Cholesterol levels

Your cholesterol levels show how much cholesterol is circulating in your blood. Your blood cholesterol levels tell you how much lipid or fat is in your blood and your cholesterol levels are expressed in milligrams per deciliter (mg/dL). High cholesterol usually has no symptoms. You can find out your blood cholesterol levels with a cholesterol or lipid profile blood test. You will need to stop eating for 10 to 12 hours before a cholesterol or lipid profile blood test, and the only liquid you may drink is water.

Total blood or serum cholesterol is a composite of different measurements. Your “total blood cholesterol” is calculated by adding your HDL (“good” cholesterol) and LDL (“bad” cholesterol) cholesterol levels, plus 20% of your triglyceride level. Here’s the formula for calculating your “total blood cholesterol”:

Total cholesterol = HDL + LDL + 20% triglycerides.

• “Total cholesterol” is the total amount of cholesterol that’s circulating in your blood. Your “Total cholesterol” should be below 200 milligrams per deciliter of blood (less than 200 mg/dL) or 5.18 mmol/L.
• Your HDL “good” cholesterol is the one number you want to be high, ideally above 60 mg/dL (1.55 mmol/L) or higher.
• Your LDL “bad” cholesterol should be below 100 mg/dL (less than 2.59 mmol/L).
• Your triglycerides should be below 150 mg/dL (less than 1.70 mmol/L). Triglycerides are the most common type of fat in your blood. Triglycerides come from food, and your body also makes them. When you eat, your body converts calories it doesn’t need into triglycerides, which are stored in fat cells. High triglyceride levels are associated with several factors, including being overweight, eating too many sweets or drinking too much alcohol, smoking, being sedentary, or having diabetes with elevated blood sugar levels.
• According to the American Heart Association, more than 43% of American adults have cholesterol levels of 200 milligrams (mg) per deciliter (dL) or higher. Talk with your doctor about what your results mean for you and how to manage your cholesterol.

“Normal cholesterol levels” are less important than your overall cardiovascular risk. Like HDL and LDL cholesterol levels, your total blood cholesterol level should be considered in context with your other known risk factors. To determine your cardiovascular risk, your doctor will consider your cholesterol test results in context with your age, sex and family history. Other risk factors, such as smoking, diabetes and high blood pressure, will be considered as well. If your risk remains uncertain, and treatment options are unclear, your doctor may consider other factors and/or request a coronary artery calcium measurement to provide greater insight into your risk and help in decision-making.

In general, you want to have a total cholesterol level below 200 mg/dL or 5.18 mmol/L. Between 200 mg/dL and 239 mg/dL, your cholesterol level is elevated or borderline-high and should be lowered if you can. With a total cholesterol level of 240 mg/dL or above, your cholesterol level is high, and there is a need for action. For example, changing your diet, beginning an exercise program, and taking statins or other cholesterol-lowering medicines are all ways to lower your cholesterol level.

Factors that can increase your risk of bad cholesterol include:

• Poor diet. Eating saturated fat, found in animal products, and trans fats, found in some commercially baked cookies and crackers and microwave popcorn, can raise your cholesterol level. Foods that are high in cholesterol, such as red meat and full-fat dairy products, will also increase your cholesterol.
• Age. Your cholesterol levels tend to rise as you get older. For instance, as you age, your liver becomes less able to remove LDL cholesterol. Even though it is less common, younger people, including children and teens, can also have high cholesterol.
• Sex. Between ages 20 and 39, men have a greater risk for high total cholesterol than women. A woman’s risk goes up after menopause. Menopause lowers levels of female hormones that may protect against high blood cholesterol. After menopause, women’s levels of total and “bad” LDL cholesterol usually go up, while their levels of “good” HDL cholesterol go down.
• Heredity. High blood cholesterol can run in families.
• Weight. Being overweight or having obesity raises your cholesterol level. Having a body mass index (BMI) of 30 or greater puts you at risk of high cholesterol.
• Race. Certain races may have an increased risk of high cholesterol.
  • Overall, non-Hispanic White people are more likely than other groups to have high levels of total cholesterol.
  • Asian Americans, including those of Indian, Filipino, Japanese, and Vietnamese descent, are more likely to have high levels of “bad” LDL cholesterol than other groups.
  • Hispanic Americans are more likely to have lower levels of “good” HDL cholesterol than other groups.
  • African Americans are more likely than other groups to have high levels of “good” HDL cholesterol.
• Lack of exercise. Being physically inactive contributes to overweight and can raise LDL and lower HDL. Exercise helps boost your body’s HDL, or “good,” cholesterol while increasing the size of the particles that make up your LDL, or “bad,” cholesterol, which makes it less harmful.
• Smoking. Cigarette smoking damages the walls of your blood vessels, making them more prone to accumulate fatty deposits. Smoking might also lower your level of HDL, or “good,” cholesterol.
• Diabetes. High blood sugar contributes to higher levels of a dangerous cholesterol called very-low-density lipoprotein (VLDL) and lower HDL cholesterol. High blood sugar also damages the lining of your arteries.

The following foods can lower your bad cholesterol.

• Vegetables such as leafy greens (spinach, collard greens, kale, cabbage), broccoli, and carrots
• Fruits such as apples, bananas, oranges, pears, grapes, and prunes
• Whole grains such as plain oatmeal, brown rice, and whole-grain bread or tortillas
• Fat-free or low-fat dairy foods such as milk, cheese, or yogurt
• Protein-rich foods:
  • Fish high in omega-3 fatty acids (salmon, tuna, and trout)
  • Lean meats such as 95% lean ground beef or pork tenderloin or skinless chicken or turkey
  • Eggs
  • Nuts, seeds, and soy products (tofu)
  • Legumes such as kidney beans, lentils, chickpeas, black-eyed peas, and lima beans
• Oils and foods high in monounsaturated and polyunsaturated fats:
  • Canola, corn, olive, safflower, sesame, sunflower, and soybean oils (not coconut or palm oil)
  • Nuts such as walnuts, almonds, and pine nuts
  • Nut and seed butters
  • Salmon and trout
  • Seeds (sesame, sunflower, pumpkin, or flax)
  • Avocados
  • Tofu

There are usually no signs or symptoms that you have high cholesterol. A blood test is the only way to detect if you have it. The American Heart Association recommends all adults age 20 or older with no other risk factors for heart disease should have their cholesterol (and other traditional risk factors) checked every four to six years. If certain factors put you at high risk, or if you already have heart disease, your doctor may ask you to check it more often. Work with your doctor to determine your risk for cardiovascular disease and stroke and create a plan to reduce your risk.

If you have risk factors or if previous testing showed that you had a high cholesterol level, more frequent testing with a full lipid panel is recommended.

Examples of risk factors other than high LDL include:

• Cigarette smoking
• Being overweight or obese
• Unhealthy diet
• Being physically inactive—not getting enough exercise
• Age (if you are a male 45 years or older or a female 50-55 years or older)
• Hypertension (blood pressure of 140/90 or higher or taking high blood pressure medications)
• Family history of premature heart disease (heart disease in a first-degree male relative under age 55 or a first-degree female relative under age 65)
• Pre-existing heart disease or already having had a heart attack
• Diabetes or prediabetes

For people who are age 20 or older:

• Younger adults should have the test every 5 years
• Men ages 45 to 65 and women ages 55 to 65 should have it every 1 to 2 years.

Children, teens, and young adults (ages 2 to 24 years old) with no risk factors should have a lipid panel once between the ages of 9 and 11 and again between 17 and 21, according to the American Academy of Pediatrics.

For people who are age 19 or younger:

• The first test should be between ages 9 to 11
• Children should have the test again every 5 years
• Some children may have this test starting at age 2 if there is a family history of high blood cholesterol, heart attack, or stroke.

Children, teens, and young adults with an increased risk of developing heart disease as adults should have earlier and more frequent screening with lipid panels. Some of the risk factors are similar to those in adults and include a family history of heart disease or health problems such as diabetes, high blood pressure, or being overweight. High-risk children should be tested between 2 and 8 years old with a fasting lipid panel, according to the American Academy of Pediatrics.

Children younger than 2 years old are too young to be tested.

Figure 1. Cholesterol levels

Table 1. Normal Cholesterol Levels

Age	Total cholesterol	Non-HDL cholesterol	LDL (“bad” cholesterol)	HDL (“good” cholesterol)
19 and younger	Below 170 milligrams per deciliter of blood (mg/dL)	Below 120 mg/dL	Below 110 mg/dL	Above 45 mg/dL
20 and older Male	125 to 200 milligrams per deciliter of blood (mg/dL)	Below 130 mg/dL	Below 100 mg/dL	40 mg/dL or higher
20 and older Female	125 to 200 milligrams per deciliter of blood (mg/dL)	Below 130 mg/dL	Below 100 mg/dL	50 mg/dL or higher

Footnotes: As you review your results, remember that you want your LDL to be low and your HDL to be high. Ideally, your HDL should be above 60 mg/dL (1.55 mmol/L). It’s the helpful cholesterol. An HDL above 60 mg/dL (greater than 1.55 mmol/L) offers you protection against heart disease.

Table 2. High Cholesterol Levels

Age	Total cholesterol	Non-HDL cholesterol	LDL (“bad” cholesterol)
19 and younger	Borderline high: 170-199 mg/dL High: 200 mg/dL or higher	Borderline high: 120-144 mg/dL High: 145 mg/dL or higher	Borderline high: 110-129 mg/dL High: 130 mg/dL or higher
20 and older	Borderline high: 200-239 mg/dL High: 240 mg/dL or higher	High: 130 mg/dL or higher	Near-optimal: 100-129 mg/dL Borderline high: 130-159 mg/dL High: 160-189 mg/dL Very high: 190 mg/dL or higher

Footnotes: High cholesterol generally means your total cholesterol is 200 mg/dL (greater than 5.18 mmol/L) or higher. But doctors use additional categories like “borderline high” and “near optimal” to break down your results. If your numbers are close to normal levels, they may be easier to manage through lifestyle and dietary changes.

Table 3. Desirable Cholesterol Levels

Desirable Cholesterol Levels
Total cholesterol	Less than 200 milligrams per deciliter of blood (mg/dL) or 5.18 mmol/L
LDL (“bad” cholesterol)	Less than 100 mg/dL (2.59 mmol/L)
HDL (“good” cholesterol)	60 mg/dL (1.55 mmol/L) or higher
Triglycerides	Less than 150 mg/dL (1.70 mmol/L)

[Source ¹ ]

What is cholesterol?

Cholesterol is a waxy, fat-like substance that’s found in all the cells in your body. Cholesterol is produced by your body and also found in some foods. Your body needs some cholesterol to make hormones, vitamin D and substances that help you digest foods. Cholesterol comes from two sources. Your liver makes all of the cholesterol your body needs to form cell membranes and to make certain hormones. Cholesterol is also found in foods from animal sources, such as egg yolks, meat, and cheese, which is called dietary cholesterol. Although we often blame the cholesterol found in foods that we eat for raising blood cholesterol, the main culprit is actually saturated fat. Foods rich in saturated fat include butter fat in milk products, fat from red meat, and tropical oils such as coconut oil.

Cholesterol travels to cells through your bloodstream in special carriers called lipoproteins. Two of the most important lipoproteins are low-density lipoprotein (LDL) and high-density lipoprotein (HDL).

There are different types of cholesterol:

• HDL stands for high-density lipoprotein or HDL-C (high-density lipoprotein cholesterol). HDL is sometimes called “good cholesterol” because it carries harmful cholesterol from other parts of your body including your arteries back to your liver. Your liver then removes the cholesterol from your body and helps protect you from heart attack and stroke. A healthy HDL-cholesterol level may protect against heart attack and stroke. If you have low HDL levels, you have a greater heart disease risk, even if your total cholesterol is below 200 mg/dL. Your doctor will evaluate your HDL and other cholesterol levels and other factors to assess your risk for heart attack or stroke. People with high blood triglycerides usually also have lower levels of HDL. Genetic factors, Type 2 diabetes, smoking, being overweight and being sedentary can all lower HDL cholesterol. Women tend to have higher levels of HDL cholesterol than men do, because the female hormone estrogen raises HDL, but this can change after menopause.
• LDL stands for low-density lipoprotein or LDL-C (low-density lipoprotein cholesterol). LDL is sometimes called “bad cholesterol” because a high LDL level leads to the buildup of plaque in your arteries. LDL is the most important lipid for predicting your heart disease risk. Low-density lipoprotein (LDL or ‘bad’) cholesterol can join with fats and other substances to build up (also known as plaque) in the inner walls of your arteries, which starts a disease process called atherosclerosis. The arteries can become clogged and narrow, and blood flow is reduced. When plaque builds up in your coronary arteries that supply blood to your heart, you are at greater risk of having a heart attack. Since LDL is the bad kind of cholesterol, a low LDL level is considered good for your heart health. A diet high in saturated and trans fat is unhealthy because it tends to raise LDL cholesterol levels. Your LDL levels may be high if you eat a diet with a lot of saturated fat, cholesterol, or both. Sometimes, an under-active thyroid called hypothyroidism may also increase LDL levels.
• VLDL stands for very low-density lipoprotein or VLDL-C (very low-density lipoprotein cholesterol). Some people also call VLDL a “bad cholesterol” because it too contributes to the buildup of plaque in your arteries. But VLDL and LDL are different; VLDL mainly carries triglycerides and LDL mainly carries cholesterol. VLDL particles are released into the blood by the liver and circulate in the bloodstream, ultimately being converted into LDL as they lose triglyceride, having carried it to other parts of the body. According to the National Heart, Lung and Blood Institute’s National Cholesterol Education Program Guidelines ATP III, there is growing evidence that VLDL plays an important role in atherogenesis, in which plaques form on the interior walls of arteries, narrowing these passageways and restricting blood flow, which can lead to heart disease and increase the risk of stroke. Currently, direct measurement of VLDL cholesterol requires specialized testing. However, since VLDL-C contains most of the circulating triglyceride (if a person is fasting) and since the composition of the different particles is relatively constant, it is possible to estimate the amount of VLDL-C based on the triglyceride value. To estimate VLDL-C, divide the triglyceride value by 5 if the value is in mg/dL or divide by 2.2 if the value is in mmol/L. In most cases, this formula provides a good estimate of VLDL-C. However, this formula becomes less accurate with increased triglyceride levels when, for example, a person has not fasted before having blood drawn. The calculation is not valid when the triglyceride level is greater than 400 mg/dl (4.5 mmol/L) because other lipoproteins are usually present. In this situation, VLDL-C may be measured directly using specialized testing.
• Triglycerides. Triglycerides are the most common type of fat in your blood. Triglycerides come from food, and your body also makes them. When you eat, your body converts calories it doesn’t need into triglycerides, which are stored in fat cells. Triglycerides are fats that provide energy for your muscles. If you eat foods with a lot of saturated fat or carbohydrates, you will raise your triglyceride levels. High triglyceride levels are associated with several factors, including being overweight, eating too many sweets or drinking too much alcohol, smoking, being sedentary, or having diabetes with elevated blood sugar levels. Elevated triglycerides levels are thought to lead to a greater risk of heart disease, but scientists do not agree that high triglycerides alone are a risk factor for heart disease. Normal triglyceride levels vary by age and sex. People with high triglycerides often have a high total cholesterol level, including a high LDL (bad) cholesterol level and a low HDL (good) cholesterol level. Many people with metabolic syndrome or diabetes also have high triglyceride levels. Extremely high triglyceride levels (more than 1000 mg/dL) can lead to abdominal pain and a life-threatening disorder of the pancreas called pancreatitis. Factors that can contribute to elevated triglyceride levels:
  • Overweight or obesity
  • Insulin resistance or metabolic syndrome
  • Diabetes mellitus, especially with poor glucose control
  • Alcohol consumption, especially in excess
  • Excess sugar intake, especially from processed foods
  • High saturated fat intake
  • Hypothyroidism
  • Chronic kidney disease
  • Physical inactivity
  • Pregnancy (especially in the third trimester)
  • Inflammatory diseases (such as rheumatoid arthritis, systemic lupus erythematosus
  • Some medications may also increase triglycerides.

LDL cholesterol

LDL (“bad”) cholesterol can contribute to the formation of plaque buildup in the arteries (atherosclerosis). This is linked to higher risk for heart attack and stroke.

You want your LDL below 70 milligrams per deciliter (mg/dl).

If you have high LDL or total cholesterol, you can lower your risk of heart disease by:

• Stop smoking if you smoke
• Maintaining a healthy weight
• Avoid foods high in saturated fat, dietary cholesterol, and extra calories
• Limiting your alcohol and salt intake
• Exercise for at least 30 minutes on most days
• Managing stress.

How to lower LDL cholesterol

You can lower your LDL cholesterol level by adopting a heart-healthy lifestyle changes. They include eating a healthy diet, weight management, and regular physical activity.

• Choose heart-healthy foods. The DASH eating plans can help you lower your “bad” LDL cholesterol. These plans encourage:
  • Limiting saturated fats found in fatty cuts of meats, dairy products, and desserts
  • Eating whole grains, fruits, and vegetables rather than refined carbohydrates such as sweets and other high-sugar foods
  • Eating a variety of nuts
  • Preparing foods with little or no salt
• Get regular physical activity. Studies have shown that physical activity can lower LDL “bad” cholesterol and triglycerides and raise your “good” HDL cholesterol. For example, resistance training among postmenopausal women may decrease total cholesterol, LDL cholesterol, and triglycerides. Before starting any exercise program, ask your provider what level of physical activity is right for you.
• Aim for a healthy weight. Research has shown that adults with overweight and obesity can lower “bad” LDL cholesterol and raise “good” HDL cholesterol by losing only 3% to 5% of their weight.
• Manage stress. Research has shown that chronic stress can sometimes increase LDL cholesterol levels and decrease HDL cholesterol levels.
• Quit smoking. If you smoke, quit. Smoking can raise your risk of heart disease and heart attack and worsen other heart disease risk factors. Talk with your doctor about programs and products that can help you quit smoking. Also, try to avoid secondhand smoke.
• Get enough good quality sleep. Getting 7 to 9 hours of sleep a day lowers your risk for high “bad” cholesterol (LDL) and total cholesterol.
• Limit alcohol. Visit the National Institute on Alcohol Abuse and Alcoholism for resources on support and treatment to stop drinking.

If your healthy lifestyle changes alone do not lower your cholesterol enough, you may also need to take medicines. There are several types of cholesterol-lowering drugs available, including statins. If you take medicines to lower your cholesterol, you still should continue with the lifestyle changes.

Some people with familial hypercholesterolemia (FH) may receive a treatment called lipoprotein apheresis. This treatment uses a filtering machine to remove LDL cholesterol from the blood. Then the machine returns the rest of the blood back to the person.

Eating a heart-healthy diet

From a dietary standpoint, the best way to lower your cholesterol is reduce your intake of saturated fat, trans fat and cholesterol. The American Heart Association recommends limiting saturated fat to less than 6% of daily calories and minimizing the amount of trans fat you eat.

Reducing these fats means limiting your intake of red meat and dairy products made with whole milk. Choose skim milk, low-fat or fat-free dairy products instead. It also means limiting fried food and cooking with healthy oils, such as vegetable oil.

A heart-healthy diet emphasizes fruits, vegetables, whole grains, poultry, fish, nuts and nontropical vegetable oils, while limiting red and processed meats, sodium and sugar-sweetened foods and beverages.

Many diets fit this general description. For example, the DASH (Dietary Approaches to Stop Hypertension) eating plan promoted by the National Heart, Lung, and Blood Institute as well as diets suggested by the U.S. Department of Agriculture and the American Heart Association are heart-healthy approaches. Such diets can be adapted based on your cultural and food preferences.

Becoming more physically active

A sedentary lifestyle lowers HDL cholesterol. Less HDL means there’s less good cholesterol to remove bad cholesterol from your arteries.

Physical activity is important. At least 150 minutes of moderate-intensity aerobic exercise a week is enough to lower both cholesterol and high blood pressure. And you have lots of options: brisk walking, swimming, bicycling or even yard work can fit the bill.

Quitting smoking

Smoking and vaping lowers HDL cholesterol.

Worse still, when a person with unhealthy cholesterol levels also smokes, risk of coronary heart disease increases more than it otherwise would. Smoking also compounds the risk from other risk factors for heart disease, such as high blood pressure and diabetes.

By quitting, smokers can lower their LDL cholesterol and increase their HDL cholesterol levels. It can also help protect their arteries. Nonsmokers should avoid exposure to secondhand smoke.

Losing weight

Being overweight or obese tends to raise bad cholesterol and lower good cholesterol. But a weight loss of as little as 5% to 10% can help improve cholesterol numbers. Losing even 5 to 10 pounds can help lower cholesterol levels.

Manage stress

Research has shown that chronic stress can sometimes raise your LDL cholesterol and lower your HDL cholesterol. Try to reduce your stress. You can do that by deep breathing and relaxation techniques. Examples include meditation and gentle exercise (such as walking or yoga). Also talking with a friend, family member, or health care professional may be helpful.

Medications for high cholesterol

Your doctor might suggest medication to help keep your cholesterol in the healthy range. The choice of medication or combination of medications depends on various factors, including your personal risk factors, your age, your health and possible drug side effects. Common choices include:

• Statins. Statins block a substance your liver needs to make cholesterol. This causes your liver to remove cholesterol from your blood. Statins can also help your body reabsorb cholesterol from built-up deposits on your artery walls, potentially reversing coronary artery disease. Choices include atorvastatin (Lipitor), fluvastatin (Lescol XL), lovastatin (Altoprev), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor). The common side effects of statins are muscle pains and muscle damage, reversible memory loss and confusion, and elevated blood sugar.
• Bile-acid-binding resins. Your liver uses cholesterol to make bile acids, a substance needed for digestion. The medications cholestyramine (Prevalite), colesevelam (Welchol) and colestipol (Colestid) lower cholesterol indirectly by binding to bile acids. This prompts your liver to use excess cholesterol to make more bile acids, which reduces the level of cholesterol in your blood.
• Cholesterol absorption inhibitors. Your small intestine absorbs the cholesterol from your diet and releases it into your bloodstream. The drug ezetimibe (Zetia) helps reduce blood cholesterol by limiting the absorption of dietary cholesterol. Ezetimibe can be used with a statin drug.
• Bempedoic acid. This newer drug works in much the same way as statins but is less likely to cause muscle pain. Adding bempedoic acid (Nexletol) to a maximum statin dosage can help lower LDL significantly. A combination pill containing both bempedoic acid and ezetimibe (Nexlizet) also is available.
• Bile-acid-binding resins. Your liver uses cholesterol to make bile acids, a substance needed for digestion. The medications cholestyramine (Prevalite), colesevelam (Welchol) and colestipol (Colestid) lower cholesterol indirectly by binding to bile acids. This prompts your liver to use excess cholesterol to make more bile acids, which reduces the level of cholesterol in your blood.
• Injectable medications. A newer class of drugs, known as PCSK9 inhibitors, can help the liver absorb more LDL cholesterol — which lowers the amount of cholesterol circulating in your blood. Alirocumab (Praluent) and evolocumab (Repatha) might be used for people who have a genetic condition that causes very high levels of LDL or in people with a history of coronary disease who have intolerance to statins or other cholesterol medications. PCSK9 inhibitors are injected under the skin every few weeks and are expensive.

If you also have high triglycerides, your doctor might prescribe:

• Fibrates. Fibrates mostly lower triglycerides and, to a lesser degree, raise HDL levels. Fibrates are less effective in lowering LDL levels. The medications fenofibrate (Tricor, Fenoglide, others) and gemfibrozil (Lopid) reduce your liver’s production of very-low-density lipoprotein (VLDL) cholesterol and speed the removal of triglycerides from your blood. VLDL cholesterol contains mostly triglycerides. Using fibrates with a statin can increase the risk of statin side effects.
• Nicotinic acid also called niacin or vitamin B3. Niacin is the generic name for nicotinic acid (pyridine-3-carboxylic acid), nicotinamide (niacinamide or pyridine-3-carboxamide), and related derivatives, such as nicotinamide riboside ². Niacin is a water-soluble B3 vitamin that should be taken only under physician supervision. Niacin limits your liver’s ability to produce LDL and VLDL cholesterol. It improves all lipoproteins—total cholesterol, LDL, triglycerides, and HDL—when taken in doses well abovethe vitamin requirement. But niacin doesn’t provide additional benefits over statins. Niacin has also been linked to liver damage and strokes, so most doctors now recommend it only for people who can’t take statins.
• Omega-3 fatty acid supplements. Omega-3 fatty acid supplements can help lower your triglycerides. They are available by prescription or over-the-counter. If you choose to take over-the-counter supplements, get your doctor’s OK. Omega-3 fatty acid supplements could affect other medications you’re taking.

If you are on such medication, you might need regular cholesterol tests to check that they are working well and that you are taking the right dose. If you decide to take cholesterol medication, your doctor might recommend liver function tests to monitor the medication’s effect on your liver.

Experts from the National Cholesterol Education Program (NCEP) say that more aggressive cholesterol treatment is needed for people at high risk of dying from a heart attack or cardiovascular disease. The basic message of the group’s recommendations is the lower the better when it comes to levels of low-density lipoprotein (LDL) or “bad cholesterol”. The updated recommendations say that almost all high-risk patients with LDL cholesterol levels of 100 mg/dL or higher should begin taking cholesterol-lowering medicine.

Lipoprotein apheresis

Some people with familial hypercholesterolemia may benefit from lipoprotein apheresis to lower their blood cholesterol levels. Lipoprotein apheresis uses a filtering machine to remove unwanted substances from the body. The machine removes “bad” LDL cholesterol from the blood, then returns the remainder of the blood to your body.

Alternative medicine

Few natural products have been proved to reduce cholesterol, but some might be helpful. With your doctor’s OK, consider these cholesterol-lowering supplements and products:

• Barley
• Plant sterols and stanols, found in oral supplements, some fortified orange juices and some margarines, such as Promise Activ
• Blond psyllium, found in seed husk and products such as Metamucil
• Oat bran, found in oatmeal and whole oats

Another popular cholesterol-lowering supplement is red yeast rice. There is evidence that red yeast rice can help lower your LDL cholesterol. Some red yeast rice products contain substances called monacolins, which are produced by the yeast. However, the U.S. Food and Drug Administration (FDA) has said that red yeast rice products that contain monacolin K, a naturally occurring form of the prescription cholesterol-lowering drug lovastatin and can cause the same types of side effects and drug interactions as lovastatin, cannot be sold legally as dietary supplements in the United States. Other red yeast rice products contain little or no monacolin K, and it is not known whether these products have any effect on cholesterol levels. Unfortunately, there is no way to know how much monacolin K is present in most red yeast rice products.

If you buy red yeast rice supplements in the United States, there’s no way to know whether you’re getting enough monacolin K to lower your LDL cholesterol. In other countries, lovastatin in red yeast rice products is potentially dangerous because there’s no way to know how much might be in a particular product or what the quality of the lovastatin is.

• Flaxseed. Studies of flaxseed preparations to lower cholesterol levels report mixed results. A 2009 review of the scientific research of flaxseed for lowering cholesterol found modest improvements in cholesterol, seen more often in postmenopausal women and in people with high initial cholesterol concentrations.
• Garlic. Some evidence indicates that taking garlic supplements can slightly lower blood cholesterol levels. A recent review of the research on garlic supplements concluded that they can lower cholesterol if taken for more than 2 months, but their effect is modest in comparison with the effects of cholesterol-lowering drugs. However, a National Center for Complementary and Integrative Health-funded study on the safety and effectiveness of three garlic preparations (fresh garlic, dried powdered garlic tablets, and aged garlic extract tablets) for lowering blood cholesterol levels found no effect. Although garlic supplements appear to be safe for most adults, they can thin the blood in a manner similar to aspirin, so use caution if you are planning to have surgery or dental work. Garlic supplements have also been found to interfere with the effectiveness of saquinavir, a drug used to treat HIV infection.
• Some soy products can have a small cholesterol-lowering effect. An analysis of data from 35 studies indicated that soy foods were more effective in lowering cholesterol than soy protein supplements and that isoflavones (substances in soy that have a weak estrogenic effect) did not lower cholesterol. The effect of soy is much smaller than that of cholesterol-lowering drugs.
• Limited evidence indicates that green tea may have a cholesterol-lowering effect. The evidence on black tea is less consistent.
• Chromium, vitamin C, artichoke extract, the herb Hibiscus sabdariffa, coenzyme Q10, and selenium have been studied for cholesterol but have not been found to be effective. Research findings don’t show clear evidence regarding the cholesterol-lowering effects of policosanol (derived from sugar cane) and guggulipid (from the mukul mirth tree in western India).

Even if you take cholesterol-lowering supplements, remember the importance of a healthy lifestyle, and take medication to reduce your cholesterol as directed. Tell your doctor which supplements you take.

HDL cholesterol

HDL stands for high density lipoprotein or HDL-C (high-density lipoprotein cholesterol). HDL is sometimes called “good cholesterol” because it carries harmful cholesterol from other parts of your body including your arteries back to your liver. Your liver then removes the cholesterol from your body and helps protect you from heart attack and stroke. A healthy HDL-cholesterol level may protect against heart attack and stroke. If you have low HDL levels, you have a greater heart disease risk, even if your total cholesterol is below 200 mg/dL. Your doctor will evaluate your HDL and other cholesterol levels and other factors to assess your risk for heart attack or stroke. People with high blood triglycerides usually also have lower levels of HDL. Genetic factors, type 2 diabetes, smoking, being overweight and being sedentary can all lower HDL cholesterol. Women tend to have higher levels of HDL cholesterol than men do, because the female hormone estrogen raises HDL, but this can change after menopause.

Experts believe HDL cholesterol may act in a variety of helpful ways that tend to reduce the risk for heart disease ³:

• High HDL cholesterol 60 mg/dL or higher is Protective against heart disease.
• HDL cholesterol scavenges and removes LDL or “bad” cholesterol.
• HDL reduces, reuses, and recycles LDL cholesterol by transporting it to the liver where it can be reprocessed.
• HDL cholesterol acts as a maintenance crew for the inner walls (endothelium) of blood vessels. Damage to the inner walls is the first step in the process of atherosclerosis, which causes heart attacks and strokes. HDL scrubs the wall clean and keeps it healthy.

People with high blood triglycerides usually also have lower HDL cholesterol. Genetic factors, type 2 diabetes, smoking, being overweight and being sedentary can all lower HDL cholesterol. Women tend to have higher levels of HDL cholesterol than men do.

A healthy HDL cholesterol level may protect against heart attack and stroke. Studies show low levels of HDL cholesterol increase the risk of heart disease. HDL cholesterol does not completely eliminate LDL cholesterol. Only one-fourth to one-third of blood cholesterol is carried by HDL.

HDL levels should be around 50 mg/dL. Some people can raise HDL by::

• Exercising for at least 30 minutes 5 times a week
• Quitting smoking
• Avoiding saturated fats
• Losing weight

Others may need medicine to get HDL to a beneficial level, and should work with your doctor on a treatment plan.

What can you do if your HDL cholesterol is Low?

If your HDL levels is low, you can take several steps to boost your HDL level and reduce your heart disease risk ⁴:

• Get physically active or exercise – Aerobic exercise for 30 to 60 minutes on most days of the week can help pump up your HDL levels. Some studies suggest that physical activity can raise HDL cholesterol. The American Heart Association recommends three to four 40-minute sessions of moderate- to vigorous-intensity aerobic activity per week for adults trying to lower their LDL cholesterol or blood pressure.
• Eat better fats. The monounsaturated and polyunsaturated fats described above can raise HDL cholesterol levels.
• Cut out trans fats. Not only do they increase LDL cholesterol, they decrease HDL cholesterol too.
• Quit smoking – Tobacco smoke lowers HDL, and quitting can increase HDL levels.
• Keep a healthy weight –  Being overweight increases LDL cholesterol and reduces HDL cholesterol levels. Losing even a few pounds will increase your HDL-C and lower your LDL-C and blood pressure. Avoiding obesity besides improving HDL levels, reduces risk for heart disease and multiple other health conditions.

Symptoms for high cholesterol

There are usually no signs or symptoms that you have high cholesterol. A blood test is the only way to detect if you have it. Most people do not know they have high blood cholesterol until they have a blood test during a routine healthcare visit.

If your cholesterol levels are very high, you may notice the following signs:

• Fatty bumps also called xanthomas on your skin, especially on the elbows, joints, knees, hands, ankles, or buttocks.
• Grayish-white rings also called arcus senilis that appear around the cornea in your eye.

These signs develop mostly in people who have very high cholesterol that runs in families or familial hypercholesterolemia.

Undiagnosed or untreated high blood cholesterol can lead to serious problems, such as heart attack and stroke. High cholesterol can cause a dangerous accumulation of cholesterol and other deposits on the walls of your arteries (atherosclerosis). These deposits (plaques) can reduce blood flow through your arteries, which can cause complications, such as:

• Chest pain also known as angina. If the arteries that supply your heart with blood (coronary arteries) are affected, you might have chest pain (angina) and other symptoms of coronary artery disease.
• Heart attack. If plaques tear or rupture, a blood clot can form at the plaque-rupture site — blocking the flow of blood or breaking free and plugging an artery downstream. If blood flow to part of your heart stops, you’ll have a heart attack.
• Stroke. Similar to a heart attack, a stroke occurs when a blood clot blocks blood flow to part of your brain.

Talk to your doctor about your risk and steps you can take to keep your cholesterol levels in a healthy range.

Why is high cholesterol bad?

Too much cholesterol in your blood is bad for you. Cholesterol can enter your artery wall, damage its integrity and lead to the formation of atherosclerotic plaque (hardened deposits). This process of plaque buildup is called atherosclerosis. It can lead to serious problems like:

• Coronary artery disease: Blocked blood flow to your heart.
• Peripheral artery disease: Blocked blood flow to your legs and arms.
• Carotid artery disease: Blocked blood flow to your brain.

Cholesterol travels through your blood on proteins called lipoproteins. One type, LDL (low-density lipoprotein), is sometimes called the “bad” cholesterol. A high LDL level leads to a buildup of cholesterol in your arteries. Another type, HDL (high-density lipoprotein), is sometimes called the “good” cholesterol. HDL carries cholesterol from other parts of your body back to your liver. Then your liver removes the cholesterol from your body.

It’s important to keep your cholesterol in check because high cholesterol levels increase the risk of heart disease and stroke. A stroke occurs when a blood clot blocks blood flow to part of your brain. If you have too much cholesterol in your blood, it can combine with other substances in the blood to form plaque. Plaque sticks to the walls of your arteries. This buildup of plaque is known as atherosclerosis. It can lead to coronary artery disease, where your coronary arteries become narrow or even completely blocked, which can cause a heart attack (myocardial infarction). A heart attack occurs when your heart muscle tissue does not receive vital oxygen and nutrients.

Atherosclerosis (buildup of plaque in arteries) is the process that causes the artery wall to get thick and stiff. The disease process begins when LDL (“bad” cholesterol) deposits cholesterol in the artery wall. Your body has an immune response to protect itself and sends white blood cells called macrophages to engulf the invading cholesterol in the artery wall. When the macrophages are full of cholesterol, they are called foam cells because of their appearance. As more foam cells collect in the artery wall, a fatty streak develops between the intima and the media. If the process is not stopped, the fatty streak becomes a plaque, which pushes the intima into the lumen, narrowing the blood flow.

The plaque develops a fibrous coating on its outer edges. But if cholesterol continues to collect in foam cells inside the plaque, the fibrous outer coating can weaken and eventually rupture. Smaller arteries downstream from the rupture can quickly become blocked. Over time, a clot may develop at the rupture site and completely block the artery.

Evidence shows that the atherosclerotic process begins in childhood and progresses slowly into adulthood. Later in life, this often leads to coronary heart disease, the leading cause of death in the United States.

High cholesterol causes

Your body naturally produces all the LDL (bad) cholesterol it needs. However, the genes you inherit and your lifestyle habits play a major role in your cholesterol levels. The most common cause of high cholesterol is an unhealthy lifestyle. An unhealthy lifestyle makes your body produce more LDL cholesterol than it needs. This can include:

• Unhealthy eating habits or unhealthy diet, such as eating lots of bad fats. One type, saturated fat, is found in some meats, dairy products, chocolate, baked goods, and deep-fried and processed foods. Eating a lot of foods high in saturated fats raises “bad” LDL cholesterol levels. Another type, trans fat, is in some fried and processed foods. Eating these fats can raise your LDL (bad) cholesterol. No more than 10% of your daily calories should come from saturated fats.
• Lack of physical activity, with lots of sitting and little exercise. This lowers your HDL (good) cholesterol.
• Smoking or exposure to tobacco smoke, which lowers HDL cholesterol, especially in women. It also raises your LDL cholesterol.
• Being overweight or obese.
• Stress may raise levels of certain hormones, such as corticosteroids. These can cause your body to make more cholesterol.
• Drinking too much alcohol (more than two drinks a day for men or one drink a day for women) can raise your total cholesterol level.
• Getting little or low-quality sleep has been linked to lower cardiovascular health.

Genetics may also cause people to have high cholesterol. For example, some people inherit genes from their mother, father or even grandparents that cause them to have too much cholesterol. This is called familial hypercholesterolemia (FH). The severity of familial hypercholesterolemia is related to the duration and degree of LDL cholesterol in the blood. Familial hypercholesterolemia is dangerous because it can cause premature atherosclerotic heart disease. If you have a family history of familial hypercholesterolemia or problems related to high cholesterol, get your cholesterol levels checked.

Lipoprotein-a also known as Lp(a) or lipoprotein(a) is a lot like LDL cholesterol (‘bad cholesterol’) but it’s more ‘sticky’ ⁵. Lipoprotein-a or Lp(a) molecule includes two protein components: apolipoprotein(a) [apo(a)] and apolipoprotein B100 (apo-B100) ⁶. If you have high levels of lipoprotein-a or Lp(a) in your blood, it can stick to your artery walls and clog them up, leading to heart disease and stroke at a young age ⁷, ⁸, ⁹, ¹⁰, ¹¹. Today, about 20-30% of people worldwide are estimated to have elevated levels of Lp(a), which are generally thought to start between 30-50 mg/dL. Currently, if a person has elevated Lipoprotein-a or Lp(a) levels, they would likely work with their cardiologist to create a plan to take steps to support heart-healthy living and minimize any risks, such as having high blood pressure or high cholesterol ¹², ¹³, ¹⁴, ¹⁵. Some patients may also consider taking LDL cholesterol-lowering treatments, such as statins or PCSK9 inhibitors ¹⁶, ¹⁷, ¹⁸, ¹⁹. In some cases, PCSK9 inhibitors have been shown to lower Lp(a) levels by about 20-30%. Lipoprotein apheresis, which removes excess Lp(a) and LDL cholesterol from the body, is another option, but for people with higher risks ²⁰, ²¹. According to the Food and Drug Administration (FDA), patients qualified for lipoprotein apheresis present with familial hypercholesterolemia, coronary artery disease and LDL-C >100 mg/dL and Lp(a) > 60 mg/dL. Lipoprotein apheresis procedure is typically performed every two weeks (in some countries weekly). During the one course (3–4 hour) the Lp(a) concentration can be lowered by 50% to 85%. Additionally, lipoprotein apheresis reduces LDL levels by 60% to 85% ²². It is expected that such Lipoprotein(a) lowering reduces the risk of atherosclerotic cardiovascular disease events.

Other medical conditions and certain medicines may also cause high cholesterol.

See your doctor about your risk of high cholesterol if you have any of the following:

• Chronic kidney disease
• Diabetes
• HIV/AIDS
• Hypothyroidism
• Lupus erythematosus
• Overweight and obesity
• Polycystic ovary syndrome (PCOS)
• Sleep apnea

For people with conditions such as lupus and HIV, the condition itself and the medicine used to treat it may lead to unhealthy cholesterol levels.

Some medicines that you take for other health problems can raise your level of “bad” LDL cholesterol or lower your level of “good” HDL cholesterol, including:

• Arrhythmia medicines, such as amiodarone
• Beta-blockers for relieving angina chest pain or treating high blood pressure
• Chemotherapy medicines used to treat cancer
• Diuretics, such as thiazide, to treat high blood pressure
• Immunosuppressive medicines, such as cyclosporine, to treat inflammatory diseases or to prevent rejection after organ transplant
• Retinoids to treat acne
• Steroids, such as prednisone, to treat inflammatory diseases such as lupus, rheumatoid arthritis, and psoriasis

Risk factors for developing high cholesterol

Factors that can increase your risk of bad cholesterol include:

• Poor diet. Eating saturated fat, found in animal products, and trans fats, found in some commercially baked cookies and crackers and microwave popcorn, can raise your cholesterol level. Foods that are high in cholesterol, such as red meat and full-fat dairy products, will also increase your cholesterol.
• Age. Your cholesterol levels tend to rise as you get older. For instance, as you age, your liver becomes less able to remove LDL cholesterol. Even though it is less common, younger people, including children and teens, can also have high cholesterol.
• Sex. Between ages 20 and 39, men have a greater risk for high total cholesterol than women. A woman’s risk goes up after menopause. Menopause lowers levels of female hormones that may protect against high blood cholesterol. After menopause, women’s levels of total and “bad” LDL cholesterol usually go up, while their levels of “good” HDL cholesterol go down.
• Heredity. High blood cholesterol can run in families.
• Weight. Being overweight or having obesity raises your cholesterol level. Having a body mass index (BMI) of 30 or greater puts you at risk of high cholesterol.
• Race. Certain races may have an increased risk of high cholesterol.
  • Overall, non-Hispanic White people are more likely than other groups to have high levels of total cholesterol.
  • Asian Americans, including those of Indian, Filipino, Japanese, and Vietnamese descent, are more likely to have high levels of “bad” LDL cholesterol than other groups.
  • Hispanic Americans are more likely to have lower levels of “good” HDL cholesterol than other groups.
  • African Americans are more likely than other groups to have high levels of “good” HDL cholesterol.
• Lack of exercise. Being physically inactive contributes to overweight and can raise LDL and lower HDL. Exercise helps boost your body’s HDL, or “good,” cholesterol while increasing the size of the particles that make up your LDL, or “bad,” cholesterol, which makes it less harmful.
• Smoking. Cigarette smoking damages the walls of your blood vessels, making them more prone to accumulate fatty deposits. Smoking might also lower your level of HDL, or “good,” cholesterol.
• Diabetes. High blood sugar contributes to higher levels of a dangerous cholesterol called very-low-density lipoprotein (VLDL) and lower HDL cholesterol. High blood sugar also damages the lining of your arteries.

Foods to lower cholesterol

You can lower cholesterol over time by eating fewer of the foods that cause high cholesterol and more of the foods that lower cholesterol. The DASH eating plan is one example. DASH stands for Dietary Approaches to Stop Hypertension. DASH diet is an eating plan that is based on research studies sponsored by the National Heart, Lung, and Blood Institute. Clinical studies have shown that DASH diet lowers high blood pressure and improves levels of cholesterol. This reduces your risk of getting heart disease. Other lifestyle changes can help lower your blood pressure. They include staying at a healthy weight, exercising, and not smoking.

The DASH eating plan:

• Emphasizes vegetables, fruits, and whole-grains
• Includes fat-free or low-fat dairy products, fish, poultry, beans, nuts, and vegetable oils
• Limits foods that are high in saturated fat. These foods include fatty meats, full-fat dairy products, and tropical oils such as coconut, palm kernel, and palm oils.
• Limits sugar-sweetened beverages and sweets

Another example of a heart-healthy diet is the Mediterranean diet. The Mediterranean diet is similar to other heart-healthy diets. It promotes foods such as fish, fruits, vegetables, beans, and whole grains. It does not include many meats, dairy products, or sweets. In other ways, the Mediterranean diet is different. For example, it allows for more calories from fats, like olive oil. The Mediterranean diet also allows for moderate intake of wine.

Studies show that the Mediterranean diet has many health benefits. These are greater when combined with exercise. The Mediterranean diet can help you lose or maintain weight. It also helps to manage your blood pressure, blood sugar, and cholesterol levels. In older adults, it can improve your brain function. Following the Mediterranean diet may also protect against some chronic diseases, such as:

• heart disease
• cancer
• type 2 diabetes
• Alzheimer’s disease
• Parkinson’s disease

You can integrate the Mediterranean diet into your lifestyle.

Here are some foods to improve your cholesterol and protect your heart. Consider using a food diary to keep track of what you eat. It’s a handy way to evaluate the healthy, not-so-healthy and unhealthy foods you’re making a part of your everyday diet.

Oatmeal, oat bran and high-fiber foods

Oatmeal contains soluble fiber, which reduces your low-density lipoprotein (LDL) cholesterol, the “bad” cholesterol. Soluble fiber is also found in such foods as kidney beans, Brussels sprouts, apples and pears.

Soluble fiber can reduce the absorption of cholesterol into your bloodstream. Five to 10 grams or more of soluble fiber a day decreases your LDL cholesterol. One serving of a breakfast cereal with oatmeal or oat bran provides 3 to 4 grams of fiber. If you add fruit, such as a banana or berries, you’ll get even more fiber.

Vegetables

A growing body of scientific evidence indicates that wholesome vegetarian diets offer distinct advantages compared to diets containing meat and other foods of animal origin. The benefits arise from lower intakes of saturated fat, cholesterol and animal protein as well as higher intakes of complex carbohydrates, dietary fiber, magnesium, folic acid, vitamin C and E, carotenoids and other phytochemicals.

Try cooking vegetables in a tiny bit of vegetable oil and add a little water during cooking, if needed. Or use a vegetable oil spray. Just one or two teaspoons of oil is enough for a package of plain frozen vegetables that serves four. Place the vegetables in a skillet with a tight cover and cook them over very low heat until done.

Add herbs and spices to make vegetables even tastier. It’s a healthier choice than opting for pre-packaged vegetables with heavy sauce or seasonings. For example, these combinations add subtle and surprising flavors:

• Rosemary with peas, cauliflower and squash
• Oregano with zucchini
• Dill with green beans
• Marjoram with Brussels sprouts, carrots and spinach
• Basil with tomatoes

Start with a small quantity of herbs and spices (1/8 to 1/2 teaspoon for a package of frozen vegetables), then let your family’s feedback be your guide. Chopped parsley and chives, sprinkled on just before serving, can also enhance the flavor of many vegetables.

Fish and omega-3 fatty acids

Fatty fish has high levels of omega-3 fatty acids, which can reduce your triglycerides — a type of fat found in blood — as well as reduce your blood pressure and risk of developing blood clots. In people who have already had heart attacks, omega-3 fatty acids may reduce the risk of sudden death. Research has shown the health benefits of eating seafood rich in omega-3 fatty acids, especially when it replaces less healthy proteins that are high in saturated fat and low in unsaturated fat. Including seafood high in omega-3 fatty acids as part of a heart-healthy diet can help reduce the risk of heart failure, coronary heart disease, cardiac arrest and the most common type of stroke (ischemic stroke).

Omega-3 fatty acids don’t affect LDL cholesterol levels. But because of omega-3 fatty acids’ other heart benefits, the American Heart Association recommends eating at least two servings of fish a week or at least 8 ounces of non-fried fish each week. Baking or grilling the fish avoids adding unhealthy fats. Prepare fish baked, broiled, grilled or boiled rather than breaded and fried, and without added salt, saturated fat or trans fat. Non-fried fish and shellfish, such as shrimp, crab and lobster, are low in saturated fat and are a healthy alternative to many cuts of meat and poultry.

The highest levels of omega-3 fatty acids are in:

• Mackerel
• Herring
• Tuna
• Salmon
• Trout

Foods such as walnuts, flaxseed and canola oil also have small amounts of omega-3 fatty acids.

Omega-3 and fish oil supplements are available. Talk to your doctor before taking any supplements.

Increase fiber and whole grains

Fiber is a substance found in plants. Dietary fiber, the kind you eat, is found in fruits, vegetables, and grains. Your body cannot digest fiber, so it passes through your intestines without being absorbed much.

Dietary fiber adds bulk to your diet. Because it makes you feel full faster and for longer, it can help you with weight loss efforts or to maintain a healthy weight.

High fiber diets can also help with constipation.

Slowly increase the amount of fiber in your diet. If you have bloating or gas, you have probably eaten too much and need to reduce the amount of fiber you eat for a few days. Drink plenty of fluids. When you increase fiber in your diet, you also need to get enough fluids. Not getting enough fluids may make constipation worse instead of better. Ask your health care provider or a dietitian how much fluid you should be getting each day.

The daily recommended intake (DRI) of fiber for adults 19 to 50 years old is 38 grams a day for men and 25 grams a day for women. To get more fiber into your diet, eat different types of foods, such as:

• Fruits
• Vegetables
• Whole grains

Vegetables, Legumes, and Nuts

Vegetables are a good source of fiber. Eat more:

• Lettuce, Swiss chard, raw carrots, and spinach
• Tender cooked vegetables, such as asparagus, beets, mushrooms, turnips, and pumpkin
• Baked potatoes and sweet potatoes with skin
• Broccoli, artichokes, squashes, and string beans

You can also get more fiber by eating:

• Legumes, such as lentils, black beans, split peas, kidney beans, lima beans, and chickpeas
• Nuts and seeds, such as sunflower seeds, almonds, pistachios, and pecans

Fruits

Fruits are another good source of fiber. Eat more:

• Apples and bananas
• Peaches and pears
• Tangerines, prunes, and berries
• Figs and other dried fruits

Grains

Grains are another important source of dietary fiber. Eat more:

• Hot cereals, such as oatmeal and farina
• Whole-grain breads
• Brown rice
• Popcorn
• High-fiber cereals, such as bran, shredded wheat, and puffed wheat
• Whole-wheat pastas
• Bran muffins

Consider these heart-smart choices:

• Toast and crush (or cube) fiber-rich whole-grain bread to make breadcrumbs, stuffing or croutons.
• Replace the breadcrumbs in your meatloaf with uncooked oatmeal.
• Serve whole fruit at breakfast in place of juice.
• Use brown rice instead of white rice and try whole grain pasta.
• Add lots of colorful veggies to your salad – carrots, broccoli and cauliflower are high in fiber and give your salad a delicious crunch.

Almonds and other nuts

Almonds, peanuts and other tree nuts can improve blood cholesterol. Walnuts are especially high in omega-3 fatty acids, the same heart-healthy fat found in oily fish, but are a lot easier to stash in your pocket or purse. A recent study concluded that a diet supplemented with walnuts can lower the risk of heart complications in people with history of a heart attack. All nuts are high in calories, so a handful added to a salad or eaten as a snack will do.

All nuts will go bad (rancid) in time so keep them in the fridge. The same goes for nut oils and nut butters in jars after you’ve opened them. Rancid nuts have an unpleasant smell and bitter taste.

Avocados

Avocados are a potent source of nutrients as well as monounsaturated fatty acids (MUFAs). Research suggests that adding an avocado a day to a heart-healthy diet can help improve LDL cholesterol levels in people who are overweight or obese.

People tend to be most familiar with avocados in guacamole, which usually is eaten with high-fat corn chips. Try adding avocado slices to salads and sandwiches or eating them as a side dish. Also try guacamole with raw cut vegetables, such as cucumber slices.

Replacing saturated fats, such as those found in meats, with MUFAs are part of what makes the Mediterranean diet heart healthy.

Olive oil

Try using olive oil in place of other fats in your diet. You can saute vegetables in olive oil, add it to a marinade or mix it with vinegar as a salad dressing. You can also use olive oil as a substitute for butter when basting meat or as a dip for bread.

Foods with added plant sterols or stanols

There is evidence that foods that contain certain added ingredients, such as plant sterols and stanols, can reduce levels of cholesterol in the blood. Sterols and stanols are substances found in plants that help block the absorption of cholesterol. Plant sterols and stanols are found in nuts, seeds and legumes, vegetable oils, breads and cereals, and fruits and vegetables. You need to eat 2 to 3 grams a day of plant sterols and stanols to assist in reducing high cholesterol. Eating more is not harmful, but you won’t get any additional benefits.

Foods that have been fortified with sterols or stanols are available.

Margarines, low-fat milks, low-fat yogurts and breakfast cereals, lower fat cheese, processed cheese and orange juice with added plant sterols can help reduce LDL cholesterol. Adding 2 grams of sterol to your diet every day can lower your LDL cholesterol by 5 to 15 percent. People who do not have high cholesterol should not eat these products regularly, particularly children and pregnant or breastfeeding women.

If you do eat foods that are designed to lower cholesterol, read the label carefully to avoid eating too much.

You should not eat foods fortified with plant sterols as a substitute for medication. You can use plant sterol-enriched foods while taking cholesterol medication, but check with your doctor first.

However, it’s not clear whether food with plant sterols or stanols reduces your risk of heart attack or stroke — although experts assume that foods that reduce cholesterol do reduce the risk. Plant sterols or stanols don’t appear to affect levels of triglycerides or of high-density lipoprotein (HDL) cholesterol, the “good” cholesterol.

Whey protein

Whey protein, which is found in dairy products, may account for many of the health benefits attributed to dairy. Studies have shown that whey protein given as a supplement lowers both LDL and total cholesterol as well as blood pressure. You can find whey protein powders in health food stores and some grocery stores.

Use liquid vegetable oils in place of solid fats

Liquid vegetable oils such as canola, safflower, sunflower, soybean and olive oil can often be used instead of solid fats, such as butter, lard or shortening. If you must use margarine, try the soft or liquid kind.

Use a little liquid oil to:

• Pan-fry fish and poultry.
• Sauté vegetables.
• Make cream sauces and soups using low-fat or fat-free milk.
• Add to whipped or scalloped potatoes using low-fat or fat-free milk.
• Brown rice for Spanish, curried or stir-fried rice.
• Cook dehydrated potatoes and other prepared foods that call for fat to be added.
• Make pancakes or waffles.

Unsaturated fat

The two kinds of unsaturated fats are: monounsaturated and polyunsaturated. Monounsaturated fats have one (“mono”) unsaturated carbon bond in the molecule. Polyunsaturated fats have more than one (“poly,” for many) unsaturated carbon bonds. Both of these unsaturated fats are typically liquid at room temperature.

Eaten in moderation, both kinds of unsaturated fats may help improve your blood cholesterol when used in place of saturated and trans fats.

Unsaturated fats are in fish, such as salmon, trout and herring, and plant-based foods such as avocados, olives and walnuts. Liquid vegetable oils, such as soybean, corn, safflower, canola, olive and sunflower, also contain unsaturated fats.

Puree fruits and veggies for baking

Pureed fruits or vegetables can be used in place of oil in muffin, cookie, cake and snack bar recipes to give your treats an extra healthy boost. For many recipes, use the specified amount of puree instead of oil. Check the mix’s package or your cookbook’s substitutions page for other conversions. You can:

• Use applesauce in spice muffins or oatmeal cookies.
• Include bananas in breads and muffins.
• Try zucchini in brownies.

Lower dairy fats

Low-fat (1%) or fat-free (skim) milk can be used in many recipes in place of whole milk or half-and-half. (Some dishes, such as puddings, may result in a softer set.)

When it comes to cheeses used in recipes, you can substitute low-fat, low-sodium cottage cheese, part-skim milk mozzarella (or ricotta) cheese, and other low-fat, low-sodium cheeses with little or no change in consistency.

Foods not to eat with high cholesterol

If you have high cholesterol you should maintain a diet that emphasizes fruits, vegetables, whole grains, low-fat dairy products, poultry, fish and nuts. Also limit your intake of red meat and sugar-sweetened foods and beverages. You should also limit both total fat and saturated fat. No more than 25 to 35 percent of your daily calories should come from dietary fats, and less than 7 percent of your daily calories should come from saturated fat. Depending upon how many calories you eat per day, here are the maximum amounts of fats that you should eat:

Table 4. Maximum amounts of total fat and saturated fat in your diet, based on calories

Calories per Day	Total Fat	Saturated Fat
1500	42-58 grams	10 grams
2000	56-78 grams	13 grams
2500	69-97 grams	17 grams

Table 5. Good and bad fats

CHOLESTEROL-RAISING FATS		HEALTHIER FATS
Saturated Fats	Trans Fats	Monounsaturated Fats	Polyunsaturated Fats
Animal Sources: butter, cheese, cream, fatty cuts of meat and processed meats (hot dog, bacon, bologna, salami, sausage), ice cream, lard, poultry skin, sour cream, whole milk Plant Sources: coconut, palm, palm kerne	Foods with a high probability of containing partially hydrogenated oils: Baked Goods biscuits, cakes, cookies, doughnuts, muffins, pancake mix, pastries, pie crust, pizza dough Fried Foods French fries, breaded chicken or breaded fish Snack Foods – crackers, microwave popcorn, stick margarine, shortening and non- dairy creamer	Nuts, seeds and natural nut butters: almonds, hazelnuts, pecans, peanuts, pine nuts, pistachios, pumpkin and sesame seeds Avocados, olives Oils: canola, extra virgin olive, peanut, sesame	High omega-3 seafood: Arctic char, Atlantic mackerel, black cod (sablefish), herring, mussels, wild salmon, sardines, trout Nuts and seeds: chia, ground flaxseeds, hemp seeds, soy nuts, sunflower seeds, walnuts Oils: soybean, safflower, corn

Saturated fat

Saturated fat is a bad fat because it raises your LDL (bad cholesterol) level more than anything else in your diet. Saturated fat is usually solid at room and refrigerator temperatures. Saturated fat is found in some meats, dairy products, cheese, chocolate, baked goods, butter, lard, and coconut and palm oils and deep-fried and processed foods. Saturated fat should make up less than 10% of your daily calories. Read food labels and choose foods that are lower in saturated fats and higher in unsaturated fats. Unsaturated fats are also known as “good” fats and are found in vegetable oils and nuts. The American Heart Association recommends a diet that emphasizes fish and poultry and limits red meat.

Foods that are high in saturated fat include:

• meat pies
• sausages and fatty cuts of meat
• butter
• lard
• cream
• hard cheese
• cakes and biscuits
• foods that contain coconut or palm oil

The amount of saturated fat in meats can vary widely, depending on the cut and how it’s prepared.

Limit saturated fats by:

• Eating leaner, lower-fat, and skinless meats instead of fatty cuts of meat and chicken with skin.
• Consuming lower-fat dairy products instead of whole-milk.
• Using certain vegetable oils (such as olive and canola oil) instead of butter, lard, and coconut and palm oils.

Here are some ways to reduce the saturated fat in meat:

• Select lean cuts of meat with minimal visible fat. Lean beef cuts include the round, chuck, sirloin or loin. Lean pork cuts include the tenderloin or loin chop. Lean lamb cuts come from the leg, arm and loin.
• Buy “choice” or “select” grades rather than “prime.” Select lean or extra lean ground beef.
• Trim all visible fat from meat before cooking.
• Broil rather than pan-fry meats such as hamburger, lamb chops, pork chops and steak.
• Use a rack to drain off fat when broiling, roasting or baking. Instead of basting with drippings, keep meat moist with wine, fruit juices or a heart-healthy oil-based marinade.
• Cook a day ahead of time. Stews, boiled meat, soup stock or other dishes in which fat cooks into the liquid can be refrigerated. Later, remove the hardened fat from the top.
• When a recipe calls for browning the meat first, try browning it under the broiler instead of in a pan.
• Eat chicken and turkey rather than duck and goose, which are usually higher in fat. Choose white meat most often when eating poultry.
• Remove the skin from chicken or turkey before cooking. If your poultry dries out too much, first try basting with wine, fruit juices or a heart-healthy oil-based marinade. Or leave the skin on for cooking and then remove it before eating.
• Limit processed meats such as sausage, bologna, salami and hot dogs. Many processed meats – even those with “reduced fat” labels – are high in calories and saturated fat. Such foods are often high in sodium, too. Read labels carefully and eat processed meats only occasionally.
• Doughnuts, cookies, crackers, muffins, pies and cakes are examples of foods high in trans fat. Don’t eat them often.
• Limit commercially fried foods and baked goods made with shortening or partially hydrogenated vegetable oils. These foods are very high in fat, and it’s likely to be trans fat.
• Limit fried fast food. Commercial shortening and deep-frying fats are still made by hydrogenation and contain saturated and trans fats.
• Opt for naturally occurring unhydrogenated vegetable oils such as canola, safflower, sunflower or olive oil.
• Look for processed foods made with unhydrogenated oil rather than saturated fat or hydrogenated (or partially hydrogenated) vegetable oils.
• Use soft margarine as a substitute for butter and choose soft margarines (liquid or tub varieties) over harder stick forms. Look for “0 g trans fat” on the Nutrition Facts label.

Try to replace foods containing saturated fats with foods that are high in unsaturated fats, such as:

• avocados or olives
• oily fish (for example, mackerel and salmon)
• nuts (for example, almonds and cashews)
• seeds (for example, sunflower and pumpkin)
• vegetable oils and spreads (for example, sunflower, olive, corn, walnut and rapeseed oils)

Trans fat

Trans fat also known as trans fatty acids or “partially hydrogenated oils” is another bad fat; it can raise your LDL (bad cholesterol) and lower your HDL (good cholesterol). Trans fat is mostly in foods made with hydrogenated oils and fats, such as stick margarine, crackers, and french fries. Trans fats are created in an industrial process that adds hydrogen to liquid vegetable oils to make them more solid. Instead of these bad fats, try healthier fats, such as lean meat, nuts, and unsaturated oils like canola, olive, and safflower oils.

Limit trans fats as much as possible by:

• Limiting foods high in trans fats. This includes foods made with partially hydrogenated oils such as some desserts, microwave popcorn, frozen pizza, stick margarines, and coffee creamers.
• Reading the nutrition labels and choosing foods that do not contain trans fats.

Dairy products and meats naturally contain very small amounts of trans fats. You do not need to avoid these foods because they have other important nutrients.

Limit foods with cholesterol

If you are trying to lower your cholesterol, you should have less than 200 mg a day of cholesterol. Cholesterol is in foods of animal origin, such as liver and other organ meats, egg yolks, shrimp, and whole milk dairy products. Choose reduced fat dairy foods such as milk (preferably unflavored), yogurt (preferably unflavored) and cheese. You can eat smaller amounts of eggs and lean poultry but limit red meat to 1-3 times a week.

Limit salt (sodium)

You should try to limit the amount of sodium (salt) that you eat to no more than 2,300 milligrams (about 1 teaspoon of salt) a day. If you have high blood pressure, you may need to limit sodium (salt) even more. Children younger than age 14 may need to eat even less sodium (salt) each day based on their sex and age. That includes all the sodium you eat, whether it was added in cooking or at the table, or already present in food products. Limiting salt won’t lower your cholesterol, but it can lower your risk of heart diseases by helping to lower your blood pressure. You can reduce your sodium by instead choosing low-salt and “no added salt” foods and seasonings at the table or while cooking. Flavor your foods with herbs and spices rather than salt, and avoid processed foods, prepackaged foods, sauces and canned foods as these contain a lot of salt too.

Try these shopping and cooking tips to help you choose and prepare foods that are lower in sodium:

• Read food labels and choose products that have less sodium for the same serving size.
• Choose low-sodium, reduced-sodium, or no-salt-added products.
• Choose fresh, frozen, or no-salt-added foods instead of pre-seasoned, sauce-marinated, brined, or processed meats, poultry, and vegetables.
• Eat at home more often so you can cook food from scratch, which will allow you to control the amount of sodium in your meals.
• Flavor foods with herbs and spices instead of salt.
• When cooking, limit your use of premade sauces, mixes, and instant products such as rice, noodles, and ready-made pasta.

Avoid added sugar

You should limit the amount of calories you get each day from added sugars. Sweetened drinks, snacks, and sweet treats are the main source of added sugars in the United States. These include sodas, sweetened coffee and tea, energy drinks, cakes, pies, ice cream, candy, syrups, and jellies. Limit these types of foods and drinks.

Reading the Nutrition labels on foods you buy and eat can help you figure out how much fat, saturated fat, cholesterol, fiber, added sugar and sodium is in the foods that you buy.

Some foods, such as fruit, contain natural sugars. Added sugars do not occur naturally in foods but instead are used to sweeten foods and drinks. They include brown sugar, corn syrup, dextrose, fructose, glucose, high-fructose corn syrup, raw sugar, and sucrose.

In the United States, sweetened drinks, snacks, and sweets are the major sources of added sugars.

• Sweetened drinks include soft drinks or sodas, fruit drinks, sweetened coffee and tea, energy drinks, alcoholic drinks, and favored waters. Sweetened drinks account for about half of all added sugars consumed.
• Snacks and sweets include grain-based desserts such as cakes, pies, cookies, brownies, doughnuts; dairy desserts such as ice cream, frozen desserts, and pudding; candies; sugars; jams; syrups; and sweet toppings.

Lower how much sugar you eat or drink by:

• Choosing drinks without added sugar such as water, low-fat or fat-free milk, or 100% vegetable juice.
• Choosing unsweetened foods for snacks or dessert.
• Eating sweetened drinks, snacks, and desserts less often and in smaller amounts.

Foods to avoid with high cholesterol

You can lower cholesterol over time by eating fewer of the foods that cause high cholesterol and more of the foods that lower cholesterol.

Saturated fats are found in all animal foods and some plant sources. You can reduce the amount of saturated fat in your food and have a healthy diet.

The following foods may be high in saturated fats. Many of them are also low in nutrients and have extra calories from sugar:

• Baked goods (cake, doughnuts, Danish)
• Fried foods (fried chicken, fried seafood, French fries)
• Fatty cuts of meat or processed meats (bacon, sausage, chicken with skin, cheeseburger, steak)
• Whole-fat dairy products (butter, ice cream, pudding, cheese, whole milk)
• Solid fats such as coconut oil, palm, and palm kernel oils (found in packaged foods)

Here are some examples of popular food items with the saturated fat content in a typical serving:

• 12 ounces (oz) or 340 g, steak — 20 g
• Cheeseburger — 10 g
• Vanilla shake — 8 g
• 1 tbsp (15 mL) butter — 7 g

It is fine to treat yourself to these types of foods once in a while. But, it is best to limit how often you eat them and limit portion sizes when you do.

You can cut how much saturated fat you eat by substituting healthier foods for less healthy options. Replace foods high in saturated fats with foods that have polyunsaturated and monounsaturated fats. Here is how to get started:

• Replace red meats with skinless chicken or fish a few days a week.
• Use canola or olive oil instead of butter and other solid fats.
• Replace whole-fat dairy with low-fat or nonfat milk, yogurt, and cheese.
• Eat more fruits, vegetables, whole grains, and other foods with low or no saturated fat.

Trans fats are made when food makers turn liquid oils into solid fats, like shortening or margarine. Trans fats can be found in many fried, “fast” packaged, or processed foods, including:

• Anything fried and battered
• Shortening and stick margarine
• Cakes, cake mixes, pies, pie crust, and doughnuts

Animal foods, such as red meats and dairy, have small amounts of trans fats. But most trans fats come from processed foods.

Trans fats are found in many processed and packaged foods. Note that these foods are often low in nutrients and have extra calories from sugar:

• Cookies, pies, cakes, biscuits, sweet rolls, and donuts
• Breads and crackers
• Frozen foods, such as frozen dinners, pizza, ice cream, frozen yogurt, milk shakes, and pudding
• Snack foods
• Fast food
• Solid fats, such as shortening and margarine
• Nondairy creamer

Not all packaged foods have trans fats. It depends on the ingredients that were used. That is why it is important to read labels.

While it is fine to treat yourself to sweets and other high-fat foods once in a while, it is best to avoid food with trans fats completely.

You can cut how much trans fat you eat by substituting healthier foods for less healthy options. Replace foods high in trans and saturated fats with foods that have polyunsaturated and monounsaturated fats. Here is how to get started:

• Use safflower or olive oil instead of butter, shortening, and other solid fats.
• Switch from solid margarine to soft margarine.
• Ask what type of fats foods are cooked in when you eat out at restaurants.
• Avoid fried, packaged, and processed foods.
• Replace meats with skinless chicken or fish a few days a week.
• Replace whole-fat diary with low-fat or nonfat milk, yogurt, and cheese.

Limit alcohol

Alcohol adds extra calories, which can lead to weight gain. Being overweight can raise your LDL level and lower your HDL level. Too much alcohol can also increase your risk of heart diseases because it can raise your blood pressure and triglyceride level. One drink is a glass of wine, beer, or a small amount of hard liquor, and the recommendation is that:

• Men should have no more than two drinks containing alcohol a day
• Women should have no more than one drink containing alcohol a day.

Your doctor may recommend that you reduce the amount of alcohol you drink or that you stop drinking alcohol. Alcohol can:

• Add calories to your daily diet and possibly cause you to gain weight.
• Raise your blood pressure and levels of triglyceride fats in your blood.
• Contribute to or worsen heart failure in some people, such as some people who have cardiomyopathy.
• Raise your risk of other diseases such as cancer.

If you do not drink, you should not start. You should not drink if you are pregnant, are under the age of 21, taking certain medicines, or if you have certain medical conditions, including heart failure.

What is familial hypercholesterolemia?

Familial hypercholesterolemia is a genetic condition where your liver can’t process cholesterol properly and this leads to a severely elevated low-density lipoprotein (LDL) “bad” cholesterol in your blood that lead to atherosclerotic plaque deposition in the coronary arteries and proximal aorta at an early age, leading to an increased risk for cardiovascular disease. The gene that causes familial hypercholesterolemia is inherited. Familial hypercholesterolemia is present from birth and because a defect (mutation) in a gene changes how your body processes cholesterol. In familial hypercholesterolemia patients, genetic mutations make the liver incapable of metabolizing or removing excess low-density lipoprotein (LDL) “bad” cholesterol, from your blood. The result is very high low-density lipoprotein (LDL) “bad” cholesterol levels which can lead to atherosclerotic plaques deposition in the coronary arteries and proximal aorta occurring at an early age, leading over time to an increased risk for cardiovascular disease and even narrowing of your heart valves, which by definition includes coronary artery disease (coronary heart disease) manifesting as angina and myocardial infarction [heart attack] and stroke ²³.

Familial hypercholesterolemia is the most common inherited cardiovascular disease:

• About 1 in 200-250 people worldwide have familial hypercholesterolemia ²⁴
• In the United States alone, an estimated 1.3 million people live with familial hypercholesterolemia. Yet only 10% of them are diagnosed. Nearly 2 million people in the US might have familial hypercholesterolemia and not even know it. Perhaps they won’t know it until they have a heart attack.
• Over 90% of people with familial hypercholesterolemia have not been properly diagnosed ²⁴
• Familial hypercholesterolemia runs in families. If one parent has familial hypercholesterolemia, each child has a 50% chance of having familial hypercholesterolemia ²⁵
• If left untreated, men have a 50% rise of having a heart attack by age 50. Untreated women have a 30% risk by age 60 ²⁶
• 1 in 160,000 to 1 in 1 million people have homozygous familial hypercholesterolemia ²⁴. Homozygous familial hypercholesterolemia is more likely to occur in countries where the prevalence of heterozygous familial hypercholesterolemia is very high, especially those where consanguinity (marriage between relatives) is common.
• Familial hypercholesterolemia is even more common in certain populations such as French Canadians, Ashkenazi Jews, Lebanese, and South African Afrikaners. Lebanese Christians (1 in every 85 people), Afrikaners in South Africa (1/72 – 1/100), French Canadians (1 in every 270 people), and Ashkenazi Jews originating from Lithuania (1 in every 67 people) known as a founder affect.

Familial hypercholesterolemia gene mutations are passed from parent to child. To have the condition, children need to inherit an altered copy of the gene from one parent.

Familial hypercholesterolemia is not easy to diagnose. Your doctor may suspect familial hypercholesterolemia if:

• a routine blood test shows you have a high cholesterol level
• you have a heart attack or stroke, especially if it happens at a young age
• other members of your family have a history of premature heart disease or stroke
• other members of your family have been diagnosed with familial hypercholesterolemia.

You may also notice physical changes to your body that suggest you have familial hypercholesterolemia. Your doctor will perform a simple physical exam to check for these symptoms. These can include:

• Tendon xanthomata: This is swelling on your knuckles, knees or your Achilles tendon at the back of your ankle. It’s caused by a build-up of excess cholesterol.
• Xanthelasmas: These are small lumps of cholesterol that build up in the skin around the bottom of your eye and on your eyelid. They are usually pale yellow in color.
• Corneal arcus: This is a pale white ring around your iris, the colored part of your eye. If you’re under 50 years old and have corneal arcus, it’s possible that you have familial hypercholesterolemia.

There are two forms of familial hypercholesterolemia:

Heterozygous familial hypercholesterolemia

• If you have inherited this genetic mutation from one parent, then you will have Heterozygous familial hypercholesterolemia. Heterozygous familial hypercholesterolemia occurs in 1 in 250 people worldwide. Most people with familial hypercholesterolemia have one affected gene and one normal gene (heterozygous familial hypercholesterolemia). An estimated 70%-95% of familial hypercholesterolemia results from a heterozygous pathogenic variant in one of three genes (APOB, LDLR, PCSK9).
• Until recently, it was believed that 1/500 people (630,000 people in the U.S.) had heterozygous familial hypercholesterolemia while about 1/1,000,000 people (300 people in the U.S.) had homozygous familial hypercholesterolemia. New studies suggest that heterozygous familial hypercholesterolemia and homozygous familial hypercholesterolemia are more common. It is now believed that 1/250 people (or 1.3 million people in the U.S. alone) have heterozygous familial hypercholesterolemia and 1/160,000 (or 2,000 people in the U.S.) have homozygous familial hypercholesterolemia. Even though homozygous familial hypercholesterolemia is still rare, it is a lot more common than we once thought. If you think that you or someone you know may have familial hypercholesterolemia, talk to your doctor.
• Heterozygous familial hypercholesterolemia: LDL-C > 160 mg/dL (4 mmol/L) for children and >190 mg/dL (5 mmol/L) for adults and with one first degree relative similarly affected or with positive genetic testing for an LDL-C raising gene defect (LDL receptor [LDLR], apolipoprotein-B [apo B] or proprotein convertase subtilisin/kexin type 9 [PCSK9])

Homozygous familial hypercholesterolemia

• If you inherit familial hypercholesterolemia from both parents, it is much more severe in its consequences. This form of familial hypercholesterolemia is called Homozygous familial hypercholesterolemia. Homozygous familial hypercholesterolemia is very rare, occurring in about 1 in 160,000 to one million people worldwide. Most individuals with homozygous familial hypercholesterolemia experience severe coronary artery disease by their mid-20s and the rate of either death or coronary bypass surgery by the teenage years is high. Severe aortic stenosis is also common.
• Homozygous familial hypercholesterolemia: LDL-C > 400 mg/dL (10 mmol/L) and one or both parents:
  1. having clinically diagnosed familial hypercholesterolemia,
  2. positive genetic testing for an LDL-C raising (LDL receptor, apo B or PCSK9) gene defect, or
  3. autosomal recessive familial hypercholesterolemia If LDL-C > 560 mg/dL (14 mmol/L) or LDL-C > 400 mg/dL (10 mmol/L) with
  4. aortic valve disease or
  5. xanthomata at less than 20 years of age, homozygous familial hypercholesterolemia highly likely.

Doctors measure blood cholesterol in milligrams per deciliter (mg/dL).

Adults with familial hypercholesterolemia may have untreated low-density lipoprotein (LDL-C) “bad” cholesterol levels that range from 190mg/dL to 400mg/dL or even higher. Children with familial hypercholesterolemia generally have low-density lipoprotein (LDL-C) “bad” cholesterol levels above 160mg/dL, but in pre-teens, levels can be even lower.

• High-density lipoprotein (HDL-C) “good” cholesterol levels are desirable and somewhat protect against coronary heart disease.
• High LDL-C “bad” cholesterol levels are undesirable and contribute to coronary heart disease risk.

All individuals with familial hypercholesterolemia should be considered “high risk” (i.e., increased ~20-fold) for coronary artery disease (coronary heart disease). Recent data suggest that individuals with an LDL “bad” cholesterol >190 mg/dL (>4.9 mmol/L) and a pathogenic variant in one of the genes (APOB, LDLR, PCSK9 & unknown genes) have a 22-fold increased risk for coronary heart disease, while those without a pathogenic variant have a sixfold increased risk for coronary artery disease over the general population ²⁷.

Figure 2. Familial hypercholesterolemia inheritance pattern

Footnote: HeFH = Heterozygous familial hypercholesterolemia; HoFH = Homozygous familial hypercholesterolemia

Figure 3. LDL cholesterol burden in individuals with or without familial hypercholesterolemia as a function of the age of initiation of Statin therapy

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

Therefore, if you have familial hypercholesterolemia, your LDL-cholesterol levels will be very high, leading to narrowing or blockage of blood vessels (atherosclerosis). This process starts prior to birth and can ultimately result in heart disease, heart attack, or stroke. Because people with familial hypercholesterolemia have excessive cholesterol levels since before their birth, their risk of heart disease is 20 times greater than that of the general population. If a child has Homozygous familial hypercholesterolemia (inherited the familial hypercholesterolemia gene from both parents), she is exposed to an even higher risk, because her LDL-cholesterol levels are extraordinarily elevated and lead to progressive heart disease very early in life (often in the teens). Other cardiovascular disease risk factors include smoking, over-weight, high blood pressure, and a sedentary life. If you have familial hypercholesterolemia, eliminate smoking, control your weight and blood pressure, and lead a physically active lifestyle. All these are important factors, together with medical therapy and a healthful diet, in lowering your risk of an early heart attack.

Familial hypercholesterolemia is a lifelong condition. It’s not a temporary condition, like the common cold; it’s in your genes. When you have familial hypercholesterolemia, 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. Familial hypercholesterolemia also means controlling weight, not smoking, eating a balanced diet low in saturated fat, and exercising. What is more, Familial hypercholesterolemia means bringing your family together to understand the impact of this disease. Familial hypercholesterolemia means living healthy, as individuals and as a family.

The good news is familial hypercholesterolemia is treatable! If familial hypercholesterolemia is found early, serious problems of the heart and blood vessels may be prevented or dramatically delayed by taking steps to protect yourself. These include:

• Not smoking.
• Exercising regularly.
• Eating a healthy diet low in saturated and trans fats.
• Taking medications.
• Going on LDL-apheresis.

Familial hypercholesterolemia in almost all cases requires aggressive treatment through a combined approach – medication, low-fat diet, exercise, weight control and not smoking. Familial hypercholesterolemia involves heart-healthy meals, regular exercise to get the blood flowing, controlling your weight and eliminating smoking. Because obesity and smoking are risk factors for heart disease and those with familial hypercholesterolemia are already at a 20 times higher risk, it is important to adapt to a healthy lifestyle.

Nearly 100% of people with familial hypercholesterolemia will require cholesterol-lowering medications. For some people with familial hypercholesterolemia, more aggressive measures are needed, including LDL-apheresis (a very simple procedure in which LDL-C cholesterol is removed from the blood on a weekly or biweekly basis.)

The American Academy of Pediatrics recommends that if a family has a pattern of early heart attacks or heart disease defined as before age 55 for men and 65 for women, children in that family should have cholesterol testing after the age of 2 years and before age 10.

It is important to find familial hypercholesterolemia and take action at any age, because when treated, the risk of heart disease can be reduced to levels similar to those of the general population.

Is there a cure for familial hypercholesterolemia?

Familial hypercholesterolemia is not curable. However, it is treatable. Now, more than ever, there are various treatment options for people with Familial hypercholesterolemia. This realistically means that individuals with Familial hypercholesterolemia could lead normal lives, if diagnosed early and treated adequately.

What is the difference between Heterozygous and Homozygous Familial Hypercholesterolemia?

Heterozygous Familial Hypercholesterolemia (Hefamilial hypercholesterolemia) is the most common form of familial hypercholesterolemia (1 in 250 worldwide have it) caused when a child inherits one copy of a “bad gene” from one parent. Homozygous Familial Hypercholesterolemia (Hofamilial hypercholesterolemia) is a very rare, but extremely severe form of familial hypercholesterolemia (roughly 1 in 160,000 have it) caused when a child gets a “bad gene” from both parents. Typically, Heterozygous familial hypercholesterolemia remains invisible for longer and Homozygous familial hypercholesterolemia 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).

How is Familial Hypercholesterolemia different from Hypercholesterolemia or Hyperlipidemia?

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. familial hypercholesterolemia is a life-threatening disorder.

One of the most common scenarios in patients with familial hypercholesterolemia is being told that they have high cholesterol and that they need to change their diet. However, with familial hypercholesterolemia, 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 familial hypercholesterolemia, 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 and removing it.

How is familial hypercholesterolemia diagnosed? Is there a specific blood test for it?

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). Learn more about familial hypercholesterolemia diagnosis in a section below.

I have been diagnosed with Familial hypercholesterolemia but I don’t want to take medication. Can I lower my cholesterol through a low-fat diet?

Familial hypercholesterolemia 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, familial hypercholesterolemia requires aggressive treatment. Consult an familial hypercholesterolemia specialist to find the best therapy regime for you.

Familial hypercholesterolemia cause

Familial hypercholesterolemia is an inherited genetic condition affecting cholesterol metabolism. Familial hypercholesterolemia is caused by mutation in the gene for the LDL receptor, which is involved in LDL recycling. Mutations in other genes can also cause inherited high cholesterol. Those genes include the PCSK9 gene and the gene for Apolipoprotein B.

Familial hypercholesterolemia is an autosomal dominant disorder with essentially complete penetrance. What this means is that if you have inherited the familial hypercholesterolemia 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 familial hypercholesterolemia. If someone else in your family has familial hypercholesterolemia (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 familial hypercholesterolemia gene to your children. However, if someone in your family has familial hypercholesterolemia 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 familial hypercholesterolemia 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 familial hypercholesterolemia. If an adult has an LDL cholesterol level > 190mg/dL there is a stronger suspicion for Familial hypercholesterolemia.

In familial hypercholesterolemia there is a “dose effect” so that homozygous familial hypercholesterolemia (two defective genes – one from each parent) is more severe than heterozygous familial hypercholesterolemia (one defective and one normal gene).

• Heterozygous familial hypercholesterolemia occurs when a child inherits a nonfunctional copy of one of their familial hypercholesterolemia genes from an affected parent and a functional copy from their unaffected parent. Each egg or sperm they produce has a 50% chance of getting the nonfunctional copy (passing down familial hypercholesterolemia) and a 50% chance of getting the functional copy, Therefore, the risk of passing the familial hypercholesterolemia from the affected parent to a child is 50% in each pregnancy. New, spontaneous variants appear to be very rare.
• Most individuals with homozygous familial hypercholesterolemia have inherited one mutated gene from each parent, such that each parent has heterozygous familial hypercholesterolemia. These parents have a 25% risk in each pregnancy to have a child with homozygous familial hypercholesterolemia, a 50% chance of having a child with heterozygous familial hypercholesterolemia and a 25% chance that the child will inherit a normal gene from each parent. The risk is the same for males and females.

If you have Familial hypercholesterolemia, each of your children has a 50% chance of having familial hypercholesterolemia.

• When one parent has heterozygous familial hypercholesterolemia and the other has homozygous familial hypercholesterolemia, there is a 50% chance with each pregnancy to have a child with heterozygous familial hypercholesterolemia and a 50% chance to have a child with homozygous familial hypercholesterolemia.
• When one parent has homozygous familial hypercholesterolemia and the other has two normal genes, all children will have heterozygous familial hypercholesterolemia.
• When both parents have homozygous familial hypercholesterolemia, all children will have homozygous familial hypercholesterolemia.

Figure 4. Familial hypercholesterolemia autosomal dominant inheritance pattern

There are two forms of Familial hypercholesterolemia.

1. Heterozygous (HeFM) – Heterozygous Familial hypercholesterolemia inherited from only 1 parent
2. Homozygous (HoFM) – Homozygous Familial hypercholesterolemia inherited from both parents (patients with Homozygous Familial hypercholesterolemia are at an even higher risk of early heart disease)

If Familial hypercholesterolemia is left untreated, it can lead to heart disease, heart attack, or stroke.

Familial hypercholesterolemia genetics

Parents can give a disorder to their children through their DNA, which is made up of genes. Genes have all the characteristics that a person gets from their parents (such as eye color, hair color, height, etc.), and some may be mutated and not work properly. When a person gets a mutated gene, they can have mild or severe problems depending on the type of mutation.

LDL is generated in the circulation by the delipidation and modification of very low density lipoproteins (VLDL) secreted by the liver. There are three different genes that may be mutated in familial hypercholesterolemia. The most common gene codes for a protein called the LDL receptor (LDLR). LDL receptors in the liver remove LDL-C “bad cholesterol” from the blood. A LDL receptor (LDLR) gene variant is the most common cause of heterozygous familial hypercholesterolemia, accounting for ~90% of pathogenic variants. If a person has a mutated gene for the LDL receptor, the level of LDL-C “bad cholesterol” in his or her blood will increase. Genes that make other proteins, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) and apolipoprotein B (ApoB), may also be mutated and decrease the removal of LDL-C “bad cholesterol” from the blood. If a person has a mutated gene for any of these proteins, the level of cholesterol in her or her blood will increase.

Apolipoprotein B100 (apoB100) is the major structural apoprotein of VLDL and LDL. LDL is cleared from the circulation by hepatic LDL-receptor with apoB100 acting as the ligand for the receptor. A pathogenic variant in the APOB gene is responsible for ~10% of familial hypercholesterolemia cases; this variation is seen most commonly in those of European Caucasian ancestry. Apolipoprotein B-100 is a protein that binds to LDL receptors, which enables uptake of lipoproteins by the liver and reduces the cholesterol level in the blood. Pathogenic variants in the APOB gene lead to faulty uptake and increased cholesterol level. The major pathophysiological abnormality in homozygous familial hypercholesterolemia is decreased LDL clearance although hepatic overproduction of apoB100-containing lipoproteins may further exacerbate the hyperlipidaemia.

PCSK9 gene variants are responsible for only a small percentage of familial hypercholesterolemia cases. The normal PCSK9 gene codes for an enzyme that breaks down the cholesterol receptors after they have done their job. A pathogenic variant in this gene is unlike most variants, which cause dysfunction of the affected gene. The PCSK9 variant increases the gene’s function, leading to too few remaining LDL receptors and thus an increase in the LDL cholesterol level.

People can have one or two of these mutated genes. When a person has one of these mutated genes (either for the LDL receptor, PCSK9, or ApoB), he or she has heterozygous familial hypercholesterolemia. So, the difference between heterozygous familial hypercholesterolemia and homozygous familial hypercholesterolemia is that a person with homozygous familial hypercholesterolemia has two mutated genes. Two mutated genes greatly increase a person’s blood cholesterol level and the risk of a heart attack.

I have been diagnosed with Familial hypercholesterolemia. I want to get my family tested, but they refuse. How do I convince them?

First and foremost it is important to remember that familial hypercholesterolemia runs in families. If you have familial hypercholesterolemia, 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.

I have heard the term “cascade screening” in relation to familial hypercholesterolemia. What is cascade screening?

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 familial hypercholesterolemia. Because familial hypercholesterolemia 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 familial hypercholesterolemia, they need to test the rest of their immediate family members for familial hypercholesterolemia too.

Familial hypercholesterolemia prevention

Familial hypercholesterolemia 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. Scientists like to say that with familial hypercholesterolemia you inherit the condition, but not the heart attack. If left untreated, familial hypercholesterolemia 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.

Homozygous familial hypercholesterolemia

Homozygous familial hypercholesterolemia is a rare but exceedingly aggressive form of familial hypercholesterolemia. If both parents have familial hypercholesterolemia, there is a 25% chance that their child or children will have homozygous familial hypercholesterolemia (along with a 50% chance that their children will have heterozygous familial hypercholesterolemia). However, if a child is diagnosed with homozygous familial hypercholesterolemia, that means both parents have some form of familial hypercholesterolemia.

Homozygous familial hypercholesterolemia leads to aggressive atherosclerosis (narrowing and blocking of blood vessels). This process starts even before birth and progresses rapidly. It can affect the coronary arteries, carotid arteries, aorta, and aortic valve . If left untreated, heart attack or sudden death are likely to occur as early as the teenage years and sometimes even in early childhood.

Homozygous familial hypercholesterolemia is much less common than heterozygous familial hypercholesterolemia, but lives can be saved if it is identified and treated early in childhood. When a person with homozygous familial hypercholesterolemia is not treated with medications, the low-density lipoprotein cholesterol (LDL-C, “bad cholesterol”) level is between 500-1000 mg/dL – over 4 times the normal level.

The prevalence of homozygous familial hypercholesterolemia is markedly increased in certain regions of the world and may be as high as one in thirty thousand in some populations. Populations with a very high prevalence of homozygous familial hypercholesterolemia include Afrikaners in South Africa, French Canadians, Christian Lebanese and Japanese from the Hokuriku district. These regions are characterized by a high prevalence of heterozygous familial hypercholesterolemia (estimated to be one in seventy to a hundred for Afrikaners in South Africa) which results from founder effects that occur when small, isolated populations increase in size rapidly with little outside genetic admixture ²⁸.

It is important to remember that homozygous familial hypercholesterolemia is a serious medical condition and is life-threatening if not treated at a young age, preferably beginning in early childhood. A child or adult with homozygous familial hypercholesterolemia needs life-long medications and other specialized treatments to lower the LDL-C and prevent heart attacks. This requires the expertise of a lipid specialist.

My Child has homozygous familial hypercholesterolemia (HoFH) – what do I need to know?

Many couples learn that they both have heterozygous familial hypercholesterolemia (HeFH) when they have a baby who has homozygous familial hypercholesterolemia (HoFH). When two people with heterozygous familial hypercholesterolemia have a child, they have a 1 in 4 (25%) chance that their child will have a completely normal cholesterol profile, a 2 in 4 (50%) chance that their child will have heterozygous familial hypercholesterolemia, in which case the child will have an LDL level similar to his/her parents, and finally a 1 in 4 (25%) chance that the child will have inherited a gene for familial hypercholesterolemia from each parent, in which case the child will have a cholesterol level far exceeding either parent’s level (see Figure 3 – Familial hypercholesterolemia autosomal dominant inheritance pattern – above). These children are often diagnosed at around the age of 2 when they develop xanthomas (orange cholesterol deposits on the elbows, buttocks, legs, ankles, on the tendons of the fingers and between the fingers). These physical findings prompt a cholesterol profile. In children with homozygous familial hypercholesterolemia, the LDL cholesterol is often over 500 and can be as high as 1000 mg/dL.

• Children with homozygous familial hypercholesterolemia must see a lipodologist for immediate cholesterol lowering therapies

If your child has homozygous familial hypercholesterolemia, he or she will require immediate cholesterol lowering medications. Your child’s response to the medications depends on their particular genetic mutation. Some children will respond quite well to high dose statins combined with exetimibe (Zetia®) and a bile acid sequestrant. Other children will require more heroic measures such as LDL-apheresis. This is a procedure in which LDL cholesterol is physically removed from the blood every week. In the past, liver transplant was often considered in homozygous familial hypercholesterolemia patients, but it is rarely necessary today. Children with homozygous familial hypercholesterolemia require close follow-up with a cholesterol specialist. Children with untreated homozygous familial hypercholesterolemia develop very early atherosclerosis, often experiencing heart attacks in their teens. It is therefore crucial to treat children with homozygous familial hypercholesterolemia early and aggressively. Because the aortic valve (all the blood in the heart passes through this valve on its way to the body) can develop cholesterol plaque in homozygous familial hypercholesterolemia, children with this diagnosis often undergo much more involved heart evaluations than do children with heterozygous familial hypercholesterolemia. This can include heart catheterizations and echocardiograms. The future is bright for children with homozygous familial hypercholesterolemia – there are many new treatments being studied which have the potential to lower their LDL level profoundly.

Women with familial hypercholesterolemia and pregnancy

What will happen to my cholesterol level during pregnancy?

Cholesterol increases significantly during pregnancy by about 25-50%. Women with familial hypercholesterolemia experience the same increase, but since they are starting out at a much higher baseline, they can get extremely high cholesterol during pregnancy.

What if I become pregnant while on a statin?

If you become pregnant, stop your statin medications immediately. Other cholesterol lowering medications, including Niacin and ezetimibe (Zetia©), should also be stopped. Fibrates such as feno-brate and gem-brozil are typically not used in patients with familial hypercholesterolemia. These are primarily triglyceride-lowering medications, but if you are on one of these medications, it too should be stopped. In terms of the risk associated with taking cholesterol lowering medications during pregnancy, there are conflicting reports in the literature. In animal studies, some statins have been found to cause skeletal defects. Ezetimibe, niacin, and fibrates have all been associated with birth defects, too. Since we don’t recommend these agents during pregnancy, the human data comes from women who have unplanned pregnancies. In most cases the cholesterol-lowering medications were stopped in the first trimester, and although most babies were perfectly normal, there have been some rare reports of structural birth defects. Should you inadvertently take a statin or other cholesterol-lowering medication during pregnancy we recommend seeing an obstetrician for an immediate assessment.

Can I continue to take my cholesterol medications during pregnancy?

With the exception of the bile acid sequestrants such as Welchol©, cholesterol-lowering medications should be stopped prior to pregnancy to avoid extremely high cholesterol. The bile acid sequestrants are not absorbed into your blood stream so they pose no risk to you or your baby. The guidelines on when to stop cholesterol-lowering medications vary. The National Lipid Association recommends discontinuation of cholesterol-lowering medications 4 weeks prior to attempting to become pregnant. The National Institute of Clinical Excellence (NICE) guidelines, on the other hand, recommend stopping cholesterol-lowering medications 3 months before attempting to conceive. Both the National Lipid Association and National Institute of Clinical Excellence guidelines caution women not to take cholesterol medications during pregnancy or while nursing. Some women with familial hypercholesterolemia might be off their cholesterol-lowering medications for a prolonged period of time in order to become pregnant. The longer you are off your cholesterol-lowering medications, the greater the possibility that you will have plaque build-up in your heart arteries and potentially accumulate extremely high cholesterol as well.

How can I keep my cholesterol under control during pregnancy?

Women with familial hypercholesterolemia must come off their cholesterol lowering medications (except bile acid sequestrants) during pregnancy – this increases your cholesterol immediately. Then, just like everyone else, between the 18-36th week of pregnancy cholesterol can increase by as much as 50%. Eating a low fat, low cholesterol diet during pregnancy is extremely important, and if you have not been on a bile acid sequestrants such as Welchol© in the past it is important to begin. Welchol© is not absorbed into your blood stream so is safe during pregnancy. Some people notice some gastrointestinal disturbances (gas) with Welchol© but this agent does lower the LDL-Cholesterol by about 15%, so it seems worth the effort. Again, it is important to emphasize the benefits of diet. We encourage you to work with a registered dietitian who has experience in either a lipid, cardiology, or endocrinology clinic.

Each time you have a baby, you have a 50/50 chance of passing on the abnormal gene.

Is my baby likely to inherit familial hypercholesterolemia?

If you have heterozygous familial hypercholesterolemia, then your baby has a 50% chance of having familial hypercholesterolemia (see Figure 3 above). In the same way that you inherited a gene for LDL cholesterol removal from each of your parents, your baby will inherit one gene for LDL cholesterol removal from you and one from your partner. Because you have one normal gene and one abnormal gene, each time you have a baby you have a 50/50 chance of passing on the abnormal gene. If you have homozygous familial hypercholesterolemia or your partner also has heterozygous familial hypercholesterolemia, then the stakes are much higher and it is recommend you see a lipid specialist or genetic counselor. Familial hypercholesterolemia is a genetic disorder characterized by very high LDL-cholesterol. Familial hypercholesterolemia is an autosomal dominant disorder (see Figure 3 above), which means if you inherit a single gene for familial hypercholesterolemia from one of your parents, you will have familial hypercholesterolemia. Other disorders are autosomal recessive disorders in which you must inherit a gene from each parent in order to display the disease. Although scientists still have much more to learn about the genetics of familial hypercholesterolemia, they know that most people with familial hypercholesterolemia have a defect in the gene for the LDL receptor (LDLR). This is a receptor that sits on your liver cells and allows you to remove LDL cholesterol from your blood stream. Having one defective LDL receptor leads to about a doubling of the normal LDL cholesterol level in the blood. There are other less common genetic defects that can lead to similar LDL levels. These include a defect in apolipoprotein B (Apo B), which is the protein on LDL cholesterol that allows the LDL receptor to recognize and remove LDL-Cholesterol from the blood. Still an even rarer defect is a “Gain of Function” mutation in PCSK9 (proprotein convertase subtilisin/kexin type 9). PCSK9 is a protein that is responsible for destroying LDL receptors. If your PCSK9 works too well it will destroy more LDL receptors and you will be left with an elevated LDL cholesterol. There are probably other genetic defects leading to familial hypercholesterolemia that we have not yet discovered for predicting and regulating extremely high cholesterol.

Should I become pregnant?

This is a personal choice and something you need to discuss with your partner and your health care team. It is important to know that if your cholesterol rises dramatically during pregnancy, there are some options. One such option is LDL-apheresis. This is a dialysis-like procedure that physically removes LDL-cholesterol from the blood stream on a weekly or bi-weekly basis. This 3-hour procedure involves removing blood from one arm and passing it through a special column designed to extract the LDL cholesterol, then returning the blood to the other arm. LDL-apheresis has been successfully performed during pregnancy on many young women with very high cholesterol levels. Other women are successfully managed with diet and bile acid sequestrants. Finally, there are many ways to create a family. Some people choose to adopt and others create a family with the help of a gestational surrogate.

Should I Nurse My Baby?

Although everyone must decide what is best for their family, most lipid specialists would advise limiting breast feeding to 6 months, at which point you can resume your cholesterol lowering medications.

If I have trouble getting pregnant should I consider infertility medications?

Many infertility medications increase cholesterol dramatically. If you are contemplating infertility treatments, it is crucial for you to have a cholesterol specialist, also known as a lipidologist. Your lipidologist should work closely with your infertility physician. You should monitor your cholesterol very closely during these treatments and have a plan for limiting the number of cycles you go through.

Men with familial hypercholesterolemia

Why do men tend to experience heart disease a decade earlier than the women in their family?

Although the answer to this is not 100% certain, there are likely several reasons. The first is puberty. As young men go through puberty, their HDL “good cholesterol” (protective cholesterol) tends to fall. This does not happen to young women. A low HDL is an additional risk factor for early heart disease. Thus not only is a young man with familial hypercholesterolemia at risk due to his elevated LDL, compared to the women in his family, he very likely has a lower HDL. Additionally, women (even women with familial hypercholesterolemia) tend to be relatively protected from symptomatic heart disease until menopause – probably due to estrogen. An aside to women reading this: please notice the word symptomatic. Although it is unusual for a woman with familial hypercholesterolemia to have a heart attack before menopause, your elevated LDL cholesterol means you are still putting cholesterol into your artery wall. Women have smaller heart arteries than men, and it doesn’t take long after going through menopause to block those arteries – so women need to be treated early, too. In the past, but not currently, more men than women smoked. Smoking is poison for everyone, but for people with familial hypercholesterolemia, smoking is doubly poisonous. Smoking can lower the HDL and leads to chemical modifications (oxidation) of LDL. Oxidized LDL is more dangerous than non-oxidized LDL. It is therefore possible that in the past, smoking set men with familial hypercholesterolemia up for earlier heart disease than their non-smoking female relatives. The bottom line is that if you smoke you should quit!

Are men less likely to be treated for their elevated LDL than women?

Once a man develops heart disease, there is no evidence that men are less likely to be aggressively treated for their cholesterol. In fact, in the past there was even evidence that women were less aggressively treated for their heart disease than were men. Familial hypercholesterolemia is treatable if accurately diagnosed. The fact is, the only way you will know if you have high cholesterol is if you get tested. The current national recommendation is that all Americans undergo cholesterol testing between ages 9-11. If you have not yet been tested, especially if you have a strong family history of heart disease, it’s imprtant you get tested. Knowledge is power. If you are found to have familial hypercholesterolemia, get treated, and work to reduce all other risk factors. If you are overweight, try hard to get to a healthier weight. If you smoke, please quit. Both losing weight and quitting smoking can be difficult—but the sooner you do it, the healthier you will be. If you have high blood pressure, then exercise, salt restriction, weight loss, and medications when necessary are all important. Finally, if you have diabetes, work on weight loss through diet and exercise, and, if necessary, take prescribed medications.

I have been diagnosed with familial hypercholesterolemia, are there any other lab studies I should have?

Anyone who has familial hypercholesterolemia should also have a measurement for Lp(a), which is an inherited lipid found in the blood. Lp(a) is really the combination of an LDL particle and a clotting particle. People living with familial hypercholesterolemia who also have a high Lp(a) level are at even higher risk for early heart disease than are people who simply have a high LDL level. You can imagine that if Lp(a) contains an LDL particle it can block up the arteries; adding to that a clotting particle makes the risk even higher. Most heart attacks are caused when a cholesterol plaque inside a heart artery ruptures and subsequently a blood clot forms on top of the ruptured plaque. The combination of a ruptured plaque and a blood clot might completely prevent blood from flowing in the heart artery. If the blockage is not opened quickly, a heart attack will ensue. Lp(a) can be measured in two different ways. If your test is measured in mg/dL then a normal level is less than 30 mg/dL. Some labs measure in nmols/L, in which case the goal is a level < 74 nmol/L.

Can anything be done to lower Lp(a)?

Unfortunately, Lp(a) is quite difficult to treat. If your level is very elevated, it is unlikely to normalize with medication. Although there have not been any formal studies performed to assess whether lowering Lp(a) reduces cardiac risk, it makes sense to try to lower this lipoprotein. Of the currently available cholesterol lowering medications, only niacin significantly lowers Lp(a). Estrogen does have some Lp(a) lowering properties, but estrogen is not used in men. Lp(a) can also be lowered by LDL-apheresis. Although LDL-apheresis, a dialysis like procedure, is typically used to lower LDL cholesterol, sometimes the procedure is approved by insurance companies specifically to lower Lp(a). Some of the cholesterol lowering medications currently in development appear to significantly lower Lp(a).

How much can I lower my risk if I take cholesterol lowering medications?

Again, it is difficult to give you a precise percentage. In any given person, the overall degree of risk reduction will likely depend on the age at which cholesterol-lowering medications are started, and the number of other risk factors a person has for the development of heart disease, such as diabetes, cigarette smoking, high blood pressure, and high Lp(a). Some general statements can be made. In studies (many 5 or more years in length) performed in people with very high cholesterol, including many with familial hypercholesterolemia, statins have been shown to reduce the risk of a future heart attack by over 30%. In observational studies of familial hypercholesterolemia patients performed in Europe, it appears that long-term statin therapy is capable of lowering lifetime risk to that of the general population.

Note that studies show statins reduce chances of a future heart attack by 30%.

I know statins can lower my risk for a heart attack, but every time I take a statin my muscles and joints ache what can I do?

Thankfully, this is not a common problem, but if it is your situation it can be miserable.

First, it is important to make sure that a person does not have an underlying condition known to increase the risk for the development of statin myopathy, such as muscle aches when taking a statin. People with an under active thyroid are significantly more likely to experience statin myopathy than people with a normally functioning thyroid gland, so make sure your health care provider checks this. If you are found to have a hypothyroid problem, once this has been corrected, you may well be able to tolerate statins. Certain medications can lead to an increase blood level of statins. These include, among others, drugs used to treat HIV, certain antibiotics, and another type of cholesterol lowering medication known as gemfibrozil (Lopid®). If this is your situation, your health care provider should make a change. These medications really should not be used with statins. People with underlying liver or kidney disease and people who are frail may be more likely to develop statin myopathy. These people are typically treated with lower doses of statins. Some studies have found Asians with heart attacks in the family are more likely to develop statin myopathy and as such, are also often treated with lower doses of statins.

Finally, as with so many medical conditions, recently genetic factors have been found to play a role in determining who develops statin myopathy. When it comes to statins, they are not all created equal. One large study—The PRIMO Study—found that of the statins simvastatin (Zocor®) was most likely to cause muscle aches and fluvastatin (Lescol®) was least likely. Unfortunately, Lescol® is the least potent statin. That said, other more potent statins including atrovastatin (Lipitor®) and rosuvastatin (Crestor®) are less likely than simvastatin to cause aches. In general, an approach to statin intolerance is to try different statins, one at a time. If a statin causes pain, speak to your doctor about stopping that particular statin medication. Once you feel better you can try a different statin, or a lower dose of the same statin. In some cases, every other day, or even every 3rd or 4th day dosing is effective. If a person with familial hypercholesterolemia can only tolerate low dose, or intermittent statin dosing, he/she will likely need to tighten his/her diet, and almost certainly will require additional medications. Other choices which may be additive to statins include bile acid sequestrants (Welchol®, Questran®, Colestid®), cholesterol absorption inhibitors (Zetia®), or niacin (Niaspan®). Other options for further LDL reduction include LDL apheresis and participation in clinical trials.

My doctor has asked me to begin LDL-apheresis. Is this likely to lower my risk of a heart attack?

LDL-apheresis is a dialysis-like procedure, performed every week in people with homozygous familial hypercholesterolemia and every other week in persons with heterozygous familial hypercholesterolemia. A person has homozygous familial hypercholesterolemia if he/she has inherited 2 genes for familial hypercholesterolemia, one from each parent, and a person with heterozygous familial hypercholesterolemia has inherited one gene for familial hypercholesterolemia. Apheresis literally means “to take out.” In the case of LDL-apheresis, LDL cholesterol is physically removed from the blood. Blood is removed from one arm, specially treated to remove the LDL cholesterol, then returned into the other arm. The procedure, which typically takes between 2-4 hours, can lower LDL by as much as 80% and also dramatically lowers Lp(a). Unfortunately, over a short period of time a person’s level rebounds – this is why it needs to repeated frequently. Although for obvious reasons (scientists will always know who is getting the procedure and who is not), it is impossible to conduct placebo-controlled trials to assess the effectiveness of LDL-apheresis. Several studies have compared the outcomes of patients receiving medications along with LDL-apheresis to those receiving medications without LDL-apheresis. It appears that long term use of LDL-apheresis may reduce cardiac risk anywhere from 44 – 72% above and beyond the use of medications alone. Finally, if your doctor has recommended LDL-apheresis it is likely that your LDL [or Lp(a)] remains very high despite maximally tolerated cholesterol lowering medications.

I have familial hypercholesterolemia. How likely is it that my child will also have familial hypercholesterolemia?

If you have heterozygous familial hypercholesterolemia, as long as your partner doesn’t also have heterozygous familial hypercholesterolemia, your child has a 50 % chance of having familial hypercholesterolemia. In exactly the same way that you inherited a gene for LDL cholesterol removal from each of your parents, your child has inherited one gene for LDL cholesterol removal from you and one from your partner, which reduces the risk of heart attacks in family.

Familial hypercholesterolemia life expectancy

The risk of complications of hypercholesterolaemia can be significantly reduced by therapies that lower serum cholesterol levels. Studies show statins reduce chances of a future heart attack by 30%.

Lowering cholesterol by 1% reduces the risk of coronary artery disease by 2%.

The treatment of other modifiable risk factors such as smoking, high blood pressure and diabetes will further decreases the risk of complications of hypercholesterolaemia.

Maintaining an appropriate weight, eating a low fat diet and exercising can also have a significant impact on cholesterol levels and improve long-term outcomes.

Familial hypercholesterolemia symptoms

Depending on the severity or form of familial hypercholesterolemia you have (Heterozygous vs. Homozygous), symptoms can start appearing in childhood or they might not appear until much later in life. Because familial hypercholesterolemia is caused by a defective gene, it is present in the body from birth. However, this is not necessarily obvious. In fact, this is doctors like to call it the “invisible” disease. Many people with familial hypercholesterolemia 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 Familial hypercholesterolemia 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 Familial hypercholesterolemia. Here’s a formula to help you remember the two main signs of Familial hypercholesterolemia:

Xanthomas are collections of cholesterol under the skin or tendons. They are yellow bumps that can be small and hard to see. These are often found in the folds of skin and buttocks in children. Also, there can be xanthomas on the tendons at the ankles and hands. Children often have xanthomas without any signs of heart problems in early childhood.

Tendon xanthoma occurs in three fourth of middle-aged patients and is largely discovered in the Achilles tendon. It may also occur in the extensor area of the dorsum of the hand, heel or the knee. Since xanthomas (patches of yellowish cholesterol buildup) may be manifested only to the extent of thickening of a tendon, familial hypercholesterolemia patients may be overlooked by clinicians without due concern. Xanthelasma or early arcus cornealis may also be observed.

Xanthomas may worsen with age as a result of extremely high cholesterol levels. Xanthomas can occur around the eyelids and within the tendons of the elbows, hands, knees, and feet.

From figure 5 below:

• (A) Lateral borders of thickened Achilles’ tendons are shown with arrows.
• (B) Tendinous xanthomas can also occur in the extensor tendons of the hands (shown), feet, elbows and knees.
• (C) Xanthelasmas are cholesterol deposits in the eyelids.
• (D) Arcus cornealis (corneal arcus) is a greyish-white ring of cholesterol infiltration around the corneal rim (arrow). A corneal arcus at a young age can mean that the child has homozygous familial hypercholesterolemia.

Figure 5. Familial hypercholesterolemia – Physical signs of heterozygous familial hypercholesterolemia, as a result of cholesterol deposition within macrophages in specific sites. 

Heart and blood vessel disease

A heart murmur may be the result of narrowing of the opening of the aortic valve by cholesterol buildup. A child with aortic valve disease and high LDL-C may have homozygous familial hypercholesterolemia. Cholesterol plaque builds up in the coronary arteries supplying blood to the heart, the carotids taking blood to the brain, the arteries to the kidneys, and other arteries. Blockage of the flow of blood to the heart may cause chest pain, shortness of breath, dizziness, or irregular heartbeats. Special tests of the heart such as a EKG (electrocardiogram), echocardiogram, CT angiogram or cardiac catheterization are recommended to check the aortic valve and coronary arteries at diagnosis and at least every 5 years.

Familial hypercholesterolemia diagnosis

Homozygous familial hypercholesterolemia can be diagnosed through genetic testing (DNA testing) or a clinical diagnosis utilizing one of three well-accepted sets of criteria — Simon Broome (UK), Dutch Lipid Clinic Network (Netherlands), or MEDPED (US).

DNA testing confirms the diagnosis and is considered the “gold standard”, but is not always necessary or feasible. DNA testing should definitely be considered when it’s not clear whether an individual is affected or not, and is very helpful for testing family members. Recent studies also suggest that individual risks for coronary artery disease vary among the affected gene and type of DNA variation (substitution vs. partial deletion of a gene, etc.).

Unfortunately, genetic testing is not commonly used in some countries including the U.S. Also, not everyone with homozygous familial hypercholesterolemia has the same signs and symptoms. If you have any of the above signs or symptoms, please talk to your doctor.

Once an individual is diagnosed with familial hypercholesterolemia (either with or without the use of DNA testing) a process called “cascade screening”, “cascade testing” or “family screening” (testing of close relatives, in a step-wise fashion) is recommended to identify those with familial hypercholesterolemia before symptoms appear, so that early and intensive treatment can be initiated and disease and death prevented. If a pathogenic variant is identified, risk in the patient’s first degree relatives (parent, sibling, child) and when appropriate, more distant relatives, can be assessed via DNA testing by tracing the altered gene through the family. If DNA testing is not performed, another version of cascade screening can be implemented using cholesterol testing. Cascade screening by either means has been shown to be effective in finding patients with familial hypercholesterolemia who were not being appropriately treated. A genetic counselor can help a family through this process.

Cascade screening has been shown in numerous studies to be cost-effective and has been recommended by the National Institute for Health and Clinical Excellence (NICE) in the UK. The Office of Public Health Genomics at the Centers for Disease Control and Prevention considers cascade screening of relatives of those with FH a “Tier 1 application” which means that there is good evidence that implementation will prevent disease and save lives.

Homozygous familial hypercholesterolemia is easily identified in infants and young children by the presence of planar xanthomas, corneal arcus, and exceedingly high total and LDL-C; LDL-C is usually greater than 400 mg/dL. The parents are “obligate heterozygotes” who are considered to have heterozygous familial hypercholesterolemia until proven otherwise.

Clinical Testing and Workup

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with FH, the following evaluations are recommended in adults and children:

• Pre-treatment lipid values
• Lipoprotein(a) levels when possible as lipoprotein(a) is an additional risk factor for coronary heart disease
• Exclusion of concurrent illnesses (kidney disease, acute myocardial infarction, infection) that can affect lipid values
• Lipid panel including total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides
• Consultation with a lipid specialist or clinician with expertise in familial hypercholesterolemia
• Medical genetics or a genetic counseling consultation

In children, noninvasive imaging modalities (e.g., measurement of carotid intima-media thickness) are recommended in some guidelines to help inform treatment decisions.

Level of LDL-C

This is extremely important. The higher the LDL-C, the more likely it is that a person has homozygous familial hypercholesterolemia (LDL-C > 500 mg/dL).

Family History

This is key. If both parents have very high LDL-C (>190 mg/dL) and/or history of heart disease before age 55-65, this may suggest that they both have familial hypercholesterolemia and can each pass a mutated gene to their children. When each parent has heterozygous familial hypercholesterolaemia, by chance, 1 of 4 children will have a normal cholesterol level, 2 of 4 children will have heterozygous familial hypercholesterolaemia and 1 of 4 children will have homozygous familial hypercholesterolemia. Prenatal DNA testing may be available if the mutations are identified in the parents. Download our family tree to track your family history.

Response to cholesterol-lowering medications

If a person is living a healthy lifestyle and taking cholesterol-lowering medications like statins, and/or cholesterol absorption inhibitors, and/or bile acid sequestrates and still has high cholesterol level (> 300 mg/dL), they may have homozygous familial hypercholesterolemia.

Diagnostic Criteria for Familial Hypercholesterolemia

There are currently three accepted resources for familial hypercholesterolemia diagnosis:

1. The Simon Broome criteria,
2. The MEDPED Criteria, and
3. The Familial Hypercholesterolemia Dutch Lipid Clinic Criteria.

Table 5. Simon Broome Diagnostic Criteria For Familial Hypercholesterolemia

Point	Criteria
1	Total cholesterol levels > 290mg/dL (7.5 mmol/L) or LDL-C > 190 mg/dL (4.9 mmol/L) in adults. Total cholesterol levels > 260 mg/dL (6.7 mmol/L) or LDL-C > 155 mg/dL (4.0 mmol/L)
2	Tendon xanthomas in the patient or tendon xanthomas in a first or second degree relative.
3	DNA-based evidence of an LDL-receptor mutation, familial defective apo B-100, or a PCSK9 mutation.
4	Family history of myocardial infarction before age 50 years in a second degree relative or before age 60 years in a first degree relative.
5	Family history of elevated total cholesterol > 290 mg/dL (7.5 mmol/L) in an adult first or second-degree relative. Family history of elevated totacl cholesterol > 260 mg/dL (6.7 mmol/L) in a child, brother, or sister 16 years or younger.

DIAGNOSIS

Definite familial hypercholesterolemia = 1+2 or 3 Possible familial hypercholesterolemia = 1+4 or 5

[Source ²⁹ ]

Table 6. Dutch Lipid Clinic Network Diagnostic Criteria For Familial Hypercholesterolemia

Note: *Premature = < 55 years in men; < 60 years in women

LDL-C = low density lipoprotein cholesterol; FH, familial hypercholesterolemia.
LDLR = low density lipoprotein receptor
Apo B = apolipoprotein B
PCSK9 = Proprotein convertase subtilisin/kexin type 9

[Source ³⁰  ]

Table 7. MEDPED Diagnostic Criteria For Familial Hypercholesterolemia

FH = familial hypercholesterolemia

Note: *The total cholesterol cutpoints for familial hypercholesterolemia is dependent upon the confirmed cases of familial hypercholesterolemia in the family. If familial hypercholesterolemia is not diagnosed in the family, then the cutpoint for diagnosis is as per “general population.”

[Source ³¹ ]

Familial hypercholesterolemia treatment

The treatments for Hofamilial hypercholesterolemia can be quite complex and anyone with this disease is advised to be under the care of a lipid specialist. Familial hypercholesterolemia management can include a combination approach – statins, cholesterol absorption inhibitors, and bile acid sequestrants. Often, Homozygous familial hypercholesterolemia patients will require even more intensive therapy to bring their LDL cholesterol (“bad cholesterol”) levels down.

Lifestyle and dietary changes

Lifestyle changes, such as exercising and eating a healthy low-fat diet, are the first line of defense against high cholesterol. Specific recommendations include:

• Reducing the amount of saturated fat in your diet to less than 6-10 percent of your daily calories. The most harmful types of fat are saturated fat and trans fat, which are found in foods from animal sources, such as meat and dairy products, as well as packed snacks, fast food, and baked goods (biscuits, cakes, etc). As a rule of thumb, avoid too much processed foods. Try to eat fresh by cooking homemade healthy meals from scratch. LESS! whole milk, butter, egg yolks, snacks (chips), deep-fried fast food (fries, deep-fried chicken), processed meat (sausage, pâté), liver, organ meats, frozen foods (waffles, pies, pizzas, breaded fish). BEWARE OF HIDDEN TRANS FATS (“partially hydrogenated…”)
• Consuming 25 to 35 grams of soluble fiber a day.  As a rule of thumb, think plants (not animals): fruits, vegetables, grains, and beans. MORE! barley, oatmeal, sunflower seeds, almonds, soy, tofu, edamame, chickpeas, black beans, kidney beans, lentils, Brussels sprouts, carrots, apples, bananas, pears, oranges, grapefruit, prunes, blackberries.
• Add plant sterols and plant stanols to your diet. They actively reduce LDL-cholesterol and can be found in certain food supplements and substitutes (look for margarine or cheese that states “With added plant sterols/stanols”). An enhanced daily consumption of 2000 to 2500 mg of plant sterols/stanols per day may lower LDL-cholesterol by up to 15%!
• Increasing physical activity.
• Maintaining a healthy body weight.
• Not smoking. And quit smoking if you smoke.

With familial hypercholesterolemia, your doctor likely will also recommend that you take medication to help lower your LDL “bad” cholesterol levels. The specific medication or medications depend on various factors, including your risk factors, your age, your current health and possible side effects.

Medications

Common medication choices include:

• Statins. Statins — among the most commonly prescribed medications for lowering cholesterol — block a substance your liver needs to make cholesterol. This causes your liver to remove cholesterol from your blood. Statins may also help your body reabsorb cholesterol from built-up deposits on your artery walls, potentially reversing coronary artery disease. Choices include atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Altoprev,), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor). Not everyone can take statins especially women who are trying to conceive, pregnant, or nursing. Talk to you doctor about other therapy options.
• Bile-acid-binding resins. Your liver uses cholesterol to make bile acids, a substance needed for digestion. The medications cholestyramine (Prevalite), colesevelam (Welchol) and colestipol (Colestid) lower cholesterol indirectly by binding to bile acids. This prompts your liver to use excess cholesterol to make more bile acids, which reduces the level of cholesterol in your blood.
• Cholesterol absorption inhibitors. Your small intestine absorbs the cholesterol from your diet and releases it into your bloodstream. The drug ezetimibe (Zetia) helps reduce blood cholesterol by limiting the absorption of dietary cholesterol. Zetia can be used in combination with any of the statin drugs.
• Combination cholesterol absorption inhibitor and statin. The combination drug ezetimibe-simvastatin (Vytorin) decreases both absorption of dietary cholesterol in your small intestine and production of cholesterol in your liver. It’s unknown whether Vytorin is more effective in reducing heart disease risk than taking simvastatin by itself.
• Injectable medications. A new class of drugs can help the liver absorb more LDL cholesterol — which lowers the amount of cholesterol circulating in your blood. The Food and Drug Administration recently approved alirocumab (Praluent) and evolocumab (Repatha) for people who have a genetic condition that causes very high levels of LDL. These drugs may also be used for people who have had heart attacks or strokes and need additional lowering of their LDL levels. These injectable drugs are administered at home one or two times a month.
• PCSK9 Inhibitor – antibodies that bind the PCSK9 enzyme. Normally, LDL is recycled in the liver by binding to receptors that move it through the cell. The PCSK9 enzyme weakens this process by connecting to and disabling the receptors, therefore increasing LDL in the liver. When the PCSK9 inhibitor is introduced, it binds to the enzyme stopping it from attaching to the receptors and getting in the way of the recycling process.
• Lomitapide (marketed as Juxtapid in the U.S.) – Lomitapide works by partially blocking a protein responsible for fatty substances forming in the gut and liver. By blocking this protein, lomitapide helps reduce how much fat is absorbed and lowers the level of LDL cholesterol in your blood. If you take lomitapide you should consume less than 20 per cent of your calories from fat as this has been shown to help reduce unwanted gastrointestinal (stomach related) side effects. This is lower than normally recommended for a heart healthy diet, but advice and support is available to help you make this change. Lomitapide is approved as an adjunct to a low-fat diet and other lipid lowering treatments. It is an oral capsule.
• Mipomersen (marketed as Kynamro in the U.S.) -Mipomersen is an antisense drug that leads to the decline of apoB RNA in the liver (apoB is necessary for the formation of LDL particles). It is administered as a weekly injection.

Medications for high triglycerides

If you also have high triglycerides, your doctor may prescribe:

• Fibrates. The medications fenofibrate (Tricor) and gemfibrozil (Lopid) decrease triglycerides by reducing your liver’s production of very-low-density lipoprotein (VLDL) cholesterol and by speeding up the removal of triglycerides from your blood. VLDL cholesterol contains mostly triglycerides.
• Niacin. Niacin (Niaspan) decreases triglycerides by limiting your liver’s ability to produce LDL and VLDL cholesterol. But niacin doesn’t usually provide any additional benefit than using statins alone. Niacin has also been linked to liver damage and stroke, so most doctors now recommend it only for people who can’t take statins.
• Omega-3 fatty acid supplements. Omega-3 fatty acid supplements can help lower your triglycerides. They are available by prescription or over-the-counter. If you choose to take over-the-counter supplements, get your doctor’s OK first. Omega-3 fatty acid supplements could affect other medications you’re taking. Fish is a great source of healthy omega-3 fats. The American Heart Association recommends eating 3.5 ounces of fish (especially oily, omega-3 rich fish) at least twice a week. Note: Tilefish, shark, swordfish, and king mackerel have high mercury content and should be eaten only occasionally.

Tolerance varies

Tolerance of medications varies from person to person. The reported side effects are muscle pains, stomach pain, constipation, nausea and diarrhea. If you decide to take cholesterol-lowering medication, your doctor may recommend liver function tests to monitor the medication’s effect on your liver.

LDL Apheresis

LDL apheresis (also called lipoprotein apheresis) can be performed on homozygous familial hypercholesterolemia patients as well as more serious heterozygous familial hypercholesterolemia patients. This procedure involves blood cleansing every other week (or sometimes weekly) with a special machine that looks like a dialysis machine. The procedure takes between one and a half to three hours, and typically drops LDL levels by 70%. Unfortunately, LDL rises over time and, for this reason, repeat treatments are necessary. About 60 lipoprotein apheresis centers exist in the US.

Children or Adults with Homozygous familial hypercholesterolemia

Early initiation of therapy and monitoring using CT coronary angiography and other imaging are recommended; these patients often require additional treatment strategies, as pharmacological treatment and lifestyle changes may not be sufficient. Statins are usually started as soon as the diagnosis is made (though may not be effective as explained above). Two new drugs (lomitapide and mipomersen) have now been FDA-approved for the treatment of adults with homozygous familial hypercholesterolemia and should be considered for these patients, especially if LDL-C level cannot be controlled using other drugs. A PCSK9 inhibitor (evolocumab) was also approved for homozygous familial hypercholesterolemia. Additional options include LDL apheresis or liver transplantation.

LDL Apheresis

Using a process similar to kidney dialysis, blood is withdrawn from a vein via a catheter and processed to remove LDL particles. Normal blood products are returned via another catheter. LDL-C levels will decrease approximately 50% but will rise between apheresis sessions, so they are necessary approximately weekly or every other week. The procedure is effective and well tolerated though time-consuming and only available in 50-60 sites in the US.

Liver transplantation

Liver transplant is extraordinarily rare and may become even less common with the new medications available. As the donor liver will have normal LDL receptors, the LDL cholesterol quickly normalizes after the procedure, but the risks of any organ transplant are significant and include complications from major surgery and the effects of lifelong suppression of the immune system. Donor organs are often not available. Patients with familial pathogenic APOB or PCSK9 gene variants have normal LDL receptors, so liver transplantation is not an option for them.

Various imaging modalities such as echocardiograms, CT angiograms and cardiac catheterization may be recommended to monitor individuals with homozygous familial hypercholesterolemia.

Children and cholesterol treatment

Diet and exercise are the best initial treatment for children age 2 and older who have high cholesterol, or who are obese. Children age 10 and older might be prescribed cholesterol-lowering drugs, such as statins, if they have extremely high cholesterol levels.

Current recommendations from both the National Lipid Association and American Academy of Pediatrics recommend beginning cholesterol lowering medications at around the age of 8 for children with familial hypercholesterolemia. Statins are the drugs of first choice. By the age of 8, a child should be able to swallow pills. At least one drug company has experimented with a chewable flavored statin, but this is not yet on the market.

Six statins are FDA-approved for children 10 years of age and older (age 8 years and older for pravastatin):

• rosuvastatin (Crestor®),
• atorvastatin (Lipitor®),
• simvastatin (Zocor®),
• pravastatin (Pravachol®),
• lovastatin (Mevacor®),
• fluvastatin (Lescol®)

Depending on which statin is used and at what dose, reductions in LDL of 50% or more can be achieved with the two most potent statins rosuvastatin (Crestor®), atorvastatin (Lipitor®)]. And thankfully, Lipitor® has recently become available as a generic.

National Lipid Association and American Academy of Pediatrics guidelines: Children with familial hypercholesterolemia begin medications around 8 years of age

If your child fails to achieve an LDL of < 130 mg/dL or an LDL reduction from baseline of at least a 50%, consideration should be given to adding an additional medication. In this situation your child’s health care provider might suggest a bile acid sequestrant such as [colesevelam (Welchol®), cholestyramine (Questran®), or colestipol (Colestid®). These medications work in the intestines and are not absorbed into the blood stream. Although these medications can lower cholesterol by 10-20% and appear to be very safe, only one, colesevelam (Welchol®), has been approved for use in the pediatric population. Unfortunately, many children complain of gas while on a bile acid sequestrant.

Finally, ezetimibe (Zetia®) is a medication that inhibits the absorption of cholesterol from the intestines. It can lower the LDL by about 20% and has been studied in children and found to be well tolerated. It is now approved by the FDA for use in children over the age of 10. If your child is not able to achieve his/her goal cholesterol with a single cholesterol lowering medication, it is often appropriate to ask for a referral to a cholesterol (lipid) specialist. Many parents see a cholesterol specialist for the initiation of cholesterol-lowering medications but follow-up with their pediatrician, family doctor or nurse practitioner once their child’s levels are under control.

Once my child begins medication, how often should he/she be seen?

Some doctors typically see a child back 6 weeks after they start a medication. Subsequent visits might occur every 3 to 6 months. To assess liver function, blood should be drawn prior to starting therapy. The need for follow-up liver function tests is generally determined by your child’s health care provider. Repeat cholesterol profiles are usually drawn at least twice a year.

What are some of the side effects of cholesterol lowering medications?

I have already noted that the bile acid sequestrants can cause gas. The statins are typically very well tolerated but in some cases they can cause muscle and joint aches and can rarely cause liver function and muscle function abnormalities. Thankfully, in almost all situations, these side effects can be reversed with either stopping the drug or reducing the dose. And although Zetia® tends also to be very well tolerated, it too can occasionally cause abdominal pain and diarrhea. When Zetia is taken in conjunction with a statin, rare cases of muscle and liver function abnormalities have occurred.

After my child’s cholesterol level normalizes, can he/she come off the medication?

Unfortunately, because familial hypercholesterolemia is caused by a defective gene, there is currently no cure. Medications can help normalize the cholesterol in a person with familial hypercholesterolemia but if they are discontinued, the genetic disorder is again revealed. Cholesterol-lowering medications only work while you are taking them.

Cholesterol-lowering medications only work while you are taking them.

My teen has an awful diet. What should I do?

This is a very common situation that are encountered countless times in clinical practice. Teens with familial hypercholesterolemia are like any other teen, but obviously the stakes are higher for children with familial hypercholesterolemia. It is very frustrating to see your son or daughter’s eating habits deteriorate. Best advice is to set a good example; make the foods you serve at home as healthy as possible.

My child hates to take his/her medications. What can I do?

Stick with it. The medications are crucial – there is strong evidence that statins reduce the risk of heart attack, stroke and total mortality. And heart disease is what kills young adults with familial hypercholesterolemia. Your child is not at risk of a heart attack right now (unless your child has homozygous familial hypercholesterolemia), but he/she is at risk in the future. Just when people with familial hypercholesterolemia should be enjoying their own children (and you, your grandchildren), a heart attack can strike – sometimes these heart attacks can be fatal. You have to stress the importance of getting your child into the habit of taking his/her medicines. Make it a family affair – take your medications together.

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