C-reactive protein (CRP) is a substance found in human blood. It is a protein produced by the liver. The level of CRP rises when there is inflammation throughout the body, 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.
If a doctor suspects that a patient may have an infection, a blood test may be ordered to check for levels of CRP and other substances in the blood. The CRP test can also be used to monitor the progress of a chronic condition such as cancer or arthritis, and to see how the body is responding to a particular medication. If CRP levels drop after a medication change, it suggests that the medication may be working, causing the infection to die down. Normal ranges for CRP vary, depending on the patient and his or her medical history.
In addition to being useful in the evaluation of particular medical conditions, levels of this protein can also be used as a yardstick for general health. Using what is known as an highly sensitive CRP (hs-CRP) test, a laboratory can detect the very low levels of CRP present in the blood of people without active infections. Higher levels of ambient CRP appear to be linked with an increased risk of cardiovascular disease, hypertension, and diabetes.
In addition to infection, several other things appear to be able to impact CRP production. A high amount of dietary fat can cause an increase in CRP, especially if the fat comes from transfats. Pregnancy also appears to elevate CRP levels. Liver disease can also alter the level of CRP in the blood, since the liver is involved in the production of C-reactive protein. If a hs-CRP test comes back with a somewhat high level, a doctor may ask a few questions to rule out these potential causes.
The body produces CRP in response to infection, making it a substance which can be targeted in blood tests which look for signs of systemic infection. A CRP test is a quick and relatively painless procedure which can be performed on an outpatient basis at a hospital or medical clinic, and it can provide rapid information about a patient's condition.
Under normal conditions, low levels of CRP are present in the blood. When an infection occurs, the liver and fat cells start to produce CRP, at levels which can vary, depending on the nature of the infection. Specific diseases can sometimes attach particular sugars to CRP, leaving tell-tale fingerprints which have potential diagnostic uses. Once the infection is resolved, the CRP breaks down, returning to negligible or low levels.
Blood is typically drawn from a vein, usually from the inside of the elbow or the back of the hand. The site is cleaned with germ-killing medicine (antiseptic). The health care provider wraps an elastic band around the upper arm to apply pressure to the area and make the vein swell with blood.
Next, the health care provider gently inserts a needle into the vein. The blood collects into an airtight vial or tube attached to the needle. The elastic band is removed from your arm.
Once the blood has been collected, the needle is removed, and the puncture site is covered to stop any bleeding.
In infants or young children, a sharp tool called a lancet may be used to puncture the skin and make it bleed. The blood collects into a small glass tube called a pipette, or onto a slide or test strip. A bandage may be placed over the area if there is any bleeding.
At the laboratory, your blood sample is mixed with a liquid called an antiserum, which contains substances that look for the specific protein.
No preparation is necessary for this test.
When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing.
The CRP test is a general test to check for inflammation in the body. It is not a specific test. That means it can reveal that you have inflammation somewhere in your body, but it cannot pinpoint the exact location.
Your doctor may order this test to:
Check for flare-ups of inflammatory diseases such as rheumatoid arthritis, lupus, or vasculitis
Determine if anti-inflammatory medicine is working to treat a disease or condition
However, a low CRP level does not always mean that there is no inflammation present. Levels of CRP may not be increased in people with rheumatoid arthritis and lupus. The reason for this is unknown.
A more sensitive CRP test, called a high-sensitivity C-reactive protein (hs-CRP) assay, is available to determine a person's risk for heart disease. Many consider a high CRP level to be a risk factor for heart disease. However, it is not known whether CRP is merely a sign of cardiovascular disease or if it actually plays a role in causing heart problems.
Normal CRP values vary from lab to lab. Generally, there is no CRP detectable in the blood.
Your doctor may also use a highly sensitive test called hs-CRP to help determine your risk of heart disease. According to the American Heart Association:
You are at low risk of developing cardiovascular disease if your hs-CRP level is lower than 1.0mg/L
You are at average risk of developing cardiovascular disease if your levels are between 1.0 and 3.0 mg/L
You are at high risk for cardiovascular disease if your hs-CRP level is higher than 3.0 mg/L
Note: Normal value ranges may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results.
The examples above show the common measurements for results for these tests. Some laboratories use different measurements or may test different specimens.
A positive test means you have inflammation in the body. This may be due to a variety of different conditions, including:
Cancer
Connective tissue disease
Heart attack
Infection
Inflammatory bowel disease (IBD)
Lupus
Pneumococcal pneumonia
Rheumatoid arthritis
Rheumatic fever
Tuberculosis
This list is not all inclusive.
Note: Positive CRP results also occur during the last half of pregnancy.
Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.
Other risks associated with having blood drawn are slight but may include:
Excessive bleeding
Fainting or feeling light-headed
Hematoma (blood accumulating under the skin)
Infection (a slight risk any time the skin is broken)
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Statin drugs both lower cholesterol and lower hs-CRP levels. Very recent evidence in high risk patients from two studies, 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.
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.