International Journal of Cardiology
Volume 106, Issue 3 , Pages 291-297 , 26 January 2006

The novel role of C-reactive protein in cardiovascular disease: Risk marker or pathogen

Received 13 September 2004 ,Revised 19 January 2005 ,Accepted 19 January 2005.

References 

  1. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135–1143
  2. Bermudez EA, Rifai N, Buring J, Manson JE, Ridker PM. Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol. 2002;22:1668–1673
  3. Hulthe J, Wikstrand J, Mattsson-Hulten L, Fagerberg B. Circulating ICAM-1 (intercellular cell-adhesion molecule 1) is associated with early stages of atherosclerosis development and with inflammatory cytokines in healthy 58-year-old men: the Atherosclerosis and Insulin Resistance (air) Study. Clin Sci (Lond). 2002;103:123–129
  4. Du Clos TW. Function of C-reactive protein. Ann Med. 2000;32:274–278
  5. Taskinen S, Kovanen PT, Jarva H, Meri S, Pentikainen MO. Binding of C-reactive protein to modified low-density-lipoprotein particles: identification of cholesterol as a novel ligand for C-reactive protein. Biochem J. 2002;367:403–412
  6. Stein MP, Edberg JC, Kimberly RP, et al. C-reactive protein binding to fcgammariia on human monocytes and neutrophils is allele-specific. J Clin Invest. 2000;105:369–376
  7. Blake GJ, Ridker PM. C-reactive protein: a surrogate risk marker or mediator of atherothrombosis?. Am J Physiol Regul Integr Comp Physiol. 2003;285:R1250–R1252
  8. Yasojima K, Schwab C, McGeer EG, McGeer PL. Generation of C-reactive protein and complement components in atherosclerotic plaques. Am J Pathol. 2001;158:1039–1051
  9. Ouchi N, Kihara S, Funahashi T, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation. 2003;107:671–674
  10. Yasojima K, Schwab C, McGeer EG, McGeer PL. Human neurons generate C-reactive protein and amyloid P: upregulation in alzheimer's disease. Brain Res. 2000;887:80–89
  11. Cleland SJ, Sattar N, Petrie JR, Forouhi NG, Elliott HL, Connell JM. Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin Sci (Lond). 2000;98:531–535
  12. Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation. 2001;104:365–372
  13. Wong M, Toh L, Wilson A, et al. Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation. Arthritis Rheum. 2003;48:81–89
  14. Wu T, Trevisan M, Genco RJ, Dorn JP, Falkner KL, Sempos CT. Periodontal disease and risk of cerebrovascular disease: the First National Health and Nutrition Examination Survey and its follow-up study. Archives of Internal Medicine. 2000;160:2749–2755
  15. Kalayoglu MV, Libby P, Byrne GI. Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease. JAMA. 2002;288:2724–2731
  16. Espinola-Klein C, Rupprecht HJ, Blankenberg S, et al. Impact of infectious burden on progression of carotid atherosclerosis. Stroke. 2002;33:2581–2586
  17. Kiechl S, Werner P, Egger G, et al. Active and passive smoking, chronic infections, and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Stroke. 2002;33:2170–2176
  18. Sander D, Winbeck K, Klingelhofer J, Etgen T, Conrad B. Reduced progression of early carotid atherosclerosis after antibiotic treatment and Chlamydia pneumoniae seropositivity. Circulation. 2002;106:2428–2433
  19. Jackson LA, Yu O, Heckbert SR, et al. Influenza vaccination is not associated with a reduction in the risk of recurrent coronary events. Am J Epidemiol. 2002;156:634–640
  20. 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
  21. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102:2165–2168
  22. Torzewski J, Torzewski M, Bowyer DE, et al. C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. Arterioscler Thromb Vasc Biol. 1998;18:1386–1392
  23. Wang CH, Li SH, Weisel RD, et al. C-reactive protein upregulates angiotensin type 1 receptors in vascular smooth muscle. Circulation. 2003;107:1783–1790
  24. 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
  25. Li L, Roumeliotis N, Sawamura T, Renier G. C-reactive protein enhances lox-1 expression in human aortic endothelial cells: relevance of lox-1 to C-reactive protein-induced endothelial dysfunction. Circ Res. 2004;95:877–883
  26. Devaraj S, Kumaresan PR, Jialal I. Effect of C-reactive protein on chemokine expression in human aortic endothelial cells. J Mol Cell Cardiol. 2004;36:405–410
  27. Danenberg HD, Szalai AJ, Swaminathan RV, et al. Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice. Circulation. 2003;108:512–515
  28. Das UN. Obesity, metabolic syndrome X, and inflammation. Nutrition. 2002;18:430–432
  29. Esposito K, Pontillo A, Di Palo C, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA. 2003;289:1799–1804
  30. Banks RE, Forbes MA, Storr M, et al. The acute phase protein response in patients receiving subcutaneous IL-6. Clin Exp Immunol. 1995;102:217–223
  31. Mohamed-Ali V, Pinkney JH, Panahloo A, Goodrick S, Coppack SW, Yudkin JS. Relationships between plasma leptin and insulin concentrations, but not insulin resistance, in non-insulin-dependent (type 2) diabetes mellitus. Diabet Med. 1997;14:376–380
  32. Pickup JC, Mattock MB, Chusney GD, Burt D. Niddm as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia. 1997;40:1286–1292
  33. Ford ES. Body mass index, diabetes, and C-reactive protein among U.S. adults. Diabetes Care. 1999;22:1971–1977
  34. Chambers JC, Eda S, Bassett P, et al. C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European Whites. Circulation. 2001;104:145–150
  35. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973–979
  36. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836–843
  37. Schillinger M, Exner M, Amighi J, et al. Joint effects of C-reactive protein and glycated hemoglobin in predicting future cardiovascular events of patients with advanced atherosclerosis. Circulation. 2003;108:2323–2328
  38. Burnett JR, Watts GF, Vasikaran SD. C-reactive protein: a new cardiovascular risk factor?. Med J Aust. 2000;173:117–118
  39. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. 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
  40. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107:363–369
  41. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA. 1998;279:1477–1482
  42. Blake GJ, Rifai N, Buring JE, Ridker PM. Blood pressure, C-reactive protein, and risk of future cardiovascular events. Circulation. 2003;108:2993–2999
  43. Cao JJ, Thach C, Manolio TA, et al. C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the cardiovascular health study. Circulation. 2003;108:166–170
  44. Curb JD, Abbott RD, Rodriguez BL, et al. C-reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation. 2003;107:2016–2020
  45. Hashimoto H, Kitagawa K, Hougaku H, et al. C-reactive protein is an independent predictor of the rate of increase in early carotid atherosclerosis. Circulation. 2001;104:63–67
  46. 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
  47. Danesh J, Wheeler JG, Hirschfield GM, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004;350:1387–1397
  48. Casl MT, Surina B, Glojnaric-Spasic I, et al. Serum amyloid A protein in patients with acute myocardial infarction. Ann Clin Biochem. 1995;32(Pt 2):196–200
  49. 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
  50. Toss H, Lindahl B, Siegbahn A, Wallentin L. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. Frisc Study Group. Fragmin during instability in coronary artery disease. Circulation. 1997;96:4204–4210
  51. James SK, Armstrong P, Barnathan E, et al. Troponin and C-reactive protein have different relations to subsequent mortality and myocardial infarction after acute coronary syndrome: a Gusto-IV substudy. J Am Coll Cardiol. 2003;41:916–924
  52. Lindmark E, Diderholm E, Wallentin L, Siegbahn A. Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or noninvasive strategy. JAMA. 2001;286:2107–2113
  53. Mueller C, Buettner HJ, Hodgson JM, et al. Inflammation and long-term mortality after non-ST elevation acute coronary syndrome treated with a very early invasive strategy in 1042 consecutive patients. Circulation. 2002;105:1412–1415
  54. Gaspardone A, Crea F, Versaci F, et al. Predictive value of C-reactive protein after successful coronary-artery stenting in patients with stable angina. Am J Cardiol. 1998;82:515–518
  55. Horne BD, Muhlestein JB, Strobel GG, Carlquist JF, Bair TL, Anderson JL. Greater pathogen burden but not elevated C-reactive protein increases the risk of clinical restenosis after percutaneous coronary intervention. Am Heart J. 2002;144:491–500
  56. Zhou YF, Csako G, Grayston JT, et al. Lack of association of restenosis following coronary angioplasty with elevated C-reactive protein levels or seropositivity to Chlamydia pneumoniae. Am J Cardiol. 1999;84:595–598[A8]
  57. Goldberg A, Zinder O, Zdorovyak A, et al. Diagnostic coronary angiography induces a systemic inflammatory response in patients with stable angina. Am Heart J. 2003;146:819–823
  58. Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ. Early inflammation and dementia: a 25-year follow-up of the Honolulu–Asia Aging Study. Ann Neurol. 2002;52:168–174
  59. Balk EM, Lau J, Goudas LC, et al. Effects of statins on nonlipid serum markers associated with cardiovascular disease: a systematic review. Ann Intern Med. 2003;139:670–682
  60. Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005;352:20–28
  61. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med. 2005;352:29–38
  62. Ehrenstein MR, Jury EC, Mauri C. Statins for atherosclerosis—as good as it gets?. N Engl J Med. 2005;352:73–75
  63. Di Napoli M, Papa F. Angiotensin-converting enzyme inhibitor use is associated with reduced plasma concentration of C-reactive protein in patients with first-ever ischemic stroke. Stroke. 2003;34:2922–2929
  64. Solheim S, Arnesen H, Eikvar L, Hurlen M, Seljeflot I. Influence of aspirin on inflammatory markers in patients after acute myocardial infarction. Am J Cardiol. 2003;92:843–845
  65. Church TS, Barlow CE, Earnest CP, Kampert JB, Priest EL, Blair SN. Associations between cardiorespiratory fitness and C-reactive protein in men. Arterioscler Thromb Vasc Biol. 2002;22:1869–1876
  66. Ockene IS, Matthews CE, Rifai N, Ridker PM, Reed G, Stanek E. Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem. 2001;47:444–450
  67. Pearson TA, Mensah GA, Alexander RW, 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

PII: S0167-5273(05)00434-1

doi: 10.1016/j.ijcard.2005.01.068

International Journal of Cardiology
Volume 106, Issue 3 , Pages 291-297 , 26 January 2006

Article Tools

* Image Usage & Resolution