Cholesterol

What is cholesterol?

Cholesterol is a chemical compound that is naturally produced

by the body and is a combination of lipid (fat) and steroid.
Cholesterol is a building block for cell membranes and for
hormones like estrogen and testosterone. About 80% of the
body's cholesterol is produced by the liver, while the rest
comes from our diet. . Dietary cholesterol comes mainly from
meat, poultry, fish, and dairy products. Organ meats, such as
liver, are especially high in cholesterol content, while foods of
plant origin contain no cholesterol. After a meal, dietary
cholesterol is absorbed from the intestine and stored in the
liver. The liver is able to regulate cholesterol levels in the
blood stream and can secrete cholesterol if it is needed by the
body.

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
Total cholesterol is the sum of LDL (low density)
artery walls and disposing of them through the
cholesterol, HDL (high density) cholesterol, VLDL
liver. Thus, high levels of LDL cholesterol and low
(very low density) cholesterol, and IDL (intermediate
levels of HDL cholesterol (high LDL/HDL ratios)
density) cholesterol.
are risk factors for atherosclerosis, while low levels
of LDL cholesterol and high level of HDL
cholesterol (low LDL/HDL ratios) are desirable.
What determines the level of LDL cholesterol in the blood?

The liver manufactures and secretes LDL cholesterol into the blood. It also removes LDL cholesterol from
the blood by active LDL receptors on the surface of its cells. A decrease number of liver cell 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 (hyper= more + cholesterol + emia= in blood) 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 one of the primary public health initiatives preventing
atherosclerosis and heart attacks. 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 and widening the arteries;

preventing the rupture of cholesterol plaques, which initiates blood clot formation and blocks
blood vessels;

decreasing the risk of heart attacks; and

decreasing the risk of strokes.

The same measures that decrease narrowing in coronary arteries also may 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
Therapeutic lifestyle changes to lower LDL cholesterol involves losing excess weight, exercising regularly,
and following a diet that is low in saturated fat and cholesterol.

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. 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 children and adults with average LDL
cholesterol blood levels, putting them at risk of developing coronary
What are the current NCEP cholesterol treatment guidelines?
Controlling blood cholesterol levels may decrease the risk of heart attack and stroke. The National
Institute of Health, the American Heart Association and the American College of Cardiology publish
guidelines to help physicians and patients with this risk reduction. The most recent consensus in 2004
recommended the following: (the expected release date for the new guidelines is the summer of 2010):

Consider more intensive LDL cholesterol-lowering for people at very high, high, and moderately
high risk for a heart attack. For example, for patients with a very high risk of heart attacks, the
LDL cholesterol treatment goal remains at <100mg/dl, but the report advised doctors to consider
the option of lowering the LDL cholesterol (usually using a statin plus lifestyle changes) to <70
mg/dl.

Initiate therapeutic lifestyle changes to modify lifestyle-related risk factors ( obesity, physical
inactivity, metabolic syndrome, high blood triglyceride levels and low HDL cholesterol levels).
Lifestyle changes have the potential to reduce heart attack and stroke risks through several
mechanisms beyond the lowering of LDL cholesterol.

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.

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.

Age should not be a consideration since older persons also benefit

from lowering LDL cholesterol. 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 LDL Consider drugs +

Risk category LDL goal Initiate TLC if LDL is:
goal option TLC if LDL is:
High risk <100 mg/dl >100 mg/dl >100 mg/dl

Very high risk <100 mg/dl <70 mg/dl >100 mg/dl >100 mg/dl
 Moderately high >130mg/dl, consider
risk (10 yr. risk <130 mg/dl <100 mg/dl >130 mg/dl drug option if LDL is
10%-20%) 100-129 mg/dl
Moderate risk (10
<130 mg/dl >130 mg/dl >160 mg/dl
yr. risk <10%)
>190 mg/dl,
consider drug
Lower risk <160 mg/dl >160 mg/dl
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 (for example, 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.)
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 <10% risk of heart attack within 10 years.
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 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 tend to be lower in persons who smoke cigarettes, are overweight and inactive, and in
people with type II diabetes mellitus.
HDL cholesterol is higher in people who are lean, exercise regularly, and do not smoke cigarettes.
Estrogen increases a person's HDL cholesterol, which explains why women generally have higher HDL
levels than men do.
For individuals with low HDL cholesterol levels, a high total or LDL cholesterol blood level further
increases the incidence of atherosclerosis and heart attacks. Therefore, the combination of high levels of
total and LDL cholesterol with low levels of HDL cholesterol is undesirable whereas the combination of
low levels of total and LDL cholesterol and high levels of HDL cholesterol is favorable.
What are 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 <40 mg/dl is considered
undesirable and measures should be taken to increase it.
How can levels of HDL cholesterol be raised?

The first step in increasing HDL cholesterol levels (and decreasing LDL/HDL ratios) is therapeutic life
style changes. When these modifications are insufficient, medications are used. In prescribing
medications or medication combinations, doctors have to take into account medication side effects as well
as the presence or absence of other abnormalities in cholesterol profiles.
Regular aerobic exercise, loss of excess weight (fat), and cessation of smoking cigarettes will increase
HDL cholesterol levels. Regular alcohol consumption (such as one drink a day) will also raise HDL
cholesterol. Because of other adverse health consequences of excessive alcohol consumption, alcohol is
not recommended as a standard treatment for low HDL cholesterol.
On the positive side, vigorous exercisers such as long-distance runners tend to have high HDL
cholesterol levels. Before menopause, women tend to have higher HDL cholesterol than men their age.

What are triglycerides 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.
The liver removes triglyceride from the blood, and it synthesizes and packages triglyceride into VLDL
(very low-density lipoprotein) particles and releases them back into the blood circulation.
Do high triglyceride levels cause atherosclerosis?
Whether elevated triglyceride levels in the blood lead to atherosclerosis and heart attacks is controversial.
While abnormally high triglyceride levels may be a risk factor for atherosclerosis, it is difficult to
conclusively prove that elevated triglyceride by itself can cause atherosclerosis. Elevated triglyceride
levels are 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?
High triglyceride levels may be genetic or they may be acquired. Examples of inherited
hypertriglyceridemia (hyper=high + triglyceride + emia= in blood) 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.

Is lowering LDL cholesterol enough?

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.
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