Skip to main content
Log in

C-reactive protein: The pawn has been promoted to queen

  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

C-reactive protein (CRP) is one of the acute phase reactants that can increase its serum level up to 100-fold during systemic inflammation. Its clinical use was limited in the past because of its lack of specificity in differentiating infection from other inflammatory processes. With the advent of a high sensitivity assay, CRP was found to be a superb predictor in identifying apparently healthy men and women at risk for developing future cardiovascular events, such as heart attacks and strokes. CRP’s predictive power is most likely due to its stability, reproducibility, and proatherogenic properties. Developing consensus to incorporate CRP determination into clinical practice guidelines will be the subject of intense debate and at the same time provide clinical research opportunities in the years to come.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Tillett WS, Francis T Jr: Serological reactions in pneumonia with a non-protein somatic fraction of pneumonococcus. J Exp Med 1930, 52: 561–571.

    Article  CAS  Google Scholar 

  2. Thompson D, Pepys MB, Wood SP: The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure Fold Des 1999, 7: 169–177.

    Article  PubMed  CAS  Google Scholar 

  3. Ganter U, Arcone R, Toniatti C, et al.: Dual control of C-reactive protein gene expression by interleukin-1 and interleukin-6. Embolism J 1989, 8: 3773–3779.

    CAS  Google Scholar 

  4. Gabay C, Kushner I: Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999, 340: 448–454.

    Article  PubMed  CAS  Google Scholar 

  5. Zee RY, Ridker PM: Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis. Atherosclerosis 2002, 162: 217–219.

    Article  PubMed  CAS  Google Scholar 

  6. Vickers MA, Green FR, Terry C, et al.: Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovasc Res 2002, 53: 1029–1034.

    Article  PubMed  CAS  Google Scholar 

  7. Yasojima K, Schwab C, McGeer EG, et al.: Generation of C-reactive protein and complement components in atherosclerotic plaques. Am J Pathol 2001, 158: 1039–1051.

    PubMed  CAS  Google Scholar 

  8. Ockene IS, Matthews CE, Rifai N, et al.: Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem 2001, 47: 444–450.

    PubMed  CAS  Google Scholar 

  9. Haverkate F, Thompson SG, Pyke SD, et al.: Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997, 349: 462–466.

    Article  PubMed  CAS  Google Scholar 

  10. Morrow DA, Rifai N, Antman EM, et al.: C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A substudy. Thrombolysis in Myocardial Infarction. J Am Coll Cardiol 1998, 31: 1460–1465.

    Article  PubMed  CAS  Google Scholar 

  11. Liuzzo G, Biasucci LM, Gallimore JR, et al.: The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994, 331: 417–424.

    Article  PubMed  CAS  Google Scholar 

  12. Ueda S, Ikeda U, Yamamoto K, et al.: C-reactive protein as a predictor of cardiac rupture after acute myocardial infarction. Am Heart J 1996, 131: 857–860.

    Article  PubMed  CAS  Google Scholar 

  13. Ridker PM, Rifai N, Pfeffer MA, et al.: Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998, 98: 839–844.

    PubMed  CAS  Google Scholar 

  14. Chew DP, Bhatt DL, Robbins MA, et al.: Incremental prognostic value of elevated baseline C-reactive protein among established markers of risk in percutaneous coronary intervention. Circulation 2001, 104: 992–997.

    PubMed  CAS  Google Scholar 

  15. Rossi E, Biasucci LM, Citterio F, et al.: Risk of myocardial infarction and angina in patients with severe peripheral vascular disease: predictive role of C-reactive protein. Circulation 2002, 105: 800–803.

    Article  PubMed  Google Scholar 

  16. Buffon A, Liuzzo G, Biasucci LM, et al.: Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty. J Am Coll Cardiol 1999, 34: 1512–1521.

    Article  PubMed  CAS  Google Scholar 

  17. Ridker PM: High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001, 103: 1813–1818.

    PubMed  CAS  Google Scholar 

  18. Ridker PM, Rifai N, Rose L, et al.: Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002, 347: 1557–1565.

    Article  PubMed  CAS  Google Scholar 

  19. Abramson JL, Weintraub WS, Vaccarino V: Association between pulse pressure and C-reactive protein among apparently healthy US adults. Hypertension 2002, 39: 197–202.

    Article  PubMed  CAS  Google Scholar 

  20. Pradhan AD, Manson JE, Rifai N, et al.: C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001, 286: 327–334.

    Article  PubMed  CAS  Google Scholar 

  21. Tchernof A, Nolan A, Sites CK, et al.: Weight loss reduces C-reactive protein levels in obese postmenopausal women. Circulation 2002, 105: 564–569.

    Article  PubMed  Google Scholar 

  22. Chung MK, Martin DO, Sprecher D, et al.: C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001, 104: 2886–2891.

    PubMed  CAS  Google Scholar 

  23. Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al.: Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 2002, 105: 2462–2464.

    Article  PubMed  CAS  Google Scholar 

  24. Schmidt R, Schmidt H, Curb JD, et al.: Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol 2002, 52: 168–174.

    Article  PubMed  Google Scholar 

  25. Pai JK, Curhan GC, Cannuscio CC, et al.: Stability of novel plasma markers associated with cardiovascular disease: processing within 36 hours of specimen collection. Clin Chem 2002, 48: 1781–1784.

    PubMed  CAS  Google Scholar 

  26. Kaplan MH, Volanakis JE: Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. J Immunol 1974, 112: 2135–2147.

    PubMed  CAS  Google Scholar 

  27. Torzewski M, Rist C, Mortensen RF, et al.: C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler Thromb Vasc Biol 2000, 20: 2094–2099.

    PubMed  CAS  Google Scholar 

  28. Cermak J, Key NS, Bach RR, et al.: C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993, 82: 513–520.

    PubMed  CAS  Google Scholar 

  29. Pasceri V, Willerson JT, Yeh ET: Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000, 102: 2165–2168.

    PubMed  CAS  Google Scholar 

  30. Pasceri V, Cheng JS, Willerson JT, et al.: Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001, 103: 2531–2534.

    PubMed  CAS  Google Scholar 

  31. Verma S, Li SH, Badiwala MV, et al.: Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation 2002, 105: 1890–1896.

    Article  PubMed  CAS  Google Scholar 

  32. Zwaka TP, Hombach V, Torzewski J: C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation 2001, 103: 1194–1197.

    PubMed  CAS  Google Scholar 

  33. Verma S, Wang CH, Li SH, et al.: A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 2002, 106: 913–919.

    Article  PubMed  CAS  Google Scholar 

  34. Venugopal SK, Devaraj S, Yuhanna I, et al.: Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 2002, 106: 1439–1441.

    Article  PubMed  CAS  Google Scholar 

  35. Yeh ET, Anderson HV, Pasceri V, et al.: C-reactive protein: linking inflammation to cardiovascular complications. Circulation 2001, 104: 974–975.

    PubMed  CAS  Google Scholar 

  36. Pasceri V, Yeh ET: A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation 1999, 100: 2124–2126.

    PubMed  CAS  Google Scholar 

  37. Lagrand WK, Niessen HW, Wolbink GJ, et al.: C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation 1997, 95: 97–103.

    PubMed  CAS  Google Scholar 

  38. Griselli M, Herbert J, Hutchinson WL, et al.: C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med 1999, 190: 1733–1740.

    Article  PubMed  CAS  Google Scholar 

  39. Szalai AJ, VanCott JL, McGhee JR, et al.: Human C-reactive protein is protective against fatal Salmonella enterica serovar typhimurium infection in transgenic mice. Infect Immun 2000, 68: 5652–5656.

    Article  PubMed  CAS  Google Scholar 

  40. Xia D, Samols D: Transgenic mice expressing rabbit C-reactive protein are resistant to endotoxemia. Proc Natl Acad Sci U S A 1997, 94: 2575–2580.

    Article  PubMed  CAS  Google Scholar 

  41. Zouki C, Beauchamp M, Baron C, et al.: Prevention of in vitro neutrophil adhesion to endothelial cells through shedding of L-selectin by C-reactive protein and peptides derived from C-reactive protein. J Clin Invest 1997, 100: 522–529.

    Article  PubMed  CAS  Google Scholar 

  42. Ahmed N, Thorley R, Xia D, et al.: Transgenic mice expressing rabbit C-reactive protein exhibit diminished chemotactic factor-induced alveolitis. Am J Respir Crit Care Med 1996, 153: 1141–1147.

    PubMed  CAS  Google Scholar 

  43. Filep JG, Herman F, Kelemen E, et al.: C-reactive protein inhibits binding of platelet-activating factor to human platelets. Thromb Res 1991, 61: 411–421.

    Article  PubMed  CAS  Google Scholar 

  44. Gershov D, Kim S, Brot N, et al.: C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 2000, 192: 1353–1364.

    Article  PubMed  CAS  Google Scholar 

  45. Liu S, Manson JE, Buring JE, et al.: Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. Am J Clin Nutr 2002, 75: 492–498.

    PubMed  CAS  Google Scholar 

  46. Imhof A, Froehlich M, Brenner H, et al.: Effect of alcohol consumption on systemic markers of inflammation. Lancet 2001, 357: 763–767.

    Article  PubMed  CAS  Google Scholar 

  47. Crook MA, Scott DA, Stapleton JA, et al.: Circulating concentrations of C-reactive protein and total sialic acid in tobacco smokers remain unchanged following one year of validated smoking cessation. Eur J Clin Invest 2000, 30: 861–865.

    Article  PubMed  CAS  Google Scholar 

  48. Geffken D, Cushman M, Burke G, et al.: Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 2001, 153: 242–250.

    Article  PubMed  CAS  Google Scholar 

  49. Siegel AJ, Stec JJ, Lipinska I, et al.: Effect of marathon running on inflammatory and hemostatic markers. Am J Cardiol 2001, 88: 918–920.

    Article  PubMed  CAS  Google Scholar 

  50. Ikonomidis I, Andreotti F, Economou E, et al.: Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 1999, 100: 793–798.

    PubMed  CAS  Google Scholar 

  51. Ridker PM, Cushman M, Stampfer MJ, et al.: Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997, 336: 973–979.

    Article  PubMed  CAS  Google Scholar 

  52. Ridker PM, Rifai N, Pfeffer MA, et al.: Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1999, 100: 230–235.

    PubMed  CAS  Google Scholar 

  53. Ridker PM, Rifai N, Clearfield M, et al.: Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001, 344: 1959–1965.

    Article  PubMed  CAS  Google Scholar 

  54. Plenge JK, Hernandez TL, Weil KM, et al.: Simvastatin lowers C-reactive protein within 14 days: an effect independent of low-density lipoprotein cholesterol reduction. Circulation 2002, 106: 1447–1452.

    Article  PubMed  CAS  Google Scholar 

  55. Azar RR, Rinfret S, Theroux P, et al.: A randomized placebo-controlled trial to assess the efficacy of antiinflammatory therapy with methylprednisolone in unstable angina (MUNA trial). Eur Heart J 2000, 21: 2026–2032.

    Article  PubMed  CAS  Google Scholar 

  56. Gebbie A: Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health Initiative Randomized Controlled Trial. Writing Group for the Women’s Health Initiative# 10; Investigators. JAMA 2002, 288: 321–333.

    Article  Google Scholar 

  57. Lowe GD, Upton MN, Rumley A, et al.: Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein--a cross-sectional population survey. Thromb Haemost 2001, 86: 550–556.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yeh, E.T.H., Palusinski, R.P. C-reactive protein: The pawn has been promoted to queen. Curr Atheroscler Rep 5, 101–105 (2003). https://doi.org/10.1007/s11883-003-0080-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-003-0080-4

Keywords

Navigation