CRP-hs - Kresser Institute Membership Site

Marker Name: CRP-hs

REFERENCE RANGES FOR CRP-hs:

Laboratory reference range: 0–3 mg/L

Functional reference range: 0–1 mg/L

DESCRIPTION:

CRP-hs stands for high sensitivity C-reactive protein. C-reactive protein is an acute phase reactant, which is the name given to proteins that enter the bloodstream in large numbers in response to inflammation and tissue injury.¹ C-reactive protein elevations following pneumococcal pneumonia was the first instance of an acute phase reactant described in man.² C-reactive protein can participate in several stages of inflammation, and it has both pro- and anti-inflammatory functions.³ One of the major functions of C-reactive protein is to find a phosphocholine, which is present on foreign pathogens and damaged cells.⁴ Thus, C-reactive protein improves recognition and elimination of pathogens and necrotic and apoptotic cells.³ C-reactive protein can also activate monocytes and the complement system, which is a key component of the innate (non-adaptable) immune system. Interaction with complement proteins and monocytes may exacerbate tissue damage in pro-inflammatory settings.^3,5 C-reactive protein may also be an early predictor of cardiovascular disease and occult atherosclerosis, though this is unsettled in the literature.^6-8

Hepatocytes are the main source of acute phase reactants, including C-reactive protein.³ Interleukin-6 (IL-6) is the main driver of C-reactive protein, though IL-1 beta, tumor necrosis factor-alpha, and interferon gamma also stimulate production of the protein.⁹ These cytokines may have inhibitory or synergistic effects on C-reactive protein and other acute phase reactants depending on the specific inflammatory state and the local milieu.¹ The system is regulated so tightly that virtually any form of tissue injury, infection, inflammation, or non-physiological stressors can cause CRP to be synthesized and released.^8,10 Levels of C-reactive protein can vary in the blood by a thousand-fold or more.^1,11 The half-life of C-reactive protein is approximately 19 hours, and the sole determinant of C-reactive protein concentration is the synthesis rate.^12,13 CRP is cleared from the plasma and catabolized by hepatocytes.¹⁴

C-reactive protein is a biological entity, and high sensitivity describes the sensitivity with which the assay measures the biological entity. There is nothing fundamentally different between the C-reactive protein measured with traditional and high sensitivity assay methods; the high sensitivity C-reactive protein is simply intended to measure relatively low levels of normal C-reactive protein.^3,8

CRP-hs is, indeed, a highly sensitive assay for C-reactive protein, and concentrations in the blood of 0.3 mg/dL and higher may indicate some form of inflammation. In general, values greater than 1 mg/dL are considered a sign of clinically significant inflammation.¹⁵ CRP values between 0.3 and 1 mg/dL may indicate cigarette smoking, hypertension, obesity, or another relatively minor inflammation.³ Infection often causes markedly elevated levels of CRP ( i.e., > 50 mg/dL.)¹⁶ Even though C-reactive protein is an “acute” phase reactant, elevated levels of C-reactive protein can be found in both acute and chronic inflammatory states.³ Likewise, elevated C-reactive protein may be found after trauma or infarction and during the course of certain cancers. Virtually any stressor can raise C-reactive protein levels.⁸ CRP is a sensitive indicator of inflammation but almost completely nonspecific.³

The “normal” level of CRP is unknown, such that any detectable CRP may reflect a clinical abnormality, however minor.³ Therefore, no clinical state exists in which CRP is considered abnormally low.

When C-reactive protein is used to assess inflammation, it may be ordered with erythrocyte sedimentation rate (ESR). The high sensitivity assay for C-reactive protein is often used to calculate cardiovascular risk and is usually measured with other markers, such as a lipid panel and hemoglobin A1c.¹⁷

It is important to note that CRP-hs has high intraindividual variability, meaning levels can vary substantially from reading to reading in a single person with no pathological changes. Therefore, a single measurement of CRP-hs may not reflect an individual’s typical CRP-hs level. Repeat measurements may be required to establish an individual’s true mean CRP-hs concentration.^18-21

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS: High in:^{1,11,12,22,23}

Obesity
Cigarette smoking
Diabetes mellitus
Hypertension
Physical inactivity
Sleep disturbance
Chronic fatigue
Depression
Other inflammatory conditions
Cardiovascular disease
Infection
Malignancy
Uremia
Rheumatoid arthritis
Polymyalgia rheumatica
Giant cell arteritis
Systemic lupus erythematosus
Drugs
- Oral estrogens

Low in:^1,10,15

Not clinically relevant

FUNCTIONAL RANGE INDICATIONS:

High in:

Same as conventional indications

Low in:

Same as conventional indications

References: