What are the uses of C-Reactive Protein (CRP) in clinical practice?

Clinical Uses of C-Reactive Protein (CRP)

CRP is primarily used for cardiovascular risk stratification in intermediate-risk patients and as a marker of systemic inflammation in infectious and inflammatory conditions. 1

Primary Clinical Applications

Cardiovascular Risk Assessment

CRP measurement is most beneficial in patients at intermediate cardiovascular risk (10-20% 10-year risk) to guide decisions about initiating or intensifying preventive therapy. 2, 3

• Risk stratification categories: Low risk <1.0 mg/L; average risk 1.0-3.0 mg/L; high risk >3.0 mg/L 1
• The high-risk tertile (>3.0 mg/L) carries approximately twice the relative risk compared to the low-risk tertile 3
• Two separate measurements, optimally 2 weeks apart, should be obtained and averaged in metabolically stable patients 1
• If CRP level is ≥10 mg/L, repeat testing and evaluate for sources of infection or inflammation 1, 2

Important caveat: CRP measurement has a Class IIa recommendation for intermediate-risk patients but should NOT be used to guide treatment in high-risk patients (>20% 10-year risk) or those with established cardiovascular disease, who require intensive treatment regardless of CRP levels. 1, 3

Inflammatory and Infectious Disease Monitoring

CRP serves as an objective marker of inflammation with levels correlating well with disease activity in specific gastrointestinal and systemic inflammatory conditions. 4, 5

• Crohn's disease: CRP correlates well with clinical disease activity and predicts prognosis and relapse 4
• Ulcerative colitis: CRP is less reliable except in severe, extensive colitis 4
• Acute pancreatitis: CRP levels correlate with disease activity and predict prognosis 4
• Bacterial infections: CRP is elevated in meningitis, neonatal sepsis, and occult bacteremia, though it cannot diagnose these entities and normal levels should never delay antibiotic coverage 6
• Appendicitis: May be useful as an adjunct to serial examinations in equivocal presentations where CT scan is not readily available 6

Secondary Prevention and Acute Coronary Syndromes

In patients with stable coronary disease or acute coronary syndromes, CRP measurement may identify those at higher risk for recurrent events, but secondary prevention measures should NOT depend on CRP determination (Class III recommendation). 1, 2

• CRP can assess likelihood of recurrent events including death, myocardial infarction, or restenosis after percutaneous coronary intervention 3
• Management guidelines for acute coronary syndromes should not be dependent on CRP levels 1

What CRP Should NOT Be Used For

Serial testing of CRP should NOT be used to monitor effects of treatment (Class III, Level of Evidence C). 1, 2

• While statins reduce CRP levels, the response is heterogeneous with many nonresponders, and it is unknown if responders with lowered CRP have greater risk reduction than nonresponders 1
• CRP should not be treated as an isolated therapeutic target; focus on comprehensive cardiovascular risk reduction instead 2

Measurement and Interpretation Guidelines

CRP results should be expressed only as milligrams per liter (mg/L) to one decimal point. 1

• High-sensitivity CRP (hs-CRP) assays can accurately detect concentrations down to 0.3 mg/L 1
• CRP is stable in serum or plasma at room temperature or frozen for extended periods 1
• Measurements can be obtained fasting or nonfasting 1

Factors That Elevate CRP Independent of Cardiovascular Risk

Multiple non-cardiovascular conditions can elevate CRP, requiring clinical context for interpretation. 1, 3

• Inflammatory bowel disease, rheumatoid arthritis, and chronic alcoholism 1
• Elevated blood pressure, elevated BMI, cigarette smoking 3
• Metabolic syndrome/diabetes, low HDL/high triglycerides 3
• Estrogen/progestogen hormone use 3
• Chronic infections and inflammation 3

Practical Clinical Algorithm

1. Calculate 10-year cardiovascular risk using established risk calculators 2
2. For intermediate-risk patients (10-20% 10-year risk): Obtain two CRP measurements 2 weeks apart and average them 1, 2
3. If CRP >10 mg/L persists: Evaluate for non-cardiovascular causes of inflammation 2, 3
4. If CRP 3-10 mg/L in intermediate-risk patients: Consider more aggressive risk factor modification and potentially statin or aspirin therapy based on post-hoc trial analyses 2
5. For high-risk patients or established CVD: Treat aggressively regardless of CRP level 3

Critical pitfall: CRP has no role in diagnosing specific infectious entities, and a normal CRP level should never delay appropriate antibiotic coverage in suspected serious bacterial infections. 6