C-reactive protein

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C-reactive protein (CRP) is one of the circulating blood proteins that help the host defense system begin immune defense by phagocytosis performed by macrophage. Its opsonization of target cells is much less precise than from immunoglobulin generated by B-lympocytes for T8 lymphocytes. When activated, it binds, with the antigen, to a surface receptor on macrophages and opsonize the threatening cells.

Medical use

Detecting inflammation

Along with the erythrocyte sedimentation rate, an elevated c-reactive protein suggests that an acute inflammatory disorder exists.[1] The c-reactive protein may be a more accurate predictor inflammatory disease than the erythrocyte sedimentation rate[2]

Normal c-reactive protein levels have been used to help health care providers reduce antibiotic use.[3]

Predicting risk of atherosclerosis

Altought the CRP molecule itself does not seem to directly cause vascular disease[4][5], its presence may help prediction coronary heart disease.

Abnormal high sensitivity CRP values may assist in assessing lipid measurements in apparently healthy people due to the theory that chronic inflammation precedes atherosclerosis.[6] However, a review found that the ability of the CRP to add to other methods of predicting coronary heart disease such as the Framingham risk tool is limited[6] except in one study (AUC increased from 0.735 to 0.750)[7]. In one study, the CRP did not add to the coronary calcium score.[8]

Studies that report benefit use the natural logarithm transformation of the CRP and measure the net reclassification rate rather than the c-index. Most, but not all[9], recent studies have transformed the CPR levels prior to analysis.[10] First, an analysis of Framingham data showed small improvement from using the log of the CRP (AUC increased from 0.795 to 0.799 and 12% of patients had improved estimates - net reclassification improvement (NRI) = 11%).[11] Second, the hsCRP added similarly to the predictions in the Women's Health Study.[12] Third, the transformed hsCRP improved the classifiation of Swedish subjects, if the subjects had intermediate-risk (10-year predicted risk, 6% to <20%).[13] Fourth, a Scottish cohort found that the transformed CRP did not add much to the prediction of coronary heart disease, but this cohort only reported the c-index.[14] However, the transformed hsCRP is not always a significant predictor.[15]

The natural logarithm transformation of the CRP is part of the Reynolds score which has been proposed as an improvement to the Framingham risk for the prediction of coronary heart disease (AUC increased from 0.689 to 0.700 in men[16] and from 0.805 to 0.808 in women[17]). The Reynolds score has been validated in the Women's Genome Health Study.[18] An online calculator is at http://www.reynoldsriskscore.org/.

Risk factor modification, particularly the use of aspirin and the hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins), may reduce plaque inflammation.[19] Statin therapy benefited about 1 of every 170 patients with LDL cholesterol less than 130 mg per deciliter (3.4 mmol per liter), Framingham risk score of 10%, and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher who took rosuvastatin 20 mg daily for 2 years if they are similar to the patients in the JUPITER randomized controlled trial (number needed to treat for two years is 170).[20][21] The frequency of death from any cause fell from 2.8% to 2.2% (number needed to treat for two years is 180). However, this trial was stopped early after an interim analysis so it is likely that the results are exaggerated.

Predicting reduction in heart disease from therapy with statins

In patients without previous heart disease, LDL cholesterol less than 130 mg per deciliter (3.4 mmol per liter), and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher, hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin) therapy benefited about 1 of every 170 patients who took rosuvastatin 20 mg daily for 2 years in the JUPITER randomized controlled trial (number needed to treat for two years is 170).[20][21] The frequency of death from any cause fell from 2.8% to 2.2% (number needed to treat for two years is 180). However, this trial was stopped early after an interim analysis so it is likely that the result is exaggerated.

However, the Heart Protection Study found benefit from primary prevention for patients with and without a high CRP who received simvastatin over 5 years.[22]

Lowering the C-reactive protein

Obesity and unhealthy diet may raise CRP.[23]

Medications

Both aspirin[24] and statins (lovastatin[25] and rosuvastatin[20]) can lower the C-reactive protein with a synergistic effect from combining both drugs[26]. Aspirin is especially effect in reducing coronary heart disease among people with eleveate C-reactive proteins.[27]

References

  1. Husain TM, Kim DH (Spring 2002), "C-Reactive Protein and Erythrocyte Sedimentation Rate in Orthopaedics", University of Pennsylvania Orthopedic Journal 15: 13-16
  2. Colombet I, Pouchot J, Kronz V, Hanras X, Capron L, Durieux P et al. (2010). "Agreement between erythrocyte sedimentation rate and C-reactive protein in hospital practice.". Am J Med 123 (9): 863.e7-13. DOI:10.1016/j.amjmed.2010.04.021. PMID 20800157. Research Blogging.
  3. Cals JW, Butler CC, Hopstaken RM, Hood K, Dinant GJ (2009). "Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial". BMJ 338: b1374. PMID 19416992. PMC 2677640[e]
  4. Zacho J, Tybjaerg-Hansen A, Jensen JS, Grande P, Sillesen H, Nordestgaard BG (October 2008). "Genetically elevated C-reactive protein and ischemic vascular disease". N. Engl. J. Med. 359 (18): 1897–908. DOI:10.1056/NEJMoa0707402. PMID 18971492. Research Blogging.
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  11. Wilson PW, Pencina M, Jacques P, Selhub J, D'Agostino R, O'Donnell CJ (2008). "C-reactive protein and reclassification of cardiovascular risk in the Framingham Heart Study.". Circ Cardiovasc Qual Outcomes 1 (2): 92-7. DOI:10.1161/CIRCOUTCOMES.108.831198. PMID 20031795. PMC PMC3033831. Research Blogging.
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  13. Melander, Olle; Christopher Newton-Cheh, Peter Almgren, Bo Hedblad, Goran Berglund, Gunnar Engstrom, Margaretha Persson, J. Gustav Smith, Martin Magnusson, Anders Christensson, Joachim Struck, Nils G. Morgenthaler, Andreas Bergmann, Michael J. Pencina, Thomas J. Wang (2009-07-01). "Novel and Conventional Biomarkers for Prediction of Incident Cardiovascular Events in the Community". JAMA 302 (1): 49-57. DOI:10.1001/jama.2009.943. Retrieved on 2009-07-06. Research Blogging.
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  18. Paynter NP, Chasman DI, Buring JE, Shiffman D, Cook NR, Ridker PM (January 2009). "Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3". Ann. Intern. Med. 150 (2): 65–72. PMID 19153409[e]
  19. F Brian Boudi, Chowdhury H Ahsan, James L Orford, Andrew P Selwyn (Aug 10, 2006), "Atherosclerosis", eMedicine
  20. 20.0 20.1 20.2 Ridker PM, Danielson E, Fonseca FA, et al (November 2008). "Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein". N. Engl. J. Med.. DOI:10.1056/NEJMoa0807646. PMID 18997196. Research Blogging. Cite error: Invalid <ref> tag; name "pmid18997196" defined multiple times with different content Cite error: Invalid <ref> tag; name "pmid18997196" defined multiple times with different content
  21. 21.0 21.1 Ridker PM (November 2003). "Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: rationale and design of the JUPITER trial". Circulation 108 (19): 2292–7. DOI:10.1161/01.CIR.0000100688.17280.E6. PMID 14609996. Research Blogging.
  22. (2011) "C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20 536 patients in the Heart Protection Study.". Lancet 377 (9764): 469-76. DOI:10.1016/S0140-6736(10)62174-5. PMID 21277016. Research Blogging.
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