicator of FH.
Genetic Testing: This can confirm a diagnosis by identifying mutations in genes like the LDLR, APOB, or PCSK9. Not every individual with FH requires genetic testing, but it’s especially useful for identifying at-risk family members.
Family History: FH is inherited, so a family history of early-onset heart disease or high cholesterol may prompt testing for relatives.
Tendon Xanthomas: A physical examination may reveal thickening or lumps in the tendons, particularly the Achilles tendon and wrist extensors, where cholesterol buildup can occur. These deposits are a hallmark sign of FH.
Coronary Artery Calcium Score: A specialized CT scan can reveal calcified plaque in the coronary arteries, which can help assess the risk of heart disease in FH patients.
The Dutch Lipid Clinic Network Criteria is often used to determine the likelihood of FH based on lipid levels, family history, and clinical symptoms like xanthomas.
What to Do About FH
Managing FH requires an aggressive, multifaceted approach to lower cholesterol levels and reduce the risk of cardiovascular disease. Talk to your primary care physician (PCP) about your FH and get a referral for a cardiologist for further treatment. Here's a breakdown of treatments:
Medications:
Statins: These are the cornerstone of treatment, as they inhibit cholesterol production in the liver and lower LDL cholesterol levels by up to 50%. See the FAQ regarding what to do if you have a statin intolerance.
PCSK9 Inhibitors: These newer medications can further lower LDL cholesterol by preventing its breakdown, offering an additional 60% reduction.
Ezetimibe: This drug limits cholesterol absorption in the intestines, usually combined with statins for better control.
Bile Acid Sequestrants: These medications help the body excrete cholesterol in bile and are sometimes used alongside statins.
Evinacumab: An FDA-approved drug for individuals with homozygous FH (severe form of FH), reducing cholesterol production through a unique mechanism.
Dietary Changes:
While dietary cholesterol typically doesn’t affect most people’s blood cholesterol, individuals with FH might be hyper-responders. They should experiment with a low-saturated fat diet or a Mediterranean Paleo approach, which emphasizes monounsaturated fats (from olive oil, avocado, and nuts) and fiber-rich foods.
A low-carb diet can sometimes worsen cholesterol levels in FH patients, especially if it leads to increased intake of saturated fat. Each individual must find the right balance between carbohydrate and fat intake.
Including fiber supplements like psyllium or foods like oats and legumes may help reduce LDL levels by promoting cholesterol excretion.
Lifestyle Modifications:
Consistent exercise can increase HDL (good cholesterol) and improve overall cardiovascular health.
Weight management is crucial, as obesity is linked to higher LDL cholesterol levels and worsened outcomes in FH.
Ensuring adequate, high-quality sleep and managing stress also play a role in controlling cholesterol levels and improving heart health.
Thyroid Health:
Thyroid dysfunction can complicate cholesterol management. Even subclinical hypothyroidism is associated with elevated cholesterol. Testing thyroid function is essential in those struggling with high cholesterol, as treating hypothyroidism may significantly lower LDL levels.
Family Screening:
Since FH is inherited, family members should be screened for high cholesterol, especially siblings and children, to catch the condition early and begin preventive treatments. Talk to your pediatrician about screening your kids for FH if this runs in your family. See the FAQ for more.
Long-term Monitoring:
Individuals with FH need lifelong monitoring of their lipid levels and cardiovascular health. This may include regular lipid panels, assessments of Achilles tendon and wrist extensors for xanthomas, and imaging tests to assess plaque buildup in the arteries.
While FH presents significant health challenges, early detection and aggressive treatment can drastically reduce the risk of premature cardiovascular disease, helping individuals lead healthier, longer lives.
FAQ
How early should you test children for Familial Hypercholesterolemia (FH)?
Children with a family history of Familial Hypercholesterolemia (FH) should ideally be tested for elevated cholesterol levels as early as age 2. According to clinical guidelines, children at high risk—those with a family history of early-onset cardiovascular disease or known high cholesterol—should undergo screening between the ages of 2 and 10. Early testing is crucial because lifestyle changes or treatments can be initiated to reduce the risk of heart disease, even in childhood.
For children without risk factors, general cholesterol screening is recommended around ages 9 to 11 and again during adolescence (ages 17 to 21).
I experience muscle and joint pain from statins. Could I have statin intolerance?
It’s possible you have statin intolerance, a condition where people experience side effects like muscle and joint pain while taking statins. Before stopping the medication, it's important to rule out other factors. Conditions like an underactive thyroid can increase the likelihood of pain, and certain medications (e.g., some antibiotics or HIV treatments) can interact with statins, making symptoms worse.
Since not all statins affect the body the same way, discuss with your healthcare provider about trying different statins to see if you can tolerate another type with fewer side effects.
What is the difference between FH and high cholesterol?
FH is a specific genetic disorder causing extremely high cholesterol levels due to a defect in cholesterol processing. High cholesterol, on the other hand, can result from various factors, including diet, lifestyle, and other health conditions, and may not be genetic.
Can FH be inherited from one or both parents?
FH can be inherited from either one (heterozygous FH) or both parents (homozygous FH). Heterozygous FH is more common and less severe, while homozygous FH is rarer and more severe, often leading to severe cholesterol levels and early onset of heart disease.
What other conditions are associated with FH?
Individuals with FH may also be at risk for atherosclerosis (buildup of cholesterol in the arteries) and peripheral vascular disease. They might experience early onset of heart disease, including heart attacks, often in their 30s or 40s.
How often should individuals with FH have their cholesterol levels checked?
Individuals with FH should have their cholesterol levels monitored regularly, typically every 3 to 6 months. This frequent monitoring helps to manage and adjust treatment plans effectively.
Q: What are the long-term health implications of FH?
Without treatment, FH can lead to early heart disease, including heart attacks and strokes. Individuals with FH may also face an increased risk of coronary artery disease and may experience complications from untreated high cholesterol over time.
Can FH be managed without medication?
While lifestyle changes can help manage FH, medication is often necessary to effectively lower cholesterol levels. Statins and other lipid-lowering drugs are commonly prescribed to achieve and maintain target cholesterol levels.
If I choose not to take medication, when will I have a heart attack?
It’s impossible to predict exactly when a heart attack might occur without treatment, but research suggests that around 25% of men and women with untreated familial hypercholesterolemia may experience their first heart attack in their early forties. Managing FH through lifestyle changes and medications can significantly lower this risk and delay cardiovascular events.
Are there any new treatments or research advancements for FH?
Research is ongoing into new treatments for FH, including PCSK9 inhibitors, which can significantly lower LDL cholesterol. Advances in gene therapy and novel medications are also being explored as potential treatments.
How can I find support or connect with others who have FH?
Support groups and organizations such as the Familial Hypercholesterolemia Foundation and the National Lipid Association provide resources, information, and community support for individuals and families affected by FH.
Is FH more common in certain populations?
FH is present in all populations but may be more commonly identified in certain ethnic groups. For instance, it is known to be particularly prevalent in individuals of Dutch, French Canadian, and Lebanese descent due to genetic factors in these populations.
Related:
