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Dyslipidemia

(Hyperlipidemia)

by Anne Carol Goldberg, MD

Dyslipidemia is a high level of lipids (cholesterol, triglycerides, or both) carried by lipoproteins in the blood (see Overview of Cholesterol and Lipid Disorders). This term includes hyperlipoproteinemia (hyperlipidemia), which refers to abnormally high levels of total cholesterol, low density lipoprotein (LDL)—the bad—cholesterol, or triglycerides, as well as an abnormally low level of high density lipoprotein (HDL)—the good—cholesterol.

  • Lifestyle, genetics, disorders, 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.

Levels of lipoproteins and therefore lipids, particularly 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 (see Atherosclerosis) increases as the total cholesterol level 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), those that supply blood to the brain (causing cerebrovascular disease), and those that supply the rest of the body (causing peripheral arterial disease). Therefore, having a high total cholesterol level also increases the risk of having a heart attack or stroke. 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 (see Hypolipidemia).

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) 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, 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.

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 considered a disorder because it decreases the risk of atherosclerosis. However, a low level of HDL cholesterol (defined as less than 40 mg/dL) increases the risk. Experts consider an LDL cholesterol level of less than 100 mg/dL optimal.

Whether high triglyceride levels increase the risk of a heart attack or stroke is uncertain. Triglyceride levels higher than 150 mg/dL are considered abnormal, but high levels do not appear to increase risk for everyone. For people with high triglyceride levels, the risk of heart attack or stroke is increased if they also have a low HDL cholesterol level, diabetes, kidney disease, or many close relatives who have had atherosclerosis (family history).

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

Desirable Lipid Levels in Adults

Lipid

Desirable Level (mg/dL)*

Total cholesterol

Less than 200 mg/dL

Low-density lipoprotein (LDL) cholesterol

Less than 100 mg/dL

High-density lipoprotein (HDL) cholesterol

More than 40 mg/dL

Triglycerides

Less than 150 mg/dL

*mg/dL = milligrams per deciliter of blood.

Causes

Factors that cause dyslipidemia are categorized into

  • Primary: Genetic (hereditary) causes

  • Secondary: Lifestyle and other causes

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.

Cholesterol and triglyceride levels are highest in people with hereditary 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. Consequences of hereditary dyslipidemias can include premature atherosclerosis, which can lead to angina or heart attacks. Peripheral arterial disease is also a consequence, often causing decreased blood flow to the legs, with pain during walking (claudication—see Peripheral Arterial Disease:Arteries of the Legs and Arms). Stroke is another possible consequence. Very high triglyceride levels can cause pancreatitis (see Overview of Pancreatitis).

In lipoprotein lipase deficiency and apolipoprotein CII deficiency, rare disorders caused by the lack of certain proteins needed for the removal of triglyceride-containing particles, 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. 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, it can cause pancreatitis, which is occasionally fatal. People who have this disorder must avoid eating fats of all types—saturated, unsaturated, and polyunsaturated.

In familial hypercholesterolemia, the total cholesterol level is high. This severe disorder affects about 1 of 250 people. 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). 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. 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 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 (see Controlling Diseases by Purifying the Blood), a method of filtering the blood to lower LDL levels. Early diagnosis and treatment can decrease the increased risk of heart attack and stroke.

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 (see Metabolic Syndrome).

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

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 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.

In familial hypertriglyceridemia, triglyceride levels are high. This disorder affects about 1% of people. In some families affected by this disorder, atherosclerosis tends to develop at a young age, but in others, it does not. When applicable, losing weight and limiting alcohol 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.

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.

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 and kidney dysfunction. Examples of substances include excessive alcohol consumption and use of certain drugs 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. This disorder can cause pancreatitis, 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.

Secondary dyslipidemia

Secondary causes contribute to many cases of dyslipidemia and include the following:

  • Consuming a diet high in saturated fats, trans fats, and cholesterol

  • Having diabetes or certain other disorders

  • Being physically inactive

  • Consuming large amounts of alcohol

  • Using certain drugs

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.

Some disorders cause lipid levels to increase. Diabetes that is poorly controlled or chronic kidney disease can cause total cholesterol levels or triglyceride levels to increase. Some liver disorders (particularly primary biliary cirrhosis) and an underactive thyroid gland (hypothyroidism) can cause the total cholesterol level to increase.

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 (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

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. Pancreatitis can cause severe abdominal pain and is occasionally fatal.

Diagnosis

  • 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 (hereditary 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.

Screening

The lipid profile should be measured in all adults 20 years and older, and the measurement should be repeated every 4 to 6 years.

Screening is usually repeated until people are in their 80s. In addition to measuring lipid levels, doctors also screen for other risk factors for cardiovascular disease, such as high blood pressure, diabetes, or a family history of high lipid levels.

Pediatricians recommend that all children between the ages of 9 and 11 undergo blood testing to screen for high lipid levels. Children may undergo screening at age 2 if they have family members who have high lipid levels or who developed coronary artery disease at a young age.

Treatment

  • 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 5 times a week.

Lipid-lowering diet

A diet low in saturated fat and cholesterol can lower the LDL cholesterol level. Experts recommend limiting calories from fat to no more than 25 to 35% of the total calories consumed over several days. 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 Table: 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 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, some 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 fruits, vegetables, 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.

Limiting Fat and Cholesterol in the Diet

Type of Fat

Recommended Amounts

Food Sources

Saturated

No more than 5–6% of total calories

Meats

Nonskim dairy products, such as whole milk, cheese, and butter

Artificially hydrogenated vegetable oils

Coconut oil

Polyunsaturated

Replace saturated fat with polyunsaturated and monounsaturated fat

Some vegetable oils, such as soybean oil, corn oil, and safflower oil

Fatty fish, such as salmon, mackerel, herring, and trout

Some nuts and seeds, such as walnuts and sunflower seeds

Monounsaturated

Replace saturated fats with polyunsaturated and monounsaturated fat

Canola oil

Olive oil

Nuts

Avocado

Cholesterol

Decrease intake of foods high in saturated fat and cholesterol

Egg yolks

Organ meats, such as liver

Meat

Poultry

Nonskim dairy products

A Practical Approach to a Low-Cholesterol, Low-Saturated Fat Diet

Foods to Reduce

Foods to Choose

Meats and meat products

Fatty cuts of beef, lamb, and pork

Spareribs

Organ meats, such as liver

Regular cold cuts

Sausage

Hot dogs

Fish

Chicken and turkey (without the skin)

Lean cuts of beef, lamb, pork, and veal

Dairy products and eggs

Whole milk

Evaporated or condensed whole milk

Cream

Half-and-half

Most nondairy creamers

Nonfat (skim) milk

1% fat milk

Buttermilk

Whipped toppings

Low or nonfat whipped toppings

Whole-milk yogurt

Whole-milk cottage cheese

Cheeses (such as blue, Roquefort, Camembert, cheddar, and Swiss)

Cream cheese

Sour cream

Ice cream

Nonfat or low-fat yogurt

Low-fat cottage cheese

Low-fat cheeses

Low or nonfat sour cream

Sherbet, sorbet, and frozen low-fat yogurt (limit sugar-containing foods if triglycerides are high)

Butter and butter-margarine mixtures

Less solid forms of margarines made from liquid vegetable oils (packaged in a tub or squeeze bottle)

Margarine products containing a plant sterol or stanol

Egg yolks (to less than 3 a week)

Cholesterol-free egg substitutes

Egg whites (2 whole egg whites can be substituted for 1 egg in recipes)

Commercial baked goods

Pies

Cakes

Doughnuts

Croissants

Pastries

Muffins

Biscuits

High-fat crackers

High-fat cookies

Egg noodles

Breads made with several eggs

Homemade baked goods made with unsaturated oils

Angel food cake

Low-fat cookies and crackers (limit sugar-containing foods if triglycerides are high)

Whole-grain* (oatmeal, bran, rye, and multigrain) breads and cereals

Saturated fats and oils

Chocolate

Cocoa powder

Carob

Nonfat chocolate syrup

Coconut oil

Palm oil

Lard

Bacon

Unsaturated vegetable oils: canola, olive, corn, safflower, sesame, soybean, and sunflower

Dressings

Dressings made with egg yolk

Low-fat mayonnaise and salad dressings made with liquid oils

Fruits and vegetables

Fruits and vegetables prepared in butter, saturated fats, cream, or sauces made with saturated fat

Fresh, frozen, canned, and dried fruits or vegetables*

Coconut

Seeds and nuts*

*Fruits, vegetables, grains, seeds, and nuts contain no cholesterol, and most contain little or no saturated fat.

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 (see Overview of Coronary Artery Disease) 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:

  • Bile acid binders

  • Fibric acid derivatives

  • Niacin

  • Cholesterol absorption inhibitors

  • Supplements of omega-3 fats

  • Statins

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.

Treating children may be challenging. And there are no studies that show that treating high lipid levels in children will reduce the risk of treated children developing heart disease when they are adults. Nevertheless, 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 Drugs

Type

Mechanism of Action

Indications

Some Side Effects

Bile acid binders

Cholestyramine

Colesevelam

Colestipol

Bind bile acids in the intestine, causing the acids to be excreted rather than used to make bile and causing the liver to remove more LDL cholesterol from the bloodstream to make bile

High LDL cholesterol

Abdominal pain

Binding of some other drugs (reducing their effectiveness)

Bloating

Constipation

Nausea

Increase in triglyceride level (especially in people with high triglyceride levels)

Cholesterol absorption inhibitor

Ezetimibe

Decreases cholesterol absorption in the small intestine

High LDL cholesterol

Few serious side effects

Face and lip swelling (rare)

Loose stools

Muscle aches (rare)

Fibric acid derivatives

Bezafibrate*

Ciprofibrate*

Fenofibrate

Gemfibrozil

Increase the breakdown of lipids and speed the removal of VLDL from the bloodstream

May decrease VLDL production by the liver

High triglycerides

Dysbetalipoproteinemia

Possibly high VLDL cholesterol

Abdominal pain

Bloating

Diarrhea

Gallstones

High liver enzyme levels

Muscle aches due to inflammation (myositis)

Nausea

Rash

Niacin

Niacin

Slows removal of HDL

Lowers triglyceride levels

At high doses, decreases production rate of VLDL, which is used to synthesize LDL

High triglycerides

High LDL and VLDL cholesterol

Dysbetalipoproteinemia

Digestive upset

Flushing

Gout

High blood sugar level (hyperglycemia)

High liver enzyme levels

Itching

Ulcers

Statins (HMG-CoA reductase inhibitors)

Atorvastatin

Fluvastatin

Lovastatin

Pitavastatin

Pravastatin

Rosuvastatin

Simvastatin

Block the synthesis of cholesterol, increasing the removal of LDL from the bloodstream

High LDL cholesterol, triglycerides, or both

Bloating

Constipation (mild)

Fatigue

Headache

Loose stools

Rarely, high liver enzyme levels

Rarely, muscle aches due to inflammation (myositis) or degeneration (rhabdomyolysis)

Fat supplements

Omega-3 fatty acids

Lower levels of triglycerides

May decrease production of VLDL

High triglycerides

Belching

Diarrhea

Microsomal triglyceride transfer protein inhibitor

Lomitapide

Inhibits triglyceride secretion

Familial hypercholesteremia in people who have 2 abnormal genes (are homozygous)

Diarrhea

Liver damage

Oligonucleotide inhibitor of apolipoprotein B

Mipomersen

Lowers level of LDL

Lowers level of apolipoprotein B

Familial hypercholesteremia (homozygous)

Flu-like symptoms

Liver damage

Skin reactions at injection sites

HDL = high density lipoprotein; HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; LDL = low density lipoprotein; VLDL = very low density lipoprotein.

*Not available in the United States.

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 decreases 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.

Resources In This Article

Drugs Mentioned In This Article

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