What is C-reactive protein (CRP)?

C-Reactive Protein (CRP): An Essential Inflammatory Marker

C-reactive protein (CRP) is a prototypical acute-phase protein produced by the liver in response to inflammatory cytokines that serves as an exquisitely sensitive systemic marker of inflammation and tissue damage. 1

Basic Characteristics and Function

• CRP is a phylogenetically conserved plasma protein that participates in the systemic response to inflammation, belonging to the pentraxin family of proteins with a cyclic homopentameric structure 2, 3
• It is synthesized primarily by the liver in response to inflammatory cytokines including interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) 1
• CRP levels can increase dramatically (up to 1000-fold) very rapidly after the onset of inflammation and decrease just as rapidly with the resolution of the inflammatory stimulus 3
• It functions as a pattern recognition molecule, binding to specific molecular configurations typically exposed during cell death or found on pathogen surfaces 2

Clinical Significance and Measurement

• CRP is one of the most requested laboratory tests due to its value as a robust inflammatory biomarker across a wide range of clinical conditions 1
• For clinical practice, CRP has the most conducive analyte and assay characteristics among inflammatory markers 4
• High-sensitivity CRP (hsCRP) assays can detect concentrations accurately down to 0.3 mg/L, allowing assessment of low-grade inflammation relevant to cardiovascular risk 4
• CRP results should be expressed in milligrams per liter (mg/L) to one decimal point 4

Interpretation of CRP Levels

• For cardiovascular risk assessment, CRP levels are categorized into three risk groups: low risk (<1.0 mg/L), average risk (1.0-3.0 mg/L), and high risk (>3.0 mg/L) 4
• CRP levels ≥10 mg/L generally indicate acute inflammation, and patients with such levels should be evaluated for sources of infection or inflammation 4
• Conventional CRP cutoffs: 10-40 mg/L for mild inflammation and 40-200 mg/L for acute inflammation and bacterial infection 3
• For stable patients requiring CRP measurement, two readings (optimally 2 weeks apart) should be taken and averaged 4

Role in Different Diseases

Cardiovascular Disease

• hsCRP is an independent marker of cardiovascular risk that may be used at the physician's discretion in patients at intermediate risk (10-20% risk of coronary heart disease per 10 years) 4
• It may help direct further evaluation and therapy in primary prevention of cardiovascular disease 4
• CRP is not only a marker but may be a direct mediator of inflammatory reactions through its structural isoforms (pCRP* and mCRP) that can activate platelets, leukocytes, endothelial cells, and complement 5

Gastrointestinal Diseases

• In Crohn's disease, CRP levels correlate well with clinical disease activity and can predict prognosis and relapse 6
• CRP is less reliable as an inflammatory marker in ulcerative colitis, except in cases of severe, extensive colitis 6
• In major abdominal surgery, CRP is useful for quantifying the magnitude of postoperative systemic inflammatory response, with levels below 159 mg/L on postoperative day 3 indicating low likelihood of infectious complications 4

Other Conditions

• CRP is valuable in diagnosing and monitoring various inflammatory conditions including sepsis, trauma, and malignancies 1
• Elevated CRP has been associated with increased risk of colorectal cancer and may indicate more advanced disease 6
• In dialysis patients, elevated CRP predicts all-cause and cardiovascular mortality 4

Clinical Cautions and Limitations

• Serial testing of hsCRP should not be used to monitor treatment effects 4
• Application of secondary prevention measures and management guidelines for acute coronary syndromes should not depend on hsCRP levels 4
• Patients with persistently unexplained marked elevation of hsCRP (>10 mg/L) after repeated testing should be evaluated for non-cardiovascular causes 4
• Other inflammatory markers (cytokines, other acute-phase reactants) besides CRP should not be measured for coronary risk determination 4
• CRP may be elevated in various non-infectious inflammatory conditions such as inflammatory bowel disease, rheumatoid arthritis, and long-term alcoholism 4

Recent Developments

• CRP has received renewed interest as a biomarker of severity in COVID-19 1
• Growing evidence suggests CRP is not merely a marker but also a direct mediator of inflammatory reactions through its conformational changes 5
• Understanding CRP's "activation process" may allow development of novel anti-inflammatory drugs for a range of inflammatory diseases 5