What are the causes of elevated C reactive protein (CRP) levels?

Causes of Elevated C-Reactive Protein (CRP) Levels

C-reactive protein (CRP) elevations are primarily caused by infectious, inflammatory, and tissue-damaging conditions, with levels potentially rising up to 500 mg/L during acute illness, though various non-pathological factors can also influence baseline levels. 1

Primary Causes of CRP Elevation

Infectious Causes

• Bacterial infections (particularly significant elevations, median ~120 mg/L) 1
• Viral infections (typically lower elevations than bacterial, median ~32 mg/L) 1
• Fungal and parasitic infections
• Respiratory tract infections 1
• Septicemia 1

Inflammatory Conditions

• Autoimmune diseases (e.g., rheumatoid arthritis) 1
• Inflammatory bowel disease (particularly Crohn's disease) 2
• Systemic inflammatory diseases (median CRP ~65 mg/L) 1
• Vasculitis
• Pelvic inflammatory disease 3

Tissue Damage/Injury

• Myocardial infarction/cardiovascular disease 1, 4
• Trauma and surgery
• Burns
• Pancreatitis 2
• Tissue necrosis

Malignancy

• Solid tumors (median CRP ~46 mg/L) 1
• Lymphoma
• Leukemia

Chronic Conditions Associated with Inflammation

• Atherosclerosis 1, 4
• Chronic kidney disease 1
• Obesity 1
• Metabolic syndrome
• Diabetes mellitus

Factors Influencing Baseline CRP Levels

Demographic and Lifestyle Factors

• Age (tends to increase with aging) 1
• Sex (differences in baseline levels) 1
• Race/ethnicity (higher in certain populations) 1
• Body mass index (positively correlated) 1
• Smoking (can cause persistent elevation) 1
• Socioeconomic status 1
• Physical activity (regular exercise can lower baseline) 1
• Diet (certain dietary patterns affect levels) 1
• Sleep patterns 1

Medication Effects

• Medication use can affect levels 1
• Statin therapy (tends to lower CRP)
• Hormone replacement therapy (may increase CRP)

Clinical Interpretation Guidelines

CRP Level Categories

• Low risk: <1.0 mg/L 1
• Average risk: 1.0-3.0 mg/L 1
• High risk: >3.0 mg/L 1
• Potential acute inflammation/infection: >10 mg/L 1

Important Clinical Considerations

1. For stable patients: Two measurements (optimally 2 weeks apart) should be averaged 1
2. If CRP >10 mg/L: Test should be repeated and patient examined for sources of infection or inflammation 1
3. Very high levels (>50 mg/L) strongly suggest acute infection or severe inflammation 1
4. Disease-specific patterns:
   • Bacterial infections typically cause higher elevations than viral infections 1
   • Crohn's disease shows better CRP correlation than ulcerative colitis 2
   • CRP predicts cardiovascular risk and mortality in both general and CKD populations 1

Pitfalls in CRP Interpretation

1. Not all elevated CRP values >10 mg/L indicate acute infection

   • The 10 mg/L cutoff is based on outdated studies with different population characteristics 1
   • 33% of hospitalized patients with various conditions had CRP <10 mg/L despite active disease 1

2. Single measurements can be misleading

   • CRP levels vary over time, especially in chronic conditions 1
   • Serial measurements provide more reliable information 1

3. Population differences affect interpretation

   • CRP levels are generally higher in current US populations than historical cohorts 1
   • Genetic factors influence baseline CRP levels 1
   • Asian CKD patients tend to have lower inflammation prevalence than European or North American patients 1

4. Normal CRP does not rule out serious conditions

   • A normal CRP should never delay antibiotic coverage when infection is suspected 3

By understanding these diverse causes of CRP elevation and their interpretation, clinicians can more effectively use CRP as a diagnostic and monitoring tool while avoiding common interpretive pitfalls.