From the Guidelines
It is possible for a patient to have naturally elevated C-reactive protein (CRP) levels that do not necessarily indicate inflammation, and this should be considered when interpreting CRP results in clinical practice. Some individuals have genetically determined baseline CRP levels that are higher than the typical reference range without having any underlying inflammatory condition, a phenomenon sometimes called constitutional elevation [ 1 ]. This can be a normal variant for that specific person. In such cases, a single elevated CRP measurement may not be clinically significant and should be interpreted in the context of the patient's medical history, symptoms, and other laboratory findings.
To determine if elevated CRP truly represents inflammation, clinicians should establish the patient's personal baseline through repeated measurements over time when they are healthy, look for significant changes from this baseline during suspected inflammatory states, and correlate CRP levels with other inflammatory markers and clinical symptoms [ 1 ]. The genetic variation in baseline CRP production is influenced by polymorphisms in the CRP gene and other regulatory factors, which can lead to consistent elevations without pathological significance.
Key Considerations for CRP Measurement
- CRP results should be expressed only as milligrams per liter and to 1 decimal point [ 1 ].
- Risk assessment should be modeled after the lipids approach via 3 risk categories: low risk, average risk, and high risk, with cutpoints of low risk (1.0 mg/L), average risk (1.0 to 3.0 mg/L), and high risk (3.0 mg/L) [ 1 ].
- If a CRP level is 10 mg/L, the test should be repeated and the patient examined for sources of infection or inflammation [ 1 ].
Clinical Implications
- CRP should never be interpreted in isolation but always as part of a comprehensive clinical assessment [ 1 ].
- The use of hs-CRP as an independent predictor of increased coronary risk is supported by the best evidence to date [ 1 ].
- Clinical judgment is required to adjust risk within a risk category by measurement of hs-CRP [ 1 ].
From the Research
C-Reactive Protein Levels and Inflammation
- C-Reactive Protein (CRP) is a widely used marker of systemic inflammation, but its levels can be influenced by various factors, including noninfectious conditions and physiological factors 2, 3.
- A study found that 17.6% of cases with markedly elevated CRP levels could not be attributed to a specific diagnosis, suggesting that some individuals may have naturally high CRP levels 4.
- Another study noted that CRP levels can be affected by factors such as age, sex, alcohol consumption, physical activity, body mass index (BMI), and the presence of metabolic syndrome 5.
Factors Affecting CRP Levels
- BMI appeared to be the main determinant of serum CRP concentrations in a population with no overt inflammatory disease 5.
- Serum interleukin-6 concentrations were positively associated with high CRP and normal ESR values 5.
- Physiological factors, such as noninfectious conditions and resolution of inflammation, can contribute to abnormally high ESR/low CRP readings or vice versa 2, 3.
Clinical Implications
- CRP and ESR lack sensitivity or specificity, and should be used only in combination with clinical history and physical exam for diagnosis and monitoring of pathological conditions 2, 3.
- A novel diagnostic algorithm has been proposed to carefully assess CRP levels for a precise diagnosis of a medical condition 6.
- Clinicians should be aware of the potential for discordant patterns between CRP and ESR values, and consider factors such as age and BMI when interpreting these results 5.