What causes elevated C-Reactive Protein (CRP)?

From the Guidelines

Elevated C-reactive protein (CRP) is primarily caused by inflammation in the body, which can be triggered by various factors, including infection, tissue injury, or chronic inflammatory conditions, as well as lifestyle factors and certain medications. CRP is produced by the liver in response to inflammatory signals, particularly interleukin-6, released during these conditions 1. Common causes of elevated CRP include bacterial infections, viral infections, autoimmune disorders, tissue damage from surgery or trauma, and cardiovascular disease. Lifestyle factors that can raise CRP include obesity, smoking, lack of exercise, and poor diet, as highlighted in a recent study on the role of diet in maintaining gut health 1. Certain medications like hormone replacement therapy may also increase CRP levels.

Key Factors Contributing to Elevated CRP

• Infection: bacterial, viral, or fungal infections can cause a significant increase in CRP levels
• Tissue injury: trauma, surgery, or burns can lead to elevated CRP
• Chronic inflammatory conditions: autoimmune disorders, such as rheumatoid arthritis, lupus, and inflammatory bowel disease, can cause persistent elevation of CRP
• Lifestyle factors: obesity, smoking, lack of exercise, and poor diet can contribute to increased CRP levels
• Medications: certain medications, such as hormone replacement therapy, can increase CRP levels The degree of elevation often correlates with the severity of inflammation - minor elevations (5-10 mg/L) typically indicate low-grade inflammation, while significant elevations (>100 mg/L) suggest serious infection or inflammation, as noted in a study on the application of CRP in clinical practice 1. CRP rises rapidly within 6-8 hours of an inflammatory stimulus and can increase thousandfold during acute inflammation, making it a valuable marker for detecting and monitoring inflammatory conditions. It is essential to consider these factors when interpreting CRP levels and to use a thoughtful approach to limit the impact of inherent bias, as recommended in a recent study 1.

From the Research

Causes of Elevated C-Reactive Protein (CRP)

Elevated C-Reactive Protein (CRP) levels have been associated with various conditions, including:

• Inflammatory diseases, such as cardiovascular disease, type 2 diabetes mellitus, and age-related macular degeneration 2
• Infectious diseases, such as bacterial infections, with Gram-positive cocci, Gram-negative bacilli, and fungal infections being common causes 3
• Chronic somatic disorders, including osteoporosis, asthma, diabetes, chronic bronchitis/emphysema, myocardial infarction, and fibromyalgia/chronic pain syndrome 4
• Gastrointestinal diseases, such as Crohn's disease and acute pancreatitis, where CRP levels correlate well with clinical disease activity 5
• Neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, where CRP may play a role in the pathogenesis of these diseases 2

Disease-Specific Elevations in CRP

Specific diseases have been associated with varying levels of CRP elevation, including:

• Osteoporosis, with mean CRP levels of 6.53 mg/l 4
• Asthma, with mean CRP levels of 5.01 mg/l 4
• Chronic bronchitis/emphysema, with mean CRP levels of 4.42 mg/l 4
• Diabetes, with mean CRP levels of 4.53 mg/l 4
• Myocardial infarction, with mean CRP levels of 4.27 mg/l 4
• Fibromyalgia/chronic pain syndrome, with mean CRP levels of 4.79 mg/l 4

Prognostic Value of CRP

Elevated CRP levels have been associated with poor prognosis and increased risk of certain diseases, including:

• Colorectal cancer, where elevated CRP levels are a marker of poor prognosis 5
• Cardiovascular disease, where elevated CRP levels are a useful marker to identify patients at risk 6
• Infectious diseases, where extremely elevated CRP values (≥500 mg/L) are associated with high mortality rates 3