What does a high C-Reactive Protein (CRP) test result indicate?

What Does a High C-Reactive Protein (CRP) Test Result Indicate?

A high CRP result indicates the presence of inflammation in the body, with levels >3 mg/L suggesting low-grade chronic inflammation, levels 3-10 mg/L indicating moderate inflammation, and levels >10 mg/L pointing to acute inflammation or infection that requires investigation for the underlying cause. 1, 2

Understanding CRP Levels and Risk Categories

CRP is an acute-phase protein produced by the liver in response to inflammatory cytokines (IL-6 and TNF-α), with normal concentrations typically below 3 mg/L in healthy individuals. 1

Risk stratification for cardiovascular disease follows these cutpoints established by the CDC/AHA based on 15 populations involving 40,000 persons: 3

• Low risk: <1.0 mg/L
• Average risk: 1.0-3.0 mg/L
• High risk: >3.0 mg/L (represents a 2-fold increase in relative cardiovascular risk compared to low-risk tertile)

For acute inflammation assessment, the traditional interpretation uses: 1, 2

• <3 mg/L: Normal range
• 3-10 mg/L: Low-grade chronic inflammation
• >10 mg/L: Acute inflammation or infection requiring further evaluation

Clinical Conditions Associated with Elevated CRP

Bacterial infections cause the highest CRP elevations, with median levels reaching high inflammatory ranges, while viral infections typically cause only moderate elevations. 2

Chronic inflammatory conditions produce moderate CRP elevations: 2

• Rheumatoid arthritis (median levels in moderate inflammatory range)
• Inflammatory bowel disease (particularly Crohn's disease, though less reliable in ulcerative colitis) 3, 4

Other significant causes include: 2

• Solid tumors (can raise CRP to high inflammatory levels)
• Chronic kidney disease (elevates CRP and predicts cardiovascular mortality)
• Acute pancreatitis (correlates well with disease activity) 4

Lifestyle and demographic factors influence baseline CRP: 1, 2

• Smoking approximately doubles the risk of elevated CRP
• Obesity and lack of exercise increase levels
• Age, sex, race, and socioeconomic status affect baseline values

When to Investigate Further

If CRP >10 mg/L is identified, initiate a search for an obvious source of infection or inflammation, discard that result, and remeasure CRP in 2 weeks. 3 This threshold obscures any prediction of coronary risk that might be attributed to the elevated level.

Patients with persistently unexplained marked elevation of CRP (>10 mg/L) after repeated testing should be evaluated for non-cardiovascular causes such as infection or inflammation. 3, 1

When encountering elevated CRP, assess the magnitude and consider investigation for concurrent acute infection or inflammatory disease if CRP >10 mg/L. 2 Screen for acute illness by checking temperature and symptoms of infection/injury, and examine liver enzymes to rule out fatty liver disease. 2

Cardiovascular Risk Assessment

For primary prevention of cardiovascular disease, the CDC/AHA recommends that hsCRP measurement is reasonable as an adjunct to major risk factors to further assess absolute risk, particularly in patients at intermediate risk (10-20% 10-year CHD risk). 3, 1 However, screening of the entire adult population is not recommended. 3

In patients with stable coronary disease or acute coronary syndromes, elevated CRP predicts recurrent myocardial infarction, death, and restenosis after percutaneous coronary intervention in a manner independent of troponin levels. 3, 1 Among patients with acute coronary syndromes, levels >10 mg/L have better predictive value. 3

Critical Management Principles

Treatment should target the underlying cause rather than the CRP level itself, and serial testing of CRP should not be used to monitor effects of treatment. 1 This is a Class III recommendation (evidence against use for this purpose). 3

Secondary preventive interventions with proven efficacy should not be dependent on CRP levels. 3 The early management of patients with acute coronary syndromes should not be driven by CRP results. 3

Application of secondary prevention measures should not depend on CRP determination, and available evidence does not support using CRP as a guide for treatment of acute coronary syndrome. 3, 1

Proper Testing Methodology

To reduce within-individual variability, perform the hsCRP assay in a metabolically stable person without obvious inflammatory or infectious conditions. 3

Two assays, averaged, fasting or nonfasting, and optimally 2 weeks apart, provide a more stable estimate of this marker's level. 3 Results should be expressed as mg/L only. 3

Important Caveats

CRP is a non-specific marker that can be elevated in many conditions, and no single value can rule in or rule out a specific diagnosis. 5, 6 In the emergency department setting, CRP must be interpreted in clinical context. 6

In ulcerative colitis, CRP is less reliable as a marker of inflammation and disease activity compared to Crohn's disease, except perhaps for severe, extensive colitis. 3, 4 Faecal calprotectin is a more sensitive and specific biomarker for inflammatory bowel disease monitoring. 3

30-40% of US adults now exhibit CRP >3 mg/L, making historical cutoffs less discriminatory in the modern population. 2