The C-reactive protein (CRP) test is a blood test that measures the level an inflammatory marker – a substance that the body releases in response to inflammation. High levels of CRP in the blood mean there is inflammation somewhere in the body.
The interest in CRP as an indicator of heart disease has emerged as researchers have learned more about atherosclerosis, or "hardening of the arteries." In recent years, scientists have learned that atherosclerosis is an inflammatory process in which immune system cells are activated in response to a local injury inside the arteries. These white blood cells release inflammatory chemicals that contribute to the atherosclerotic process and are one component of arterial plaque deposits. When a plaque deposit rupture, a heart attack or stroke can result. In response to this inflammation, CRP and other inflammatory markers in the blood rise.
Physicians may use a particularly sensitive type of CRP test called a high-sensitivity CRP(hs-CRP)assay to assess a patients risk for heart problems. By measuring CRP, physicians can measure the level of inflammation in the body and help identify people who may be at risk for a heart attack or other cardiovascular event.
CRP, however, has drawbacks as an indicator for heart disease. Because CRP levels rise in response to inflammation anywhere in the body, it is a non-specific marker, meaning that elevated CRP levels do not necessarily indicate atherosclerosis or increased risk for cardiovascular events. In fact, CRP levels rise in response to many illnesses and chronic diseases, including bronchitis, gastritis, diabetes, high blood pressure and cancer. It can also rise in response to physical trauma (e.g., burns, fractures, surgery).
Because CRP levels are not specific to any one area of the body, some researchers have concluded that CRP testing is not as reliable as cholesterol, blood pressure and other risk factors in predicting cardiovascular disease in healthy people. Further studies in this area are necessary. Nevertheless, most experts agree that CRP levels can be a very useful measurement in people diagnosed with cardiovascular disease.
Patients who are scheduled for a CRP test will be asked not to eat or drink anything for 12 hours before the test.
About CRP tests
The C-reactive protein (CRP) test is a blood test that measures the level of CRP in the blood. CRP is a substance produced by the liver that increases whenever there is inflammation somewhere in the body. In general, CRP levels rise whenever there is an immune system response or activation.
When the immune system senses injury or a foreign invader (e.g., harmful bacteria), immune system cells secrete inflammatory chemicals. These are chemical signals that launch an inflammatory cascade as the body begins the healing process. CRP is produced in response to elevations in these inflammatory chemicals. CRP is also produced in response to blood coagulation.
While inflammation is a natural and essential part of the healing process, inappropriate immune system responses can further aggravate, or even cause diseases. In the case of atherosclerosis, there is evidence that the immune system is activated in response to injury to the inner lining of arteries, or endothelium. This immune response causes white blood cells to gather at the site of the injury. These white blood cells are eventually incorporated into the plaque deposits that can cause heart attacks and strokes.
The immune system is also inappropriately inactivated in the case of autoimmune diseases (diseases in which the immune system targets its own tissue for destruction). Examples of autoimmune disease include rheumatoid arthritis (but not osteoarthritis) and systemic lupus erythematosus. In any of these cases, levels of CRP will rise in response to inflammation.
Finally, CRP levels may rise dramatically in response to acute injuries, such as trauma or heart attack, when the immune system mounts a massive response to injury and large amounts of blood coagulation factors are released.
Specific conditions that are known to cause a rise in CRP levels include:
Heart attack. An event that results in permanent heart damage or death. It is also known as a myocardial infarction, because part of the heart muscle (myocardium) may die (infarction). A heart attack occurs when one of the coronary arteries becomes severely or totally blocked, usually by a blood clot. When the heart muscle does not receive the oxygen-rich blood that it needs, it will begin to die. Over time, the accumulated effects of this damage can lead to heart failure.
Unstable angina. A temporary and often recurring chest pain, pressure or discomfort that occurs when part of the heart is not getting enough oxygen–rich blood (cardiac ischemia). As opposed to stable angina, which occurs at predictable times (e.g., during exercise), unstable angina occurs at unpredictable times. People with unstable angina are at much higher risk for a heart attack than those with stable angina.
Rheumatic fever. A disease characterized by the inflammation of many connective tissues throughout the body, particularly in the heart, joints and central nervous system (the brain and spinal cord). The condition is the result of “strep throat” that has not been treated by antibiotics.
Rheumatoid arthritis. A degenerative, autoimmune disease marked by pain, stiffness and/or swelling of the joints that eventually results in destruction of the joint. Rheumatoid arthritis may also have systemic effects (e.g., effects throughout the body) and is characterized by high levels of inflammation and activation of the immune system.
Systematic lupus erythematosus. An autoimmune disease in which the body produces autoantibodies, or immune system cells that are targeted at its own tissue. Lupus can affect a variety of organs throughout the body, including the heart, lungs, kidneys, joints and nervous system. Like arthritis, lupus is an inflammatory condition characterized by activation of the body's immune system against itself.
Tuberculosis. A contagious bacterial infection usually found in the lungs.
Pneumococcal pneumonia. A contagious bacterial infection that results in acute inflammation of the lungs.
Cancer. A potentially fatal disease marked by malignant tumors in any part of the body.
Postoperative infection. CRP tests are sometimes performed following surgery because high levels may indicate the presence of infection. While an erythrocyte sedimentation rate test is also used for this purpose, CRP levels may be better tools for early detection because they will show an elevation more quickly.
Trauma (e.g., injuries or burns). During any sort of trauma, the immune system is activated to help the body heal, thus resulting in inflammation at the site of the wound and increases inflammatory markers such as CRP in the bloodstream. In addition, large amounts of blood coagulation factors are released.
Heat stroke. A condition marked by prolonged exposure to the sun that results in a high body temperature and the inability to sweat, leading to collapse. Heatstroke will produce moderate elevations in CRP levels.
High blood pressure (hypertension), diabetes and glucose intolerance (all of which are independent risk factors for heart disease) can also cause an increase in CRP levels. Recent studies have also found an association between CRP levels and the risk of sudden cardiac death and the likelihood of complications following cardiac procedures (e.g., stenting, coronary artery bypass graft).
There are two main types of CRP test. The conventional CRP test is commonly used to identify the presence of inflammation in the body as a result of infection, tissue injury or inflammatory disorders. A physician may recommend a different type of CRP test called a high-sensitivity CRP (hs-CRP)assay to identify risk factors for heart disease. An hs-CRP assay is designed to detect inflammation below the levels normally detected with a conventional CRP test.
Many experts agree that CRP testing, especially hs-CRP assays, can yield important information in people diagnosed with cardiovascular disease, such as the severity of the disease and the effectiveness of therapy. Some studies have also indicated that hs-CRP may be helpful in predicting a heart attack or stroke in an apparently healthy person. However, more research is needed to fully evaluate the role that CRP plays in cardiovascular health. Other recent research findings include:
CRP is produced not only in the liver but also in the endothelial cells that line the inside of arteries. This is consistent with the emerging understanding of atherosclerosis as an inflammatory disease that begins with an injury to the endothelium, resulting in a localized immune system response. Researchers have discovered that, long before there are any clinical signs of coronary artery disease, the endothelial layer of these people is inflamed. Some research indicated that, at the endothelial layer, CRP is not simply a marker of inflammation but also contributes to damage to the arteries.
CRP levels are significantly associated with other cardiovascular risk factors, including age, smoking, high blood pressure, body mass index, diabetes and others. This means that people with other risk factors for heart disease are also more likely to have elevated CRP levels.
Women generally have higher levels of CRP than men, but CRP has predictive value for cardiac events for both men and women.
The American Heart Association and the U.S. Centers for Disease Control and Prevention issued joint guidelines on CRP and hs-CRP testing in 2003. The guidelines suggest:
CRP testing should be measured twice, with the values averaged, optimally two weeks apart, to obtain the most accurate measurement.
No testing is warranted for people with a low risk of developing cardiovascular disease (less than 10 percent risk in 10 years). This risk is determined by a coronary risk profile worksheet.
Testing may help physicians direct therapy to prevent heart attack and stroke for those with risk scores in the intermediate range (10 to 20 percent risk in 10 years).
Patients at high risk of a heart attack or stroke (greater than 20 percent in 10 years), or who have been diagnosed with cardiovascular disease should be treated intensively regardless of CRP levels.
Factors that may affect results
Factors that may interfere with the accuracy of a C-reactive protein (CRP) or a high sensitivity CRP (hs-CRP) assay include:
Diet. Patients will be advised not to eat or drink anything for 12 hours prior to testing.
Pregnancy. Women in the last half of the pregnancy cycle will have some CRP in their blood, which is normal.
Stress. Periods of psychological stress can mildly increase CRP levels.
Exercise. Strenuous exercise can moderately increase CRP levels.
Intrauterine devices (IUDs). Devices that are inserted into the uterus to prevent pregnancy. IUDs can sometimes cause inflammation, which will mildly increase CRP levels.
In addition, taking some types of the following medications may affect CRP test results:
Statins. Cholesterol-reducing medications that are often considered a first line of treatment for patients with high cholesterol levels (hypercholesterolemia). Statins have been found to reduce CRP blood levels.
Corticosteroids. Anti-inflammatory medications containing steroids that are similar to the naturally occurring hormone cortisone can inhibit or reduce the inflammatory response.
Birth control pills. Medications that alter the reproductive cycle of women to prevent pregnancy. These medications may result in a false-positive CRP test (i.e., the test results suggest that inflammation is present when it actually is not). Similarly, estrogen-replacement therapy to treat the symptoms of menopause has also been found to elevate CRP levels.
Abnormal CRP test results
The presence of high levels of C-reactive protein (CRP) in the blood means that one or more parts of the body are inflamed. A CRP test cannot determine the location of inflammation or its cause. Therefore, the test is often used in conjunction with other diagnostic tests to confirm a diagnosis related to infection or inflammation.
A conventional CRP test is considered positive for inflammation if it shows CRP levels above 10 milligrams per liter (mg/L). A physician may recommend a different type of CRP test called a high-sensitivity CRP (hs-CRP)assay to identify risk factors for heart disease. An hs-CRP assay is designed to detect inflammation below the levels normally detected with a conventional CRP test.
Hs-CRP levels and risks are interpreted based on studies of individuals who are divided into groups based on their hs-CRP levels (in milligrams per liter [mg/L]). Some studies, for example, create three groups (tertiles), categorizing the risk of heart disease-related events as follows:
Tertile 1: Low risk
< 1.0 mg/L
Tertile 2: Moderate risk
1.0 to 3.0 mg/L
Tertile 3: High risk
> 3.0 mg/L
Other researchers create four groups (quartiles), and even five (quintiles), such as:
Quintile 1: Lowest risk
< 0.55 mg/L
Quintile 2: Low-mid risk
0.55 to 0.99 mg/L
Quintile 3: Mid-high risk
1.0 to 2.1 mg/L
Quintile 4: High-risk
2.1 to 3.8 mg/L
Quintile 5: Highest risk
3.9 to 15 mg/L
Frequency of CRP testing
A C-reactive protein (CRP) test is generally used as a diagnostic tool, especially in cases of suspected heart disease. However, because it cannot identify the specific location of the inflammation, they are usually used in conjunction with other diagnostic tests.
Most patients will not require regular testing and the American Heart Association does not recommend regular CRP tests for people who are at a low risk for cardiovascular disease. However, CRP levels can also be used to monitor the progress of treatments aimed at reducing chronic inflammation. As inflammation in the body decreases, so do CRP levels. Therefore, some patients will have a series of CRP tests performed over the course of their treatment.
Questions for your doctor
Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions related to C-reactive protein (CRP) testing:
How high is my CRP level?
Would I benefit from an hs-CRP test?
Should I get it tested again?
What factors may be contributing to elevated CRP?
Are there any medications I can take to reduce CRP?
What effect does this have on my risk for a cardiovascular event?
Should I begin treatment for prevention of a cardiovascular event?
What lifestyle changes can I make to lower my CRP level? Exercise?
I've read that some foods, such as refined sugar, are "pro-inflammatory." Does this mean that my CRP level might be elevated in response to my diet? Will changing my diet reduce my CRP level?
If I lower my CRP level, will I reduce my risk of a cardiovascular event?
Are there any dietary supplements or nutrients that might help lower my CRP level? Conversely, are there any I should avoid?
