C Reactive Protein (CRP)


Article Author:
Sara Nehring


Article Editor:
Bhupendra Patel


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Updated:
4/21/2019 10:31:25 PM

Introduction

C-reactive protein (CRP) was discovered by Tillett and Francis in 1930. The name CRP arose because it was first identified as a substance in the serum of patients with acute inflammation that reacted with the "c" carbohydrate antibody of the capsule of pneumococcus.

CRP is a pentameric protein synthesized by the liver, whose level rise in response to inflammation. 

There are numerous causes of an elevated C-reactive protein.  These include acute and chronic conditions, and these can be infectious or non-infectious in etiology. However, markedly elevated levels of CRP are most often associated with an infectious cause (an example of pathogen-associated molecular pattern recognition).  Trauma can also cause elevations in CRP (alarmin response). More modest elevations tend to be associated with a broader spectrum of etiologies, ranging from sleep disturbances to periodontal disease.  High-sensitivity CRP only denotes the assay process used, allowing for detection of lower levels of CRP, and not a different, or more specific, differential diagnosis.

CRP is an acute-phase reactant protein that is primarily induced by the IL-6 action on the gene responsible for transcription of CRP during the acute phase of an inflammatory/infectious process. There is some question of whether dysregulation of the role of CRP in clearance of apoptotic cells and cellular debris plays a role in the pathogenesis of systemic lupus erythematosus (SLE), but this has not been definitively demonstrated. It has been demonstrated to have some protective properties in rabbit studies on lung tissue in alveolitis by reducing neutrophil-mediated damage to the alveoli and protein leakage into the lung.

CRP has both proinflammatory and anti-inflammatory properties. It plays a role in recognition of foreign pathogens and damaged cells by binding to the phosphocholine arm when it is present. It can activate the complement system and also activates phagocytic cells via Fc receptors to expedite removal of cellular debris and damaged or apoptotic cells and foreign pathogens. This can become pathologic, however, when it is activated by antibodies displaying the phosphocholine arm in auto-immune processes, such as idiopathic thrombocytopenic purpura (ITP). It can also worsen tissue damage in certain cases due to activation of the complement system and thus inflammatory cytokines.[1][2][3]

Specimen Collection

A blood specimen is taken from a peripheral venous draw. The patient's medications should be reviewed, as these can affect the outcome of the test. Fasting is not required before the blood draw. There are no special procedures required. The specimen takes only a few minutes to obtain.  Complications include oozing at the draw site, bruising or mild tenderness at the site, or very rarely, infection at the venipuncture site.

A phlebotomist performs the procedure in most cases. The phlebotomist secures a snug, rubber band around the upper arm, and the patient pumps his or her fist several times. The phlebotomist palpates the vein to confirm the location and cleanses the area with an alcohol prep pad. Once the area air dries, the practitioner introduces a needle into the vein and draws a vial of blood. He or she removes the band from the patient's arm, and then removes the needle and applies pressure to the venipuncture site until hemostasis occurs, usually within one minute. A bandage is applied over the site, and the test is complete.

Other bodily fluids, such as synovial fluid, can be tested for in this manner, but frequently are not.

Indications

This test is performed when the physician suspects acute or chronic inflammation (e.g, SLE or rheumatoid arthritis (RA)) or infection. There are some that also use this as a cardiac screening tool (hs-CRP); however, studies are underway to determine the validity of this application for the test, as it is elevated in so many other conditions (e.g, diabetes, insomnia, stress, inflammation). There is some correlation between cardiovascular risk and elevated hs-CRP, but the application of this is still controversial among various groups of physicians,  and it is currently undergoing more study.[4][5][6]

Normal and Critical Findings

Lab values vary, and there is no standard at present.  However, in general, the results is reported in either mg/dL or mg/L. Hs-CRP is usually reported in mg/L. Levels in the 0.3 mg/dL to -1 mg/dL are considered mild and are usually seen with diabetes, hypertension (HTN), periodontitis, sedentary lifestyle, cigarette smoking, and many other non-inflammatory processes. In general, significant inflammation or infection is considered present at levels greater than 1 mg/dL. Levels greater than 10 mg/dL are usually related to acute bacterial infection. Viral infections will also elevate CRP, but not to the same degree as other etiologies.  When compared to ESR in an infectious state, CRP will rise and fall more rapidly. In autoimmune states, it may not have the same level of elevation as ESR.

There is also an early study demonstrating that there is a correlation between stroke recurrence within one year and elevated hs-CRP coupled with a National Insitute of Health Stroke Scale (NIHSS) greater than 6, after initial acute ischemic stroke. When coupled with elevated alpha-defensin levels, CRP testing done on synovial fluid has been shown in one small study to be highly sensitive and specific for peri-prosthetic infection when CRP was greater than 3 mg/L in the fluid.

When used for cardiac risk stratification, hs-CRP levels less than 1 mg/dL are considered low risk. Levels between 1 mg/dL and 3 mg/dL are considered moderate risk and a level greater than 3 mg/dL is considered high risk for development of cardiovascular disease.[7][8]

Interfering Factors

Certain medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) will falsely decrease CRP levels. Statins, as well, have been known to reduce CRP levels falsely. The decreased CRP levels occur with both NSAIDs and statins because these drugs reduce inflammatory response in the body. Recent injury or illness can falsely elevate levels, particularly when using this test for cardiac risk stratification. Magnesium supplementation also can decrease CRP levels.

Complications

Given the highly variable causality of elevated CRP, marginal elevations in the CRP can be difficult to interpret and should not be used as an isolated test result interpreted as appropriate for the clinical picture. It is useful in suggesting infection versus inflammation if the levels are extremely high, but levels from 1 mg/dL to 10 mg/dL can be difficult to interpret accurately. Chronic conditions, such as arthritis or lupus, can make these levels elevated chronically, making it harder to determine if there is any significance to an elevated hs-CRP level when using it as a predictive marker for cardiovascular disease.

Clinical Significance

High levels of CRP, greater than 10 mg/dL, are associated with infection about 80% of the time. If the level exceeds 50%, then that number rises to around 94%. Numbers greater than 1 mg/dL are considered to be associated with clinically significant inflammation.


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C Reactive Protein (CRP) - Questions

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C Reactive Protein (CRP) - References

References

Cleland DA,Eranki AP, Procalcitonin 2019 Jan;     [PubMed]
Jungen MJ,Ter Meulen BC,van Osch T,Weinstein HC,Ostelo RWJG, Inflammatory biomarkers in patients with sciatica: a systematic review. BMC musculoskeletal disorders. 2019 Apr 9;     [PubMed]
Kramer NE,Cosgrove VE,Dunlop K,Subramaniapillai M,McIntyre RS,Suppes T, A clinical model for identifying an inflammatory phenotype in mood disorders. Journal of psychiatric research. 2019 Feb 10;     [PubMed]
Eschborn S,Weitkamp JH, Procalcitonin versus C-reactive protein: review of kinetics and performance for diagnosis of neonatal sepsis. Journal of perinatology : official journal of the California Perinatal Association. 2019 Mar 29;     [PubMed]
Darooghegi Mofrad M,Milajerdi A,Koohdani F,Surkan PJ,Azadbakht L, Garlic Supplementation Reduces Circulating C-reactive Protein, Tumor Necrosis Factor, and Interleukin-6 in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials. The Journal of nutrition. 2019 Apr 5;     [PubMed]
Dick AG,Magill N,White TCH,Kokkinakis M,Norman-Taylor F, C-reactive protein: what to expect after bony hip surgery for nonambulatory children and adolescents with cerebral palsy. Journal of pediatric orthopedics. Part B. 2019 Apr 3;     [PubMed]
Lee Y,McKechnie T,Doumouras AG,Handler C,Eskicioglu C,Gmora S,Anvari M,Hong D, Diagnostic Value of C-Reactive Protein Levels in Postoperative Infectious Complications After Bariatric Surgery: a Systematic Review and Meta-Analysis. Obesity surgery. 2019 Mar 21;     [PubMed]
Johns I,Moschonas KE,Medina J,Ossei-Gerning N,Kassianos G,Halcox JP, Risk classification in primary prevention of CVD according to QRISK2 and JBS3 'heart age', and prevalence of elevated high-sensitivity C reactive protein in the UK cohort of the EURIKA study. Open heart. 2018;     [PubMed]

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