Download High Sensitivity C-Reactive Protein (hs-CRP)

Technical Bulletin
Number 116
High Sensitivity C-Reactive Protein (hs-CRP)
Introduction
Why High Sensitivity CRP?
Over 50% of coronary events occur in
individuals with low to moderate low
density lipoprotein (LDL) cholesterol.1
The search for additional predictive
risk factors has recently focused on the
role
of
inflammation
in
the
development of atherosclerosis. High
sensitivity C-reactive protein, or hsCRP, is a systemic marker of
inflammation and an effective marker
for long-term risk assessment.2
Low level increases in CRP have been
reported in various conditions and
disease states that are thought to be
associated with inflammation.2,5-7
The most prominently studied utility
has been for cardiovascular disease,
where CRP has been reported to
predict cardiovascular outcomes
independently of other conventional
markers of risk.2,8,9Increases in CRP are
nonspecific and should be interpreted
in the context of a complete clinical
evaluation. If elevated values are
observed in an apparently healthy
individual, the test should be repeated
in order to help rule out a recent
response to undetected infection or
tissue injury.
What is CRP?
C-reactive protein (CRP) is an acute
phase reactant that responds as a
sensitive, though nonspecific, marker
of systemic inflammation.
The
pentameric, globular protein is
synthesized by the liver in response to
stimuli from circulating inflammatory
cytokines. CRP has traditionally been
used as a systemic marker of infection
and tissue injury.3 An expanding body
of research now indicates that CRP
likely
plays
a
direct,
active
inflammatory role in blood vessels,
leading to the development of
atherosclerosis.4
Within 24–48 hours of an infectious or
noninfectious stimulus, CRP levels
may rise up to 3000-fold over
circulating levels seen in apparently
healthy individuals, typically less than
10 mg/L.3 CRP levels in conditions
characterized by chronic inflammation,
such as rheumatoid arthritis and
certain other rheumatic disorders, are
likewise characterized by significant
elevations. Conventional CRP assays
have therefore been optimized to
facilitate measurement of dynamic
increases in concentration. But this is
achieved at the expense of sensitivity
to detect low level increases due to
more subtle causes of inflammation.
Conventional CRP assays that can
accommodate very large increases
have not been optimized for the highly
sensitive detection of the low level
increases characterizing these clinical
applications. CRP levels in apparently
healthy individuals can be below
0.2 mg/L,10 requiring high sensitivity –
or hs-CRP – assays.
How are hs-CRP Results
Interpreted?
Hs-CRP values range between 0.3 and
8.6 mg/L in healthy men and between
0.2 and 9.1 mg/L in healthy women
who are not taking hormone
Low grade
replacement therapy.10
inflammation may occur in apparently
healthy individuals, placing them at
increased risk of the conditions noted
above.
In a recent scientific statement,9 the
Centers for Disease Control and
Prevention (CDC) and the American
Heart Association (AHA) recommended
the following interpretation of hs-CRP
results:
• < 1 mg/L Low Risk
• 1–3 mg/L Average Risk
• > 3 mg/L High Risk
Increases in CRP are nonspecific,
however, and should be interpreted in
the context of a complete clinical
evaluation. Hs-CRP values > 8 mg/L
observed in an apparently healthy
individual should be repeated in order
to help rule out a recent response to
undetected infection or tissue injury.9
Standardization of hs-CRP
The CDC is coordinating a project to
standardize
hs-CRP
assays.
Cholestech participated in the first
phase of this project which concluded
that it is feasible to use Certified
Reference Material (CRM) 470 as a
secondary reference material for
hs-CRP assays.11 The second phase of
the standardization project involves
working with manufacturers to ensure
accurate calibrator value assignment
and to normalize assay results.
Cholestech
standardizes
the
Cholestech LDX® hs-CRP assay using
diluted CRM470, and intends to adjust
its process in accord with CDC
recommendations.
Differences Among
hs-CRP Methods
A variety of methods are employed by
the various manufacturers of hs-CRP
assays.
These include several
immunoturbidometric
approaches,
chemiluminescence,
particleenhanced immunonephelometry, and
the
lateral
flow
immunoassay
technique of the Cholestech LDX
hs-CRP assay. Like Cholestech, most
manufacturers claim to standardize
their assays using CRM470. However,
differences in standardization are
clearly evident,11,12 likely as a result of
differences in assay methodologies and
manufacturing processes.
Testing hs-CRP on the
Cholestech LDX
Cholestech LDX hs-CRP is an in vitro
diagnostic test for the quantitative
determination C-reactive protein in
whole blood or serum. Measurement of
CRP is useful as an aid in the detection
and evaluation of infection, tissue
injury, inflammatory disorders, and
associated diseases. Cholestech LDX
hs-CRP tests are for use in laboratories
certified for moderate complexity
testing. Instructions for running the
hs-CRP test will be found in the
package insert in each box of hs-CRP
cassettes. Please read the hs-CRP
package insert before running an
hs-CRP test and note the following:
• Fingerstick samples are collected
using a Cholestech LDX 50 µL
Capillary Tube. Please note that this
is a different volume/capillary tube
than any other Cholestech LDX test
that you might already perform.
• Fingerstick samples must be applied
to the cassette within 5 minutes
after collection. Place the cassette
into the drawer of the analyzer
immediately after dispensing the
sample into the well.
• After pressing Run, hs-CRP results
will be displayed in 6 minutes
(results will be displayed in 4
minutes for serum or plasma
samples).
• Hematocrit levels between 30% and
55% do not affect results.
Quality Control
Quality control should be run routinely
to show that your Cholestech LDX
System is giving accurate results.
Ensure that sample type is set to
Serum mode in the Configuration
menu. Controls must be tested:
• With each new shipment of
cassettes (even if cassettes are from
the same lot previously received).
• With each new lot of cassettes
received.
• As required by your laboratory’s
standard Quality Control procedures.
• Each day that patient samples are
tested.
• If your local or state regulations
require more frequent testing of
Quality Control material.
Note that if you will be running
fingerstick or whole blood samples
after you have tested Quality Control
materials, be sure to change the
sample type in the Configuration menu
to Whole Blood mode.
The quality control results should be
within range before testing patient
samples. Refer to the Cholestech LDX
User Manual if they are not. Contact
Cholestech
Technical
Service
(1.800.733.0404) prior to testing
patient samples.
CPT Code
hs-CRP
and bacterial infection in preterm infants. Eur
J Pediatr 1990; 149:424-7.
6. Spector TD, Hart DJ, Nandra D, Doyle DV et
al. Low-level increases in serum C-reactive
protein are present in early osteoarthritis of
the knee and predict progressive disease.
Arthritis Rheum 1997; 40:723-7.
7. Schmidt R, Schmidt H, Curb JD, Masaki K et
al. Early inflammation and dementia: a 25year follow-up of the Honolulu-Asia Aging
Study. Ann Neurol 2002; 52:168-74.
8. Danesh J, Whincup P, Walker M, Lennon L et
al. Low grade inflammation and coronary
heart disease: prospective study and updated
meta-analyses. BMJ 2000; 321:199-204.
9. Pearson TA, Mensah GA, Alexander RW,
Anderson JL 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; 107:499511.
10.Rifai N, Ridker PM. Population distributions
of C-reactive protein in apparently healthy
men and women in the United States:
implication for clinical interpretation. Clin
Chem 2003; 49:666-9.
11.Kimberly MM, Vesper HW, Caudill SP, Cooper
GR et al. Standardization of immunoassays
for measurement of high-sensitivity C-reactive
protein. Phase I: evaluation of secondary
reference materials. Clin Chem 2003;
49:611-6.
86141
References
1. Wilson PW, D'Agostino RB, Levy D, Belanger
AM et al. Prediction of coronary heart disease
using risk factor categories.
Circulation
1998; 97:1837-47.
12. Roberts WL, Moulton L, Law TC, Farrow G et
al. Evaluation of nine automated highsensitivity C-reactive protein methods:
implications for clinical and epidemiological
applications. Part 2. Clin Chem 2001;
47:418-25.
2. Ridker PM. Clinical application of C-reactive
protein for cardiovascular disease detection
and
prevention.
Circulation
2003;
107:363-9.
3. Pepys MB. C-reactive protein fifty years on.
Lancet 1981; 1:653-7.
4. Szmitko PE, Wang CH, Weisel RD, de
Almeida JR et al. New markers of
inflammation and endothelial cell activation:
Part I. Circulation 2003; 108:1917-23.
5. Wasunna A, Whitelaw A, Gallimore R,
Hawkins PN, Pepys MB. C-reactive protein
Cholestech LDX is a registered trademark of Cholestech Corporation. CPT is a registered trademark of the American Medical Association.
© 2005 Cholestech Corporation MKT13226 Rev. A 08/05 Printed in USA.
To assist you with any
further questions, please call
Technical Service:
1.800.733.0404
3347 Investment Blvd.
Hayward, CA 94545 U.S.A.
Tel 800 733.0404
Fax 510 732.7227
www.cholestech.com