What is C-Reactive Protein (CRP)?

C-Reactive Protein (CRP): A Key Inflammatory Biomarker

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to inflammatory cytokines, serving as a sensitive but non-specific marker of inflammation that can be used to detect and monitor inflammatory conditions, assess disease activity, and predict outcomes in specific clinical scenarios. 1

What is CRP?

CRP is a ring-shaped pentameric protein synthesized in the liver via CRP gene transcription in response to inflammatory stimuli 2. It is a phylogenetically conserved plasma protein that participates in the systemic response to inflammation 3. Key characteristics include:

• Functions as a pattern recognition molecule that binds to specific molecular configurations exposed during cell death or found on pathogen surfaces 3
• Part of the innate immune response, with rapid synthesis within hours after tissue injury or infection 3
• Exists in different conformational forms including native pentameric CRP and monomeric CRP (mCRP) 4

Normal CRP Levels and Clinical Significance

CRP levels correlate with the intensity of inflammatory response:

CRP Level	Clinical Significance
<1.0 mg/L	Low cardiovascular risk
1.0-3.0 mg/L	Average cardiovascular risk
>3.0 mg/L	High cardiovascular risk
10-40 mg/L	Mild inflammation
40-200 mg/L	Acute inflammation/bacterial infection
>500 mg/L	Severe acute illness
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In healthy adults, normal CRP serum concentrations typically range between 0.8 mg/L and 3.0 mg/L 2.

CRP Production and Kinetics

The production and kinetics of CRP follow a specific timeline:

• Secretion begins 4-6 hours after an inflammatory stimulus (mediated by cytokines, particularly interleukin-6) 5
• CRP concentration doubles approximately every 8 hours 5
• Reaches peak levels at 36-50 hours after initial stimulus 5
• The sole determinant of CRP plasma levels is its synthesis rate, which is proportional to the inflammatory insult intensity 5

Clinical Applications of CRP

Diagnostic Value

• Sensitivity of 68-92% and specificity of 40-67% as a marker of bacterial infection 5
• Limited diagnostic value due to inability to differentiate bacterial infections from non-infectious causes of inflammation 5
• CRP level of 0.5 mg/L effectively rules out significant acute bacterial infection or inflammatory process 1
• CRP >50 mg/L increases likelihood of pneumonia in patients with respiratory symptoms 1

Monitoring Disease Activity

• Useful in monitoring inflammatory conditions like rheumatoid arthritis 6
• In Crohn's disease, CRP correlates well with disease activity and can predict need for treatment escalation 1
• Regular assessment beneficial in dialysis patients to identify sources of inflammation 1

Cardiovascular Risk Assessment

• High-sensitivity CRP (hsCRP) >3 mg/L indicates increased cardiovascular risk 1
• Associated with atherosclerosis, coronary artery disease, and peripheral arterial disease 2

CRP in Specific Clinical Contexts

Infections

• CRP and procalcitonin (PCT) can help clinicians diagnose surgical infections 5
• PCT can guide early discontinuation of antibiotics in critically ill patients and in patients undergoing intervention for acute peritonitis 5
• CRP has been reported useful in diagnosing appendicitis with sensitivity of 93-96% 5

Perioperative Assessment

• The magnitude of postoperative systemic inflammatory response corresponds to the amount of surgical trauma 5
• CRP is useful in quantifying the magnitude of the postoperative systemic response 5
• Infectious complications after major abdominal surgery are very unlikely in patients with CRP below 159 mg/L on postoperative day 3 5

Critical Care

• In ICU patients with fever but no clear focus of infection, measuring either PCT or CRP is suggested to rule out bacterial infection 5
• CRP test results are available within minutes with point-of-care assays or within an hour with laboratory-based assays 5

Limitations of CRP

• Single CRP measurement should never be used in isolation to make clinical decisions 1
• Normal CRP does not rule out serious disease and should never delay appropriate treatment 1
• CRP levels can be affected by medications (statins can lower CRP), lifestyle factors, and comorbidities 1
• Unlike PCT, CRP concentrations can be affected by neutropenia, immunodeficiency, and use of nonsteroidal anti-inflammatory drugs 5

High-Sensitivity CRP (hsCRP)

• More sensitive assay for detecting lower levels of CRP relevant for cardiovascular risk assessment 1
• American Heart Association categorizes cardiovascular risk based on hsCRP as: low risk (<1.0 mg/L), average risk (1.0-3.0 mg/L), and high risk (>3.0 mg/L) 1
• If hsCRP >10 mg/L, the test should be repeated and non-cardiovascular causes of inflammation evaluated 1

CRP in Chronic Diseases

CRP has been associated with numerous chronic conditions:

• Cardiovascular disease
• Type 2 diabetes mellitus
• Age-related macular degeneration
• Hemorrhagic stroke
• Alzheimer's disease
• Parkinson's disease
• Autoimmune diseases (Systemic Lupus Erythematosus, rheumatoid arthritis)
• Various cancers (breast, colorectal, ovarian, prostate, lung) 2, 4

CRP is a versatile biomarker that provides valuable information about inflammatory processes in the body, though its interpretation must always be done in the appropriate clinical context.