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Dyslipidemia

(Hyperlipidemia)

By

Michael H. Davidson

, MD, FACC, FNLA, University of Chicago Medicine;


Vishnu Priya Pulipati

, MD, Warren Clinic Endocrinology

Last full review/revision Aug 2021| Content last modified Aug 2021
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Topic Resources
  • Lifestyle, genetics, disorders (such as low thyroid hormone levels or kidney disease), drugs, or a combination can contribute.

  • Atherosclerosis can result, causing angina, heart attacks, strokes, and peripheral arterial disease.

  • Doctors measure levels of triglycerides and the various types of cholesterol in blood.

  • Exercise, dietary changes, and drugs can be effective.

Important fats (lipids) in the blood are

  • Cholesterol

  • Triglycerides

Cholesterol is an essential component of cell membranes, of brain and nerve cells, and of bile, which helps the body absorb fats and fat-soluble vitamins. The body uses cholesterol to make vitamin D and various hormones, such as estrogen, testosterone, and cortisol. The body can produce all the cholesterol that it needs, but it also obtains cholesterol from food.

Triglycerides, which are contained in fat cells, can be broken down, then used to provide energy for the body’s metabolic processes, including growth. Triglycerides are produced in the intestine and liver from smaller fats called fatty acids Fats Carbohydrates, proteins, and fats supply 90% of the dry weight of the diet and 100% of its energy. All three provide energy (measured in calories), but the amount of energy in 1 gram (1/28 ounce)... read more . Some types of fatty acids are made by the body, but others must be obtained from food.

  • Chylomicrons

  • High-density lipoproteins (HDL)

  • Low-density lipoproteins (LDL)

  • Very low density lipoproteins (VLDL)

Levels of lipoproteins and therefore lipids, particularly low-density lipoprotein (LDL) cholesterol, increase slightly as people age. Levels are normally slightly higher in men than in women, but levels increase in women after menopause. The increase in levels of lipoproteins that occurs with age can result in dyslipidemia.

The risk of developing atherosclerosis Atherosclerosis Atherosclerosis is a condition in which patchy deposits of fatty material (atheromas or atherosclerotic plaques) develop in the walls of medium-sized and large arteries, leading to reduced or... read more Atherosclerosis increases as the total cholesterol level (which includes LDL, HDL, and VLDL cholesterol) increases, even if the level is not high enough to be considered dyslipidemia. Atherosclerosis can affect the arteries that supply blood to the heart (causing coronary artery disease Overview of Coronary Artery Disease (CAD) Coronary artery disease is a condition in which the blood supply to the heart muscle is partially or completely blocked. The heart muscle needs a constant supply of oxygen-rich blood. The coronary... read more Overview of Coronary Artery Disease (CAD) ), those that supply blood to the brain (causing stroke Overview of Stroke A stroke occurs when an artery to the brain becomes blocked or ruptures, resulting in death of an area of brain tissue due to loss of its blood supply (cerebral infarction) and symptoms that... read more ), and those that supply the rest of the body (causing peripheral arterial disease Overview of Peripheral Arterial Disease Peripheral arterial disease results in reduced blood flow in the arteries of the trunk, arms, and legs. Most often, doctors use the term peripheral arterial disease to describe poor circulation... read more Overview of Peripheral Arterial Disease ). Therefore, having a high total cholesterol level also increases the risk of having a heart attack Acute Coronary Syndromes (Heart Attack; Myocardial Infarction; Unstable Angina) Acute coronary syndromes result from a sudden blockage in a coronary artery. This blockage causes unstable angina or heart attack (myocardial infarction), depending on the location and amount... read more Acute Coronary Syndromes (Heart Attack; Myocardial Infarction; Unstable Angina) or stroke Overview of Stroke A stroke occurs when an artery to the brain becomes blocked or ruptures, resulting in death of an area of brain tissue due to loss of its blood supply (cerebral infarction) and symptoms that... read more .

Having a low total cholesterol level is generally considered better than having a high one. However, having a very low cholesterol level may not be healthy either (hypolipidemia Hypolipidemia Hypolipidemia is abnormally low levels of lipids in the blood (total cholesterol less than 120 mg/dL [3.1 mmol/L] or low-density lipoprotein (LDL) cholesterol less than 50 mg/dL [1.3 mmol/L]... read more ).

Although there is no natural cutoff between normal and abnormal cholesterol levels, for adults, a total cholesterol level of less than 200 milligrams per deciliter of blood (mg/dL [< 5.1 mmol/L]) is desirable. And many people benefit from keeping the lipid level even lower. In parts of the world (such as China and Japan) where the average cholesterol level is 150 mg/dL (3.8 mmol/L), coronary artery disease is less common than it is in countries such as the United States. The risk of a heart attack more than doubles when the total cholesterol level approaches 300 mg/dL (7.7 mmol/L).

The total cholesterol level is only a general guide to the risk of atherosclerosis. Levels of the components of total cholesterol—particularly LDL and HDL cholesterol—are more important. A high level of LDL (bad) cholesterol increases the risk. A high level of HDL (good) cholesterol is not usually considered a disorder because it decreases the risk of atherosclerosis. However, a low level of HDL cholesterol (defined as less than 40 mg/dL [less than 1 mmol/L]) is associated with increased risk. Experts consider an LDL cholesterol level of less than 100 mg/dL (2.6 mmol/L) desirable.

A high level of HDL—the good—cholesterol may be beneficial and is not considered a disorder. A level that is too low increases the risk of atherosclerosis.

Lipoprotein (a) is a combination of LDL with an additional protein attached to it. Levels higher than about 30 mg/dL (or 75 nmol/L) are associated with increased risk of atherosclerosis. High levels are inherited. Lipoprotein (a) is not affected by diet or most lipid-lowering drugs. It usually only needs to be measured once.

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Causes of Dyslipidemia

Factors that cause dyslipidemia are categorized into

  • Primary: Genetic (hereditary) causes

  • Secondary: Lifestyle and other causes

Both primary and secondary causes contribute to dyslipidemia in varying degrees. For example, a person with a hereditary hyperlipidemia may have even higher lipid levels if the person also has secondary causes of hyperlipidemia.

Primary (hereditary) dyslipidemia

Primary causes involve gene mutations that cause the body to produce too much LDL cholesterol or triglycerides or to fail to remove those substances. Some causes involve underproduction or excessive removal of HDL cholesterol. Primary causes tend to be inherited and thus to run in families. Some of the genetic causes of dyslipidemia are discussed here and elsewhere in THE MANUAL Other Rare Hereditary Disorders of Lipid Metabolism Lipid metabolism disorders are hereditary metabolic disorders. Hereditary disorders occur when parents pass the defective genes that cause these disorders on to their children. There are different... read more Other Rare Hereditary Disorders of Lipid Metabolism .

Cholesterol and triglyceride levels are highest in people with primary dyslipidemias, which interfere with the body’s metabolism and elimination of lipids. People can also inherit a tendency for HDL cholesterol to be unusually low.

In people who have a genetic disorder that causes high triglyceride levels (such as familial hypertriglyceridemia or familial combined hyperlipidemia), certain disorders and substances can increase triglycerides to extremely high levels. Examples of disorders include poorly controlled diabetes Diabetes Mellitus (DM) Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar (glucose) levels to be abnormally high. Urination and thirst are... read more and chronic kidney disease Chronic Kidney Disease Chronic kidney disease is a slowly progressive (months to years) decline in the kidneys’ ability to filter metabolic waste products from the blood. Major causes are diabetes and high blood pressure... read more . Examples of substances include excessive alcohol consumption and use of certain drugs, such as estrogens (taken by mouth), that increase triglyceride levels. Symptoms can include fatty deposits (eruptive xanthomas) in the skin on the front of the legs and back of the arms, an enlarged spleen and liver, abdominal pain, and a decreased sensitivity to touch due to nerve damage. These disorders can cause pancreatitis Overview of Pancreatitis Pancreatitis is inflammation of the pancreas. The pancreas is a leaf-shaped organ about 5 inches (about 13 centimeters) long. It is surrounded by the lower edge of the stomach and the first... read more , which is occasionally fatal. Limiting fat intake (to less than 50 grams a day) can help prevent nerve damage and pancreatitis. Losing weight and not drinking alcohol can also help. Lipid-lowering drugs may be effective.

Familial combined hyperlipidemia

In familial combined hyperlipidemia, the levels of cholesterol, triglycerides, or both may be high. This disorder affects about 1 to 2% of people. The lipid levels typically become abnormal after age 30 but sometimes at a younger age, especially in people who are overweight, who have a diet that is very high in fat, or who have metabolic syndrome Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), high blood pressure, resistance to the effects of insulin (insulin resistance) or diabetes,... read more .

Treatment of familial combined hyperlipidemia involves limiting intake of saturated fat, cholesterol, and sugar as well as exercising and, when applicable, losing weight. Many people with this disorder need to take lipid-lowering drugs.

Familial dysbetalipoproteinemia

In familial dysbetalipoproteinemia, levels of very low density lipoprotein (VLDL) and total cholesterol and triglycerides are high. These levels are high because an unusual form of VLDL accumulates in the blood. Fatty deposits (xanthomas) may form in the skin over the elbows and knees and in the palms, where they can cause yellow creases. This uncommon disorder results in the early development of severe atherosclerosis. By middle age, atherosclerosis often produces blockages in the coronary and peripheral arteries.

Treatment of familial dysbetalipoproteinemia involves achieving and maintaining recommended body weight and limiting intake of cholesterol, saturated fats, and carbohydrates. A lipid-lowering drug is usually needed. With treatment, lipid levels can be improved, the progression of atherosclerosis may be slowed, and the fatty deposits in the skin may become smaller or disappear.

Familial hypercholesterolemia

In familial hypercholesterolemia, the total cholesterol level is high. People may have inherited one abnormal gene or they may have inherited two abnormal genes, one from each parent. People who have two abnormal genes (homozygotes) are more severely affected than people who have only one abnormal gene (heterozygotes). About 1 in 200 people are heterozygotes, and 1 in 250,000 to 1 in 1 million people are homozygotes. Affected people may have fatty deposits (xanthomas) in the tendons at the heels, knees, elbows, and fingers. Rarely, xanthomas appear by age 10. Familial hypercholesterolemia can result in rapidly progressive atherosclerosis and early death due to coronary artery disease Overview of Coronary Artery Disease (CAD) Coronary artery disease is a condition in which the blood supply to the heart muscle is partially or completely blocked. The heart muscle needs a constant supply of oxygen-rich blood. The coronary... read more Overview of Coronary Artery Disease (CAD) . Children with two abnormal genes may have a heart attack or angina by age 20, and men with one abnormal gene often develop coronary artery disease between ages 30 and 50. Women with one abnormal gene are also at increased risk, but the risk usually starts about 10 years later than in men. People who smoke or have high blood pressure, diabetes, or obesity may develop atherosclerosis even earlier.

Treatment of familial hypercholesterolemia begins with following a diet that is low in saturated fats and cholesterol. When applicable, losing weight, stopping smoking, and increasing physical activity are advised. One or more lipid-lowering drugs are usually needed. Some people require apheresis Plasma exchange In apheresis, blood is removed from a person and then returned after substances are removed from it. Apheresis can be used to Obtain healthy blood components from a donor to transfuse to a person... read more , a method of filtering the blood to lower LDL levels. Some people with homozygous familial hypercholesterolemia may benefit from liver transplantation Liver Transplantation Liver transplantation is the surgical removal of a healthy liver or sometimes a part of a liver from a living person and then its transfer into a person whose liver no longer functions. (See... read more . Early diagnosis and treatment can decrease the increased risk of heart attack and stroke.

Familial hypertriglyceridemia

In familial hypertriglyceridemia, triglyceride levels are high. This disorder affects about 1% of people. In some families affected by this disorder, atherosclerosis Atherosclerosis Atherosclerosis is a condition in which patchy deposits of fatty material (atheromas or atherosclerotic plaques) develop in the walls of medium-sized and large arteries, leading to reduced or... read more Atherosclerosis tends to develop at a young age, but in others, it does not. When applicable, losing weight and limiting alcohol and carbohydrate consumption often lower triglyceride levels to normal. If these measures are ineffective, use of a lipid-lowering drug can help. For people who also have diabetes, good control of the diabetes is important.

Hypoalphalipoproteinemia

In hypoalphalipoproteinemia, the HDL cholesterol level is low. A low HDL cholesterol level is often inherited. Many different genetic abnormalities can cause the low HDL level. Since drugs that raise HDL cholesterol do not decrease the risk of atherosclerosis, hypoalphalipoproteinemia is treated by lowering LDL cholesterol.

Lipoprotein lipase deficiency and apolipoprotein CII deficiency

Lipoprotein lipase deficiency and apolipoprotein CII deficiency are rare disorders caused by the lack of certain proteins needed for the removal of triglyceride-containing particles. In these disorders, the body cannot remove chylomicrons from the bloodstream, resulting in very high triglyceride levels. Without treatment, levels are often considerably higher than 1,000 mg/dL (11 mmol/L). Symptoms appear during childhood and young adulthood. They include recurring bouts of abdominal pain, an enlarged liver and spleen, and pinkish yellow bumps in the skin on the elbows, knees, buttocks, back, front of the legs, and back of the arms. These bumps, called eruptive xanthomas, are deposits of fat. Eating fats worsens symptoms. Although this disorder does not lead to atherosclerosis Atherosclerosis Atherosclerosis is a condition in which patchy deposits of fatty material (atheromas or atherosclerotic plaques) develop in the walls of medium-sized and large arteries, leading to reduced or... read more Atherosclerosis , it can cause pancreatitis Overview of Pancreatitis Pancreatitis is inflammation of the pancreas. The pancreas is a leaf-shaped organ about 5 inches (about 13 centimeters) long. It is surrounded by the lower edge of the stomach and the first... read more , which is occasionally fatal. People who have this disorder must strictly limit the amount of all types of fat—saturated, unsaturated, and polyunsaturated—in their diet. People may need to take vitamin supplements to make up for nutrients missing from their diets. There are some therapies in development for treatment of lipoprotein lipase deficiency and apolipoprotein CII deficiency.

Secondary dyslipidemia

Secondary causes contribute to many cases of dyslipidemia.

The most important secondary cause of dyslipidemia is

Some other common secondary causes include the following:

Some people are more sensitive to the effects of diet than others, but most people are affected to some degree. One person can eat large amounts of animal fat, and the total cholesterol level does not rise above desirable levels. Another person can follow a strict low-fat diet, and the total cholesterol does not fall below a high level. This difference seems to be mostly genetically determined. A person’s genetic makeup influences the rate at which the body makes, uses, and disposes of these fats. Also, body type does not always predict levels of cholesterol. Some overweight people have low cholesterol levels, and some thin people have high levels. Eating excess calories can result in high triglyceride levels, as can consuming large amounts of alcohol.

Did You Know...

  • Body type does not predict cholesterol levels. Some overweight people have low cholesterol levels, and some thin people have high cholesterol levels.

Use of drugs such as estrogens (taken by mouth), oral contraceptives, corticosteroids, retinoids, thiazide diuretics (to some extent), cyclosporine, tacrolimus, and antiviral drugs used to treat human immunodeficiency virus Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and can cause acquired immunodeficiency syndrome (AIDS). HIV is transmitted... read more Human Immunodeficiency Virus (HIV) Infection (HIV) infection and AIDS can cause cholesterol and/or triglyceride levels to increase.

Cigarette smoking, HIV infection, poorly controlled diabetes, or kidney disorders (such as nephrotic syndrome) may contribute to a low HDL cholesterol level. Drugs such as beta-blockers and anabolic steroids can lower the HDL cholesterol level.

Symptoms of Dyslipidemia

High lipid levels in the blood usually cause no symptoms. Occasionally, when levels are particularly high, fat is deposited in the skin and tendons and forms bumps called xanthomas. Sometimes people develop opaque white or gray rings at the edge of the cornea. Very high triglyceride levels can cause the liver or spleen to enlarge, a tingling or burning sensation in the hands and feet, difficulty breathing, and confusion and may increase the risk of developing pancreatitis Overview of Pancreatitis Pancreatitis is inflammation of the pancreas. The pancreas is a leaf-shaped organ about 5 inches (about 13 centimeters) long. It is surrounded by the lower edge of the stomach and the first... read more . Pancreatitis can cause severe abdominal pain and is occasionally fatal.

Symptoms of Dyslipidemia

Diagnosis of Dyslipidemia

  • Blood tests to measure cholesterol levels

Blood Tests to Measure Cholesterol Levels

Levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides—the lipid profile—are measured in a blood sample. Because consuming food or beverages may cause triglyceride levels to increase temporarily, people must fast at least 12 hours before the blood sample is taken.

When lipid levels in the blood are very high, special blood tests are done to identify the specific underlying disorder. Specific disorders include several hereditary disorders (primary dyslipidemias), which produce different lipid abnormalities and have different risks.

Did You Know...

  • Margarines made primarily from liquid oil (squeeze or tub margarines) and those that contain plant stanols or sterols, unlike stick margarines, are healthier substitutes for butter for people who need to limit their butter.

Screening

The fasting lipid profile, is the levels of total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol measured after a person fasts for 12 hours. Doctors usually do this test every 5 years starting at age 20 as part of assessing whether the person is at risk of coronary artery disease Overview of Coronary Artery Disease (CAD) Coronary artery disease is a condition in which the blood supply to the heart muscle is partially or completely blocked. The heart muscle needs a constant supply of oxygen-rich blood. The coronary... read more Overview of Coronary Artery Disease (CAD) .

In children and adolescents, screening with a fasting lipid profile is recommended between the ages of 2 and 8 years if the child has risk factors, such as a family member with severe dyslipidemia or one who developed coronary artery disease at a young age. In children with no risk factors, screening with a non-fasting lipid profile is usually done once before the child reaches puberty (usually between age 9 to 11) and once more between the ages of 17 to 21.

Treatment of Dyslipidemia

  • Lose weight

  • Exercise

  • Decrease saturated fats in the diet

  • Often lipid-lowering drugs

Usually, the best treatment for people is to lose weight if they are overweight, stop smoking if they smoke, decrease the total amount of saturated fat and cholesterol in their diet, increase physical activity, and then, if necessary, take a lipid-lowering drug.

Regular physical activity can help lower triglyceride levels and increase the HDL cholesterol level. An example is walking briskly for at least 30 minutes daily.

Treating children may be challenging. The American Academy of Pediatrics and the National Health, Lung, and Blood Institute recommend treatment for some children with high lipid levels. Diet changes are recommended. Lipid-lowering drugs may be given to some children with very high lipid levels who do not respond to changes in diet, particularly children with familial hypercholesterolemia.

Lipid-lowering diet

A diet low in saturated fat and cholesterol can lower the LDL cholesterol level. However, people with high triglyceride levels also need to avoid consuming large amounts of sugar (whether in foods or beverages), refined flour (such as is used in most commercial baked goods), and starchy foods (such as potatoes and rice).

The type of fat consumed is important (see Types of Fat Types of Fat Coronary artery disease is a condition in which the blood supply to the heart muscle is partially or completely blocked. The heart muscle needs a constant supply of oxygen-rich blood. The coronary... read more Types of Fat ). Fats may be saturated, polyunsaturated, or monounsaturated. Saturated fats increase cholesterol levels more than other forms of fat. Saturated fats should provide no more than 5 to 7% of total calories consumed each day. Polyunsaturated fats (which include omega-3 fats and omega-6 fats) may help decrease levels of triglycerides and LDL cholesterol in the blood. The fat content of most foods is included on the label of the container.

Large amounts of saturated fats occur in meats, egg yolks, full-fat dairy products, some nuts (such as macadamia nuts), and coconut. Vegetable oils contain smaller amounts of saturated fat, but only some vegetable oils are truly low in saturated fats.

Margarine, which is produced from polyunsaturated vegetable oils, is usually a healthier substitute for butter, which is high in saturated fat (about 60%). However, stick margarines (and some processed foods) contain trans fats, which may increase LDL (bad) cholesterol levels and lower HDL (good) cholesterol levels. Margarines made primarily from liquid oil (squeeze or tub margarines) contain less saturated fat than butter, contain no cholesterol, and contain fewer trans fats than stick margarines. Margarines (and other food products) that contain plant stanols or sterols can help lower total and LDL cholesterol levels.

Did You Know...

  • Eating oat bran, oatmeal, beans, peas, rice bran, barley, citrus fruits, strawberries, and apple pulp can help lower cholesterol.

Eating lots of vegetables, fruits, and whole grains, which are naturally low in fat and contain no cholesterol, is recommended. Also recommended are foods rich in soluble fiber, which binds fats in the intestine and helps lower the cholesterol level. Such foods include oat bran, oatmeal, beans, peas, rice bran, barley, citrus fruits, strawberries, and apple pulp. Psyllium, usually taken to relieve constipation, can also lower the cholesterol level.

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Lipid-lowering drugs

Treatment with lipid-lowering drugs depends not only on the lipid levels but also on whether coronary artery disease, diabetes, or other major risk factors for coronary artery disease Risk Factors Coronary artery disease is a condition in which the blood supply to the heart muscle is partially or completely blocked. The heart muscle needs a constant supply of oxygen-rich blood. The coronary... read more Risk Factors are present. For people who have coronary artery disease or diabetes, the risk of heart attack or stroke can be decreased by the use of the lipid-lowering drugs called statins. People who have very high cholesterol levels or who have other high risk factors for heart attack or stroke also may benefit from taking lipid-lowering drugs.

There are different types of lipid-lowering drugs:

  • Statins

  • Cholesterol absorption inhibitors

  • Bile acid binders

  • PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors

  • Fibric acid derivatives

  • Supplements of omega-3 fats

  • Niacin

  • Bempedoic acid

Each type lowers lipid levels by a different mechanism. Consequently, the different types of drugs have different side effects and may affect lipid levels differently. Following a diet low in saturated fat when drugs are used is recommended.

Lipid-lowering drugs do more than lower lipid levels—they can also prevent coronary artery disease. In addition, statins have been shown to reduce the risk of early death.

People with very high triglyceride levels and who are at risk of pancreatitis may need both diet changes and triglyceride-lowering drugs, usually a fibrate or prescription omega-3 fatty acids.

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Procedures to reduce cholesterol

Medical procedures that lower cholesterol levels are reserved for people with very high levels of LDL cholesterol that do not respond to diet and lipid-lowering drugs. Such people include those with familial hypercholesterolemia. LDL apheresis is the most commonly done procedure. LDL apheresis is a non-surgical procedure where blood is drawn from the person and the LDL component is separated from the rest of the blood in a special machine. The blood (minus the LDL component) is then returned to the person.

Treating causes of elevated cholesterol

Any conditions that cause or are risk factors for elevations in cholesterol levels also need to be treated. So people with diabetes Diabetes Mellitus (DM) Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar (glucose) levels to be abnormally high. Urination and thirst are... read more should carefully control their blood glucose levels. Kidney disease, liver disease, and hypothyroidism Hypothyroidism Hypothyroidism is underactivity of the thyroid gland that leads to inadequate production of thyroid hormones and a slowing of vital body functions. Facial expressions become dull, the voice... read more Hypothyroidism are also treated. If a drug is causing the cholesterol elevation, doctors may give the person a lower dose or a different drug instead.

Monitoring treatment

Doctors usually do blood tests 2 to 3 months after treatment has started to determine whether lipid levels are decreasing. Once lipid levels have decreased sufficiently, doctors do blood tests once or twice a year. Doctors no longer use specific targets for lipid levels. Instead, doctors try to lower the lipid levels by a certain percentage, typically about 30 to 50%.

Because some lipid-lowering drugs can sometimes cause muscle and liver problems, doctors usually do blood tests when the person starts drug therapy. Then, if the person develops side effects, initial (baseline) measurements are available for comparison.

Drugs Mentioned In This Article

Generic Name Select Brand Names
LIVALO
NEORAL, SANDIMMUNE
CRESTOR
LIPITOR
No US brand name
ZOCOR
WELCHOL
LESCOL
LOPID
PRAVACHOL
REPATHA
COLESTID
PRALUENT
JUXTAPID
ALTOPREV
PROGRAF
ZETIA
NIACOR, NIASPAN
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