What is cholesterol?
Cholesterol is a fatty substance (a lipid) that is an important part of the outer lining (membrane) of cells in the body of animals. Cholesterol is also found in the blood circulation of humans. The cholesterol in a person's blood originates from two major sources; dietary intake and liver production. Dietary cholesterol comes mainly from meat, poultry, fish, and dairy products. Organ meats, such as liver, are especially high in cholesterol content, while foods of plant origin contain no cholesterol. After a meal, cholesterol is absorbed by the intestines into the blood circulation and is then packaged inside a protein coat. This cholesterol-protein coat complex is called a chylomicron.
The liver is capable of removing cholesterol from the blood circulation as well as manufacturing cholesterol and secreting cholesterol into the blood circulation. After a meal, the liver removes chylomicrons from the blood circulation. In between meals, the liver manufactures and secretes cholesterol back into the blood circulation.
What are LDL and HDL cholesterol?
LDL cholesterol is called "bad" cholesterol, because elevated levels of LDL cholesterol are associated with an increased risk of coronary heart disease. LDL lipoprotein deposits cholesterol on the artery walls, causing the formation of a hard, thick substance called cholesterol plaque. Over time, cholesterol plaque causes thickening of the artery walls and narrowing of the arteries, a process called atherosclerosis.
HDL cholesterol is called the "good cholesterol" because HDL cholesterol particles prevent atherosclerosis by extracting cholesterol from the artery walls and disposing of them through the liver. Thus, high levels of LDL cholesterol and low levels of HDL cholesterol (high LDL/HDL ratios) are risk factors for atherosclerosis, while low levels of LDL cholesterol and high level of HDL cholesterol (low LDL/HDL ratios) are desirable.
Total cholesterol is the sum of LDL (low density) cholesterol, HDL (high density) cholesterol, VLDL (very low density) cholesterol, and IDL (intermediate density) cholesterol.
What determines the level of LDL cholesterol in the blood?
The liver not only manufactures and secretes LDL cholesterol into the blood; it also removes LDL cholesterol from the blood. A high number of active LDL receptors on the liver surfaces is associated with the rapid removal of LDL cholesterol from the blood and low blood LDL cholesterol levels. A deficiency of LDL receptors is associated with high LDL cholesterol blood levels.
Both heredity and diet have a significant influence on a person's LDL, HDL and total cholesterol levels. For example, familial hypercholesterolemia (FH) is a common inherited disorder whose victims have a diminished number or nonexistent LDL receptors on the surface of liver cells. People with this disorder also tend to develop atherosclerosis and heart attacks during early adulthood.
Diets that are high in saturated fats and cholesterol raise the levels of LDL cholesterol in the blood. Fats are classified as saturated or unsaturated (according to their chemical structure). Saturated fats are derived primarily from meat and dairy products and can raise blood cholesterol levels. Some vegetable oils made from coconut, palm, and cocoa are also high in saturated fats.
Does lowering LDL cholesterol prevent heart attacks and strokes?
Lowering LDL cholesterol is currently the primary focus in preventing atherosclerosis and heart attacks. Most doctors now believe that the benefits of lowering LDL cholesterol include:
- Reducing or stopping the formation of new cholesterol plaques on the artery walls;
- Reducing existing cholesterol plaques on the artery walls;
- Widening narrowed arteries;
- Preventing the rupture of cholesterol plaques, which initiates blood cot formation;
- Decreasing the risk of heart attacks; and
Decreasing the risk of strokes. The same measures that retard atherosclerosis in coronary arteries also benefit the carotid and cerebral arteries (arteries that deliver blood to the brain).
How can cholesterol be lowered?
Therapeutic lifestyle changes to lower cholesterol
Lowering LDL cholesterol involves losing excess weight, exercising regularly, and following a diet that is low in saturated fat and cholesterol.
Medications to lower cholesterol.
Medications are prescribed when lifestyle changes cannot reduce the LDL cholesterol to desired levels. The most effective and widely used medications to lower LDL cholesterol are called statins. Most of the large controlled trials that demonstrated the heart attack and stroke prevention benefits of lowering LDL cholesterol used one of the statins. Other medications used in lowering LDL cholesterol and in altering cholesterol profiles include nicotinic acid (niacin), fibrates such as fenofibrate (Tricor), resins such as cholestiramine (Questran), and ezetimibe, Zetia.
What are “normal” cholesterol blood levels?
There are no established “normal” blood levels for total and LDL cholesterol. In most other blood tests in medicine, normal ranges can be set by taking measurements from large number of healthy subjects. For example, normal fasting blood sugar levels can be established by performing blood tests among healthy subjects without diabetes mellitus.
Unfortunately, the normal range of LDL cholesterol among “healthy” adults (adults with no known coronary heart disease) in the United States may be too high. The atherosclerosis process may be quietly progressing in many healthy adults with average LDL cholesterol blood levels, putting them at risk of developing coronary heart diseases in the future.
Why is HDL the good cholesterol?
HDL is the good cholesterol because it protects the arteries from the atherosclerosis process. HDL cholesterol extracts cholesterol particles from the artery walls and transports them to the liver to be disposed through the bile. It also interferes with the accumulation of LDL cholesterol particles in the artery walls.
The risk of atherosclerosis and heart attacks in both men and is strongly related to HDL cholesterol levels. Low levels of HDL cholesterol are linked to a higher risk, whereas high HDL cholesterol levels are associated with a lower risk.
Very low and very high HDL cholesterol levels can run in families. Families with low HDL cholesterol levels have a higher incidence of heart attacks than the general population, while families with high HDL cholesterol levels tend to live longer with a lower frequency of heart attacks.
Like LDL cholesterol, life style factors and other conditions influence HDL cholesterol levels. HDL cholesterol levels are lower in persons who smoke cigarettes, eat a lot of sweets, are overweight and inactive, and in patients with type II diabetes mellitus.
HDL cholesterol is higher in people who are lean, exercise regularly, and do not smoke cigarettes. Estrogen increases a person's HDL cholesterol, which explains why women generally have higher HDL levels than men do.
For individuals with low HDL cholesterol levels, a high total or LDL cholesterol blood level further increases the incidence of atherosclerosis and heart attacks. Therefore, the combination of high levels of total and LDL cholesterol with low levels of HDL cholesterol is undesirable whereas the combination of low levels of total and LDL cholesterol and high levels of HDL cholesterol is favorable.
What are the treatment guidelines for low HDL cholesterol?
In clinical trials involving lowering LDL cholesterol, scientists also studied the effect of HDL cholesterol on atherosclerosis and heart attack rates. They found that even small increases in HDL cholesterol could reduce the frequency of heart attacks. For each 1 mg/dl increase in HDL cholesterol, there is a 2 to 4% reduction in the risk of coronary heart disease. Although there are no formal NCEP (please see discussion above) target treatment levels of HDL cholesterol, an HDL level of <40 mg/dl is considered undesirable and measures should be taken to increase it.
How can levels of HDL cholesterol be raised?
The first step in increasing HDL cholesterol levels (and decreasing LDL/HDL ratios) is therapeutic life style changes. When these modifications are insufficient, medications are used. In prescribing medications or medication combinations, doctors have to take into account medication side effects as well as the presence or absence of other abnormalities in cholesterol profiles.
Regular aerobic exercise, loss of excess weight (fat), and cessation of smoking cigarettes will increase HDL cholesterol levels. Regular alcohol consumption (such as one drink a day) will also raise HDL cholesterol. Because of other adverse health consequences of excessive alcohol consumption, alcohol is not recommended as a standard treatment for low HDL cholesterol.
Medications that are effective in increasing HDL cholesterol include nicotinic acid (niacin), fenofibrate (Tricor), estrogen, and to a much lesser extent, the statin drugs.
What are triglycerides, chylomicrons, and VLDL?
Triglyceride is a fatty substance that is composed of three fatty acids. Like cholesterol, triglyceride in the blood either comes from the diet or the liver. Also, like cholesterol, triglyceride cannot dissolve and circulate in the blood without combining with a lipoprotein. Thus, after a meal, the triglyceride and cholesterol that are absorbed into the intestines are packaged into round particles called chylomicrons before they are released into the blood circulation.
A chylomicron is a collection of cholesterol and triglyceride that is surrounded by a lipoprotein outer coat. (Chylomicrons contain 90% triglyceride and 10% cholesterol.)
The liver removes triglyceride and chylomicrons from the blood, and it synthesizes and packages triglyceride into VLDL (very low-density lipoprotein) particles and releases them back into the blood circulation.
Do high triglyceride levels cause atherosclerosis?
Whether elevated triglyceride levels in the blood lead to atherosclerosis and heart attacks is controversial. While most doctors now believe that an abnormally high triglyceride level is a risk factor for atherosclerosis, it is difficult to conclusively prove that elevated triglyceride by itself can cause atherosclerosis. However, it is increasingly recognized that elevated triglyceride is often associated with other conditions that increase the risk of atherosclerosis, including obesity, low levels of HDL- cholesterol, insulin resistance and poorly controlled diabetes mellitus, and small, dense LDL cholesterol particles.
What are the causes of elevated triglyceride levels?
In some people, abnormally high triglyceride levels (hypertriglyceridemia) are inherited. Examples of inherited hypertriglyceridemia disorders include mixed hypertriglyceridemia, familial hypertriglyceridemia, and familial dysbetalipoproteinemia.
Hypertriglyceridemia can often be caused by non-genetic factors such as obesity, excessive alcohol intake, diabetes mellitus, kidney diseasu, and estrogen- containing medications such as birth control pills.
How can elevated blood triglyceride levels be treated?
The first step in treating hypertriglyceridemia is a low fat diet with a limited amount of sweets, regular aerobic exercise, loss of excess weight, reduction of alcohol consumption, and stopping smoking. In patients with diabetes mellitus, meticulous control of elevated blood sugar is also important.
When medications are necessary, fibrates (such as Lopid or Tricor), nicotinic acid, and statin medications can be used. Lopid not only decreases triglyceride levels but also increases HDL cholesterol levels and LDL cholesterol particle size. Nicotinic acid lowers triglyceride levels, increases HDL cholesterol levels and the size of LDL cholesterol particles, as well as lowers the levels of Lp (a) cholesterol.
The statin drugs have been found effective in decreasing triglyceride as well as LDL cholesterol levels and, to a lesser extent, in elevating HDL cholesterol levels. In some patients, a combination of Lopid or Tricor with adjunctive statin therapy (see below) may be prescribed. While this combination is often effective in patients with complex lipid disorders, the potential for side effects may be increased and such patients should be under strict medical supervision.
Which medications are use to treat lipid disorders?
Lipid altering medications are used in lowering blood levels of undesirable lipids such as LDL cholesterol and triglycerides and increasing blood levels of desirable lipids such as HDL cholesterol. Several classes of medications are available in the United States, including HMG CoA reductase inhibitors (statins), nicotinic acid, fibric acid derivatives, and medications that decrease intestinal cholesterol absorption (bile acid sequestrants and cholesterol absorption inhibitors). Some of these medications are primarily useful in lowering LDL cholesterol, others in lowering triglycerides, and some in elevating HDL cholesterol. Medications also can be combined to more aggressively lower LDL, as well as in lowering LDL and increasing HDL at the same time.
Lipid altering medications commonly used in the United States
|
Medication class |
Medication examples |
Effects on blood lipids |
|
statins |
Pravachol, Mevacor, Lipitor, Lescol, Crestor, Zocor |
Most effective in lowering LDL, mildly effective in increasing HDL, mildly effective in lowering triglycerides |
|
Nicotinic acid (Niacin) |
Niacin, Niaspan, Slo-Niacin |
Most effective in increasing HDL, effective in lowering triglycerides, mildly to modestly effective in lowering LDL |
|
Fibric acid |
Lopid, Tricor |
Most effective in lowering triglycerides, effective in increasing HDL, minimally effective in lowering LDL |
|
Bile acid sequestrants |
Questran, Welchol, Colestid |
Mildly to modestly effective in lowering LDL, no effect on HDL and triglycerides |
|
Cholesterol absorption inhibitors |
Zetia |
Mildly to modestly effective in lowering LDL, no effect on HDL and triglycerides |
|
Combining nicotinic acid with statin |
Advicor (lovastatin+niaspan) |
Effective in lowering LDL and triglycerides and increasing HDL |
|
Combining a statin with an absorption inhibitor |
Vytorin (Zocor + Zetia) |
Synergistic in lowering LDL and effective in lowering LDL with low doses of each ingredient |