What is C-Reactive Protein (CRP)?

How Is C-Reactive Protein (CRP) Associated With the Risk of Cardiovascular

Disease?

How Is C-Reactive Protein (CRP) Related to the Risk of Hypertension?

Why hs-CRP ?

What Do the hs-CRP Test Results Mean?

Why Is it Important to Have Both hs-CRP and Cholesterol Measured?

Is hs-CRP the Only "Novel Risk Factor" for Heart Disease?

What Role Does C-Reactive Protein (CRP) Play in Diabetes and the Metabolic
Syndrome?

Do Diabetes Treatments Affect Inflammation?

Is C-Reactive Protein (CRP) Specifically Related To Cardiovascular Disease?

At What Age Is CRP Testing Appropriate?

How Can I Lower My C-Reactive Protein (CRP) Level?

What Do Aspirin and the "Statin" Drugs Do?

Do patients taking statin drugs need to have hs-CRP measured in follow-up?

Which People Should Be Tested for hs-CRP?

FAQ Answers Apr 07

What is C-Reactive Protein (CRP)? back to top

C-reactive protein (CRP) is a molecule produced in response to inflammation, which occurs

when the body is exposed to a major trauma or infection. CRP is therefore a marker of
inflammation. CRP is not only produced within the liver, but also appears to be produced in
both visceral fat and within coronary vessels. It has recently been discovered that CRP also
plays a role in heart disease.

The amount of CRP produced by the body varies from person to person, and this is affected by
an individual's genetic makeup (accounting for almost half of the variation in CRP levels
between different people) and lifestyle. Higher CRP levels tend to be found in individuals who
smoke, have high blood pressure, are overweight and don't exercise, whereas lean, athletic
individuals tend to have lower CRP levels.

Research shows that too much inflammation can sometimes have adverse effects on the blood
vessels which transport oxygen and nutrients throughout our bodies. Atherosclerosis, which
involves the formation of fatty deposits or plaques in the inner walls of the arteries, is now
considered in many ways an inflammatory disorder of the blood vessels, similar to how
arthritis is an inflammatory disorder of the bones and joints. Inflammation not only affects the
atherosclerotic phase of heart disease, but also the rupturing of plaques which can then travel
and interfere with blood flow, causing a heart attack.

Many studies have shown an association between elevated levels of inflammatory markers
(including CRP) and the future development of heart disease. This is true even for apparently
healthy men and women who have normal cholesterol levels. The reason CRP can be used by
physicians as part of the assessment of a patient's risk for heart disease, is because it is a stable
molecule and can be easily measured with a simple blood test.

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How Is C-Reactive Protein (CRP) Associated With the Risk of
back to top
Cardiovascular Disease?

Several major studies have shown that C-Reactive Protein (CRP) levels in apparently healthy
men and women are strongly predictive of the future risk of heart attack, stroke, sudden
cardiac death as well as the development of peripheral arterial disease. In patients already
suffering from heart disease, doctors can use CRP levels to determine which patients are at
high risk for recurring coronary events. Since high levels of CRP are indicative of a 2-3 fold
higher risk of cardiovascular disease, your doctor may want to measure your CRP level,
perhaps at the same time as measuring your cholesterol level. Even after taking into account
all other risk factors, those with elevated CRP levels have a risk 50-70 percent higher.

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How Is C-Reactive Protein (CRP) Related to the Risk of Hypertension? back to top

In the last decade or so several studies have suggested that hypertension or high blood
pressure, is in part an inflammatory disorder. As early as 1997 it was found that the risk of
having a future stroke went up with increasing levels of hs-CRP in apparently healthy men.
This finding was confirmed in a large study of healthy women by 2002. Since hypertension is
a major risk factor for the development of stroke, these outcomes suggested to doctors that
inflammation (indicated by high hs-CRP levels) and hypertension may be working together to
increase the chances of having a stroke.

In more recent major studies done in initially healthy women, those having a high hs-CRP
level on top of high blood pressure were at much greater risk of having a future event such as
a heart attack or stroke. Furthermore, the risk of developing hypertension in the future was
greater in those individuals having higher hs-CRP levels, even in the presence of low blood
pressure in the beginning. These studies have prompted further research to find out more about
the role of inflammation in hypertension.

The Val-MARC (Valsartan - Managing BP Aggressively and Evaluating Reductions in

hsCRP) trial is currently investigating whether blood pressure reduction with Diovan
(valsartan) will decrease hs-CRP levels and if the dose of medication used would influence
any effect on hs-CRP levels. If you would like to learn more or may be interested in
participating in this study, please call 1-888-526-4745 or go to http://www.valmarctrial.com
on the Internet.

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Why hs-CRP ? back to top

To measure your C-Reactive Protein (CRP) level, your doctor will need to order the "high-
sensitivity" CRP or
hs-CRP test from the laboratory. This is a simple blood test designed for
greater accuracy in measuring CRP, which allows the physician to use the result in
the assessment of cardiovascular risk.

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What Do the hs-CRP Test Results Mean? back to top

hs-CRP levels are expressed in terms of milligrams per liter (mg/L). Concerning your hs-CRP
level and cardiovascular risk, a level of less than 1mg/L indicates lower risk, a level between 1
and 3mg/L indicates moderate risk, and a level higher than 3mg/L indicates a higher risk. As
research has shown, this may hold true even if your LDL cholesterol levels are low.
If your hs-CRP level is very high, above 10mg/L, you should have the test repeated after 2-3
weeks, as the high hs-CRP level may reflect an acute infection that you are experiencing at the
time. You should therefore have your hs-CRP evaluated only when feeling well. If upon repeat
testing your hs-CRP level remains high, then you are most probably in the higher
cardiovascular risk group.

In middle-aged Americans, the average hs-CRP level is between 1.0 and 2.0 mg/L. About one
quarter of Americans have a hs-CRP level above 3mg/L, placing them in the higher risk
group.

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Why Is it Important to Have Both hs-CRP and Cholesterol Measured? back to top

High hs-CRP and high LDL or "bad" cholesterol levels represent different pathways leading to
heart disease. Therefore doing measurements of both of these provides the doctor with more
information about your cardiovascular risk than measuring LDL cholesterol alone. Persons
with high hs-CRP and high LDL cholesterol are at greatest risk and those with low hs-CRP
and low LDL cholesterol are at lowest risk.

If your hs-CRP or LDL cholesterol levels are high, your doctor may advise you to adopt some
lifestyle changes such as losing weight, stopping smoking, exercising and following a
recommended diet, all of which will lower your cardiovascular risk as well as hs-CRP levels.
There are also some medications you may wish to consider.

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Is hs-CRP the Only "Novel Risk Factor" for Heart Disease? back to top

Besides C-Reactive Protein (CRP), there are other novel risk factors for heart disease such as
homosysteine and lipoprotein(a), among others. hs-CRP however is the inflammatory marker
with the strongest predictive value for future cardiovascular events, and has been shown to add
prognostic information to that obtained from cholesterol screening. In the future, it is possible
that other markers of inflammation beyond CRP will be introduced.

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What Role Does C-Reactive Protein (CRP) Play in Diabetes and the
back to top
Metabolic Syndrome?

High hs-CRP levels also predict increased risk of developing type 2 diabetes. In some patients,
this increased inflammation comes from obesity, as fat cells secrete proteins which stimulate
the production of C-Reactive Protein (CRP).

Patients with the metabolic syndrome have an increased chance of developing heart disease
and diabetes. Individuals are currently classified as having the metabolic sydrome if they meet
3 of the following 5 criteria: low HDL or "good" cholesterol, obesity, high triglycerides,
increased blood sugar levels or high blood pressure. These however don't represent all the
components or contributing factors in the metabolic syndrome. CRP levels are known to
increase with the number of metabolic syndrome components present, and since they provide
the physician with added information on the risk of cardiovascular disease and diabetes, many
physicians include a test for hs-CRP when screening a patient for the metabolic syndrome.
Certain types of medical specialists such as endocrinologists and other physicians who are
especially concerned with the prevention of diabetes and heart disease, are more likely to
order this test.
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Do Diabetes Treatments Affect Inflammation? back to top

Diabetes and high hs-CRP levels both increase the risk of having a future heart attack or
stroke. Diabetes is linked to increased inflammation (detectable by the hs-CRP test), and this
inflammation has harmful effects on the blood vessel walls over time.

The primary goal of diabetes treatments is to lower blood sugar levels. Diabetic patients may
need to take extra medications to control their blood pressure and/or cholesterol levels, and
some of these may have the additional effect of reducing inflammation.

Some diabetes treatments also reduce inflammation, as seen by the changes in blood levels of
a variety of molecules including C-reactive protein, that are involved in the inflammatory
process. Diabetes treatments with known anti-inflammatory effects include insulin and drugs
of the insulin sensitizing kind, such as the "glitazones" and metformin.

If you are diabetic and your hs-CRP level is high, your doctor may advise you to make some
lifestyle changes to reduce your risk of a heart attack or stroke, such as quitting smoking,
exercising more and following a healthy diet.

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Is C-Reactive Protein (CRP) Specifically Related To Cardiovascular

back to top
Disease?

Because C-Reactive Protein (CRP) levels increase in response to a variety of stimuli in the
form of major trauma or infection, there has been some concern about whether hs-CRP levels
are truly related to the risk of heart disease specifically. However several studies have now
shown that measurement of high-sensitivity CRP in stable individuals is in fact highly
predictive of cardiovascular events. Therefore chronically elevated CRP levels do indicate an
increased risk of heart disease as well as the increased rate of atherosclerosis seen in diabetic
patients.

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At What Age Is CRP Testing Appropriate? back to top

The best time to start getting tested for hs-CRP would probably be sometime in your 30's,
when your doctor may start checking your cholesterol levels. If you are in your teens or 20's,
there is evidence which strongly suggests that your current hs-CRP level is predictive of hs-
CRP levels later on in your life. Elevated C-Reactive Protein (CRP) levels provide information
on cardiovascular risk over the following 30-40 years. This becomes very useful for your
physician as he/she can detect risk years in advance and have the opportunity to initiate
lifestyle and/or pharmacologic interventions in order to prevent heart attack or stroke.

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How Can I Lower My C-Reactive Protein (CRP) Level? back to top

Since an association between elevated hs-CRP levels and cardiovascular risk has only recently
been established, it remains to be seen whether lowering C-Reactive Protein (CRP) will result
in a direct lowering of cardiovascular risk. You and your physician should be on the lookout
for new information on lowering CRP levels and the effect this has on cardiovascular risk.
The good news is that the best ways to lower CRP are the same as measures you should take
to lower your cardiovascular risk, that is, diet, exercise, blood pressure control and stopping
smoking.

Because studies have shown that people with normal cholesterol but elevated hs-CRP levels
are still at higher risk than people with normal cholesterol and hs-CRP levels, CRP assessment
is a useful way to identify more patients at risk for heart disease.

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What Do Aspirin and the "Statin" Drugs Do? back to top

Studies have shown that aspirin, an antiplatelet and anti-inflammatory drug, reduced the risk
of a first-ever heart attack in men, and this protection was greatest among those individuals
having high levels of inflammation as indicated by elevated hs-CRP levels. You should not
start taking aspirin without consulting your physician, who will decide if it is appropriate for
you based on the potential risks and benefits.

Cholesterol lowering drugs, in particular the "statins" are well-known to reduce the risk of
first-ever heart attacks and strokes, as well as recurrent events. Statins work mainly by
lowering LDL cholesterol levels but they also lower C-Reactive Protein (CRP), which may
have an additional clinical benefit. They are currently prescribed for patients with known heart
disease, high LDL cholesterol and diabetes. To learn more about the statin drugs, please see
the Cardiology Patient Page by Gotto (Statins: powerful drugs for lowering cholesterol: advice
for patients, Circulation 2002;105:1514–1516).

It is currently being investigated whether individuals with low LDL but high CRP levels
would also benefit from taking statin drugs, in terms of reduced cardiovascular risk. The trial
that is underway to test this hypothesis is called the JUPITER trial, and if you wish to you
participate in this study, please call 1-888-660-8254 or go to http://www.JUPITERstudy.com
on the Internet.

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Do patients taking statin drugs need to have hs-CRP measured in follow-

back to top
up?

Statin drugs both lower cholesterol and lower hs-CRP levels. Very recent evidence in high risk
patients from two studies, the PROVE IT trial and the REVERSAL trial, both indicate that
reducing hs-CRP levels with statin therapy lowers the risk of recurrent heart attacks and
cardiac deaths. This is potentially important for patient care as it suggests that getting hs-CRP
levels down aggressively may be of similar importance as aggressively lowering cholesterol
levels - in both of these new studies, the patients who did the best were those who not only
lowered cholesterol but also lowered hs-CRP levels. The best way to do this is through
lifestyle changes including weight loss, exercise, and smoking cessation. Patients who are at
high risk and taking statin drugs and who have elevated hs-CRP levels may want to consult
with their physicians about whether the dose of statin is optimal for them.

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Which People Should Be Tested for hs-CRP? back to top

According to the Centers for Disease Control and Prevention and the American Heart
Association, hs-CRP evaluation should be a part of the global risk assessment in individuals
concerned about their vascular risk. This testing is likely to be most useful in patients at an
intermediate level of risk, where the hs-CRP level would provide additional prognostic
information allowing more patients to be aware of their increased risk so they can begin timely
preventive measures by way of positive lifestyle changes. Many physicians do a hs-CRP
evaluation concurrently with cholesterol evaluation, making use of the same blood sample. C-
Reactive Protein (CRP) is by no means mandatory, but should be done when your physician
sees it as appropriate.

Other patients for whom the Centers for Disease Control and Prevention and the American
Heart Association endorse hs-CRP evaluation are those with a prior history of heart attack,
and those admitted to hospital for acute heart disease syndromes. Patients coming to the
Emergency department with chest pains may also have their CRP evaluated in order to assess
their risk for coronary disease.