Cholesterol is a waxy

Cholesterol is a waxy, fat-like substance made in the liver and other
cells. It’s also found in certain foods, such as dairy products, eggs,
and meat.

Your body needs some cholesterol to function properly.

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Its cell walls, also known as membranes, need cholesterol to produce
hormones, vitamin D, and the bile acids that
help you digest fat.

But the body only needs a limited amount of cholesterol.
When there’s too much, health problems, such as heart disease, may
develop.

Cholesterol travels through the blood attached to a protein.
The combination protein and cholesterol is called a lipoprotein.

There are three types of lipoproteins in your blood: high density, low
density, and very low density.

The specific type depends on how much protein there is in relation
to fat.

?Low density lipoproteins (LDL) are also called “bad” cholesterol
because it can cause plaque buildup on the walls of arteries. The more
LDL there is in the blood, the greater the risk of heart disease.

?High density lipoproteins (HDL) are also called “good” cholesterol. It
helps the body get rid of LDL. Maintaining a higher level of HDL is good. If
your HDL level is low your risk of heart disease goes up.

?Ver y low density lipoproteins (VLDL) are similar to LDL in that it
contains mostly fat and not much protein.

?Triglycerides, another type of fat, are carried in the blood by VLDL.
Excess calories, alcohol, or sugar in your body are converted into
triglycerides and stored in fat cells throughout your body.

DIET
Saturated fat and cholesterol in the food you eat increase
cholesterol levels. To lower your cholesterol level, try to
reduce the saturated fat and cholesterol in your diet.

WEIGHT
In addition to being a risk factor for heart disease, being overweight
can also increase cholesterol. Losing weight can help lower your LDL
and total cholesterol. And it can also increase the level of HDL.

EXERCISE
Regular exercise can lower LDL and raise HDL. You should try to be
physically active for at least 30 minutes on most days.

AGE AND GENDER
As you get older, cholesterol levels rise. Before menopause, women
tend to have lower total cholesterol levels than men. After
menopause, though, women’s LDL levels tend to rise.

DIABETES
Poorly controlled diabetes increases cholesterol levels. Having
control of your diabetes can cause your cholesterol levels to fall.

HEREDITY
Your genes partly determine how much cholesterol your body
makes. High blood cholesterol can run in families.

OTHER FACTORS
Certain medications and medical conditions can cause high
cholesterol.

High cholesterol, also known as hypercholesterolemia, is a major risk
factor for heart disease and stroke.

Abnormal levels of LDL cholesterol or HDL cholesterol are treated
with a low-fat diet, exercise, and medications such as statins.

High cholesterol is associated with an elevated risk of cardiovascular
disease.

That can include coronary heart disease, stroke, and peripheral
vascular disease.

High cholesterol has also been linked to diabetes and high blood
pressure.

To prevent or manage these conditions, work with your doctor to see
what steps you need to take to lower your cholesterol.

The main risk from high cholesterol is coronary
heart disease if the cholesterol level is too high,
Cholesterol can build up in the walls of your
arteries.

Over time, this buildup called plaque) causes
hardening of the arteries or atherosclerosis.

This causes arteries to become narrowed, which
slows the blood flow to the heart muscle.

Reduced blood flow can result in angina (chest pain)
or in a heart attack if a blood vessel gets blocked
completely

CHOLESTEROL AND STROKE
Atherosclerosis causes arteries that lead to the brain to become
narrowed and even blocked.

If a vessel carrying blood to the brain is blocked completely, you
could have a stroke.

CHOLESTEROL AND PERIPHERAL VASCULAR DISEASE
High cholesterol also has been linked to peripheral vascular disease.
This refers to diseases of blood vessels outside the heart and brain.

In this condition, fatty deposits build up along artery walls and affect
blood circulation. This occurs mainly in arteries that lead to the legs
and feet.

CHOLESTEROL AND DIABETES
Diabetes can upset the balance between HDL and LDL cholesterol
levels. People with diabetes tend to have LDL particles that stick to
arteries and damage blood vessel walls more easily.

Glucose (a type of sugar) attaches to lipoproteins (a cholesterol-
protein package that enables cholesterol to travel through blood).

Sugarcoated LDL remains in the bloodstream longer and may lead to
the formation of plaque.

People with diabetes tend to have low HDL and high triglyceride
(another kind of blood fat) levels. Both of these boost the risk of
heart and artery disease.

CHOLESTEROL AND HIGH BLOOD PRESSURE
High blood pressure (also called hypertension) and high cholesterol
also are linked.

When the arteries become hardened and narrowed with cholesterol
plaque and calcium, the heart has to strain much harder to pump
blood through them.

As a result, blood pressure becomes abnormally high. High blood
pressure is also linked to heart disease.

Everyone older than age 20 should get their cholesterol levels
measured at least once every five years.

High cholesterol does not cause symptoms; so many people are
unaware that their cholesterol levels are too high.

Lowering cholesterol levels that are too high lessens the risk for
developing heart disease and reduces the chance of a heart attack or
dying of heart disease, even if you already have it.

To assess your cholesterol level, your doctor will usually ask for a
simple blood test called a lipoprotein profile. The lipoprotein profile
evaluates the following:

?HDL (high density lipoprotein cholesterol, also called “good”
cholesterol)

?LDL (low density lipoprotein cholesterol, also called “bad”
cholesterol)

?Total cholesterol level

?Triglycerides

In addition to the blood test, your doctor will perform a full physical
exam, discussing your medical history, checking your heart rate,
listening to your heartbeat, and taking your blood pressure.
If your cholesterol is found to be high, especially if you have other
risk factors for heart disease, your doctor will recommend various
treatment options ranging from dietary and lifestyle changes to
medication to lower your cholesterol.

LDL Cholesterol
LDL cholesterol can build up on the walls of your arteries and
increase your chances of getting heart disease. That is why LDL
cholesterol is referred to as “bad” cholesterol. The lower your LDL
cholesterol number, the lower your risk.

If your LDL is 190 or more, it is considered very high. Your doctor
will most likely recommend a statin in addition to making healthy
lifestyle choices. Statins are medicines that can help lower
cholesterol levels.

You may also need to take a statin even though your LDL level is
lower than 190. After figuring your 10-year risk, your doctor will
recommend a percentage by which you should try to lower your
LDL level through diet, exercise, and medication if necessary.

HDL Cholesterol
When it comes to HDL cholesterol — “good” cholesterol – a higher
number means lower risk. This is because HDL cholesterol protects
against heart disease by taking the “bad” cholesterol out of your
blood and keeping it from building up in your arteries. A statin can
slightly increase your HDL, as can exercise.

Triglycerides
Triglycerides are the form in which
most fat exists in food and the body.
A high triglyceride level has been
linked to higher risk of coronary
artery disease. Here’s the breakdown.

Triglycerides
Triglyceride
Categor y
Less than 150 Normal
150 – 199 Mildly High
200 – 499 High
500 or higher Very high

Total Cholesterol
Your total blood cholesterol is a measure of LDL cholesterol, HDL
cholesterol, and other lipid components.

Your doctor will use your total cholesterol number when
determining your risk for heart disease and how best to manage it.

Doctors emphasize diet, exercise, and weight loss to reduce
cholesterol. Medications are another important option to lower heart
disease risk.

If you have high blood pressure, high cholesterol, or a history of
heart problems, you have a higher risk of heart attack and stroke.

You can lower your risk by making this small change: At each meal,
choose foods that are good for your heart.

Most diets are based on foods you shouldn’t eat. Instead, take a
positive approach and focus on foods that are good for you.

Eat more beans, legumes (like lentils), seeds, and nuts. Your weekly
target: 4 servings of either nuts, seeds, or legumes such as black beans,
garbanzos (also called chickpeas), or lentils.

Eat more vegetables, fr uits, and whole grains. The fiber in these foods
helps lower “bad” LDL cholesterol. Put these on your plate with every
meal to reach these daily amounts: At least 5 cups of fruits and
vegetables and three 1-ounce servings of whole grains a day.

Celebrate each pound you lose. Small steps add up. Dropping even 5 or
10 pounds — even if you’re still technically overweight afterward — will
cut your risk of having a heart attack or stroke by lowering your blood
pressure, cholesterol, and blood sugar levels.

Feed your body regularly. When you skip a meal, you’re more likely to
overeat later. For some people, eating 5 to 6 mini-meals works best to
limit calories, help control blood sugars, and regulate metabolism. For
others, 3 meals a day works better, since extra meals can trigger
overeating. See which approach works for you.

Eating sterol and stanol-containing foods is an easy way to
lower your LDL cholesterol, which helps reduce the risk of
heart disease

The New Low-Cholesterol Diet: Plant Sterols and Stanols
Plant sterols and stanols are substances that occur naturally in
small amounts in many grains, vegetables, fruits, legumes, nuts,
and seeds. Since they have powerful cholesterol-lowering
properties, manufacturers have started adding them to foods.
You can now get stanols or sterols in margarine spreads,
orange juice, cereals, and even granola bars.

On a molecular level, sterols and
stanols look a lot like cholesterol.

So when they travel through
your digestive tract, they get in the
way.

They can prevent real cholesterol
from being absorbed into your
bloodstream.

Instead of clogging up your
arteries, the cholesterol just goes
out with the waste.

Plant stanol esters help block the absorption of cholesterol.
Research shows that three servings a day can reduce cholesterol by
20 points.

Experts have been studying the effects of food fortified with plant
sterols for decades.

One important study of people with high cholesterol found that less
than an ounce of stanol-fortified margarine a day could lower “bad”
LDL cholesterol by 14%.

The results were published in The New England Journal of Medicine.

You can also find plant sterols or
stanols in some cooking oils, salad
dressings, milk, yogurt, snack bars,
and juices.

Indeed, so many fortified products are
headed to grocery store shelves that
you’ll soon have a dizzy array of
choices.

But check the label carefully.

While plant sterols are healthy,
extra calories are not.

Excess calories simply lead to excess
pounds.

Nuts get a bad rap because of fat and calories. But they’re
a great weapon against LDL, the bad cholesterol.

The New Low-Cholesterol Diet: Nuts
Nuts get a bad rap. A lot of people still see them as salty,
fatty, and high calorie but also have lots of protein, fiber,
healthy monounsaturated fats, vitamins, nutrients, and
antioxidants. And many studies have shown that nuts have
powerful cholesterol-lowering effects.

The Nuts

Basically, nuts are good,
They’re high in vitamins, minerals,
and good monounsaturated fat,
which can lower cholesterol.

Along with almonds and walnuts,
the FDA gave its qualified health
claim to peanuts, hazelnuts, pecans, some pine nuts, and
pistachios.

How Much Do You Need?

You can get the health benefits of nuts from just a
handful a day. About 1 to 1.5 ounces is plenty,
experts say. The high protein and fiber in nuts make
them very filling. Make sure you don’t overdo it.

Improve total cholesterol with omega-3 fatty acids found
in salmon, tuna, sardines, and more.

The term “fatty fish” may sound unappealing, but actually these are
the tastiest and healthiest foods from the sea. Oily fish such as
salmon, tuna, sardines, mackerel, and trout are full of omega-3 fatty
acids — good fats unlike the bad saturated fat you find in most meats.
These fish should be a staple of everyone’s heart-healthy diet.

Omega-3 fatty acids have been shown to lower triglycerides, which
are a type of fat in the bloodstream. Experts aren’t sure of the exact
mechanism. Omega-3 fatty acids may also slow down the growth of
plaques in the arteries and reduce inflammation throughout the
body.

Getting daily omega-3 fatty acids from fish oil could lower triglyceride
levels by 25%-30%. The results were published in The American Journal
of Clinical Nutrition in 1997.

Fatty fish typically are cold-water fish. You have many good choices when
it comes to fatty fish. The American Dietetic Association recommends:
?Salmon, Tuna
?Trout, Herring, Sardines, Mackerel

Three ounces of salmon alone offers about 1 gram of EPA and DHA. If
these fish aren’t to your taste, you can also try white fish such as halibut
or trout. A 3.5-ounce serving of trout offers about 1 gram of EPA, plus
DHA.

?EPA and DHA stand for eicosapentaenoic acid
and docosahexaenoic acid respectively. These fatty
acids are omega-3 fats, which are found in cold water
fish.

?EPA DHA are highly unsaturated fats because they
contain six and five double bonds on their long
structural chains. These polyunsaturated fats play a
very important role with the function of our bodies.

It can really bring down your bad LDL cholesterol levels without
lowering your good cholesterol. The same goes for oat bran, which is
in some cereals, baked goods, and other products.

How Do Oats Help?
Oatmeal is full of soluble fiber, which we know lowers LDL levels.
Experts aren’t exactly sure how, but they have some ideas. When you
digest fiber, it becomes gooey. Researchers think that when it’s in
your intestines, it sticks to cholesterol and stops it from being
absorbed. So instead of getting that cholesterol into your system —
and your arteries — you simply get rid of it as waste.

Hypercholesterolemia medications
go in many types:
?Statins (HMG CoA Reductase
Inhibitors)
?Fibrates
?Niacin
?Cholesterol absorption inhibitors
?Bile acid sequestrants
?Omega-3 fatty acids, which we
talked about in previous slides.

Mechanism of action:
HMG CoA reductase inhibitors competitively inhibit the activity of HMG
CoA reductase, the rate-limiting enzyme in cholesterol synthesis.
Inhibition of this enzyme results in a transient, modest decrease in
cellular cholesterol concentration .

The decrease in cholesterol concentration activates a cellular signaling
cascade culminating in the activation of sterol regulatory element
binding protein (SREBP), a transcription factor that up-regulates
expression of the gene encoding the LDL receptor.

Increased LDL receptor expression causes increased uptake of plasma
LDL, and consequently decreases plasma LDL-cholesterol concentration.
Approximately 70% of LDL receptors are expressed by hepatocytes, with
the remainder expressed by a variety of cell types in the body.

CLINICAL USES
?Hypercholesterolemia
?Familial Hypercholesterolemia (Atorvastatin might be an exception)
?Coronary atherosclerosis
?Prophylaxis for coronary atherosclerosis.

ADVERSE EFFECTS AND CONTRAINDICATIONS
HMG-CoA inhibitors are contraindicated in pregnancy. Limited evidence
from animal and human studies indicates that statins should not be taken
during pregnancy.

Liver disfunction: Elevations of serum aminotransferase activity (up to
three times normal) occur in some patients. This is often intermittent and
usually not associated with other evidence of hepatic toxicity. In some
patients, who may have underlying liver disease or a history of alcohol
abuse, levels may exceed three times normal. This finding portends
more severe hepatic toxicity.

A relatively common side effect of the statins
(perhaps 1% of patients) is myositis, thatis,
inflammation of skeletal muscle accompanied by
pain, weakness, and high levels of serum keratine
kinase.

Rhabdomyolysis, i.e., disintegration of muscle with
urinary excretion of myoglobin and kidney damage,
is serious side effect.

Crestor :

WHAT IS CRESTOR?
Crestor is in a group of drugs called
HMG CoA reductase inhibitors, or
“statins.”

Rosuvastatin reduces levels of “bad”
cholesterol (low-density
lipoprotein, or LDL) and
triglycerides in the blood, while
increasing levels of “good”
cholesterol (high-density
lipoprotein, or HDL).

Crestor is used to lower cholesterol
and triglycerides (types of fat) in
the blood.

?Crestor is also used to lower the risk of stroke, heart attack, and other
heart complications in people with diabetes, coronary heart disease,
or other risk factors.
?Crestor is used in adults and children who are at least 10 years old.

IMPORTANT INFORMATION
?You should not take Crestor if you are allergic to rosuvastatin, if you
are pregnant or breast-feeding, or if you have liver disease. Stop
taking this medication and tell your doctor right away if you become
pregnant.
?Before taking Crestor, tell your doctor if you have ever had liver or
kidney disease, diabetes, or a thyroid disorder, if you are of Chinese
descent, or if you drink more than 2 alcoholic beverages daily.

BEFORE TAKING THIS MEDICINE
You should not take Crestor if you are allergic to rosuvastatin, if you are pregnant
or breast-feeding, or if you have liver disease.
To make sure you can safely take Crestor, tell your doctor if you have any of these
other conditions:
?history of liver disease
?history of kidney disease
?diabetes;
?a thyroid disorder

CRESTOR SIDE EFFECTS
Rare
?Dark-colored urine fever
?muscle cramps or spasms
?muscle pain, stiffness, tenderness, wasting, or weakness
?unusual tiredness or weakness

GENERAL DOSING INFORMATION
?The dose range for CRESTOR is 5 to 40 mg orally once daily. The usual
starting dose is 10-20 mg.
?CRESTOR can be administered as a single dose at any time of day, with or
without food.
?When initiating CRESTOR therapy or switching from another HMG-CoA
reductase inhibitor therapy, the appropriate CRESTOR starting dose
should first be utilized, and only then titrated according to the patient’s
response and individualized goal of therapy.
?After initiation or upon titration of CRESTOR, lipid levels should be
analyzed within 2 to 4 weeks and the dosage adjusted accordingly.

Rosuvastatin

Heterozygous Familial Hypercholesterolemia in
Pediatric Patients (10 to 17 years of age)
The usual dose range of CRESTOR is 5-20 mg/day; the
maximum recommended dose is 20 mg/day (doses
greater than 20 mg have not been studied in this patient
population).

Homozygous Familial Hypercholesterolemia
The recommended starting dose of CRESTOR is 20 mg
once daily. Response to therapy should be estimated
from preapheresis LDL-C levels.

Dosing in Asian Patients
In Asian patients, consider initiation of CRESTOR therapy
with 5 mg once daily due to increased rosuvastatin
plasma concentrations. The increased systemic exposure
should be taken into consideration when treating Asian
patients not adequately controlled at doses up to
20 mg/day .

Figure: Label of Crestor (20mg tablets). Produced by AstraZeneca™

WHAT IS ZOCOR?
Zocor belongs to a group of drugs called HMG CoA reductase
inhibitors, or “statins.” Simvastatin reduces levels of “bad”
cholesterol (low-density lipoprotein, or LDL) and triglycerides in the
blood, while increasing levels of “good” cholesterol (high-density
lipoprotein, or HDL) .

Zocor is used to lower cholesterol and triglycerides (types of fat) in
the It is also used to lower the risk of stroke, heart attack, and other
heart complications in people with diabetes, coronary heart disease,
or other risk factors.

Zocor is used in adults and children who are at least 10 years old.

IMPORTANT INFORMATION
In rare cases, Zocor can cause a condition that results in the breakdown
of skeletal muscle tissue, leading to kidney failure.

Never take Zocor in larger amounts, or for longer than recommended by
your doctor.

Taking too much of this medication may cause serious or life-threatening
side effects.

Before taking Zocor, tell your doctor if you have ever had liver or kidney
disease, diabetes, or a thyroid disorder, if you are of Chinese descent, or
if you drink more than 2 alcoholic beverages daily.

Zocor can harm an unborn baby or cause birth defects. Do not use if you
are pregnant.

ZOCOR SIDE EFFECTS

If any of the following side effects occur while taking simvastatin,
check with your doctor immediately:
More common
?Dizziness
?fainting
?fast or irregular heartbeat

Generic name: simvastatin
Dosage for m: tablet, film coated

The usual dosage range is 5 to 40 mg/day.
The recommended usual starting dose is 10 or 20 mg once a day in the
evening.

In patients with CHD or at high risk of CHD, ZOCOR can be started
simultaneously with diet.

For patients at high risk for a CHD event due to existing CHD, diabetes,
peripheral vessel disease, history of stroke or other cerebrovascular
disease, the recommended starting dose is 40 mg/day.

Lipid determinations should be performed after 4 weeks of therapy and
periodically thereafter.

Simvastatin

Figure: Label of Zocor (10mg tablets). Produced by MERCK & CO. INC™

Zetia reduces the amount of
cholesterol or other sterols that
your body absorbs from your
diet.

Zetia is used to treat high
cholesterol, along with a low-fat,
low-cholesterol diet. It is
sometimes given with other
cholesterol-lowering
medications. It is also used to
treat high blood sitosterol and
campesterol along with diet
therapy.

IMPORTANT INFORMATION
?Zetia is only part of a complete program of treatment that also includes diet,
exercise, and weight control. Follow your diet, medication, and exercise routines
very closely.

?Some cholesterol medications should not be taken at the same time. Do not take
Zetia with cholestyramine (Prevalite, Questran), colestipol (Colestid), or
colesevelam (Welchol). Wait at least 4 hours after taking any of these medicines
before you take Zetia. You may also take Zetia 2 hours before taking any of these
other medicines.

?Zetia may be taken at the same time with fenofibrate (Antara, Lipofen, Lofibra,
TriCor, Triglide), or with any of the “statin” drugs such as lovastatin (Mevacor),
simvastatin (Zocor), pravastatin (Pravachol), fluvastatin (Lescol), atorvastatin
(Lipitor), or cerivastatin (Baycol).

?In rare cases, cholesterol-lowering medication can cause a condition that results in
the breakdown of skeletal muscle tissue. This condition can lead to kidney failure.
Call your doctor at once if you have unexplained muscle pain or tenderness,
muscle weakness, fever or flu symptoms, and dark colored urine.

ZETIA SIDE EFFECTS
Some ezetimibe side effects may not need any medical attention. As your body gets
used to the medicine these side effects may disappear. Your health care professional
may be able to help you prevent or reduce these side effects, but do check with them
if any of the following side effects continue, or if you are concerned about them:

More common
?Fever
?headache
?muscle pain
?runny nose
?sore throat
Less common
?Back pain
?Body aches or pain
?Chest pain
?Chills

Active ingredient: ezetimibe
Dosage form: tablet

General Dosing Information
?The recommended dose of ZETIA is 10 mg once daily. ZETIA can be
administered with or without food.

Concomitant Lipid-Lowering Therapy
?ZETIA may be administered with a statin (in patients with primary
hyperlipidemia) or with fenofibrate (in patients with mixed
hyperlipidemia) for incremental effect. For convenience, the daily dose of
ZETIA may be taken at the same time as the statin or fenofibrate,
according to the dosing recommendations for the respective medications.

Co-administration with Bile Acid Sequestrants
?Dosing of ZETIA should occur either ?2 hours before or ?4 hours after
administration of a bile acid sequestrant.

Ezetimibe

Patients with Hepatic Impairment
?No dosage adjustment is necessary in patients with mild
hepatic impairment.

Patients with Renal Impair ment
?No dosage adjustment is necessary in patients with renal
impairment. When given with simvastatin in patients with
moderate to severe renal impairment (estimated glomerular
filtration rate