What is the significance of an unspecific elevation of High-Sensitivity C-Reactive Protein (hsCRP)?

From the Guidelines

Unspecific elevation of high-sensitivity C-reactive protein (hsCRP) requires further evaluation to determine the underlying cause, and treatment should target the underlying cause rather than the elevated hsCRP itself. The first step is to consider repeating the test after 2-3 weeks as hsCRP levels can fluctuate due to minor infections or injuries 1. If levels remain elevated (>3 mg/L), a comprehensive workup should be conducted, including a complete blood count, metabolic panel, and assessment for inflammatory conditions. Common causes include cardiovascular disease, infections, autoimmune disorders, obesity, and smoking. Lifestyle modifications are recommended, including regular exercise (30 minutes daily), Mediterranean diet, smoking cessation, and weight management if overweight. For patients with cardiovascular risk factors and persistently elevated hsCRP (>2 mg/L), statin therapy may be considered, typically starting with moderate-intensity statins like atorvastatin 10-20 mg daily or rosuvastatin 5-10 mg daily 1. Some key points to consider:

• HsCRP is an acute phase reactant produced by the liver in response to inflammation, and elevated levels indicate systemic inflammation but don't specify the source 1.
• The clinical context is crucial for proper interpretation, and treatment should target the underlying cause rather than the elevated hsCRP itself 1.
• Patients with persistently unexplained marked elevation of hsCRP (10 mg/L) after repeated testing should be evaluated for noncardiovascular causes such as infection or inflammation 1. It is essential to note that the benefits of therapy based on hsCRP levels remain uncertain, and prospective randomized clinical research studies are needed to establish the benefits of hsCRP measurement on clinical outcomes 1.

From the Research

Unspecific Elevation of hsCRP

• Unspecific elevation of hsCRP can be associated with various conditions, including cardiovascular diseases, rheumatoid arthritis, and other inflammatory diseases 2, 3, 4, 5, 6
• Studies have shown that elevated hsCRP levels are associated with an increased risk of major adverse cardiovascular events and death 2, 3
• The measurement of hsCRP can be used to identify populations at high-inflammatory risk, but it has limitations as an individual prognostic marker 4
• hsCRP levels can be influenced by various factors, including statin treatment, which has been shown to reduce hsCRP levels in patients with cardiovascular diseases 6
• In patients with rheumatoid arthritis, hsCRP levels may not reflect the inflammatory disease status, especially in those treated with IL-6 receptor antibodies 5

hsCRP Levels and Cardiovascular Risk

• hsCRP levels of less than 1 to 3, and greater than 3 mg/L are associated with lower, moderate, and higher cardiovascular risks, respectively 3
• Elevated hsCRP levels are associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death 3
• The association between hsCRP and outcomes is linear until hsCRP >5 mg/L, plateauing thereafter 2

hsCRP and Treatment

• Statins have been shown to reduce hsCRP levels in patients with cardiovascular diseases, with high-intensity statin treatment being more effective in reducing CRP levels 6
• IL-6 receptor antibodies and JAK inhibitors can also influence hsCRP levels in patients with rheumatoid arthritis, but the relationship between hsCRP and disease activity is complex 5