CRP is not what your doctor would usually test, even though it can tell you a lot about your health. This protein helps you fight infections. However, it is also a marker of low-grade inflammation and a predictor of your cardiovascular disease risk. Find out what the CRP blood test can reveal 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 the main 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) [1, 2].

Cytokines are released in response to trauma, inflammation, and infection. CRP binds to damaged tissue or pathogens in order to activate the immune system to clear them away. It also 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 cancerous growth [1].

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 its disturbance [1].

Aside from the liver, other tissues–such as the arteries, lungs, and kidneys–can also produce small amounts of CRP [1, 5, 6].

The body produces CRP as an attempt to restore balance and health shortly after injury, infection, or inflammation. Constantly high CRP levels, on the other hand, point to whole-body inflammation.

CRP & hs-CRP Blood Test

Both CRP tests measure the amount of the inflammatory marker C-reactive protein (CRP) in the blood.

You should normally want the high-sensitivity C-reactive protein (hs-CRP) test, not the regular CRP test. The CRP test is ordered for people with symptoms of a serious bacterial infection or chronic inflammatory disease. It measures CRP in the range from 10 to 1,000 mg/L, while hs-CRP test measures CRP in the range from 0.5 to 10 mg/L [7].

Therefore, the sensitivity of the hs-CRP test allows you to detect elevated CRP levels that would otherwise go unnoticed with a regular CRP test [7].

The regular CRP test is useful for people with serious infections or chronic diseases. Everyone else should get the more sensitive hs-CRP test to detect high CRP levels that would go unnoticed with the regular test.

CRP Normal Range

CRP is found in traces in healthy people [1].

The normal CRP levels vary between populations, with mean values ranging from under 1.0 up to 3.0 mg/l [1].

Your genes can impact your baseline CRP levels. In fact, genetics accounts for 25 – 40% of the variation in CRP levels between people [8].

CRP peaks at about 3 PM each day, with a 1% variation in CRP levels being from daily and seasonal effects. Minor changes occur during the menstrual cycle in women [9].

CRP levels also normally increase with age, while its levels also commonly rise and fluctuate in pregnancy [10, 11].

A lack of CRP elevation despite high inflammation is possible in liver failure, as well as during systemic lupus flare-ups [1].

Since healthy people produce only a small amount of CRP, normal levels range from below 3 mg/l to a tighter range of below 1 mg/l.

Impact on Heart Disease Risk

Low CRP levels are linked with a lower risk of heart disease. Elevated levels of CRP (> 3 mg/L) are associated with cardiovascular disease risk, as follows [12, 13]:

  • 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 [14].

People with kidney failure may have high CRP in the absence of clinically significant inflammation [15].

CRP Levels Above the Normal Range

Infection vs. Chronic Inflammation

In this section, we’ll dive into more complex science to understand why 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 rise the same way when the body is dealing with severe infection and when it’s faced with chronic, low-grade inflammation. CRP secretion is increased by infections (bacterial, fungal, mycobacterial, or severe viral), tissue death, trauma, cancer, and other inflammatory disorders, including atherosclerosis [16].

Bacterial infections can massively increase CRP, while viral infections and mild inflammation usually trigger a subtle rise in CRP. In response to acute infection, 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 [17, 18].

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 the production rate. CRP can be degraded by macrophages [12, 19, 20].

Compared to the acute sharp rise in CRP levels, low-grade chronic inflammation produces minor elevations of CRP in the 3- to 10-mg/L range [17].

crp_risk-large

http://circ.ahajournals.org/content/108/12/e81

Acute infections and injuries dramatically increase CRP for a short while, but its levels go back down within a couple of days. Chronic, low-grade inflammation keeps CRP levels slightly high over the long term.

Diagnosing Serious Infections

CRP is not only bad–it 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 from viruses and bacteria [1, 12].

Viral infections and mild inflammation increase in CRP levels less dramatically (10 – 40 mg/L), while bacterial infection, as well as active inflammation, can elicit much higher responses of between 40 – 200 mg/L. In some severe bacterial infections and burns, the level can increase by more than 200 mg/L [18].

In the most severe cases, CRP levels can increase 1000-fold or more, peaking at 48 h [12, 21].

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 [22].

CRP is beneficial when you are faced with a sudden infection. It quickly rises to help your immune system mount a more effective attack against bacteria and viruses.

Why Are Higher Levels of CRP Bad?

Apart from acute infection/injury, CRP is also an indicator of chronic/systemic inflammation. Increases in levels of CRP are part of the biological response to chronic stress [23].

Increased CRP levels have been found in a number of chronic conditions, such as high blood sugar, high blood pressure, obesity, diabetes, and cardiovascular disease [23, 17].

High levels are also associated with smoking and gum disease [1].

Elevated CRP levels can predict the development of type 2 diabetes, glucose disorders, and heart disease. CRP levels can predict future cardiovascular risk even in apparently healthy people [17, 12, 24].

When both CRP and cholesterol levels are high, a person’s overall risk of a cardiovascular event (such as a heart attack) increases up to 9-fold compared with that of a person with low CRP and cholesterol levels [24].

What’s more, CRP is positively correlated with measures of insulin resistance, obesity, and triglycerides and negatively correlated with HDL cholesterol [17].

Apart from being a marker of inflammation, CRP can create inflammation on its own. In cells that line blood vessels, CRP lowers nitric oxide and prostacyclin and increase the levels of inflammatory compounds (monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and plasminogen activator inhibitor-1 (PAI-1)) [17].

In monocyte-macrophages, CRP increases reactive oxygen species and proinflammatory cytokine release [17].

Also, in blood vessel muscles, CRP increases factors that cause oxidative stress and damage the blood vessels (including inducible nitric oxide (iNO), NF-kB, mitogen-activated protein kinase, and angiotensin type-1 receptor (AGTR1)) [17].

In muscles, CRP can also directly inhibit insulin signaling, preventing sugar from entering into the muscle tissues [17].

CRP is bad because it increases the risk of diabetes, heart disease, and other chronic diseases. It’s also directly inflammatory and can damage the blood vessels and increase oxidative stress in the body.

Learn More About CRP

This post is the first in a four-part series about CRP. Read the other parts to learn about:

Irregular CRP Levels?

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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. High CRP increases the risk of diabetes, heart disease, and other chronic diseases. It can also create inflammation on its own, damaging the blood vessels and increasing oxidative stress in the body.

A standard CRP blood test is good enough for people who are experiencing acute infections or injuries. Everyone else should get a high sensitivity CRP test (hs-CRP) that can detect high 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. Targeting levels below 1 mg/L is considered optimal.

About the Author

Biljana Novkovic - PHD (ECOLOGICAL GENETICS) - Writer at Selfhacked

Dr. Biljana Novkovic, PhD

PhD (Ecological Genetics)

Biljana received her PhD from Hokkaido University.

Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science & health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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