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February 9, 2010
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Improving Your Cholesterol Profile In-Depth

Medical Author Revision: Dennis Lee, M.D., Daniel Kulick, M.D.
Medical Editor: William C. Shiel Jr., MD, FACP, FACR

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?

Cholesterol, like oil, cannot dissolve in the blood unless it is combined with special proteins called lipoproteins. (Without combining with lipoproteins, cholesterol in the blood will turn into a solid substance.) The cholesterol that is secreted by the liver into the blood is combined either with very low-density lipoproteins (VLDL) or high-density lipoproteins (HDL). VLDL cholesterol is then metabolized in the bloodstream to produce LDL cholesterol. Cholesterol that is combined with low-density lipoproteins is called LDL cholesterol. Cholesterol that is combined with high-density lipoproteins is called 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. To remove LDL cholesterol from the blood, the liver relies on special proteins called LDL receptors that are normally present on the surface of liver cells. LDL receptors snatch LDL cholesterol particles from the blood and transport them inside the liver. 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. The resultant decreased activity of the LDL receptors limits the liver's ability to remove LDL cholesterol from blood. Thus, affected family members have abnormally high LDL cholesterol levels in the blood. They also tend to develop atherosclerosis and heart attacks during early adulthood.

Diets that are high in saturated fats and cholesterol decrease the LDL receptor activity in the liver, thereby raising 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?

Thirty years ago, observational studies suggested that high blood cholesterol could cause coronary atherosclerosis and heart attacks . Doctors in those days suspected (correctly) that lowering blood cholesterol could reduce heart attacks. They recommended a low fat diet and exercise to lower blood cholesterol and prescribed medications, such as statin drugs, only when diet and exercise failed.

However, doctors were not satisfied with observational studies because they are not as reliable as prospective, randomized, double-blind, placebo-controlled trials (controlled trials) in proving the safety and effectiveness of any treatment. An observational study is a retrospective analysis comparing health status of one group of subjects to another group (for example, comparing the rate of heart attacks among patients with high blood cholesterol levels to those with lower blood cholesterol levels). Observational studies can only demonstrate an association between higher cholesterol in the blood and higher risks of heart attacks. Conclusive proof that lowering one's blood cholesterol levels prevents heart attacks has to come from prospective, randomized, and placebo-controlled trials.

Therefore, researchers initiated numerous large-scale controlled trials to determine if lowering cholesterol actually prevents heart attacks. In a controlled trial, patients who are similar in age, sex, genetic background, and other characteristics, such as health status and diet are randomly assigned to receive either the test medication or a placebo. A placebo is a biologically inert substance (sugar powder or salt placed in capsules that are made to look like the test medication) that does not have any effect on the disease. The study is conducted in a double-blind fashion, meaning neither the patients nor the researchers know who is receiving the test medication or the placebo. At the end of the trial, treatment results from the medication treated group are compared to the placebo treated group to determine if the test medication is more effective than the placebo. The random assignment of study subjects and double blinding of subjects and researchers are important to eliminate human bias from these trials.

Today, many of the large, multi-year controlled trials have been completed. These trials have consistently and conclusively shown that lowering LDL cholesterol reduces the risk of heart attacks and strokes and prolongs life. These trials have further shown that the benefits of lowering cholesterol outweigh the risks of side effects of the statin medications. Therefore, doctors are much more willing to use medications, such as statins, to lower cholesterol, and the "desirable cholesterol level" has been rapidly reduced.

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 clot 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).


Next: How can LDL cholesterol levels be lowered? »

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What is a heart attack?

A heart attack (also known as a myocardial infarction) is the death of heart muscle from the sudden blockage of a coronary artery by a blood clot. Coronary arteries are blood vessels that supply the heart muscle with blood and oxygen. Blockage of a coronary artery deprives the heart muscle of blood and oxygen,causing injury to the heart muscle. Injury to the heart muscle causes chest pain and chest pressure sensation. If blood flow is not restored to the heart muscle within 20 to 40 minutes, irreversible death of the heart muscle will begin to occur. Muscle continues to die for six to eight hours at which time the heart attack usually is "complete." The dead heart muscle is eventually replaced by scar tissue.

Approximately one million Americans suffer a heart attack each year. Four hundred thousand of them die as a result of their heart attack.

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