Sunday, April 25, 2010

Dyslipidemia

Dyslipidemia is abnormal levels of lipids (cholesterol, triglycerides, or both) carried by lipoproteins in the blood. 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 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 and increase the risk of atherosclerosis.

A high level of high density lipoprotein (HDL)—the good—cholesterol is beneficial and is not considered a disorder. A level that is too low is considered dyslipidemia and increases the risk of atherosclerosis (see Atherosclerosis).

Factors that increase the risk of dyslipidemia include the following:

  • Having close relatives who have had dyslipidemia (having a family history of the disorder)
  • Being overweight
  • Consuming a diet high in saturated fats and cholesterol
  • Being physically inactive
  • Consuming large amounts of alcohol

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.

Some disorders, including some hereditary disorders (see Cholesterol Disorders: Hereditary Dyslipidemias), cause lipid levels to increase. Diabetes that is poorly controlled or kidney failure can cause total cholesterol levels or triglyceride levels to increase. Some liver disorders 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), and possibly antiviral drugs used to treat human immunodeficiency virus (HIV) infection and AIDS can cause triglyceride levels to increase.

Cigarette smoking, 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. Very high triglyceride levels can cause the liver or spleen to enlarge and may increase the risk of developing pancreatitis. Pancreatitis can cause severe abdominal pain and is occasionally fatal.

The risk of developing 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 Cholesterol Disorders: Hypolipoproteinemia). For adults, a total cholesterol level of less than 200 mg/dL is desirable. 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 decreases the risk, and 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).

Desirable Lipid Levels in Adults

Lipid

Goal (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.

Diagnosis

Levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides—the lipid profile—are measured in a blood sample. The lipid profile should be measured in all adults 20 years and older, and the measurement should be repeated every 5 years. 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.

Treatment

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

A diet low in fats 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.

The type of fat consumed is also important (see Coronary Artery Disease: Types of FatSidebar). 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 to 10% of total calories consumed each day. Polyunsaturated fats (which include omega-3 fats and omega-6 fats) and monounsaturated 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, was once thought to be 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 that contain plant stanols or sterols can slightly 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 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.

Regular physical activity can help lower the LDL cholesterol level and increase the HDL cholesterol level. An example is walking briskly for 30 to 45 minutes 3 to 4 times a week.

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 Coronary Artery Disease: Introduction) are present. For people who have coronary artery disease or diabetes, the goal for the LDL cholesterol level is 100 mg/dL or less. Consequently, such people usually require lipid-lowering drugs. For people who do not have coronary artery disease or diabetes but have two or more other risk factors for coronary artery disease, the goal is 130 mg/dL or less. For those with one or no risk factors, the goal is 160 mg/dL or less.

There are different types of lipid-lowering drugs: bile acid binders, fibric acid derivatives,niacin (a lipoprotein synthesis inhibitor), cholesterol absorption inhibitors, supplements of omega-3 fats, and 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 low-fat diet when drugs are used is recommended.

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

Limiting Fat and Cholesterol in the Diet

Type of Fat

Recommended Amounts

Food Sources

Saturated

7-10% of total calories

Less than 7% for people who have high lipid levels or coronary artery disease

Meats

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

Artificially hydrogenated vegetable oils

Polyunsaturated

Up to 10% of total calories

Omega-3 fats

Fatty fish, such as mackerel, salmon, lake trout, and tuna

Omega-6 fats

Vegetable oils, such as corn oil and safflower oil

Monounsaturated

Up to 20% of total calories

Canola oil

Olive oil

Nuts

Avocado

Cholesterol

Less than 0.3 grams (300 milligrams) a day

Less than 0.2 grams (200 milligrams) a day for people with high lipid levels or coronary artery disease

Egg yolks

Organ meats, such as liver

Meat

Poultry

Fish and other seafood

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

Whole milk

Evaporated or condensed whole milk

Cream

Half-and-half

Most nondairy creamers

Whipped toppings

Nonfat (skim) milk

½% Fat milk

1% Fat milk

Buttermilk

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

Sherbet, sorbet, and frozen low-fat yogurt

Butter and butter-margarine mixtures

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

Olive oil

Canola oil

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

Rice

Pasta

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.

TypeMechanism of ActionIndicationsSide 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 (slight)

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

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

Low HDL cholesterol

Dysbetalipoproteinemia

Possibly high VLDL cholesterol

Abdominal pain

Bloating

Diarrhea

Gallstones

High liver enzyme levels

Muscle aches due to inflammation (myositis)

Nausea

Rash

Lipoprotein synthesis inhibitor

Niacin

Slows removal of HDL

Lowers triglyceride levels

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

High triglycerides

Low HDL cholesterol

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

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

Weight gain if taken in addition to other fats (instead of as substitutes)

HDL = high density lipoprotein; HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; LDL = low density lipoprotein.
*Not available in the United States.

HEREDITARY DYSLIPIDEMIAS

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.

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 500 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 starts later.

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 benefit from a liver transplant.

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 Obesity and the Metabolic Syndrome: 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 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 triglycerides (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.

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