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Pronunciations atherosclerosis chylomicrons claudication corticosteroid hypercholesterolemia hyperchylomicronemia hyperglycemia hyperlipidemia hyperlipoproteinemias hypolipoproteinemia hypothyroidism lipoproteins lovastatin pancreatitis sclerosis triglycerides

Hyperlipoproteinemia (hyperlipidemia) is abnormally high levels of lipids (cholesterol, triglycerides, or both) carried by lipoproteins in the blood.

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 hyperlipoproteinemia and increase the risk of atherosclerosis. (A high level of HDL—the good—cholesterol is beneficial and is not considered a disorder.)

Factors that increase the risk of hyperlipoproteinemia include having close relatives who have had hyperlipoproteinemia (having a family history of the disorder), being overweight, consuming a diet high in saturated fats and cholesterol, being physically inactive, and consuming a moderate to excessive amount 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 200 mg/dL. Another person can follow a strict low-fat diet, and the total cholesterol does not fall below 260 mg/dL. 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. Eating excess calories can result in high triglyceride levels, as can excessive consumption of alcohol.

Some disorders, including some hereditary disorders (see Cholesterol Disorders: Hereditary Hyperlipoproteinemias), cause lipid levels to increase. Diabetes that is poorly controlled or kidney failure can cause total cholesterol levels or triglyceride levels to increase. Obstructive liver disease and an underactive thyroid gland (hypothyroidism) can cause the total cholesterol level to increase.

Use of drugs such as estrogens Some Trade Names
PREMARIN
(taken by mouth), oral contraceptives, corticosteroids, and thiazide diuretics (to some extent) can cause triglyceride levels to increase.

Metabolic Syndrome: A Cluster of Problems The metabolic syndrome, also called the syndrome of insulin Some Trade Names HUMULIN NOVOLIN resistance, includes high triglyceride levels, a low HDL cholesterol level, high blood pressure, resistance to the effects of insulin Some Trade Names HUMULIN NOVOLIN , a high level of sugar (glucose) in the blood, and an increased tendency to form blood clots. It also includes being overweight (particularly if fat accumulates in the abdomen). All of these problems work together to increase the risk of coronary artery disease. One fourth of the people in the United States may have this disorder. Treatment consists of weight loss, increased physical activity, use of antihypertensive drugs (to lower blood pressure), and use of aspirin Some Trade Names ECOTRIN ASPERGUM (to reduce the risk of blood clotting). Many people with metabolic syndrome need to take lipid-lowering drugs.

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. 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. Because consuming food or beverages may cause triglyceride levels to increase temporarily, a person 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 performed to identify the specific underlying disorder. Specific disorders include several hereditary disorders (hereditary hyperlipoproteinemias), which produce different lipid abnormalities and have different risks, as well as other disorders such as hypothyroidism.

Treatment

Usually, the best treatment for people who have high cholesterol or triglyceride levels 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, 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 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 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 fatty acids, which may increase LDL (bad) cholesterol levels and lower HDL (good) cholesterol levels (see Coronary Artery Disease: Types of Fat). Margarines made primarily from liquid oil (squeeze or tub margarines) contain less saturated fat than butter, contain no cholesterol, and contain fewer trans fatty acids. Margarines that contain plant stanols or sterols can lower total and LDL cholesterol levels.

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.

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 what the person's lipid levels are but also on whether the person has coronary artery disease, diabetes, or other major risk factors for coronary artery disease (see Coronary Artery Disease: Introduction). 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), 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, 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 300 mg a day (less than 200 mg a day for people with high lipid levels or heart 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 Food Category Foods to Reduce Foods to Choose Meats and meat products Fatty cuts of beef, lamb, and pork; spareribs; organ meats; regular cold cuts; sausage; and hot dogs Fish; chicken and turkey (without the skin); and lean cuts of beef, lamb, pork, and veal Dairy products Whole milk, evaporated or condensed whole milk, cream, half-and-half, most nondairy creamers, and whipped toppings Skim milk, ½% fat milk, 1% fat milk, and buttermilk   Whole-milk yogurt, whole-milk cottage cheese, cheeses (such as blue, Roquefort, Camembert, cheddar, and Swiss), cream cheese, sour cream, and 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, and margarine products containing a plant sterol or stanol   Egg yolks (to less than 3 a week) Cholesterol-free egg substitutes and 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, highfat cookies, egg noodles, and breads made with several eggs Homemade baked goods made with unsaturated oils; angel food cake; low-fat cookies and crackers; rice; pasta; and whole-grain* (oatmeal, bran, rye, and multigrain) breads and cereals Saturated fats and oils Chocolate Cocoa powder, carob, and nonfat chocolate syrup   Coconut oil, palm oil, lard, and 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 no saturated fat.

Lipid-Lowering Drugs Type Mechanism of Action Indications Side Effects Bile acid binders Cholestyramine Colesevelam Colestipol Binds 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 Constipation, abdominal pain, nausea, bloating, binding of other drugs (reducing their effectiveness), and an increased triglyceride level Fibric acid derivatives Fenofibrate Gemfibrozil Increases the breakdown of lipids and speeds the removal of VLDL from the bloodstream and may decrease VLDL production by the liver High VLDL cholesterol Low HDL cholesterol Dysbetalipoproteinemia Diarrhea, nausea, bloating, abdominal pain, rash, abnormal levels of liver enzymes, muscle inflammation, and gallstones Lipoprotein synthesis inhibitors Niacin Decreases the production rate of VLDL, which is used to synthesize LDL High LDL and VLDL cholesterol and low HDL cholesterol Dysbetalipoproteinemia Flushing, itching, digestive upset, ulcers, increased levels of liver enzymes, gout, and a high blood sugar level (hyperglycemia) Statins (HMG-CoA reductase inhibitors) Atorvastatin Fluvastatin Lovastatin Pravastatin Simvastatin Blocks the synthesis of cholesterol, increasing the removal of LDL from the bloodstream High LDL cholesterol Combined hyperlipidemia Mild constipation, loose stools, bloating, headaches, rashes, fatigue, and, rarely, increased levels of liver enzymes, muscle aches due to inflammation (myositis) and muscle degeneration (rhabdomyolysis) HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A.

Hereditary Hyperlipoproteinemias

Cholesterol and triglyceride levels are highest in people with hereditary hyperlipoproteinemias, which interfere with the body's metabolism and elimination of lipids.

In familial hyperchylomicronemia, a rare disorder, 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. 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. One sixth of men with this disorder have a heart attack by age 40, and two thirds have a heart attack by age 60. Women with this disorder are also at increased risk, but the risk starts later. About two fifths of women with the disorder have a heart attack by age 60.

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.

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.

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 (type III hyperlipoproteinemia), 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. This uncommon disorder results in the early development of severe atherosclerosis. By middle age, atherosclerosis often produces blockages in the coronary and peripheral arteries. Decreased blood flow to the legs may cause pain during walking (claudication (see Peripheral Arterial Disease: Arteries of the Legs and Arms).

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 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 severe mixed hyperlipoproteinemia, the triglyceride level is very high. In the severe form of this disorder (which is rare), the body cannot adequately metabolize and eliminate excess triglycerides. In people who have a milder form of the disorder, the triglyceride level can become very high if other conditions (such as excessive alcohol intake, poorly controlled diabetes, or kidney failure) are also present. Symptoms can include many 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. Eating fats or drinking alcohol makes symptoms worse. This disorder can cause pancreatitis, which is occasionally fatal. Eating fats can also cause recurring bouts of pancreatitis and increases the risk of death. Limiting fat intake (to less than 50 grams a day) can prevent nerve damage and pancreatitis. Losing weight and not drinking alcohol can also help. Lipid-lowering drugs may be effective.

Last full review/revision February 2003