Overview
Hypercholesterolemia, or high cholesterol,
is a high level of cholesterol in the blood that can cause
plaque to form and accumulate leading to blockages in the
arteries (atherosclerosis), increasing the risk for heart
attack, stroke, circulation problems, and death.
What Is Cholesterol?
Cholesterol is a soft, waxy fat particle (lipid) that
circulates in the blood. It has several important
functions in the body: it is a building block for all cell
membranes and many sex hormones, and is the digestive
substance released by the gall bladder.
The body produces cholesterol in the liver.
The liver, in fact, produces almost all of the cholesterol
the body needs. However, many popular foods contain
cholesterol and the substances used to produce cholesterol
particles, which can increase the amount of cholesterol in
the blood.
How Cholesterol Causes Atherosclerosis
The development of plaque and blockages in the arteries,
atherosclerosis, involves several steps.
1.
The innermost lining of the arteries (the
endothelium) is damaged or becomes dysfunctional
and cholesterol particles deposit into the damaged wall.
2.
The cholesterol becomes incorporated into a
mixture called plaque, which is composed of
cholesterol, other fatty substances, fibrous tissue, and
calcium.
3.
As more cholesterol and other substances
incorporate, the plaque grows, narrowing the artery.
Plaque build-up can grow large enough to
impede blood flow through the artery (called a blockage).
When the arteries supplying the heart with blood are
blocked, chest pain (angina) may occur; when arteries in
the legs are blocked, leg pain or cramping may occur; when
arteries supplying the brain with blood are blocked,
stroke may occur.
If the plaque ruptures, a blood clot may
develop on top of it. If the blood clot completely blocks
blood flow through a coronary artery, it may result in a
heart attack (myocardial infarction); if it occurs in an
artery supplying blood to the brain, it may result in a
stroke.
Evidence that High Cholesterol Levels are
Bad
Many studies have looked at the relationship between high
cholesterol levels and heart attack and death. In one
study of young men without known heart disease,
cholesterol levels were measured and participants were
followed for 6 years. During this time, researchers
recorded heart attacks and deaths that occurred in the
participants.
The higher the cholesterol level, the greater the
risk for having a fatal heart attack. In fact, the risk
for a fatal heart attack is about 5 times higher in those
with a cholesterol level of 300 mg/dL or more than in
those with a cholesterol level below 200 mg/dL.
The Framingham Heart Study is probably the
most famous ongoing heart study in the world. Cholesterol
levels, smoking habits, heart attack rates, and deaths in
the population of an entire town have been recorded for
over 40 years. After 30 years, over 85% of people with
cholesterol levels of 180 mg/dL or less were still alive;
almost 33% of those with cholesterol levels greater than
260 mg/dL had died.
There have been many studies examining the
relationship between cholesterol levels and heart attacks
and death. There is overwhelming evidence that high
cholesterol levels increase the risk for heart attack,
circulation problems in the legs, stroke, and death.
Screening
A committee of cholesterol experts wrote
recommendations for cholesterol screening and treatment
for the National Institutes of Health, which are
summarized in the National Cholesterol Education Program (NCEP).
The guidelines suggest that all adults have their
cholesterol levels checked at least once every 5 years.
The NCEP recommends checking the total
cholesterol and HDL cholesterol levels. However, since
many cholesterol-management decisions are based primarily
on LDL cholesterol levels, patients may consider having a
full lipid profile (total cholesterol, HDL cholesterol,
LDL cholesterol, and triglycerides). Triglyceride and
calculated LDL levels are affected by eating, so fasting
for at least 9 hours before testing is necessary.
Patients with coronary artery disease or
other forms of atherosclerosis are at the highest risk for
heart attack and stroke and benefit the most from
cholesterol-reduction therapy. Therefore, these patients
should have a full lipid profile reassessed every year.
What Cholesterol Levels Require Treatment?
There is no formula to determine what level of cholesterol
is considered "safe" and what level of cholesteral
requires treatment. Cholesterol experts, including those
who wrote the NCEP guidelines, have come up with general
recommendations based on ongoing research.
The NCEP based its recommendations, in
part, on the future risk for heart attack. This makes
sense, because someone who has no risk factors for
coronary artery disease or heart attack can tolerate a
somewhat elevated cholesterol level. In someone with
established coronary artery disease, the risks for heart
attack (or additional heart attacks) and death are much
higher, so even a mildly elevated cholesterol level must
be aggressively treated.
NCEP recommendations are based on the LDL
cholesterol level because it correlates best with risk for
heart attack and death, and because treatment of the LDL
level has been the focus of recent studies.
All these considerations make the
recommendations a little complex. Fortunately, several
general guidelines have emerged. Different physicians may
suggest different levels at which therapy should be
started, and different goals of therapy, so it is
important to discuss your levels with your doctor.
Many physicians recommend that patients
without known atherosclerosis should strive to lower their
LDL cholesterol level if it is above 160-190 mg/dL. The
more risk factors for coronary artery disease one has
(e.g., diabetes, high blood pressure, cigarette smoking,
history of premature heart disease in parents or brothers
and sisters), the less tolerance there should be for high
LDL levels. Most physicians agree that patients with known
atherosclerosis whose LDL levels are above 100-130 mg/dL
should be treated.
Target LDL Cholesterol Level
There is no golden number below which an LDL level is
considered "safe." Target levels vary, depending on the
individual. Again, one should discuss the goals of
cholesterol therapy with one's physician. The following is
presented only as a general discussion.
Many physicians follow the recommendations
of the NCEP and establish a target LDL level below 130-160
mg/dL for patients without known atherosclerosis. For
patients with no other cardiac risk factors (e.g.,
diabetes, high blood pressure, cigarette smoking, family
history of premature heart disease), a level below 160 may
be acceptable.
For those with multiple cardiac risk
factors, a level below 130 mg/dL may be considered more
desirable. For those who have atherosclerosis, many
physicians believe LDL should be brought down to a level
below 100 mg/dL, the target level set by the NCEP
Treatment
The treatment approach to abnormal lipid
levels differs depending on which lipid is high. For the
purposes of simplicity, the focus here is on management of
a high LDL ("bad") cholesterol level.
There are basically two ways to lower LDL
cholesterol: with medication (pharmacological
therapy) and without medication (nonpharmacological
therapy).
Nonpharmacological Therapy
Standard nonpharmacological therapy consists primarily of
modifying eating and exercise habits. This therapy often
modestly reduces LDL cholesterol but is not likely to
lower the LDL cholesterol level by more than about 30 mg/dL.
When can nonpharmacological therapy be
used?
For people without atherosclerosis and with modestly
elevated LDL cholesterol levels, the urgency to treat with
medication is not great. An initial 6-12 month trial of
nonpharmacological therapy may be advised by some
physicians. If the LDL cholesterol has fallen to an
acceptable level within that time frame, the patient can
continue with these interventions only. If the level
remains high, however, drug therapy should be initiated.
Changing diet can decrease the cholesterol
level by about 8%-14%, which may be enough to reach the
target level in some cases. However, diet and other
lifestyle modifications generally do not decrease LDL
levels by more than 30 mg/dL. If your LDL level is notably
elevated, you may want to discuss with your doctor the
possibility of adding drug therapy to your treatment plan.
People with established atherosclerosis
have the incentive to significantly lower their high LDL
levels. Most practitioners agree that both drug therapy
and lifestyle modifications are needed, particularly
because there is such good evidence that medication
significantly decreases the chances of having a future
heart attack or stroke and increases the chances for
living longer.
What lifestyle changes can bring about
lower LDL cholesterol levels?
Several are commonly accepted as positively impacting
elevated cholesterol levels:
-
Diet.
Minimize excess cholesterol and fat intake, especially
saturated fat. These fats raise cholesterol levels more
than any other substances. Cholesterol and saturated
fats are found primarily in foods derived from animals,
such as meats and dairy products. Unwanted cholesterol
and fats lurk in many foods that might never be
suspected of having high amounts of these substances.
Here are some dietary guidelines for reducing
cholesterol and fat consumption:
1.
Eat lean fish, poultry, and meat. Remove
the skin from chicken and trim the fat from beef before
cooking.
2.
Avoid eating commercially prepared and
processed food (cakes, cookies, etc.)
3.
Increase the relative amount of fruits,
vegetables, breads, cereals, rice, legumes, and pasta.
4.
Use skim or 1% milk.
5.
Avoid breaded fried foods.
6.
Eat no more than 2 egg yolks (or whole
eggs) per week.
7.
Use cooking oils that are high in
unsaturated fat (e.g., corn, olive, canola, safflower
oils)
8.
Use soft margarines. They contain less
saturated fat.
-
Weight loss.
Losing modest amounts of weight (even only 5-10 lbs.)
can double the reduction in LDL levels achieved through
an improved diet. Weight loss should be achieved
gradually by modestly decreasing calorie intake and
increasing exercise.
-
Exercise.
Exercise can decrease LDL levels and increase HDL levels
to some extent. For example, taking a brisk 30-minute
walk or a low-level jaunt on a treadmill 3-4 times a
week is likely to positively impact the cholesterol
profile. Patients with chest pain and/or known or
suspected heart disease should talk to their doctors
before beginning any exercise program.
Pharmacological (Drug) Therapy
The introduction of HMG-CoA reductase inhibitors
(or
statins)
significantly advanced the treatment of
hypercholesterolemia. Statins lower LDL cholesterol levels
by 20%-40%. At maximum doses, they lower LDL levels by an
amazing 40%-50%. They provide the added benefit of
modestly increasing HDL ("good") cholesterol levels,
usually by about 5%-10%.
These agents are usually well tolerated,
have few side effects, and need to be taken only once or
twice a day. Because the body produces cholesterol
primarily during the night, most of these medicines should
be taken after dinner or during the evening. A high dose
can be split and taken once in the morning and once in the
evening.
Should patients already taking one of the
older types of cholesterol-lowering medications switch to
a statin? Several things should be kept in mind. First,
some people are possibly being treated with a different
type of medication because the primary lipid problem may
not be a high LDL level but some other abnormality, such
as a markedly high triglyceride level.
Second, if treatment with an older type of
medication is working well and the patient is satisfied,
there's no reason to change. However, if the person
doesn't take the medication regularly because it's hard to
remember to take several doses every day, because it has
unpleasant side effects, or because it has failed to lower
the LDL to an acceptable level, it may be worthwhile to
discuss switching to one of the statins with a physician.
Statins.
Commonly prescribed statins include: atorvastatin (Lipitor®),
cerivastatin (Baycol®), fluvastatin (Lescol®), lovastatin
(Mevacol), pravastatin (Pravachol®), and simvastatin (Zocor®).
There are two rare but potential side
effects associated with these medications. The first,
mild inflammation of the liver, can be detected by simple
blood tests (liver function tests, or LFTs). The tests are
usually performed once or twice during the first several
months of therapy and then periodically (e.g., twice a
year) thereafter. The second very rare side effect is
muscle inflammation, soreness, pain, and weakness. Because
this occurs so rarely, no routine testing is performed.
However, a patient who develops diffuse muscle pain or
weakness should speak with his or her doctor.
Occasionally, even with high-dose statin
therapy, the LDL level may not decrease sufficiently. In
this case, another cholesterol-lowering medication may be
added.
Other medications.
These medications, when combined with a statin, may help
lower cholesterol to an acceptable level. Patients should
be aware that using the combination may increase the risk
for liver and/or muscle inflammation. These drugs include:
cholestyramine (LoCHOLEST®, Questran®), colestipol (Colestid®),
fenofibrate (Tricor®), fluvastatin (Lescol®), gemfibrozzil
(Lopid®), and niacin (Niacinol®, Niacor®, Nicolar®, Slo-Niacin®).
Alternative Treatment
Most alternative medicines and therapies
have not been subjected to scientific investigation,
making it hard to assess their effectiveness. Some
objective information, however, has emerged.
-
Garlic.
The medicinal properties of garlic (used by the
Babylonians and other ancient peoples in their
medicines) continue to be debated. The debate has
instigated a number of studies examining garlic's effect
on cholesterol levels. When combined, the results of
some of the earlier studies suggest that garlic may
lower total cholesterol levels by an average of about
9%. However, some of the recent, more well-designed
studies (in which half of the group was treated with
garlic and the other half with a placebo) have found no
beneficial effect produced by garlic on either total
cholesterol or LDL levels. What can be concluded from
this? The best that can be said, from a scientific point
of view, is that garlic may at most have a modest effect
on cholesterol levels but should not be used instead of
other interventions.
-
Oat
bran.
Oat bran mania swept across the United States a decade
ago. Research (including one report published in the
New England Journal of Medicine)
found that oat bran, per se, had little impact on
cholesterol levels. Rather, any beneficial effects were
attributable to the fact that people were eating more
oat bran and less fat.
-
Cholesterol-lowering margarine.
The Food and Drug Administration (FDA) recently approved
two of these products, Benecol® and Take Control®, for
marketing. These margarines contain plant-derived
substances that can decrease the absorption of
cholesterol in the digestive tract. They modestly reduce
cholesterol by about 7%-10%. They should not be used
instead of drug therapy but can be added to a treatment
plan for hypercholesterolemia.
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