What causes elevated C-Reactive Protein (CRP) levels?

Causes of Elevated C-Reactive Protein (CRP) Levels

Elevated CRP levels are primarily caused by inflammation, infection, tissue injury, and various chronic conditions, with bacterial infections being the most common cause of significantly elevated values (>50 mg/L). 1

Understanding CRP Levels and Their Interpretation

CRP is an acute-phase protein produced by the liver in response to inflammatory cytokines. The American Heart Association provides the following risk stratification for cardiovascular disease:

• Low risk: <1.0 mg/L
• Average risk: 1.0-3.0 mg/L
• High risk: >3.0 mg/L 1

For general inflammatory conditions, CRP levels can be categorized as:

• Normal: <10 mg/L
• Mild inflammation: 10-40 mg/L
• Acute inflammation/bacterial infection: 40-200 mg/L
• Severe acute illness: >200 mg/L (can exceed 500 mg/L) 1, 2

Common Causes of Elevated CRP

Infectious Causes

• Bacterial infections (most common cause of markedly elevated CRP)

  • Respiratory infections (pneumonia, bronchitis)
  • Urinary tract infections
  • Septicemia
  • Meningitis
  • Skin/soft tissue infections 1, 2

• Viral infections (typically cause moderate elevations)

  • Upper respiratory tract infections (10-60 mg/L, peak during days 2-4) 3
  • Influenza A and B (higher than other viral causes) 3

Inflammatory Conditions

• Autoimmune diseases
  • Rheumatoid arthritis
  • Systemic lupus erythematosus (SLE) - though CRP is often lower than expected for the degree of inflammation 1
  • Inflammatory bowel disease (more reliable in Crohn's disease than ulcerative colitis) 4

Tissue Injury

• Recent surgery
• Trauma
• Burns
• Myocardial infarction 1

Chronic Conditions

• Cardiovascular disease
  • Atherosclerosis
  • Coronary artery disease 1, 5
• Malignancies
  • Solid tumors
  • Hematologic malignancies 1, 6
• Chronic kidney disease 1
• Chronic disease-related malnutrition with inflammation (cachexia) - typically >5 mg/L but rarely exceeds 40 mg/L 1

Lifestyle and Demographic Factors

• Obesity
• Smoking
• Sedentary lifestyle
• Poor diet
• Chronic alcohol consumption
• Age, sex, socioeconomic status 1

Clinical Pearls and Pitfalls

Important Considerations

1. Context is crucial - A single elevated CRP value should not be used to make a diagnosis 1

2. Timing matters - In viral upper respiratory infections, CRP peaks during days 2-4 of illness and typically returns to normal after 7 days 3

3. Cutoff values for infection - A CRP ≥6.74 mg/L may predict infection in cancer patients with sensitivity of 91.3% and specificity of 86.6% 7

4. Extreme elevations - CRP values ≥500 mg/L are highly associated with bacterial infections (found in 87% of such cases) and carry a high 30-day mortality rate (27%) 2

Common Pitfalls

1. Assuming all elevated CRP indicates bacterial infection - Moderately elevated CRP (10-60 mg/L) is common in viral infections, especially during the first week 3

2. Ignoring clinical context - CRP should be interpreted alongside patient history, physical examination, and other laboratory results 1

3. Over-reliance on the 10 mg/L threshold - This traditional cutoff to differentiate between normal and abnormal CRP levels may not be reliable 1

4. Failure to repeat testing - For stable patients, two measurements (optimally 2 weeks apart) should be averaged 1

5. Missing secondary infections - Persistently elevated CRP after 7 days of a viral illness may indicate a secondary bacterial infection 3

Special Populations

1. Cancer patients - CRP may be elevated due to the malignancy itself, not just infection 7, 6

2. Autoimmune disease patients - CRP response may be blunted in SLE, making interpretation challenging 1

3. Cardiovascular risk assessment - hsCRP may be used at the physician's discretion in patients at intermediate risk (10-20% risk of CHD per 10 years) 5, 1