What causes elevated C-Reactive Protein (CRP)?

From the Guidelines

Elevated C-Reactive Protein (CRP) levels can be caused by various conditions that trigger inflammation in the body, including infections, autoimmune disorders, inflammatory bowel diseases, tissue damage, obesity, smoking, and chronic conditions like diabetes, as supported by the most recent study 1.

Causes of Elevated CRP

The causes of elevated CRP are diverse and can be categorized into several groups:

• Infections (bacterial, viral, or fungal)
• Autoimmune disorders like rheumatoid arthritis or lupus
• Inflammatory bowel diseases such as Crohn's disease or ulcerative colitis
• Tissue damage from conditions like heart attacks or surgeries
• Obesity, smoking, and chronic conditions like diabetes
• Certain medications like hormone replacement therapy or oral contraceptives

Mechanism of CRP Elevation

CRP is produced by the liver in response to inflammatory cytokines, particularly interleukin-6, and serves as an acute phase reactant that helps with immune system activation, as explained in 1. When inflammation is present, CRP levels can rise rapidly, sometimes increasing hundreds of times above normal within 24-48 hours.

Clinical Interpretation

It is essential to consider the clinical context when interpreting CRP levels, as they can be influenced by various factors, including demographic, behavioral, and technical factors, as discussed in 1. A more thoughtful approach that recognizes these influences is needed to limit the impact of inherent bias while not inadvertently including sick participants.

Recommendations

To accurately interpret CRP values, it is recommended to consider additional steps, such as using a clinical index of the acute phase response/infection, evaluating hepatic health, and performing statistical Winsorization, as suggested in 1.

From the FDA Drug Label

TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses Elevated concentrations of TNF are found in the synovial fluid of patients with RA, JIA, PsA, and AS and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases.

The cause of elevated C-Reactive Protein (CRP) is not directly stated in the provided text, but it is mentioned that TNF (tumor necrosis factor) plays a role in inflammatory responses and that elevated concentrations of TNF are found in various diseases. It can be inferred that inflammation, which is associated with elevated TNF, may lead to increased CRP levels. However, the exact cause of elevated CRP is not explicitly stated in the text.

From the Research

Causes of Elevated C-Reactive Protein (CRP)

• Infections: CRP levels were significantly higher in infections compared to new onset rheumatic diseases or malignancies 2
• New onset rheumatic diseases: The most common etiology of nonspecific elevations in ESR/CRP levels in patients without a previous history of rheumatic disease 2
• Malignancies: Extraordinarily high levels of serum CRP in a patient with nonspecific clinical findings should raise suspicion for non-rheumatic diagnoses, such as infection and malignancy 2
• Chronic somatic disorders: Men with self-reported myocardial infarction, asthma, diabetes, chronic bronchitis/emphysema, osteoporosis or fibromyalgia/chronic pain syndrome had significantly elevated mean levels of CRP 3
• Therapeutic ionising radiation exposure: Associations have been suggested of high-dose ionising radiation exposure with type-2 diabetes and elevated levels of C-reactive protein 4
• Renal insufficiency: Associated with increased risk of elevated ESR/low CRP discordance 5
• Low serum albumin: Associated with both kinds of discordance, elevated CRP/low ESR and elevated ESR/low CRP 5

Disease-Specific Elevations in CRP

• Osteoporosis: The highest mean values of CRP were observed in men with osteoporosis (6.53 mg/l) 3
• Asthma: Cases of asthma had an increased mean CRP level of 5.01 mg/l 3
• Chronic bronchitis/emphysema: The corresponding CRP levels were 4.42 mg/l 3
• Diabetes: Men with diabetes had a mean CRP level of 4.53 mg/l 3
• Myocardial infarction: Men with myocardial infarction had a mean CRP level of 4.27 mg/l 3
• Fibromyalgia/chronic pain syndrome: The values were 4.79 mg/l 3