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Lowering Your Cholesterol

Heart Attack Prevention Series

Medical Author Revision: Dennis Lee, M.D., Daniel Kulick, M.D.


Medical Editor: William C. Shiel Jr., MD, FACP, FACR

What is cholesterol?
How can LDL cholesterol levels be lowered?
What are the 2004 NCEP cholesterol treatment guidelines?
Why is HDL the good cholesterol?
What are triglycerides, chylomicrons, and VLDL?
What are lipid-altering medications?
What are the statin drugs?
What is nicotinic acid?
What are fibric acid derivatives (fibrates)?
What are bile acid sequestrants?
What is ezetimibe (Zetia)?
Is lowering LDL cholesterol enough?
What is lipoprotein (a), (Lp(a)) cholesterol?
Related cholesterol articles on WebMD:
Triglycerides
High cholesterol
Cholesterol levels
Related cholesterol article on eMedicineHealth:
High cholesterol

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

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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?

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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 clot
formation;
Decreasing the risk of heart attacks; and

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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 LDL cholesterol levels 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. For more,
please read the TLC, Therapeutic Lifestyle Changes article.

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 gemfibrozil (Lopid), resins such as
cholestyramine (Questran), and ezetimibe, Zetia. (An in-depth discussion of
these drugs is presented in this article starting at the heading: What are the
statin drugs?)

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. If a patient's fasting blood

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glucose falls within this normal range, he/she most likely does not have
diabetes mellitus, whereas if the patient's fasting blood sugar tests higher
than the normal range, he/she probably has diabetes mellitus and further
tests can be performed to confirm the diagnosis. Medications, such as insulin
or oral diabetes medications can be prescribed to lower abnormally high
blood sugar levels.

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.

What are the 2004 NCEP cholesterol treatment guidelines?

After reviewing these large randomized cholesterol-lowering trials, The


National Cholesterol Education Program (NCEP) expert panel published their
new recommendations. The new NCEP recommendations, presented in the
June, 2004 issue of Circulation, are:

1. The report advised physicians to consider more intensive LDL


cholesterol-lowering for people at very high, high, and moderately high
risk for a heart attack. These options include setting lower treatment
goals for LDL cholesterol and initiating cholesterol-lowering drug
therapy at lower LDL thresholds, as compared to ATP III guidelines
published in 2001. For example, for patients with a very high risk of
heart attacks, the LDL cholesterol treatment goal remains at < 70
mg/dl.
2. The report emphasized the importance of initiating therapeutic
lifestyle changes (TLC) to modify lifestyle-related risk factors
(obesity, physical inactivity, metabolic syndrome, high blood

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triglyceride levels and low HDL cholesterol levels). TLC Lifestyle
changes have the potential to reduce heart attack and stroke risks
through several mechanisms beyond the lowering of LDL cholesterol.
3. When LDL-lowering medication is used for very high, high or
moderately high risk patients, the report advises that the intensity of
LDL-lowering drug therapy be sufficient to achieve at least a 30 to 40
percent reduction in LDL cholesterol levels.
4. When a very high or high risk patient also has high blood triglyceride
or low HDL cholesterol levels, doctors may consider combining nicotinic
acid or a fibrate with a statin. Nicotinic acid and fibrates are more
effective than statins in lowering triglycerides and increasing HDL.
5. Age should not be a consideration since older persons also benefit
from lowering LDL cholesterol. Thus, it is never too late or the patient
too old to begin lifestyle changes and medications to lower LDL
cholesterol. A word of caution is in order. Elderly patients are more
likely to have liver and kidney dysfunction, and are also more likely to
be on multiple medications some of which may interfere with the
breakdown of cholesterol-lowering drugs such as statins. Thus lower
dosing may be necessary to avoid adverse side effects.

The 2004 NCEP treatment goals according to risk categories

More intense
Risk Initiate TLC if Consider drugs +
LDL goal LDL goal
category LDL is: TLC if LDL is:
option
< 100
High risk > 100 mg/dl >100 mg/dl
mg/dl
Very high < 100
< 70 mg/dl > 100 mg/dl
risk mg/dl
Moderatel > 130 mg/dl >130mg/dl, consider
y high risk drug option if LDL is
(10 yr. 100-129 mg/dl
risk 10-

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20%)
Moderate
risk (10
> 130 mg/dl >160 mg/dl
yr. risk
<10%)
>190 mg/dl, consider
Lower risk > 160 mg/dl drug optional if LDL is
160-189 mg/dl

High risk patients are those who already have coronary heart disease
(such as a prior heart attack), diabetes mellitus, abdominal aortic
aneurysm, or those who already have atherosclerosis of the arteries to
the brain and extremities (such as patients with strokes, TIA's (mini-
strokes), and peripheral vascular diseases). High risk patients also
include those with 2 or more risk factors (e.g., smoking, hypertension,
or a family history of early heart attacks) that places them at a greater
than 20 percent chance of having a heart attack within 10 years. (A
person's chance of having a heart attack can be calculated by using
the Framingham Heart Study Score Sheets, at
http://nhlbi.nih.gov/about/framingham/riskabs.htm).
Very high -risk patients are those who have coronary heart disease in
addition to having either multiple risk factors (especially diabetes), or
severe and poorly controlled risk factors (such as continued smoking),
or metabolic syndrome (a constellation of risk factors associated with
obesity, including high triglycerides and low HDL). Patients hospitalized
for acute coronary syndromes are also at very high risk.
Moderately high risk patients are those who have neither coronary
heart disease nor diabetes mellitus, but have multiple (2 or more) risk
factors for coronary heart disease that put them at a 10 to 20 percent
risk of heart attack within 10 years. (Use the Framingham Heart Study
Score Sheets, at http://nhlbi.nih.gov/about/framingham/riskabs,htm to
calculate the 10 year risk.)

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Moderate risk patients are those who have neither CHD nor diabetes
mellitus, but have 2 or more risk factors for coronary heart disease
that put them at a
Lower risk patients are those with 0 to 1 risk factor for coronary
heart disease.

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.

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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 LDL/HDL and total/HDL ratios?

The total cholesterol to HDL cholesterol ratio (total chol/HDL) is a number that
is helpful in estimating the risk of developing atherosclerosis. The number is
obtained by dividing total cholesterol by HDL cholesterol. (High ratios indicate
a higher risk of heart attacks, whereas low ratios indicate a lower risk).

High total cholesterol and low HDL cholesterol increases the ratio and is
undesirable. Conversely, high HDL cholesterol and low total cholesterol
lowers the ratio and is desirable. An average ratio would be about 4.5.
Ideally, one should strive for ratios of 2 or 3 (less than 4).

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

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

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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), gemfibrozil (Lopid), estrogen, and to a much lesser extent, the
statin drugs (discussed below). A newer medicine, fenofibrate (Tricor) has
shown much promise in selectively increasing HDL levels and reducing serum
triglycerides.

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.

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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 disease, 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

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of alcohol consumption, and stopping cigarette smoking. In patients with
diabetes mellitus, meticulous control of elevated blood glucose is also
important.

When medications are necessary, fibrates (such as Lopid), 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. A relatively new medicine, fenofibrate (Tricor), shows promise as an
effective agent in lowering serum triglyceride levels as well as raising HDL
levels, particularly in patients who have had suboptimal responses to Lopid.
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.

What are lipid-altering medications?

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

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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


Most effective in lowering
Pravachol, Mevacor,
LDL, mildly effective in increasing
statins Lipitor, Lescol, Crestor,
HDL, mildly effective in lowering
Zocor
triglycerides
Most effective in increasing
Nicotinic acid Niacin, Niaspan, Slo- HDL, effective in lowering
(Niacin) Niacin triglycerides, mildly to modestly
effective in lowering LDL
Most effective in lowering
triglycerides, effective in
Fibric acid Lopid, Tricor
increasing HDL, minimally
effective in lowering LDL
Mildly to modestly effective in
Bile acid Questran, Welchol,
lowering LDL, no effect on HDL
sequestrants Colestid
and triglycerides
Cholesterol Mildly to modestly effective in
absorption Zetia lowering LDL, no effect on HDL
inhibitors and triglycerides
Combining Effective in lowering LDL and
Advicor
nicotinic acid triglycerides and increasing
(lovastatin+niaspan)
with statin HDL
Combining a Synergistic in lowering LDL
statin with an and effective in lowering LDL
Vytorin (Zocor + Zetia)
absorption with low doses of each
inhibitor ingredient

What are the statin drugs?

The statins are the most widely used, and also the most powerful medications

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for lowering LDL cholesterol. Numerous large, randomized, double-blind,
placebo-controlled, , clinical trials (controlled trials) have shown that statins
reduce heart attacks (and strokes) and improve survival. Statins are well
tolerated with low side effect rates when used long term. Statins not only
lower blood LDL cholesterol levels, they also modestly increase HDL
cholesterol levels and modestly decrease triglyceride levels. The statins that
are now on pharmacy shelves in the U.S. (putting the generic name first
followed by the brand name in parentheses) are:

rosuvastatin ( Crestor)
fluvastatin sodium (Lescol) made by Novartis
atorvastatin calcium (Lipitor) made by Parke-Davis and Pfizer
lovastatin (Mevacor) made by Merck
pravastatin sodium (Pravachol) made by Bristol-Myers Squibb
simvastatin (Zocor) made by Merck

Studies have consistently shown that lowering LDL cholesterol with diet and
statins reduces the risk of a second heart attack. The prevention of recurrent
heart attacks in patients who have already suffered a heart attack is called
secondary prevention.

Studies have also demonstrated that reducing LDL cholesterol with lifestyle
changes and statins reduces the risk of having the first heart attack.
Prevention of heart attacks in those who have never had a heart attack is
called primary prevention.

Studies have also confirmed that reducing LDL cholesterol benefits both men
and women, and the elderly. For more, please read our article on Statins.

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How do doctors select statin drugs?

Which statin to use is an individualized decision. There are several


considerations in choosing a statin:

In patients who need intense LDL cholesterol-lowering, it is more


appropriate to use one of the more potent statins, such as atorvastatin
(Lipitor) or rosuvastatin (Crestor). Sometimes a statin may need to be
combined with another medication such as cholestyramine (Questran),
ezetimibe (Zetia) or nicotinic acid, in order to achieve the LDL
cholesterol goals.
In patients with chronic liver disease who need statin treatment, it is
important to completely abstain from alcohol and use either
pravastatin (Pravachol) or rosuvastatin (Crestor) in low doses.
(Pravastatin and rosuvastatin are safer to use in patients with liver
disease.) If LDL cholesterol goals cannot be attained with low doses of
either of these two statins, cholestyramine (Questran) or ezetimibe
(Zetia) can be added.
In patients who develop muscle aches or muscle damage with a statin,
it may be appropriate to try another statin, such as pravastatin
(Pravachol), that probably has less of a muscle toxic effect than the
other statins. In patients who are at risk of developing muscle injury
(for example a patient who is already taking gemfibrozil), pravastatin
(Pravachol) would also be a suitable statin to use.
Atorvastatin (Lipitor) and fluvastatin (Lescol) do not require dose
adjustments in patients with kidney diseases.

What is nicotinic acid (niacin)?

Nicotinic acid (niacin) is a B vitamin. An average American diet contains 15-


30 mg of niacin per day. However, in treating blood cholesterol and
triglyceride disorders, high doses (1-3 grams a day) of nicotinic acid are
necessary. Nicotinic acid is available in several preparations that include

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immediate release niacin, sustained release prescription brand Niaspan, and
over- the- counter (OTC) sustained release niacin. OTC preparations are not
federally regulated, and some OTC preparations may have no active
ingredient. Thus, they would be ineffective in either lowering LDL or raising
HDL cholesterol. Some formulations of OTC sustained release niacin have
been associated with liver toxicity and rare cases of fulminant (usually fatal
without liver transplantation) hepatitis have been reported. The prescription
brand sustained release Niaspan has been found in clinical trials to cause
only minor elevations in blood liver enzymes without causing significant liver
disease.

Nicotinic acid is most effective in increasing HDL cholesterol and it is also


modestly effective in lowering LDL cholesterol, Lp(a) cholesterol, and
triglyceride levels (see below). Nicotinic acid is most suited for individuals
whose only problem is low HDL cholesterol. Nicotinic acid used alone can
raise HDL cholesterol levels by 30% or more. Nicotinic acid is not as effective
as a statin in lowering LDL cholesterol levels. Therefore, when low HDL
cholesterol is accompanied by high LDL cholesterol, most doctors use a statin
to decrease the LDL cholesterol first. If necessary, nicotinic acid can be added
to a statin to further raise HDL cholesterol levels.

Advicor is a combination product approved for use in the United States. It is a


combination of sustained release niacin with lovastatin. Advicor is useful in
patients who need to both significantly lower their LDL cholesterol and
increase HDL cholesterol. For more, please read our article on Nicotinic acid.

What are fibric acid derivatives (fibrates)?

Fibric acid derivatives (fibrates) are effective medications in lowering blood


triglyceride levels. Fibrates lower blood triglyceride levels by inhibiting the
liver production of VLDL (the triglyceride-rich lip-protein fraction), and by
speeding up the removal of triglycerides from the blood. Fibrates are also
modestly effective in increasing blood HDL cholesterol levels. However,
fibrates are not effective in lowering LDL cholesterol. Examples of fibrates

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available in the United Sates include Gemfibrozil (Lopid) and fenofibrate
(Tricor).

Very high triglyceride levels (usually > 1000 mg/dl) can cause pancreatitis
(inflammation of the pancreas that can result in a serious an illness with
severe abdominal pain). By lowering the blood triglycerides, fibrates are used
to prevent pancreatitis.

Fibrates are not effective in lowering LDL cholesterol and cannot be used
alone in lowering LDL cholesterol levels. However, when a high risk patient
(see NCEP recommendations above) also has high blood triglyceride or low
HDL cholesterol levels, doctors may consider combining a fibrate, such as
fenofibrate (Tricor), with a statin. Such a combination will not only lower the
LDL cholesterol, but will also lower blood triglycerides and increase HDL
cholesterol levels.

Fibrates have also been used alone to prevent heart attacks especially in
patients with elevated blood triglycerides and low HDL cholesterol levels. In
one large study, gemfibrozil decreased the risk of heart attacks but did not
affect the overall survival of persons with high cholesterol levels. For more,
please read our article on Fibrates.

What are bile acid sequestrants?

Bile acid sequestrants such as Cholestyramine (Questran), colestipol


(Colestid), and colesevelam (Welchol) are medications for lowering LDL
cholesterol. Bile acid sequestrants bind bile acids in the intestine and cause
more of the bile acids to be excreted in the stool. This reduces the amount of
bile acids returning to the liver and forces the liver to produce more bile acids
to replace the bile acids lost in the stool. In order to produce more bile acids,
the liver converts more cholesterol into bile acids, which lowers the level of
cholesterol in the blood.

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Bile acid sequestrants have modest LDL cholesterol-lowering effects. Low
doses (for example 8 gram/day of Cholestyramine) can lower LDL cholesterol
by 10%-15 %. But even high doses (24 gram/day of cholestyramine) can only
lower LDL cholesterol by approximately 25%. Therefore, bile acid
sequestrants used alone are not as effective as statins in lowering LDL
cholesterol.

However, bile acid sequestrants are most useful in combining with a statin or
niacin to aggressively lower LDL cholesterol levels. The statin-bile acid
sequestrant combination can lower LDL cholesterol levels by approximately
50%, lower than a statin alone. A statin-niacin combination can substantially
reduce LDL cholesterol and elevate HDL cholesterol. For more, please read
our article on Bile Acid Sequestrants.

What is ezetimibe (Zetia)?

Ezetimibe lowers blood cholesterol by blocking the absorption of cholesterol,


including dietary cholesterol, from the intestines. It does not affect, however,
the absorption of triglycerides or fat-soluble vitamins. Ezetimibe was
approved by the FDA in October, 2002.

Ezetimibe can be used alone or together with a statin drug. Ezetimibe used
alone is modestly effective in lowering LDL cholesterol. At a dose of 10
mg/day it can reduce LDL cholesterol by approximately 17%. When used with
a statin, it can reduce LDL cholesterol level further than a statin alone.
However, there is insufficient scientific data to determine whether a statin-
ezetimibe combination actually further reduces heart attack or stroke risks. A
new combination drug, Vytorin, is available and combines 10 mg of Zetia with
20, 40, or 80 mg of Zocor.

Ezetimibe is probably most useful in avoiding having to use high doses of a


statin to achieve the 2004 NCEP LDL cholesterol targets in certain patients.
Using lower doses of a statin probably reduces the risk of muscle injury. A

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statin-ezetimibe combination may also be helpful in treating patients with
very high LDL cholesterol who cannot attain LDL cholesterol targets even with
maximal doses of statins. Ezetimibe can be taken with or without food and at
the same time as statin drugs.

Ezetimibe is well-tolerated. The overall rate of side effects with ezetimibe in


clinical studies was similar to that reported with a placebo (an inactive sugar
pill). Diarrhea, abdominal pain, back pain, joint pain, and sinusitis were the
most commonly reported side effects, occurring in 1 in every 25 to 30
patients

Is lowering LDL cholesterol enough?

Unfortunately, the prevention and treatment of atherosclerosis are more


complicated than just lowering LDL cholesterol levels. LDL cholesterol
reduction is only half of the battle against atherosclerosis. Individuals who
have normal or only mildly elevated LDL cholesterol levels can still develop
atherosclerosis and heart attacks even in the absence of other risk factors
such as cigarette smoking, high blood pressure, and diabetes mellitus.
Additionally, successfully lowering elevated LDL cholesterol levels cannot
always prevent atherosclerosis and heart attacks. In many clinical trials to
lower LDL cholesterol, there were patients who adhered to their assigned
diets, faithfully took their cholesterol-lowering medications, and successfully
lowered their LDL cholesterol to target levels, yet still suffered progressive
atherosclerosis and heart attacks. It is clear that while lowering LDL
cholesterol below NCEP target levels is an important step, there are other
factors involved.

What is lipoprotein (a), (Lp(a)) cholesterol?

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Lipoprotein (a) (Lp(a)) is an LDL cholesterol particle that is attached to a
special protein called apo(a). In large part, a person's level of Lp(a) in the
blood is genetically inherited. Elevated levels of Lp(a) (higher than 20 mg/dl
to 30 mg/dl) in the blood are linked to a greater likelihood of atherosclerosis
and heart attacks in both men and women. The risk is even more significant if
the Lp(a) cholesterol elevation is accompanied by high LDL/HDL ratios.

Certain diseases are associated with elevated Lp(a) levels. Patients on


chronic kidney dialysis and those with nephrotic syndromes (kidney diseases
that cause leakage of blood proteins into the urine) tend to have high levels
of Lp(a).

There are many theories as to how Lp(a) causes atherosclerosis although


exactly how Lp(a) accumulates cholesterol plaques on the artery walls has
not been well defined. Clinical trials conclusively proving that lowering Lp(a)
reduces atherosclerosis and the risk of heart attacks have not been
conducted. Currently, there is no international standard for determining Lp(a)
cholesterol levels and commercial sources of Lp(a) testing may not have the
same accuracy as research laboratories. Therefore, specifically measuring
and treating elevated Lp(a) cholesterol levels are not widely performed in this
country.

How can Lp(a) cholesterol levels be reduced?

Most lipid-lowering medications such as statins, Lopid, and cholestyramine


have a limited effect in lowering Lp(a) cholesterol levels. Estrogen has been
shown to lower Lp(a) cholesterol levels by approximately 20% in women with
elevated Lp(a) cholesterol. Estrogen can also increase HDL cholesterol levels
when given to postmenopausal women. Additionally, nicotinic acid (Niacin or
Niaspan) in high doses has been found to be effective in lowering Lp(a)
cholesterol levels by approximately 30%.

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***

Mr. D.T.'s Story - There Is Hope

Medical Author: Dennis Lee, M.D.

I am sure many of you have been reminded by doctors, nurses, and public
health officials to lose excess weight, quit smoking cigarettes, exercise
regularly, and eat less saturated fat and sweets. Here is a real life example of
how effective these measures can be.

Mr. DT is a healthy and active 50-year-old man. He exercises 6 days a week.


He does not smoke cigarettes. He tries to hold down fat and cholesterol
intake; he only cheats on weekends and holidays. He is slightly overweight
(only 12 pounds heavier than ideal body weight). His mild high blood pressure
has been well controlled with an oral medication called anACE inhibitor. There
is no family history of any heart diseases.

Last week, he asked his doctor for a complete blood panel that includes
cholesterol and triglyceride levels, since he has not had one for more than a
year. The nurse who drew his blood first noticed there was something wrong;
Mr. DT's serum was abnormally discolored. Before performing blood chemistry
measurements, she had to spin the blood sample in a centrifuge to separate
the red and white blood cells from the serum. Normal serum is clear yellow in
color. But Mr. DT's serum was pink and milky. Milky serum indicates excess
chylomicrons (protein complexes that contain high amounts of triglycerides
and cholesterol).

The laboratory reported the following morning that Mr. DT's cholesterol is
elevated at 260mg/dl, but more importantly his triglyceride level was 2,500
mg/dl! Normal triglyceride levels should be less than 150mg/dl. His good
cholesterol (HDL) is abnormally depressed at 20 mg/dl. These cholesterol and

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triglyceride levels not only increased his risk of developing arteriosclerosis of
the arteries, the sky high triglycerides put him at risk of developing acute
pancreatitis---a painful, serious inflammation of the pancreas.

His doctor wasted no time in placing him on a strict low saturated fat and low
sweets diet, along with a medication that lowers triglycerides and increases
HDL. Over the weekend Mr. DT adhered faithfully to the prescribed diet and
the medication without cheating. Yes, he walked away from tiramisu,
chocolate cheesecake, mud pie, and fried calamari.

The doctor called Mr. DT into his office Monday morning for a repeat blood
test, only three days into treatment. This time, his cholesterol had dropped
down to 211 mg/dl, his HDL had risen to 44 mg/dl, and most impressively his
triglyceride level had dropped from 2,500 to 35 mg/dl.

Granted, such rapid response to treatment is unusual. Most of the time we do


not enjoy such dramatic and satisfying treatment results. But this case did
teach me three lessons:

1. Periodic blood lipid tests should be performed even when you feel fine.
2. Faithfully adhering to the diets prescribed by your doctor can make a
big difference. (Also don't forget that regular exercise, quitting
cigarettes, and losing and maintaining excess weight are also
important).
3. Do not despair if you have unfavorable cholesterol and triglyeride
numbers. Work diligently with you doctor to get them right!

***

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High Cholesterol

High Cholesterol Overview


High Cholesterol Causes
High Cholesterol Symptoms
Exams and Tests
High Cholesterol Treatment
Self-Care at Home
Medical Treatment
Next Steps
Follow-up
Prevention
Outlook

High Cholesterol Overview

Cholesterol is a waxy, fatlike substance that your body needs to function


normally. Cholesterol is naturally present in cell walls or membranes

23
everywhere in the body, including the brain, nerves, muscles, skin, liver,
intestines, and heart.

Your body uses cholesterol to produce many hormones, vitamin D, and the
bile acids that help to digest fat. It takes only a small amount of cholesterol in
the blood to meet these needs. If you have too much cholesterol in your
bloodstream, the excess may be deposited in arteries, including the coronary
(heart) arteries, where it contributes to the narrowing and blockages that
cause the signs and symptoms of heart disease.

Coronary heart disease (CHD) is caused by cholesterol and fat being


deposited in the walls of the arteries that supply nutrients and oxygen
to your heart. Like any muscle, the heart needs a constant supply of
oxygen and nutrients, which are carried to it by the blood in the
coronary arteries. Fixed narrowing that is often calcified (hardened)
usually cause angina (chest pain). Less severe narrowing may contain
unstable blockages called atherosclerotic or fatty plaque. Unstable
atherosclerotic plaque can rupture, resulting in clot formation, no blood
flow, and a heart attack.

If enough oxygen-carrying blood is blocked from reaching


your heart, you may experience a type of chest pain called
angina.
If the blood supply to a portion of the heart is completely
cut off by total blockage of a coronary artery, the result is a
heart attack. This is usually due to a sudden closure of the
artery from a blood clot forming on top of unstable plaque.

A simple blood test checks for high cholesterol. Simply knowing your
total cholesterol level is not enough. A complete lipid profile measures
your LDL (low-density lipoprotein [the bad cholesterol]), total
cholesterol, HDL (high-density lipoprotein [the good cholesterol]), and
triglyceridesanother fatty substance in the blood. Government
guidelines say healthy adults should have this analysis every 5 years.

24
Updated cholesterol guidelines from the National Institutes of
Health (National Cholesterol Education Program) are
designed to help people become more aware of their
lipoprotein profile (that is your LDL, HDL, triglycerides, and
total cholesterol and their relationship to each other) and
perhaps to help at-risk people make lifestyle changes to
improve their profile.
A desirable total cholesterol level is 200 mg/dL or lower. A
desirable LDL is 100 mg/dL (130-159 is borderline high; 160
is high; 190 is very high). HDL, the "good cholesterol," should
be around 40 mg/dL or greater. With HDL, the higher the
number, the better, and 60 mg/dL is protective against heart
disease.
Too many Americans have high levels of total cholesterol and
LDL (the bad cholesterol). A diet high in saturated fat (a type
of fat found mostly in foods that come from animals and
certain oils) raises LDL levels more than anything else in your
diet. You also eat cholesterol in your diet, although the effect
of saturated fat in the diet is greater than the effect of
dietary cholesterol. Trans-fatty acids (seen in processed foods
and many "fast foods") can also increase LDL levels. Dietary
cholesterol is found only in foods from animal products.
Genetic factors combined with eating too much saturated fat
and cholesterol are the main reasons for high levels of
cholesterol that lead to heart attacks. Reducing the amount
of saturated fat and cholesterol you eat is an important step
in reducing your blood cholesterol levels. The government
has reset the standard for LDL levels so that more Americans
are included in the risk group.

Research confirms the dangers when your cholesterol levels are too
high.

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The Framingham Heart Study established that high blood
cholesterol is a risk factor for coronary heart disease (CHD).
Results of the Framingham study showed that the higher your
cholesterol level, the greater your risk.
Several studies have confirmed a direct link between high
blood cholesterol and CHD. The Lipid Research Clinics-
Coronary Primary Prevention Trial (LRC-CPPT) first showed
that lowering total and LDL (bad) cholesterol levels
significantly reduces coronary heart disease. A series of more
recent trials of cholesterol-lowering using statin drugs have
conclusively demonstrated that lowering total cholesterol and
LDL cholesterol reduces your chance of having a heart
attack, needing bypass surgery or angioplasty, and dying of
CHD-related causes.
Recent studies have shown that lowering cholesterol in
people without heart disease greatly reduces their risk for
developing heart disease in the first place. This is true for
those with high cholesterol levels and for those with average
cholesterol levels.
In 1994, the Scandinavian Simvastatin Survival Study (4S)
was the first study to show that people who took the
cholesterol-lowering class of drugs called statins (in this case,
simvastatin) reduced their risk for major CHD events (such as
a heart attack) by 34%, CHD deaths by 42%, and all deaths
by 30% in people with known coronary heart disease and
high blood cholesterol levels, compared with people who
were given a placebo (a dummy pill that looks exactly like
the medication being tested). This has been called
"secondary prevention," or prevention of a second heart
attack, because the study involved people with known heart
disease, many of whom had already had at least one heart
attack.

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A 1995 study called the West of Scotland Coronary
Prevention Study (WOSCOPS) found that lowering cholesterol
reduced the number of heart attacks and deaths from
cardiovascular causes in men with high blood cholesterol
levels who had not had a heart attack. For 5 years, more than
6,500 men with total cholesterol levels of 249-295 mg/dL
were given either a cholesterol-lowering drug or a placebo
along with a cholesterol-lowering diet. The drug that was
given is known as a statin (pravastatin), and it reduced total
cholesterol levels by 20% and LDL (bad) cholesterol levels by
26%. The study found that the overall risk of having a
nonfatal heart attack or dying from CHD was reduced by 31%
in those who received the statin. The need for bypass surgery
or angioplasty was reduced by 37%, and deaths from all
cardiovascular causes were reduced by 32%. A very
important finding was that deaths from causes other than
heart disease were not increased, and overall deaths from all
causes were reduced by 22%. This is called primary
prevention because the study subjects had not previously
had a heart attack.
In 1996, the CARE study of CHD patients with "normal"
cholesterol (LDL average of 138 mg/dL) values and a recent
heart attack was associated with 24% reduction in CHD
events. Overall death rates were not affected. The drug used
was pravastatin.
In 1998, the results of the Air Force/Texas Coronary
Atherosclerosis Prevention Study (AFCAPS/TexCAPS) showed
that lowering cholesterol in generally healthy men and
women (no previous heart disease) with average cholesterol
levels reduced their risk for a first-time major coronary event
(such as a heart attack) by 37%. Lovastatin was the drug
used in this study.

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In the 1998 LIPID study, men and women with known
CHD and mild-to-moderate elevations of LDL lowered their
risk of death by 22%, CHD deaths by 24%, and death by CHD
or nonfatal heart attack by 24%. Pravastatin was the drug
used in this study.
The Heart Protection Study, published in 2002, examined
men and women of all ages at high risk for heart disease
irrespective of their cholesterol levels. Simvastatin treatment
reduced CHD events by 24%. This study has caused some
experts to suggest that everyone at high risk for CHD would
benefit from statin therapy, regardless of their blood
cholesterol levels.
The National Health and Nutrition Examination Survey III
(NHANES III), carried out from 1988-1991, discovered that
26% of American adults had high blood cholesterol
concentrations, and 49% had desirable values.

Who has high cholesterol?

Throughout the world, cholesterol levels (measured in the


blood) vary widely. Generally, people who live in countries
where blood cholesterol levels are lower, such as Japan, have
lower rates of heart disease. Countries with very high
cholesterol levels, such as Finland, have very high rates of
coronary heart disease. However, some populations with
similar total cholesterol levels have very different heart
disease rates, suggesting that other factors also influence
risk for coronary heart disease.
High cholesterol is more common in men younger than 55
years and in women older than 55 years.
The risk for high cholesterol increases with age.

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High Cholesterol Causes

Several drugs and diseases can bring about high cholesterol, but, for most
people, a high-fat diet and inherited risk factors may be the main causes.
Your doctor will rule out the possibility that you have an underactive thyroid
or kidney or liver disease.

Heredity: Your genes influence how high your LDL (bad) cholesterol is
by affecting how fast LDL is made and removed from the blood. One
specific form of inherited high cholesterol that affects 1 in 500 people
is called familial hypercholesterolemia, which often leads to early heart
disease. But even if you do not have a specific genetic form of high
cholesterol, genes play a role in influencing your LDL cholesterol level.

Weight: Excess weight may modestly increase your LDL (bad)


cholesterol level. If you are overweight and have a high LDL cholesterol
level, losing weight may help you lower it. Weight loss especially helps
to lower triglycerides and raise HDL (good) cholesterol levels.

Physical activity/exercise: Regular physical activity may lower


triglycerides and raise HDL cholesterol levels.

Age and sex: Before menopause, women usually have lower total
cholesterol levels than men of the same age. As women and men age,
their blood cholesterol levels rise until about 60-65 years of age. After
about age 50 years, women often have higher total cholesterol levels
than men of the same age.

Alcohol use: Moderate (1-2 drinks daily) alcohol intake increases HDL
(good) cholesterol but does not lower LDL (bad) cholesterol. Doctors
don't know for certain whether alcohol also reduces the risk of heart
disease. Drinking too much alcohol can damage the liver and heart
muscle, lead to high blood pressure, and raise triglyceride levels.
Because of the risks, alcoholic beverages should not be used as a way
to prevent heart disease.

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Mental stress: Several studies have shown that stress raises blood
cholesterol levels over the long term. One way that stress may do this
is by affecting your habits. For example, when some people are under
stress, they console themselves by eating fatty foods. The saturated
fat and cholesterol in these foods contribute to higher levels of blood
cholesterol.

High Cholesterol Symptoms

High cholesterol is usually discovered on routine screening and has no


symptoms. It is more common if you have a family history of it, but lifestyle
factors (such as eating a diet high in saturated fat) clearly play a major role.

If you have a routine blood test during a physical exam or while attending a
health fair or screening at a shopping center, your blood may reveal a high
total cholesterol level, which would require further testing to determine your
LDL, HDL, and triglyceride levels (this is known as a lipid panel).

The National Cholesterol Education Program guidelines suggest that everyone


aged 20 years and older should have their blood cholesterol level measured
at least once every 5 years. It is best to have a blood test called a lipoprotein
profile to find out your cholesterol numbers. This blood test is done after a 9-
to 12-hour fast and gives information about the following items:

Total cholesterol is the sum of all the cholesterol in your blood


(serum cholesterol). The higher your total cholesterol, the greater your
risk for heart disease.

Less than 200 mg/dL is a desirable level that puts you at


lower risk for heart disease. A cholesterol level of 200 mg/dL
or greater increases your risk.
A level of 200-239 mg/dL is termed borderline high.
A level of 240 mg/dL and above is considered high blood
cholesterol. Your risk at this level is twice the risk of heart
disease compared with someone whose total cholesterol
level is 200 mg/dL.

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Low-density lipoprotein (LDL) is considered the "bad" cholesterol.
Cholesterol travels in the blood in packages called lipoproteins. Just like
oil and water, cholesterol, which is not soluble in water, and blood,
which is watery, do not mix. In order to be able to travel in the
bloodstream, the cholesterol made in the liver is combined with protein
and other substances, making a lipoprotein. This lipoprotein then
carries the cholesterol through the bloodstream. LDLs carry most of the
cholesterol in the blood, and the cholesterol from LDL is the main
source of damaging buildup and blockage in your arteries. Thus, the
more LDL cholesterol you have in your blood, the greater your risk of
heart disease. Reducing your LDL cholesterol is the main goal of
cholesterol-lowering treatment. The lower, the better.

Less than 100 mg/dL is considered optimal (best).


A level of 100-129 mg/dL is near optimal/above optimal.
A level of 130-159 mg/dL is borderline high.
A level of 160-189 mg/dL is high.
A level of 190 mg/dL and above is very high.

High-density lipoprotein (HDL) is called the "good" cholesterol.


HDLs carry cholesterol in the blood from other parts of the body back
to the liver, which leads to its removal from the body. In this way, HDL
helps keep cholesterol from building up in the walls of the arteries. If it
is not possible to have a lipoprotein profile done, knowing your total
cholesterol and HDL cholesterol can give you a general idea about your
cholesterol levels. If your total cholesterol is 200 mg/dL or more, or if
your HDL is less than 40 mg/dL, you will need to have a fasting
lipoprotein profile done.

Less than 40 mg/dL is considered a major risk factor for heart


disease.
A level of 40-59 mg/dL is better.
A level of 60 mg/dL and above is thought to protect you
against heart disease.

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Triglycerides are a form of fat carried through the bloodstream. Most
of your body's fat is in the form of triglycerides stored in fat tissue.
Only a small portion of your triglycerides is found in the bloodstream.
High blood triglyceride levels alone do not necessarily cause
atherosclerosis (the buildup of cholesterol and fat in the walls of
arteries). But some lipoproteins that are rich in triglycerides also
contain cholesterol, which causes atherosclerosis in some people with
high triglycerides; plus, high triglyceride levels are often accompanied
by other factors (such as low HDL and/or a tendency toward diabetes)
that raise heart disease risk. Therefore, high triglycerides may be a
sign of a lipoprotein problem that contributes to heart disease.

Less than 150 mg/dL is normal.


A level of 150-199 mg/dL is borderline high.
A level of 200-499 mg/dL is high.
A level of 500 mg/dL or above is very high.

Exams and Tests

High cholesterol is just one of several risk factors for coronary heart disease.
Your doctor will consider your overall risk when assessing your cholesterol
levels and discussing your treatment options.

Risk factors are conditions that increase your risk for developing heart
disease. Some risk factors can be changed and others cannot. In general, the
more risk factors you have, the greater your chance of developing coronary
heart disease. You can control some risk factors, but you cannot control
others.

Risk factors you cannot control

Age (45 years or older for men; 55 years or older for women)
Family history of early heart disease (father or brother
affected before age 55 years; mother or sister affected
before age 65 years)

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Risk factors you can control

High blood cholesterol (high total cholesterol and high LDL


[bad] cholesterol)
Low HDL (good) cholesterol
Smoking
High blood pressure
Diabetes: If you have diabetes, your risk for developing heart
disease is high. In order to reduce your high risk of getting
heart disease, you will need to lower your cholesterol under
medical supervision (in a way very similar to that of someone
with known heart disease).
Obesity/excess weight
Physical inactivity

High Cholesterol Treatment

Self-Care at Home

If you have high lipoproteins and thus high cholesterol, your doctor will work
with you to target your levels with dietary and drug treatment. Depending on
your risk factors for heart disease, your target goals may differ for lowering
your LDL cholesterol.

Diet: The National Cholesterol Education Program has created dietary


guidelines.

NCEP dietary guidelines

Total fat - Less than 30% of calories


Saturated fat - Less than 7% of calories
Polyunsaturated fat - Less than or equal to 10% of
calories
Monounsaturated fat - Approximately 10-15% of
calories
Cholesterol - Less than 200 milligrams per day

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Carbohydrates - 50-60% of calories

The new guidelines are more stringent than previous ones,


mandating more restriction on saturated fat and dietary
cholesterol.
Some people are able to reduce fat and dietary cholesterol with
vegetarian diets. Dean Ornish and his colleagues have shown
the value of a very strict fat-reduction diet in unblocking
coronary arteries. Whether these dietary restrictions are realistic
for most Americans is debatable. Moreover, such a diet also
reduces HDL and raises triglyceride levels.
Stanol esters can be included in the diet and may reduce LDL by
about 14%. Products containing stanol esters include margarine
substitutes (marketed as brand names Benecol and Take
Control).
People with higher triglycerides may benefit from a diet that is
higher in monounsaturated fat and lower in carbohydrates,
particularly simple sugars. A common source of
monounsaturated fat is olive oil.

Activity: Although exercise has little effect on LDL, aerobic exercise


may improve insulin sensitivity, HDL, and triglyceride levels and may
thus reduce your heart risk. People who exercise and control their diet
appear to be more successful in long-term lifestyle modifications that
improve their heart risk profile.

Medical Treatment

If following a low-saturated fat, low-cholesterol diet, increasing your physical


activity, and losing weight have not lowered your risk for developing coronary
heart disease after about 3 months, your doctor may consider prescribing a
cholesterol-lowering medication. If your doctor prescribes medicine, you must
still (1) follow your cholesterol-lowering diet, (2) be more physically active, (3)
lose weight if you are overweight, and (4) control or stop all of your other

34
coronary heart disease risk factors (including high blood pressure, diabetes,
and smoking).

Taking all these steps together may lessen the amount of medicine you need
or make the medicine work better, which reduces your risk for developing
coronary heart disease. Your doctor may prescribe medication for you from
the following categories:

Statins: Statins lower LDL cholesterol levels more than other types of
drugs. Statins inhibit an enzyme, HMG-CoA reductase, that controls the
rate of cholesterol production in the body. These drugs lower
cholesterol by slowing down the production of cholesterol and by
increasing the liver's ability to remove the LDL cholesterol already in
the blood.

Statins were used to lower cholesterol levels in many of the


clinical trials discussed previously. The large reductions in
total and LDL cholesterol produced by these drugs resulted in
significant reductions in heart attacks and coronary heart
disease deaths. Thanks to their safety and to their ability to
lower LDL cholesterol the number of coronary heart attacks
and heart disease deaths, statins have become the drugs
most often prescribed for lowering cholesterol.
Studies using statins have reported 20-60% lower LDL
cholesterol levels in people taking them. Statins also reduce
high triglyceride levels modestly and produce a mild increase
in HDL cholesterol.
The statins are most often given in a single dose at the
evening meal or at bedtime. It is important that these
medications be given in the evening to take advantage of the
fact that the body makes more cholesterol at night than
during the day. Newer, long-acting statins, such as
atorvastatin (Lipitor), may be administered in the morning.
You should begin to see results from the statins after several
weeks, with a maximum effect in 4-6 weeks. After about 6-8

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weeks, your doctor can do the first check of your LDL
cholesterol while you are on the medication. A second
measurement of your LDL cholesterol level must be averaged
with the first for your doctor to decide whether your dose of
medicine should be changed to help you meet your goal.
The statins are well tolerated, and serious side effects are
rare (liver problems, muscle soreness, pain, weakness). If this
happens, or if you have brown urine, contact your doctor
right away to get blood tests for possible muscle problems.
Rarely, widespread muscle breakdown, known as
rhabdomyolysis, can occur, usually in people who are taking
other drugs that interfere with the breakdown of the statin
and in people with advanced kidney problems. This is a
medical emergency. So, if you have diffuse muscle pain
and weakness, or brown urine (a possible sign of muscle
breakdown), contact your doctor immediately and stop taking
the statin medication. Some people experience an upset
stomach, gas, constipation, and abdominal pain or cramps.
These symptoms are usually mild to moderate and generally
go away as your body adjusts. Monitoring of liver function
tests is usually done in patients taking statins.

Statin drugs include the following:

Atorvastatin (Lipitor): Atorvastatin is a highly effective


drug in lowering LDL cholesterol when used in large
doses (though high doses are not commonly
used). Atorvastatin has been shown to reduce coronary
heart disease events in people with hypertension.
Fluvastatin (Lescol): Fluvastatin is the least potent
statin drug. Fluvastatin has been shown to reduce
coronary heart disease events in people after
percutaneous coronary intervention or balloon
angioplasty.

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Lovastatin (Mevacor, Altocor): Lovastatin is the first
statin to be approved by the FDA. Lovastatin is proven
to reduce coronary heart disease events.
Pravastatin (Pravachol): Pravastatin is the most
studied statin in clinical trials and is also proven to
reduce coronary heart disease events and deaths.
Simvastatin (Zocor): Simvastatin is the first drug
shown to reduce the total death rate by reducing LDL
concentrations in people with coronary heart disease.
Simvastatin is proven to reduce coronary heart disease
events and deaths.
Rosuvastatin (Crestor): Rosuvastatin is the newest
statin (cholesterol-lowering drug) approved in the
United States and the most potent of the statin drugs.
It is particularly effective in lowering very high
cholesterol levels or when a cholesterol level has not
been decreased with other drugs.

Bile acid sequestrants: These drugs bind with cholesterol-containing


bile acids in the intestines and are then eliminated in the stool. The
usual effect of bile acid sequestrants is to lower LDL cholesterol by
about 10-20%. Small doses of sequestrants can produce useful
reductions in LDL cholesterol.

Bile acid sequestrants are sometimes prescribed with a statin


to enhance cholesterol reduction. When these drugs are
combined, their effects are added together to lower LDL
cholesterol by more than 40%.
Cholestyramine (Questran, Questran Light), colestipol
(Colestid), and colesevelam (WelChol) are the 3 main bile
acid sequestrants currently available. These 3 drugs are
available as powders or tablets. They are not absorbed from
the gastrointestinal tract, and 30 years of experience with
these drugs indicates that long-term use is safe.

37
Bile acid sequestrant powders must be mixed with water or
fruit juice and must be taken once or twice (rarely, 3 times)
daily with meals. Tablets must be taken with large amounts of
fluids to avoid stomach and intestinal problems.
Sequestrant therapy may produce a variety of symptoms,
including constipation, bloating, nausea, and gas.
The bile acid sequestrants are not prescribed as the sole
medicine to lower your cholesterol if you have high
triglycerides or a history of severe constipation.
Although sequestrants are not absorbed, they may interfere
with the absorption of other medicines if taken at the same
time. You must take other medications at least 1 hour before
or 4-6 hours after the sequestrant. You should talk to your
doctor about the best time to take this medicine, especially if
you take other medications.

Cholesterol absorption inhibitors: This new class of drugs was


approved in late 2002. The drug inhibits cholesterol absorption in the
gut and has few, if any, side effects. Cholesterol absorption
inhibitors may rarely be associated with tongue swelling (angioedema).
Ezetimibe (Zetia) is the first drug in this class. Ezetimibe reduces LDL
cholesterol by 18-20%. It is probably most useful in people who cannot
take statins or as an additional drug for people who take statins but
who notice side effects when the statin dose is increased. Adding
ezetimibe to a statin is equivalent to doubling or tripling the statin
dose.
Nicotinic acid or niacin: This water-soluble B vitamin improves all
lipoproteins when given in doses well above the vitamin requirement.
Nicotinic acid lowers total cholesterol, LDL cholesterol, and triglyceride
levels, while raising HDL cholesterol levels.

There are 2 types of nicotinic acid: immediate release and


extended release.

38
The immediate-release form of crystalline niacin is
inexpensive and widely accessible without a prescription,
but, because of potential side effects, it must not be used for
cholesterol lowering without the monitoring of a doctor.
(Nicotinamide, another form of niacin, does not lower
cholesterol levels and should not be used in place of nicotinic
acid.)
If you take nicotinic acid to lower cholesterol, your doctor will
closely monitor you to avoid complications from this
medication. You should not take this medication on your own.
You may miss important side effects.
Nicotinic acid reduces LDL cholesterol levels by 10-20%,
reduces triglycerides by 20-50%, and raises HDL cholesterol
by 15-35%.
A common and troublesome side effect of nicotinic acid is
flushing or hot flashes, which are the result of blood vessels
opening wide. Most people develop a tolerance to flushing,
which can sometimes be decreased by taking the drug during
or after meals or by the use of aspirin or other similar
medications prescribed by your doctor 30 minutes prior to
taking niacin. The extended-release form may cause less
flushing than the other forms.
The effect of high blood pressure medicines may also be
increased while you are on niacin. If you are taking high
blood pressure medication, it is important to set up a blood
pressure monitoring system while you are getting used to
your new niacin regimen. A variety of gastrointestinal
symptoms, including nausea, indigestion, gas, vomiting,
diarrhea, and the activation of peptic ulcers, has been seen
with the use of nicotinic acid. Three other major adverse
effects include liver problems, gout, and high blood sugar.
Risk of the latter 3 complications increases as the dose of
nicotinic acid is increased. Your doctor may not prescribe this

39
medicine for you if you have diabetes because of the effect
on your blood sugar.
Extended-release niacin is often better tolerated than
crystalline niacin. However, its liver toxicity (liver damage) is
probably greater. Therefore, the dose of extended-release
niacin is usually limited to 2 grams per day.
If you take niacin, you should increase the dose very slowly.
Recently, a combination product of extended-release niacin
(Niaspan) and lovastatin has been released (Advicor). The
side effects of this combination product mirror those of the 2
drugs taken individually.

Fibrates: These cholesterol-lowering drugs are primarily effective in


lowering triglycerides and, to a lesser extent, increasing HDL
cholesterol levels.

Gemfibrozil (Lopid), the fibrate most widely used in the


United States, can be effective for people with high
triglyceride levels. However, gemfibrozil is not very effective
for lowering LDL cholesterol. It is used in some people with
heart disease for whom a goal of treatment is lowering
triglycerides or raising HDL. Another fibrate is fenofibrate
(Tricor), which is more effective at lowering triglycerides and
LDL cholesterol.
Some people taking fibrates may have side effects such as
stomach or intestinal discomfort. Fibrates may increase the
likelihood of your developing gallstones and can increase the
effect of medications that thin the blood. Your doctor will
monitor you. The dose of fibrates should be reduced if your
kidney function declines.

Hormone replacement therapy: The risk of heart disease is


increased in women after menopause. The increasing risk may be
related to loss of estrogen that comes with menopause. Previously,

40
women might have been treated with hormone replacement therapy
(replacing the estrogen and perhaps progestin).

Recent studies have found that women on hormone


replacement therapy did not benefit by having a lower rate of
heart-related events compared with women treated with
placebo.
Therefore, postmenopausal women who are judged by their
doctor to need drug treatment to reduce their risk for heart
disease should consider cholesterol-lowering drugs instead of
hormones because cholesterol-lowering drugs have been
shown to be safe and effective in lowering cholesterol and
reducing coronary heart disease risk.

Next Steps

Follow-up

Your lipid profile will be rechecked, depending on how you approach


your high cholesterol.
If you are changing your diet, a recheck may be done in 3 months.
If your doctor prescribes medications, your profile may be checked
in 6-12 weeks. For some medications, your doctor will also use a
blood test to monitor your liver function because there is some risk
for liver problems.

Prevention

Adoption of a healthier lifestyle, including aerobic exercise and a low-fat diet,


should reduce the prevalence of obesity, high cholesterol, and, ultimately, the
risk of coronary heart disease.

First, see your doctor. A simple blood test checks for high cholesterol.
You may be asked to fast overnight before the test. Just knowing your
total cholesterol level isn't enough. A complete lipid profile measures
your LDL, total cholesterol, HDL (the good cholesterol), and

41
triglycerides. The guidelines say healthy adults should have this
analysis every 5 years.

Next, set dietary goals based on the guidelines from the National
Cholesterol Education Program.

Strive for daily intake of less than 7% of your calories from


saturated fat and less than 200 mg of cholesterol from the food
you eat.
You may eat up to 30% of your calories from total fat, but most
should be from unsaturated fat, which doesn't raise cholesterol
levels.
Add more soluble fiber (found in cereal grains, beans, peas, and
many fruits and vegetables) and foods that contain plant stanols
and sterols (included in certain margarines and salad dressings)
to boost your LDL-lowering power. The best way to know what's
in the foods you eat is to read the nutrition label.
Lower cholesterol levels start at the grocery store. Read food
labels, and buy foods low in saturated fat and low in cholesterol.
To help you know what to look for when grocery shopping, the
National Heart, Lung, and Blood Institute has a partial shopping
list for you.

Breads - Whole wheat, rye, pumpernickel, or white


Soft tortillas - Corn or whole wheat
Hot and cold cereals - Except granola or muesli
Rice - White, brown, wild, basmati, or jasmine
Grains - Bulgur, couscous, quinoa, barley, hominy, or
millet
Fruits - Any fresh, canned, dried, or frozen without
added sugar
Vegetables - Any fresh, frozen, or (low-salt) canned
without cream or cheese sauce
Fresh or frozen juices without added sugar

42
Fat-free or 1% milk
Cheese with 3 grams of fat or less per serving
Low-fat or nonfat yogurt
Lean cuts of meat - Eye of round beef, top round,
sirloin, or pork tenderloin
Lean or extra lean ground beef
Chicken or turkey - White or light meat, skin removed
Fish - Most white meat fish is very low in fat, saturated
fat, and cholesterol.
Tuna - Light meat canned in water
Peanut butter, reduced fat
Eggs, egg whites, egg substitutes
Low-fat cookies or angel food cake
Low-fat frozen yogurt, sorbet, sherbet
Popcorn without butter or oil, pretzels, baked tortilla
chips
Margarine - Soft, diet, tub, or liquid
Vegetable oil - Canola, olive, corn, peanut, or sunflower
Nonstick cooking spray
Sparkling water, tea, lemonade

Manage your cholesterol. You can take an important first step toward a
healthier heart by enrolling in the American Heart Association's
Cholesterol Low Down Program. High cholesterol is a leading risk factor
for coronary heart disease and stroke. Sign up by phone ([800] AHA-
USA1) or online at American Heart Association's Cholesterol Low Down
Program to receive life-management tools such as a newsletter, health
risk assessment, and healthy-living cookbooks and fitness tips.
Calculate your 10-year risk of having a heart attack. The risk
assessment tool presented at this link is from the National Heart, Lung,
and Blood Institute's National Cholesterol Education Program. It uses
scientific research information to predict your chance of having a heart
attack in the next 10 years. For adults older than 20 years who do not

43
have heart disease or diabetes, click the link to assess your risk score.
Those with diabetes and others with a 10-year risk greater than 20%
are considered to have the same risk for future heart disease events as
people with known coronary heart disease. You'll need to know your
total cholesterol, HDL cholesterol level, and systolic blood pressure (the
first number).

The National Cholesterol Education Program Web site will tell you what
your LDL cholesterol goal should be. For people with known coronary
heart disease and similar risk, the LDL cholesterol goal is less than 100
mg/dL.

Prevention

Adoption of a healthier lifestyle, including aerobic exercise and a low-fat diet,


should reduce the prevalence of obesity, high cholesterol, and, ultimately, the
risk of coronary heart disease.

First, see your doctor. A simple blood test checks for high cholesterol.
You may be asked to fast overnight before the test. Just knowing your
total cholesterol level isn't enough. A complete lipid profile measures
your LDL, total cholesterol, HDL (the good cholesterol), and
triglycerides. The guidelines say healthy adults should have this
analysis every 5 years.

Next, set dietary goals based on the guidelines from the National
Cholesterol Education Program.

Strive for daily intake of less than 7% of your calories from


saturated fat and less than 200 mg of cholesterol from the food
you eat.
You may eat up to 30% of your calories from total fat, but most
should be from unsaturated fat, which doesn't raise cholesterol
levels.
Add more soluble fiber (found in cereal grains, beans, peas, and
many fruits and vegetables) and foods that contain plant stanols

44
and sterols (included in certain margarines and salad dressings)
to boost your LDL-lowering power. The best way to know what's
in the foods you eat is to read the nutrition label.
Lower cholesterol levels start at the grocery store. Read food
labels, and buy foods low in saturated fat and low in cholesterol.
To help you know what to look for when grocery shopping, the
National Heart, Lung, and Blood Institute has a partial shopping
list for you.

Breads - Whole wheat, rye, pumpernickel, or white


Soft tortillas - Corn or whole wheat
Hot and cold cereals - Except granola or muesli
Rice - White, brown, wild, basmati, or jasmine
Grains - Bulgur, couscous, quinoa, barley, hominy, or
millet
Fruits - Any fresh, canned, dried, or frozen without
added sugar
Vegetables - Any fresh, frozen, or (low-salt) canned
without cream or cheese sauce
Fresh or frozen juices without added sugar
Fat-free or 1% milk
Cheese with 3 grams of fat or less per serving
Low-fat or nonfat yogurt
Lean cuts of meat - Eye of round beef, top round,
sirloin, or pork tenderloin
Lean or extra lean ground beef
Chicken or turkey - White or light meat, skin removed
Fish - Most white meat fish is very low in fat, saturated
fat, and cholesterol.
Tuna - Light meat canned in water
Peanut butter, reduced fat
Eggs, egg whites, egg substitutes
Low-fat cookies or angel food cake

45
Low-fat frozen yogurt, sorbet, sherbet
Popcorn without butter or oil, pretzels, baked tortilla
chips
Margarine - Soft, diet, tub, or liquid
Vegetable oil - Canola, olive, corn, peanut, or sunflower
Nonstick cooking spray
Sparkling water, tea, lemonade

Manage your cholesterol. You can take an important first step toward a
healthier heart by enrolling in the American Heart Association's
Cholesterol Low Down Program. High cholesterol is a leading risk factor
for coronary heart disease and stroke. Sign up by phone ([800] AHA-
USA1) or online at American Heart Association's Cholesterol Low Down
Program to receive life-management tools such as a newsletter, health
risk assessment, and healthy-living cookbooks and fitness tips.
Calculate your 10-year risk of having a heart attack. The risk
assessment tool presented at this link is from the National Heart, Lung,
and Blood Institute's National Cholesterol Education Program. It uses
scientific research information to predict your chance of having a heart
attack in the next 10 years. For adults older than 20 years who do not
have heart disease or diabetes, click the link to assess your risk score.
Those with diabetes and others with a 10-year risk greater than 20%
are considered to have the same risk for future heart disease events as
people with known coronary heart disease. You'll need to know your
total cholesterol, HDL cholesterol level, and systolic blood pressure (the
first number).

The National Cholesterol Education Program Web site will tell you what
your LDL cholesterol goal should be. For people with known coronary
heart disease and similar risk, the LDL cholesterol goal is less than 100
mg/dL.

46
Outlook

The statin drugs have revolutionized the treatment of high cholesterol.


Coupled with treatment of high blood pressure and the use of beta-blockers,
converting enzyme inhibitors, and aspirin, it's now possible to reduce
coronary heart disease events, even in people with known blockage
(atherosclerosis).

Cholesterol reduction is certainly useful as a coronary heart disease risk-


reduction strategy for everyone, especially for those at high risk for coronary
heart disease or other forms of atherosclerosis (stroke - claudication or
atherosclerotic obstruction of arteries in the legs).

Understanding Your Cholesterol Level

What Is Cholesterol?

47
How Are Cholesterol Levels Checked?
What the Numbers Mean
What Should I Do if I Have High Cholesterol?

What Is Cholesterol?

Cholesterol, a waxy, fat-like substance, is naturally present in cell walls or


membranes everywhere in the body. Your body uses cholesterol to produce
many hormones, vitamin D, and the bile acids that help to digest fat. If you
have too much cholesterol in your bloodstream, the excess may be deposited
in the arteries of the heart, which could lead to heart disease.

How Are Cholesterol Levels Checked?

A simple blood test checks your cholesterol levels. This test measures total
cholesterol, low-density lipoproteins (LDL) cholesterol, high-density
lipoproteins (HDL) cholesterol, and triglycerides in your blood. Your doctor will
interpret your blood test results to determine if you have high cholesterol.

What the Numbers Mean

Cholesterol is measured in milligrams per deciliters (mg/dL) of blood.

Total cholesterol is the sum of all the cholesterol in your blood. Your risk for
heart disease is greater with higher levels of total cholesterol. If your total
cholesterol level falls into the high-risk category, your risk of heart disease is
twice that of someone with the same risk factors, whose total cholesterol
level is 200 mg/dL or less.

Your total cholesterol will fall into 1 of 3 categories. However, the risk of
cardiovascular disease associated with these levels of cholesterol and
triglycerides will depend upon the presence or absence of other risk factors,
such as the presence of known cardiovascular disease (eg, prior heart attack

48
or stroke), hypertension, diabetes, cigarette smoking, age, sex, and positive
family history. Thus, cardiovascular risk and treatment options must be
considered in light of your overall cardiovascular risk profile.

Desirable - Less than 200 mg/dL

Borderline High Risk - 200-239 mg/dL


High Risk - 240 mg/dL and above

LDL cholesterol is considered the bad cholesterol. Your risk of heart


disease goes up if you have a high level of LDL cholesterol in your blood.
Your LDL cholesterol level will fall into 1 of 5 categories:

Optimal - Less than 100 mg/dL

Near Optimal/Above Optimal - 100-129 mg/dL


Borderline High - 130-159 mg/dL
High - 160-189 mg/dL
Very High - 190 mg/dL and above

HDL cholesterol is considered the good cholesterol because it helps keep


cholesterol from building up in the walls of your arteries. A high level of HDL
cholesterol may protect you against heart disease, whereas a low level of
HDL cholesterol is considered to be a major risk factor for heart disease.
Your HDL cholesterol level will fall into 1 of 3 categories:

High (Desirable) - 60 mg/dL and above

Acceptable - 40-59 mg/dL


Low - 40 mg/dL and less

Triglycerides are a form of fat carried through the bloodstream. A high level
of triglycerides may be a sign of a lipoprotein problem that contributes to
heart disease.

49
Your triglyceride level will fall into 1 of 4 categories:

Normal - Less than 150 mg/dL

Borderline High - 150-199 mg/dL


High - 200-499 mg/dL
Very High - 500 mg/dL and above

What Should I Do if I Have High Cholesterol?

Because high levels of total cholesterol are associated with an increased risk
of heart disease, you and your doctor will discuss any treatment that may be
required based on your test results.

If you have high cholesterol, the main goal of a treatment program is to lower
your LDL cholesterol level. There are 2 main ways to lower your LDL
cholesterol level:

Lifestyle changes include a low-saturated fat, low-cholesterol diet;


exercise; and weight loss if you are overweight.

Drug treatment is used in conjunction with lifestyle changes. Your


doctor may add a cholesterol-lowering medicine to your treatment
program if lifestyle changes alone do not lower your LDL cholesterol
level.

If you have high triglycerides, in some circumstances, lowering these may


become the main goal of treatment. There are 2 main ways to lower your
triglycerides:
Lifestyle changes include a low carbohydrate diet, exercise, and
weight loss.
Drug treatment may be used in conjunction with lifestyle changes.
Your doctor may add a triglyceride-lowering medicine to your
treatment program if lifestyle changes alone do not lower your LDL
cholesterol level.

50
You should also control any other risk factors that could affect your LDL
cholesterol and triglyceride levels, such as high blood pressure and diabetes.
You should quit cigarette smoking if you smoke.

51