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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Last Editorial Review: 4/13/2005
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