Genetic Testing for Family Heart Disease

FH is an autosomal dominant disorder with essentially complete penetrance. What this means is that if you have inherited the FH gene, you WILL have high LDL-cholesterol (and will require therapy to lower your LDL-cholesterol). In addition, each of your children will have a 50% chance of having FH.

If someone else in your family has FH (like a brother or a sister) and has high LDL cholesterol but you have totally normal LDL-cholesterol, then you will not pass on the FH gene to your children. However, if someone in your family has FH and your cholesterol is "borderline" or mildly elevated (ask your physician what LDL-cholesterol levels would be considered borderline or elevated in your case), there is a chance that you have FH and could pass it along to your children. In this case a consultation with a lipid specialist should be considered. Generally, if an adult’s LDL-cholesterol is less than 160 mg/dL without taking cholesterol-lowering medication, there is a very low chance that they have FH. If an adult has an LDL cholesterol level > 190mg/dL there is a stronger suspicion for FH.

Depending on the severity or form of FH you have (Heterozygous vs. Homozygous), symptoms can start appearing in childhood or they might not appear until much later in life. Because FH is caused by a defective gene, it is present in the body from birth. However, this is not necessarily obvious. In fact, this is why we like to call it the “invisible” disease. Many people with FH just think they have high cholesterol that can be lowered with the right food until, one day, they are only 38 years old and they have a heart attack! Symptoms are not necessarily present. Signs of FH are different in every patient and they may or may not include the following:

  • family history of early heart disease or heart attacks (before age 55 in men and before age 65 in women)
  • high LDL-cholesterol (above 190 mg/dL in adults and above 160 mg/dL in children)
  • chest pain or angina
  • bumps or lumps on the skin (these are deposits of excess fat called xanthomas)

But remember, you don’t have to have visible symptoms to have FH. Here’s a formula to help you remember the two main signs of FH:

F+H= FH

Family history of early heart disease + High LDL-cholesterol = Familial Hypercholesterolemia

Yes, FH is a lifelong journey. It’s not a temporary condition, like the common cold; it’s in your genes. When you have FH, the most important step to take is therapies prescribed by your physician. But while this is the most essential measure, it’s not the only one. FH also means controlling weight, not smoking, eating a balanced diet low in saturated fat, and exercising. What is more, FH means bringing your family together to understand the impact of this disease. FH means living healthy, as individuals and as a family.

FH is not preventable per se. You either inherit the gene (or genes) or you don’t. What you could potentially prevent, however, is the heart disease associated with it. We like to say that with FH you inherit the condition, but not the heart attack. If left untreated, FH leads to early and aggressive heart disease, atherosclerosis (narrowing and blocking of the blood vessels), and heart attacks. This is why early diagnosis and treatment are crucial.

FH is not curable. However, it IS treatable. And we mean this in the most optimistic way possible. Now, more than ever, there are various treatment options for people with FH. This realistically means that individuals with FH could lead normal lives, if diagnosed early and treated adequately.

First and foremost it is important to remember that FH runs in families. If you have FH, the question isn’t “Does anyone else in my family have it?”. The question is “Who in my family has it?”. Of course, only you know how to best approach your relatives. But make sure they fully understand that this is a lifelong condition that requires consistent treatment and the sooner they rule it out, the better.

The Family Heart Foundation provides a Specialist Search Tool to help you find a lipid (cholesterol) / Family Heart specialist near you - click here to find a specialist. If you are not able to find one in your location, please contact us at 626-583-4674 or info@thefhfoundation.org and we will do our best to help.

FH causes excessively high LDL-cholesterol levels. This is dangerous as it leads to cholesterol getting built up in your blood vessels, leading to atherosclerosis, heart attacks, and even death. While it is important to be mindful of your diet, this is almost never enough to manage your condition.

In all cases, FH requires aggressive treatment. Consult an FH specialist to find the best therapy regime for you.

Your clue here is “Familial”. By definition, hypercholesterolemia (or hyperlipidemia) simply means high cholesterol. However, Familial Hypercholesterolemia is a lifelong condition that is inherited. Otherwise put, your genes cause it. Therefore, it is a lot more serious than simply having high cholesterol caused from diet and it requires more aggressive treatment. FH is a life-threatening disorder. Find out more here.

 

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One of the most common scenarios in patients with FH is being told that they have high cholesterol and that they need to change their diet. However, with FH, eliminating fried foods and cheesecake from your diet is not enough. While saturated foods should be completely avoided, your high LDL-cholesterol mainly has to do with your genes/ your family’s medical history.

With FH, the cause of your high cholesterol is NOT your diet. Even if you ate nothing but oats and fruits, you would still have high LDL-cholesterol because of your liver’s inability to keep up with recycling it.

Cascade screening is not a certain type of blood test or certain kind of examination. It is simply a method of finding individuals with Familial Hypercholesterolemia. This method consists of screening entire families for FH. Because FH is genetic, this means that more than one person in a family has it (because they inherited it from someone else). Cascade screening means that when a health professional diagnoses someone with FH, they need to test the rest of their immediate family members for FH too.

Diagnosis can be strongly suspected based on cholesterol levels (also called a lipid test or lipid panel). The diagnosis can be confirmed through additional information about your personal and family medical history, and certain physical exam findings (like xanthomas, bumps or lumps of cholesterol deposits on the skin).

Heterozygous Familial Hypercholesterolemia (HeFH) is the most common form of FH (1 in 250 worldwide have it) caused when a child inherits one copy of a “bad gene” from one parent. Homozygous Familial Hypercholesterolemia (HoFH) is a very rare, but extremely severe form of FH (roughly 1 in 160,000 have it) caused when a child gets a “bad gene” from both parents. Typically, Heterozygous FH remains invisible for longer and Homozygous FH manifests itself earlier, with more visible signs such as xanthomas (bumps or lumps in the skin which are deposits of excess fat) and corneal arcus (a white arc near the colored part of the eye, which is often found by an ophthalmologist).

AEM-28: This is a potential new LDL-C lowering treatment in Phase 2. It is currently in preclinical trials and has not yet been approved by the FDA.

 

Angina:  Chest pain, discomfort, or pressure resulting from insufficient blood flow and oxygen delivery to the heart muscle – typically, the result of narrowing or blockage of the coronary arteries. In some people angina is felt as arm, jaw or neck pain (pressure), or as indigestion. Angina is a symptom of Coronary Heart Disease (CHD). There are two kinds of angina. Stable angina (angina pectoris) usually occurs with exertion or stress, lasts a short time, and is relieved with rest.  Unstable angina, or acute coronary syndrome, causes unexpected chest pain, usually at rest.  All chest pain should be taken seriously and checked by a doctor, but unstable angina should be treated as an emergency and could signal a heart attack.

 

Angiography or Angiogram:  Also called Coronary Angiogram or Cardiac Catheterization, this is a diagnostic procedure in which dye is injected into the coronary arteries via a flexible catheter (a thin, hollow plastic tube) and an x-ray is taken to determine if these arteries have significant blockages.  If blockages are detected, coronary angioplasty may be performed during the procedure.

 

Angioplasty:  Otherwise known as Coronary Artery Balloon Angioplasty, Percutaneous Coronary Intervention (PCI), or Stenting, this is a procedure to widen a narrowed or blocked blood vessel to restore blood flow to the heart, or sometimes used to open neck or brain arteries to reduce the risk of a stroke.  The procedure is done by inserting a deflated balloon through the femoral artery in the groin or the radial artery in the wrist to the blocked artery with a catheter and then inflating the balloon. Often, a stent, or a small mesh tube is inserted in the vessel to keep it open and decrease the risk of another blockage.  Angioplasty can reduce symptoms due to Coronary Artery Disease (CAD), including angina, and help prevent a heart attack.  It is less invasive than Coronary Artery Bypass Graft surgery.

 

Antiplatelets:  Antiplatelet drugs prevent platelets from clumping together and forming unwanted blood clots. Examples of antiplatelet drugs include aspirin and clopidogrel (Plavix).

 

Aortic Stenosis: Aortic valve stenosis — or aortic stenosis — a narrowing of the aortic valve in the heart that prevents the valve from opening fully, obstructing blood flow from the heart into the aorta and onward to the rest of the body. Aortic stenosis may be caused by plaque build up and can be a characteristic feature of patients with Homozygous FH.

 

Apolipoprotein B: ApoB is a protein found on the surface of the LDL-C particle. It is essential for the removal of LDL because it binds to the LDL receptor, enabling the removal of LDL-C from the blood.

 

Arrhythmia: Abnormal heart rhythm, including a heartbeat that is too fast, too slow, or erratic.

 

Arteries:  Blood vessels that carry oxygenated blood from the heart throughout the body.

 

ASCVD: Atherosclerotic cardiovascular disease. Cardiovascular disease caused by plaque buildup in the arteries, including coronary death or nonfatal myocardial infarction, or fatal or nonfatal stroke.

 

Atherosclerosis:  A disease in which plaque (composed of cholesterol, other lipids, fibrous material, and cellular debris) builds up inside the coronary (and other) arteries. The plaque hardens over time and narrows the arteries, restricting blood flow.

 

Bempedoic Acid (Nexletol): This is an LDL-C-lowering treatment approved in 2020 by the FDA for LDL-C reduction in persons with either FH or ASCVD.  Bempedoic acid inhibits an enzyme that aids in the synthesis of cholesterol. This medication is also available in combination with ezetimibe and is called Nexlizet.

 

Bile Acid Sequestrants (cholestyramine (Questran, Prevalite), colestipol (Colestid), colesevalam (Welchol):  This is a treatment to lower LDL Cholesterol (LDL-C). They bind bile acids in the intestine, keeping them out of circulation and depleting the liver of bile. This upregulates bile synthesis, which requires cholesterol, and in turn upregulates LDL receptors which then lowers LDL-C in the blood.  Bile acid sequestrants can lower LDL-C by 18-25% and have been shown in clinical trials to reduce CHD events in people with high cholesterol.  Their gastrointestinal side effects mean that they are not generally preferred by patients.

 

Cardiovascular Risk Factors:  Conditions that increase the risk for developing of heart disease and stroke. Modifiable risk factors include: elevated LDL Cholesterol, elevated triglycerides, low HDL-C, elevated lipoprotein (a) (Lp(a)), smoking, diabetes or pre-diabetes, obesity or overweight, physical inactivity, high blood pressure, unhealthy diet, and stress. Non-modifiable risk factors include age, sex, and family history.  The more risk factors a person has, the higher the risk.

 

Carotid Intima-Media Thickness (CIMT):  This is a non-invasive test that is done using an ultrasound of the carotid artery in the neck.  Intima-media thickness (IMT) is a measurement of the thickness two layers of the carotid artery (intima and media) to both detect the presence, and to track the progression, of atherosclerotic disease. Carotid intima-media thickness is strongly associated with atherosclerosis.

 

Cascade Screening:  The process of systematic family tracing that begins with screening all first-degree relatives (parents, siblings, children) of an individual with known familial hypercholesterolemia (FH) (known as the proband). Cascade screening can detect FH in affected family members. Given that each first-degree relative of a person with FH has a 50% chance of inheriting the gene mutation, cascade screening is an important and effective method of identifying people at risk for early heart disease. Once affected first-degree relatives have been identified, cascade screening moves to their first-degree relatives in a stepwise fashion until all individuals with FH in the family have been identified.

 

Cholesterol:  Cholesterol is a waxy, fat-like substance that’s found in all cells of the body. It is found only in animal cells where it is used to make hormones, vitamin D, and substances that help digest foods (bile acids). Most cholesterol is produced by the liver. However, cholesterol also is found in some of the foods we eat such as egg yolks, red meat, cheese, milk, and ice cream.

 

Corneal Arcus:  A deposit of cholesterol in the clear outer covering (cornea) of the eye that usually occurs in the shape of a half moon (arcus). Corneal arcus before the age of 55 usually indicates the presence of a lipid disorder, but corneal arcus is not always a sign of a lipid disorder. Most people with FH do not have corneal arcus.

 

Coronary Artery:  An artery that supplies blood to the heart muscle. Coronary arteries arise from the aorta. The major arteries include the right coronary artery (RCA), the left main artery which quickly divides into the left anterior descending (LAD) artery and the circumflex artery.

 

Coronary Artery Bypass Grafting (CABG): Sometimes called bypass, this is an open-heart surgical procedure in which a healthy artery or vein, often a leg vein (saphenous vein) or a breast artery (mammary artery), is connected to a blocked artery to go around the blockage and restore blood flow. Multiple arteries may be bypassed during one surgery.

 

Coronary Artery Calcium (CAC) Score, Coronary Calcium Scan: A non-invasive test done with computed tomography (CT) to detect the presence of calcified plaque. Calcified plaque can be a sign of CAD.

 

Coronary Heart Disease (CHD): A narrowing of the blood vessels that supply blood to the heart (also referred to as Coronary Artery Disease – CAD). Coronary heart disease is caused by the buildup of plaque in the arteries of the heart and is the leading cause of death in the United States for men and women.

 

Evinacumab (Evkeeza): This is a LDL-C lowering treatment approved by the FDA in 2021. It is a monoclonal antibody that acts by blocking a protein known as ANGPTL3 (angiopoietin-like protein 3). Evinacumab is approved as an adjunct to other LDL-C lowering therapies in adults and children, aged 12 years or older with HoFH.

 

Ezetimibe (Zetia): A cholesterol absorption inhibitor, this treatment blocks the absorption of intestinal sterol, thereby lowering LDL-C by approximately 18-25%. It acts on NPC1L1 (Neimann Pick C1-like receptor 1) in a way that is similar to a genetic cause of low LDL-C associated with lower CVD risk. Ezetimibe is often prescribed as a second line treatment for FH, in addition to a statin for further LDL-C lowering. There is some evidence from clinical trials that ezetimibe reduces coronary artery plaque volume and major cardiovascular events, and LDL-C lowering with ezetimibe is considered to have a beneficial effect on atherosclerotic CVD.

 

Familial Hypercholesterolemia (FH): An autosomal dominant genetic disorder that impacts the body’s ability to manage LDL Cholesterol and causes elevated LDL-C from birth. FH is most often caused by mutations in the LDL Receptor gene (60-80%), but can also be caused by mutations in the ApoB gene (10%) and the PCSK9 gene (3%). Rarely, FH is caused by mutations in LDLRAP1, an autosomal recessive gene.  There are two forms of FH, Heterozygous FH, a common disorder caused by a mutation in one gene inherited from one parent, and Homozygous FH, a rare form of FH caused by a mutation in two genes, usually inherited from both parents.

 

Genetic Counselor:  Genetic counselors are healthcare professionals with specialized graduate training in both genetics and psychosocial counseling.  They can help a person understand the inheritance of their condition, the genetic testing process, the results, the implications of a genetic diagnosis, as well as other topics including cascade screening, reproductive risks, genetic discrimination, and others. You can find a genetic counselor by using the Find a Genetic Counselor tool at www.nsgc.org.

 

Gene Editing: A process of by which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Gene editing techniques include CRISPR nucleases and base editing. One example is VERVE-101 which uses adenine base editing to knock out the PCSK9 gene resulting in LDL-C reduction. To date VERVE-101 has been studied in primates. Human studies are being planned.

 

Genetic Testing:  A medical test done to identify changes in a person’s chromosomes or genes that might cause and/or predispose them to a genetic disease and also affect biological relatives. Genetic testing is done in specialized laboratories with an order from a doctor or genetic counselor. Testing is usually done on either a blood or saliva sample. FH can be diagnosed clinically, based on LDL-C and personal and family history. Genetic testing can confirm an FH diagnosis. If a patient’s specific FH-causing mutation is identified, at-risk relatives can have genetic testing to determine if they also have FH or not. Genetic testing for FH is not required for FH diagnosis and is still uncommon in the U.S. However, it is becoming more accessible and is offered by multiple commercial genetic testing companies.

 

Gene Therapy: A technique that uses genes to treat disease. A gene is inserted into a patient’s cells using a delivery method called a vector (a modified virus). It may be used to replace a mutated gene with a healthy copy of that gene. Gene therapy is still very new. The first gene therapy was approved in Europe in 2012 for Lipoprotein Lipase Deficiency (LPLD). No gene therapy has been approved yet in the U.S. by the FDA. Trials for hemophilia and Sickle Cell Disease are ongoing in the U.S.

 

High-Density Lipoprotein Cholesterol (HDL-C): Often referred to as the “good” cholesterol, high levels of this lipoprotein are associated with lower risk for heart disease.

 

Inclisiran (ALN-PCSSC): This is a potential new LDL-C lowering treatment still in development. It acts by inhibiting PCSK9 synthesis by RNA interference. It has the potential for biannual or triannual dosing by injection. It is currently in clinical trials and has not yet been approved by the FDA.

 

Ischemia:  Inadequate blood flow.

 

Lipids:  Lipids are fatty substances that cannot dissolve in blood. Cholesterol and triglycerides are lipids. They are transported in the blood as part of large molecules called lipoproteins. Lipids play important roles, including energy storage, chemical messaging, and formation of cell membranes.  However, lipid abnormalities can contribute to the development of heart disease.

 

Lipid profile:  A blood test that reports total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol. Total cholesterol, HDL, and triglycerides are measured and LDL is calculated as follows:

 

LDL = Total cholesterol – HDL – (Triglycerides/5) – this is known as the Friedewald equation.

 

Extremely high triglycerides can make this calculation inaccurate. Some results will also report non-HDL cholesterol, another measure that is calculated simply by subtracting HDL from Total Cholesterol. Another, and perhaps more accurate, way to estimate the LDL-C is using the Martin/Hopkins equation.

 

Lipid Specialist:  A physician or other health care professional (including nurse practitioners and physician assistants) with special training in the diagnosis and treatment of individuals with cholesterol (lipid) disorders.

 

Lipoprotein (LDL) apheresis:  A procedure in which a person’s blood is removed, LDL-C is filtered, and the blood is then returned to the body.  The procedure takes about 3 hours and is done every 1-2 weeks. There are about 60 apheresis centers in the U.S. Lipoprotein, or LDL, apheresis is approved by the FDA for patients for whom diet and treatment with statins have not been sufficiently effective or not tolerated, and who have LDL-C over 300 mg/dL, or patients with documented CAD and LDL-C >100 mg/dL.  Lipoprotein apheresis lowers LDL-C and Lp(a).

 

Lipoprotein(a) (Lp(a)):  An LDL-like particle with an attached protein called apolipoprotein (a) found in the bloodstream. Elevated levels of this blood lipid increase a person’s risk of developing early heart disease and stroke. Persons with FH frequently have high levels of Lp(a), which is an independent risk factor for coronary heart disease.

 

Lomitapide (brand name Juxtapid):  Lomitapide is a treatment designed to inhibit the function of microsomal triglyceride transfer protein (MTP), which plays an essential role in the liver and intestines by synthesizing lipoproteins that contain cholesterol.  Blocking MTP activity has been shown to reduce the level of LDL-C that is circulated in the bloodstream by 35-50% in individuals with homozygous FH, including those with no LDL receptors.  Lomitapide is approved by the FDA as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, only for those with HoFH.  This is an oral medication, taken daily.  People taking lomitapide must follow a very low fat diet to minimize gastrointestinal side effects. There are other potential side effects to consider.

 

Low-density lipoprotein cholesterol (LDL- C):  Sometimes called “bad” cholesterol, a high LDL-C level can lead to a buildup of cholesterol in the arteries and increase the risk of heart attack and stroke.

 

Low-density lipoprotein cholesterol receptor (LDL receptor): Low-density lipoprotein receptors are proteins on the surface of cells. These receptors play a critical role in regulating cholesterol levels by binding to LDL-C particles and removing them from the blood.  LDL receptors are particularly abundant in the liver, the organ responsible producing most cholesterol and for removing most excess cholesterol from the body. The number of low-density lipoprotein receptors on the surface of liver cells determines how quickly cholesterol (in the form of low-density lipoproteins) is removed from the bloodstream.  People with FH have either too few LDL receptors (sometimes no LDL receptors – receptor null), or have defective LDL receptors, and are therefore not able to clear LDL-C from the blood normally.

 

MGL-3196: This is a potential new LDL-C lowering treatment still in development. It acts as a liver-directed thyroid hormone receptor (THR) β-selective agonist. It is currently in clinical trials and has not yet been approved by the FDA.

 

Myocardial infarction (MI or Heart Attack):  Heart attacks most often occur as a result of coronary heart disease (CHD), also called coronary artery disease (CAD). CHD is a condition in which plaque (composed of cholesterol, other lipids, and cellular debris) builds up inside the coronary arteries – a process called atherosclerosis. When the coronary arteries are blocked, they are unable to supply oxygen-rich blood to the heart.  A heart attack is caused by a ruptured plaque that causes a blood clot and blocks the flow of blood to the heart. If blood flow is not restored quickly, this can result in damage or death to the heart muscle cells.

 

Niacin (nicotinic acid):  Prescription niacin is a treatment that lowers LDL-C by about 20-25%, triglycerides by about 50%, and raises HDL-C by about 30%.  It can lower Lp(a) by about 30% at high doses.  As monotherapy (treatment with niacin alone), it showed a reduction in recurrent heart attack and total mortality, however when added to statin therapy studies showed no further reduction in CVD events or mortality in patients with CVD and well-controlled LDL-C.  Niacin has side effects, including flushing, liver toxicity, and hyperglycemia which make it difficult to take.  It is sometimes still prescribed for FH as a third-line therapy when patients have not achieved sufficient LDL-C lowering, or when they have high Lp(a).

 

PCSK9 inhibitors (Proprotein Convertase Subtilisin/Kexin type 9 inhibitors):   A new class of LDL Cholesterol lowering drug approved by the FDA in 2015.  PCSK9 inhibitors are monoclonal antibodies that target and inactivate a specific enzyme (PCSK9) that is responsible for degrading LDL receptors in the liver before they can be recycled. Inactivating PCSK9 allows LDL receptors to be recycled and to remove additional LDL-C from the bloodstream, thus lowering LDL Cholesterol by 40-65%. PCSK9 inhibitors are approved by the FDA for use for those with FH or with ASCVD, along with maximally tolerated statins for those who have not achieved sufficient LDL-C lowering. They can also lower Lp(a) levels, though they are not approved specifically for that purpose. They are injectable drugs, administered at home every two weeks or every month. Results from outcomes trials in patients with cardiovascular disease on statin therapy showed a reduction in cardiac events, such as heart attacks, strokes, and coronary revascularization, by 15 percent. Currently available PCSK9 inhibitors are Praluent (alirocumab) and Repatha (evolocumab, also approved specifically for HoFH and for adults with primary hyperlipidemia).

 

Peripheral Artery Disease (PAD):  Atherosclerosis in the arteries leading to the legs, arms, kidneys, stomach, and head. PAD can compromise circulation and lead to complications.

 

Plasma Delipidation System (PDS-2 System) – H190001: A system recently approved by the FDA to reduce plaque build-up in the coronary arteries in individuals with HoFH who are not responsive to or cannot receive any other treatment for HoFH. This process involves collecting plasma from a patient with HoFH and treating it with a “delipidating” solution. The delipidated plasma is then returned to the patient using an infusion pump.

 

Statins: A class of drugs also known as HMG CoA reductase inhibitors. Statins are the first line of treatment for FH and have been shown in clinical trials to reduce CVD risk by 22% for each 40 mg/dL reduction in LDL-C. These medications block a critical step in cholesterol synthesis. Not only do they decrease cellular cholesterol production, they increase cellular LDL receptors, allowing for increased removal of cholesterol from the blood stream. Depending on the statin and dose, these agents can lower LDL cholesterol from 35-55%. Available statins include: lovastatin (Mevacor®) pravastatin (Pravachol®), simvastatin (Zocor®), fluvastatin (Lescol®), artorvastatin (Lipitor®), rosuvastatin  (Crestor®), and pitavastatin (Livalo®). Statins are oral medications generally taken daily. Most are now available as cost-effective generic drugs.  Some people experience side effects with statins, but often switching to a different statin can address that problem.

 

Stent: An implantable device made of expandable, metal mesh that is placed (by using a balloon catheter) at the site of a narrowed or blocked artery during an angioplasty procedure. The stent is then expanded and left in place to keep the artery open.

 

Stress Test:  A diagnostic test to determine whether there is adequate blood flow to the heart during physical activity. The patient’s echocardiogram, heart rate, and blood pressure are monitored during the test.  There are several types of stress tests which can provide different levels of information: treadmill stress test, adenosine stress test (for those who cannot exercise), stress echo, and a nuclear stress test.

 

Stroke:  A stroke occurs when blood flow to the brain is cut off, depriving brain cells of oxygen.  There are three types of stroke: hemorrhagic (when a blood vessel bleeds into the brain), ischemic (when a blood vessel is blocked by a clot), and Transient Ischemic Attack (TIA) (when blood flow is temporarily interrupted and symptoms last for less than 24 hours).  People with FH are at increased risk for stroke due to the development of atherosclerosis.  Coronary Heart Disease is more common for those with FH than stroke.

 

Triglycerides:  Triglycerides are one of the lipids found in the blood.  Triglycerides may be produced in the liver or come from the food we eat.  Blood triglyceride levels are impacted by recent fat, carbohydrate and alcohol intake, and should be measured after fasting for at least 12 hours.  Elevated triglyceride levels are considered to be a risk factor for both the development of heart disease and diabetes.   While people with FH can also have elevated triglycerides, high triglycerides are not caused by FH genes.

 

Vupanorsen (PF-07285557): This is a potential new LDL-C (and triglyceride) lowering treatment still in development. It acts as an antisense inhibitor to angiopoietin-like protein 3. It is currently in clinical trials and has not yet been approved by the FDA.

 

Xanthelasma:  An orange or yellowish, flat deposit of cholesterol on the eyelids or under the eyes.  Some people with FH will have xanthalasma, though they are not common.  They can also occur without any underlying medical condition.

 

Xanthoma: A deposit of cholesterol and/or triglycerides under the skin usually around the joints and tendons at the knuckles, elbows, knees, or Achilles tendon.   Xanthomas occur in people with several different kinds of blood lipid disorders and can be caused by unrelated disorders.  In familial hypercholesterolemia, Achilles tendon xanthomas can be a hallmark of the diagnosis, though most people with FH will not have xanthomas.