C Reactive Protein High Sensitivity
In 1930, Tillet and Francis observed a substance in the serum of individuals with Pneumococcus
infections that formed a precipitate when mixed with the C-polysaccharide coat
of Streptococcus pneumoniae. They noted that this “C-reactive” activity was absent from the
sera of healthy individuals. MacLeod and Avery subsequently characterized this substance as a
protein and introduced the term “acute phase” to describe the serum of patients with various
acute infections. Shortly thereafter, Lofstrom demonstrated the presence of the acute-phase
response (APR) in both acute and chronic inflammatory conditions; consequently, C-reactive
protein (CRP) became recognized as a nonspecific acute-phase protein.
The gene for CRP is located on the proximal long arm of chromosome 1, as are the
inflammation-related genes for serum amyloid P component and Fc receptors.
C reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to
inflammation (an acute-phase protein).CRP is synthesized by the liver in response to factors
released by fat cells (adipocytes). Plasma CRP levels can increase dramatically (100-fold or more)
after severe trauma, bacterial infection, inflammation,surgery, or neoplastic proliferation.
It is a general marker of inflammation that begins to rise four to six hours after tissue injury.
CRP also increases to much higher levels than other acute phase proteins, making it the most
sensitive indicator of small inflammatory stimuli. CRP concentration peaks at 48 hours and then
decreases with a half-life of 48 hours. Generally, a CRP level above 10 mg/L indicates significant
inflammatory disease.
C-reactive protein (CRP) has been used clinically to monitor inflammatory disease activity,
detect postoperative and neonatal infections and assess transplant rejection. Traditional CRP
assays were designed to measure CRP levels between 0.2 and 100 mg/dL.
In the mid-1990s, more sensitive methods for measurement of CRP were introduced. These
methods, referred to as high sensitivity CRP (hs-CRP), can accurately measure basal levels of CRP
throughout the currently accepted cardiovascular risk assessment range (0.20-10.0 mg/L).
Current evidence indicates that inflammation plays a central role in the pathogenesis of
atherosclerosis and thrombosis and that hs-CRP is a marker of low-grade vascular inflammation
that is predictive of future cardiovascular events. All prospective studies reported to date have
indicated that basal hs-CRP values in the highest quartile or quintile of data are associated with
a 2.3 to 4.8-fold increased relative risk of developing cardiovascular disease. These studies have
convincingly demonstrated that

hs-CRP is a risk factor for future myocardial infarction, ischemic stroke, peripheral
arterial disease and coronary heart disease mortality in apparently healthy men and
women.

In addition, elevated hs-CRP is predictive of cardiac complications in patients with
unstable angina or myocardial infarction.

It also has been shown that hs-CRP is additive with total cholesterol, low-density
lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in respect to
risk prediction.

Overweight (BMI 25-29) and obese (BMI >30) men and women have higher hs-CRP
values than normal-weight (BMI < 25) individuals.
The following table correlates hs-CRP levels with cardiovascular risk.
Quintile
hsCRPRange(mg/dL)
CV Risk Estimate
1
<0.06
Low
2
0.06 - 0.09
Mild
3
0.10 - 0.16
Moderate
4
0.17 - 0.32
High
5
>0.32
Highest
Hs-CRP should only be ordered for cardiovascular risk assessment. This assay is not useful for
monitoring patients with clinically apparent inflammatory and infectious disorders.
Specimen Type
Serum
Specimen Required
Container/Tube: Plain, red-top tube or serum gel tube
Specimen Volume: 0.5 mL of serum
Collection Instructions: Send specimen in plastic vial.
Reject Due To
Specimens other than Serum
Anticoagulants other than
NA
Hemolysis
Mild OK; Gross reject
Lipemia Mild OK; Gross reject
Icteric Mild OK; Gross reject
Transport Temperature
Frozen\Refrig <7 days OK\Ambient NO
Reference Values
Low risk: <1.0 mg/L
Average risk: 1.0-3.0 mg/L
High risk: >3.0 mg/L
Acute inflammation: >10.0 mg/L
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Tillet WS, Francis T. Serological reaction in pneumonia with a non-protein somatic fraction of
pneumococcus. J Exp Med 1930;52:561-571.Abstract
MacLeod CM, Avery OT. The occurrence during acute infections of a protein not normally present
in the blood. II. Isolation and properties of the reactive protein. J Exp Med 1943;73:183-191.
Lofstrom G. Comparison between the reaction of acute phase serum with pneumococcus Cpolysaccharide and with pneumococcus type 27. Br J Exp Pathol 1944;25:21-26.
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, III, Criqui M, et al. Markers of
inflammation and cardiovascular disease: application to clinical and public health practice: a
statement for healthcare professionals from the Centers for Disease Control and Prevention and
the American Heart Association. Circulation 2003;107:499-511.