Overview
C-reactive protein (CRP) is an acute-phase reactant synthesized and secreted mainly by hepatocytes in response to inflammatory cytokines such as interleukin-6 (IL-6), IL-1, and tumor necrosis factor-α (TNF-α). It belongs to the pentraxin family and is composed of five identical non-glycosylated polypeptide subunits, each containing 206 amino acids.
High-sensitivity C-reactive protein (hs-CRP) assays are more sensitive than routinely used CRP tests and can detect very low levels of inflammation. CRP levels rise in response to acute inflammation, infection, and tissue injury and decrease rapidly with resolution, making C-reactive protein (hs-CRP) a useful biomarker for monitoring inflammatory states and cardiovascular risk.
Symptoms
C-reactive protein itself does not cause symptoms; rather, elevated hs-CRP levels reflect underlying inflammatory or infectious conditions. Increased values may be associated with clinical manifestations of systemic inflammation, infection, tissue injury, or cardiovascular risk states. Very high C-reactive protein levels may be seen in active infection, trauma, autoimmune disease, or severe systemic inflammation.
Causes
Elevation of hs-CRP occurs due to:
- Acute and chronic inflammation
- Acute infections and tissue damage
- Autoimmune and inflammatory diseases such as rheumatoid arthritis and ankylosing spondylitis
- Acute pancreatitis
- Bacterial endocarditis
- Neonatal septicemia and meningitis
- Postoperative inflammatory complications
- COVID-19 and other systemic infections
hs-CRP is also influenced by non-inflammatory factors such as obesity, smoking, trauma, and metabolic disturbances, reflecting its role as a non-specific inflammatory marker.
Risk Factors
Individuals with increased cardiovascular risk factors, including obesity, smoking, hypertension, diabetes, and metabolic syndrome, may show elevated hs-CRP levels. Persistently raised hs-CRP levels are associated with a higher likelihood of myocardial infarction, stroke, and peripheral vascular disease.
Because hs-CRP is non-specific, elevated values must be interpreted carefully, especially in the presence of acute illness or infection.
Prevention and Diagnostic Approach
hs-CRP testing is used for screening, diagnosis, and monitoring of inflammatory and infectious conditions, as well as for cardiovascular risk stratification.
Indications for testing include:
- Screening for organic disorders
- Assessment of disease activity
- Diagnosis and management of infections
- Monitoring postoperative complications
- Treatment response monitoring
- Cardiovascular risk assessment
Sample collection and preparation:
- No special patient preparation is required
- Collect 3.0 mL of blood in a plain red-capped tube
- Separate serum as early as possible and send it to the laboratory
Methods of estimation include:
- Immunoturbidimetric assay
- Nephelometry
- Enzyme-linked immunosorbent assay (ELISA)
- Point-of-care rapid testing methods
Reference ranges and cardiovascular risk assessment:
- <1.0 mg/L: Low risk
- 1.0–3.0 mg/L: Average (moderate) risk
- >3.0 mg/L: High cardiovascular risk
Clinical interpretation:
- hs-CRP <1.0 mg/L indicates absence of low-grade inflammation and low cardiovascular disease (CVD) risk
- hs-CRP 1.0–3.0 mg/L suggests mild inflammation and moderate CVD risk, often seen in obesity or mild metabolic syndrome
- hs-CRP 3.0–10 mg/L indicates significant subclinical inflammation and high CVD risk
- hs-CRP >10 mg/L suggests active infection, trauma, autoimmune disease, or severe inflammation
- Values >100 mg/L strongly suggest severe bacterial infection, sepsis, or major tissue injury and require urgent evaluation
If an initial hs-CRP result is greater than 3.0 mg/L, repeat testing is recommended weekly for two weeks in a metabolically stable, infection-free state. The lower of the two results should be used for cardiovascular risk assessment.
Clinical Significance
hs-CRP is a sensitive marker of low-grade systemic inflammation and an independent predictor of cardiovascular events such as myocardial infarction and stroke. It plays an important role in identifying atherosclerosis risk, plaque instability, and hypertension-related complications.
Despite its usefulness, hs-CRP remains a non-specific marker and should be used only as a risk modifier, not as a standalone diagnostic test. Interpretation must always be combined with clinical evaluation and other laboratory findings.
