CRP may not be a standard blood test, but more and more doctors are using it because it can reveal a lot about your health. While this protein helps you fight infections, it is also a marker of low-grade inflammation and a predictor of your heart disease risk. Find out more about the CRP blood test and whether your levels are in the normal range.
What is C-Reactive Protein (CRP)?
CRP, short for C-reactive protein, is a ring-shaped protein and an important marker of systemic inflammation [1].
CRP is mainly made in the liver in response to inflammatory molecules called cytokines, including interleukin-6 (IL- 6), interleukin-1β (IL-1b), interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-a). These cytokines are released in response to trauma, inflammation, and infection [1, 2].
CRP binds to damaged tissue or invading microbes in order to activate the immune system to clear them away. It serves as a primary defense system against infections. By binding to microbes and damaged cells, CRP makes them ready to be devoured by white blood cells [3, 4].
This process is also called the acute-phase reaction and represents an early reaction of the body to bacterial, viral, or parasitic infection, injury, damaged cells, or cancer. Such changes are called ‘acute’ because they usually happen within hours or days following the onset of infection or injury. Their purpose is to restore balance and to remove the cause of the disturbance [1].
Once the cause of the disturbance has been taken care of, CRP levels usually drop back to normal. However, when there’s chronic low-grade inflammation in the body, CRP levels remain slightly increased [5].
Aside from the liver, other tissues — such as the arteries, lungs, and kidneys — can also produce small amounts of CRP [1, 6, 7].
CRP vs. hs-CRP Blood Test
Both of these tests measure the amount of the inflammatory marker C-reactive protein (CRP) in the blood.
The CRP test is ordered for people with symptoms of a serious bacterial infection or inflammatory diseases. It measures CRP in the range from 10 to 1,000 mg/L. Point-of-care tests that perform a CRP test within 4 minutes have now become available. Therefore CRP can assist in diagnosing serious infections in hospital settings [8, 9].
However, if you’re interested in checking for low-grade chronic inflammation or for an indication of your heart disease risk, you should do a hs-CRP test. hs-CRP test measures CRP in the range from 0.5 to 10 mg/L. The sensitivity of the hs-CRP test allows you to detect slightly elevated CRP levels that would otherwise go unnoticed with a regular CRP test [9].
CRP Normal Range
CRP is found in traces in healthy people. The normal range is usually below 1 mg/l [1].
Your genes can impact your baseline CRP levels. In fact, studies suggest that genetics accounts for around 25 – 40% of the variation in CRP levels between people. However, CRP environment and lifestyle factors, such as diet and smoking, still play a larger role [10].
CRP peaks at about 3 PM each day, with a 1% variation in CRP levels being from daily and seasonal effects [11].
Minor changes occur during the menstrual cycle in women, and levels commonly rise and fluctuate in pregnancy [11, 12].
CRP levels also normally increase with age [13].
A lack of CRP elevation despite high inflammation is possible in liver failure, as well as during lupus flare-ups [1].
On the other hand, people with kidney failure may have high CRP in the absence of clinically significant inflammation [14].
Impact on Heart Disease Risk
Scientists have found that lower CRP levels were linked with a lower risk of heart disease, and vice versa. It is now generally accepted that CRP levels can help predict the future risk of heart (cardiovascular) disease even in apparently healthy people [15, 16, 17].
CRP levels are associated with heart disease risk, as follows [16, 18, 19]:
- Low risk: hs-CRP level under 1.0 mg/L
- Average risk: between 1.0 and 3.0 mg/L
- High risk: above 3.0 mg/L
- Very high risk: 5-10 mg/L
- Above 10 mg/L – clinically significant inflammatory states
CRP levels complement cholesterol levels to give a more accurate prediction of a person’s cardiovascular risk [17].
For example, based on a study in almost 28k apparently healthy American women, when both CRP and cholesterol levels were high, a person’s overall risk of a cardiovascular event (such as a heart attack) increased up to 9-fold compared with that of a person with low CRP and cholesterol levels [17].
http://circ.ahajournals.org/content/108/12/e81
CRP Levels Above the Normal Range
Infection vs. Chronic Inflammation
In this section, we’ll dive into the science to understand how CRP levels differ between sudden infections and chronic inflammation. Skip to the next part if you just want to understand the main points.
CRP levels don’t increase the same way when the body is dealing with severe infection and when it’s faced with chronic, low-grade inflammation. CRP release is increased by infections (bacterial, fungal, mycobacterial, or viral), tissue death, trauma, cancer, and inflammatory disorders [5].
CRP plays a protective role in infection by activating the immune response. In such cases, its levels rise dramatically and quickly to help the body defend itself. CRP increases 4 to 6 hours after tissue injury or inflammation and declines rapidly with the resolution of the inflammatory process, usually within a day or two [15, 20, 1, 16].
Bacterial infections can massively increase CRP (40 – 200 mg/L or more), while viral infections and mild inflammation usually trigger a more subtle rise in CRP (10 – 40 mg/L) [15, 20]. In the most severe cases, CRP levels can increase 1000-fold or more, peaking at 48 h [16, 21].
CRP has a stable half-life of 18 – 19 h under all conditions of health and disease, so the sole determinant of circulating CRP levels is its production rate. CRP is broken down by macrophages (a type of white blood cells) [16, 22, 23].
Compared to the acute sharp rise in CRP levels, low-grade chronic inflammation produces minor elevations of CRP in the 3-10 mg/L range. These are usually long-term [15].
Why Are Higher Levels of CRP Bad?
CRP levels increase as a marker of chronic inflammatory states, such as high blood pressure (hypertension), obesity, diabetes, and heart disease. What’s more, elevated CRP is associated with insulin resistance, obesity, higher triglycerides and lower HDL cholesterol, also known as “good” cholesterol [24, 15].
This wouldn’t make CRP bad per se. Except it turns out that apart from being a marker of inflammation, CRP can also create inflammation on its own [15]!
CRP increases proinflammatory cytokine release from white blood cells [15].
In addition, studies have shown that CRP can damage blood vessels by increasing the release of inflammatory molecules in blood vessel walls and blood vessel muscles[15].
Finally, in muscles, CRP can also directly inhibit insulin signaling, preventing sugar from entering into the muscle tissues and thereby increasing insulin resistance [15].
These effects of CRP are likely an explanation as to why higher CRP levels can increase a person’s future risk of heart disease [15, 16, 17].
Takeaway
C-reactive Protein (CRP) is created by the liver in response to inflammation, infection, and injury. If you are facing a sudden infection, CRP will dramatically rise to help your immune system get rid of the invader and restore balance. Once the threat is gone, its levels quickly return back to normal.
Problems arise when CRP remains slightly high over long periods of time, such as in chronic, low-grade inflammation. That’s because CRP can also create inflammation on its own, damaging the blood vessels and increasing oxidative stress in the body.
It is now generally accepted that higher CRP levels are associated with an increased risk of diabetes of heart disease.
A standard CRP blood test is used for people who are experiencing acute infections or injuries. if you’re interested in checking for low-grade chronic inflammation or for an indication of your heart disease risk, you should get a high sensitivity CRP test (hs-CRP) that can detect slightly elevated levels that would go unnoticed with the regular test (<10 mg/l).
If your CRP levels are under 3 mg/l, you are in the normal range. Levels below 1 mg/L are considered optimal, as they are associated with below average heart disease risk.
Learn More About CRP
This post is the first in a four-part series about CRP. Read the other parts to learn about: