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Larry H Bernstein, MD, FCAP, Curator

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High sensitivity c-Reactive Protein

High sensitivity C-reactive protein (hsCRP)
Author: Larry Bernstein, M.D.,  (see Reviewers/Authors page)
Revised: 12 December 2010, last major update December 2010
Copyright: (c) 2003-2010, PathologyOutlines.com, Inc.

http://dx.doi.org:/PathologyOutlines.com/cardiac

General
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• hsCRP is an enhanced sensitivity C-reactive protein (CRP) immunoassay with a lowered measurement cutoff

Methodology
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• Laser nephelometry

Indications
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• In the JUPITER trial of apparently healthy persons without hyperlipidemia but with elevated
  high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major
  cardiovascular events ( N Engl J Med 2008;359:2195)
• This effect is thought to be due to the effect of statins on inflammation, which is detected by hsCRP
• hsCRP assessment for cardiovascular disease in asymptomatic individuals seems to be most useful for
  those classified as intermediate risk on the basis of traditional risk factors (e.g. an NCEP-ATP III global
  risk score between 5% and 20%), and who do not already warrant chronic treatment with aspirin and a statin

Limitations
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• Most useful for patients with intermediate risk for cardiovascular disease (Circ Cardiovasc Qual Outcomes
  2008;1:92, Ann Intern Med 2009;151:483)
• For low risk patients, if their risk increases 3x (e.g. from 1% to 3%), their absolute cardiovascular risk
  is still low, so the hsCRP test has no practical value
• High risk patients are candidates for chronic aspirin and lipid-lowering therapy regardless of their hsCRP test results
• However, a recent study concludes that risk based statin treatment without hs-CRP testing is more cost-effective
  than hs-CRP screening, assuming that statins have good long-term safety and provide benefits among low-risk
  people with normal hs-CRP (Circulation 2010;122:1478)

Reference ranges
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• Low risk: under 1 mg/L
• Intermediate risk: 1-3 mg/L
• High risk: > 3 mg/L

Additional references
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• Wikipedia, Circulation 2006;113:2335, N Engl J Med 2001;344:1959

How to use C-reactive protein in acute coronary care
LM. Biasucci,W Koenig, J Mair, C Mueller, M Plebani, B Lindahl, N Rifai, P Venge, C Hamm, et al.
Eur Heart J  Nov 2013;  http://dx.doi.org:/10.1093/eurheartj/eht435

In patients with acute myocardial infarction (AMI), C-reactive protein increases within 4–6 h of symptoms,
peaks 2–4 days later, and returns to baseline after 7–10 days. Because of evidence that atherosclerosis
is an inflammatory disease, high-sensitivity C-reactive protein can be used as a biomarker of risk
in primary prevention and in patients with known cardiovascular disease.
The upper reference limit is method-dependent but usually 8 mg/L for standard assays. The distribution of high-
sensitivity C-reactive protein concentrations is skewed in both genders with a 50th percentile of 1.5 mg/L (excluding
women on hormone replacement therapy).  C-reactive protein concentrations are increased by smoking, obesity, and
hormone replacement therapy and reduced by exercise, moderate alcohol drinking, and statin use. Correction for these
factors is essential in reference range studies.
C-reactive protein assays are not standardized. We recommend the use of third-generation high-sensitivity C-reactive
protein assays that combine features of standard and high-sensitivity C-reactive protein assays. Required assay precision
should be < 10% in the range of 3 and 10 mg/L.