What is C-Reactive Protein (CRP) and how is it used in clinical practice?

C-Reactive Protein (CRP): Clinical Applications and Interpretation

C-reactive protein (CRP) is an acute-phase protein synthesized by the liver in response to inflammatory cytokines that serves as a biomarker of inflammation, with applications in monitoring disease activity, assessing cardiovascular risk, and evaluating treatment response across various clinical conditions.

What is CRP?

CRP is a phylogenetically conserved plasma protein that functions as a pattern recognition molecule in the innate immune system. It was first identified in 1930 and named for its ability to react with the C-polysaccharide of Streptococcus pneumoniae 1, 2.

Key characteristics of CRP include:

• Produced primarily by hepatocytes in response to pro-inflammatory cytokines (IL-6, IL-1β, TNF-α)
• Exists in different conformational forms: native pentameric CRP and monomeric CRP (mCRP) 3
• Participates in the systemic response to inflammation
• Plasma concentration increases rapidly (within hours) after tissue injury or infection 2
• Functions in host defense as part of the innate immune response

Clinical Applications of CRP Testing

1. Assessment of Inflammatory Status

CRP levels can be categorized into different risk and inflammatory states 4:

• Low risk: <1.0 mg/L
• Average risk: 1.0-3.0 mg/L
• High risk: >3.0 mg/L
• Mild inflammation: 10-40 mg/L
• Acute inflammation/bacterial infection: 40-200 mg/L
• Severe acute illness: >500 mg/L

2. Cardiovascular Risk Assessment

• For cardiovascular risk assessment, high-sensitivity CRP (hsCRP) assays with detection limits down to 0.3 mg/L should be used 4
• Two measurements (optimally 2 weeks apart) in metabolically stable patients should be averaged for clinical decision-making 4
• If hsCRP >10 mg/L, the test should be repeated and non-cardiovascular causes of inflammation evaluated 4

3. Monitoring Disease Activity in Inflammatory Conditions

CRP is particularly useful for monitoring:

• Inflammatory bowel disease activity
• Rheumatoid arthritis and response to therapy
• Infections and response to antibiotics
• Post-surgical inflammation and complications

4. Gastrointestinal Disease Assessment

In ulcerative colitis, CRP has limited utility for ruling out moderate to severe endoscopic inflammation due to:

• Low sensitivity (63%) and moderate specificity (77%) 5
• High false negative rates (18.5% in intermediate pretest probability scenarios) 5
• High false positive rates (19.5% in low pretest probability scenarios) 5

5. Chronic Kidney Disease

• Elevated CRP predicts all-cause and cardiovascular mortality in patients with kidney disease, including those on dialysis 4
• Serial CRP measurements can help monitor treatment effectiveness in dialysis patients 4

Limitations of CRP Testing

1. Limited specificity: CRP has moderate specificity (40-67%) as a marker of bacterial infection 4, 1

2. Context-dependent interpretation: In the emergency department, CRP must be interpreted in clinical context; no single value can rule in or rule out a specific diagnosis 1

3. Individual variability: Significant inter-individual variability in CRP response exists due to genetic factors 4

4. Timing considerations: CRP rises within 4-6 hours of stimulus, peaks at 48-72 hours, and has a half-life of 19 hours

Factors Affecting CRP Levels

Several factors can influence baseline CRP levels:

• Smoking (increases CRP by 66%) 4
• Obesity (BMI ≥30 associated with elevated CRP) 4
• Age (tends to increase with age)
• Medications (statins, aspirin may lower CRP)
• Chronic conditions (diabetes, hypertension, kidney disease)

Best Practices for CRP Testing and Interpretation

1. Always interpret CRP in clinical context

   • Consider patient's symptoms, medical history, and other laboratory findings
   • A normal CRP should never delay treatment when clinically indicated 1

2. Use appropriate CRP assay for the clinical question

   • Standard CRP for acute inflammation/infection
   • High-sensitivity CRP (hsCRP) for cardiovascular risk assessment

3. Serial measurements are more informative than single values

   • Monitor trends to assess treatment response
   • Repeat measurements after 3 months of treatment to evaluate response 4

4. Consider factors that may affect baseline CRP levels

   • Obesity, smoking, chronic conditions
   • Recent trauma or surgery

Conclusion

CRP is a valuable biomarker with applications across multiple clinical scenarios. Its proper use requires understanding its biological function, limitations, and appropriate clinical context for interpretation. While it serves as an important tool for detecting and monitoring inflammation, it should be used as part of a comprehensive clinical assessment rather than in isolation.