Indicators of inflammation in patients with coronary atherosclerosis – role of usCRP in diagnosis and disease progression prediction

Authors: M. Samoš 1;  R. Pullmann 2;  S. Funiak 1;  M. Stančík 1;  M. Mokáň 1
Authors‘ workplace: I. interná klinika Jesseniovej lekárskej fakulty UK a UN Martin, Slovenská republika, prednosta prof. MUDr. Marián Mokáň, DrSc., FRCP Edin. 1;  Ústav klinickej biochémie Jesseniovej lekárskej fakulty UK a UN Martin, Slovenská republika, prednosta prof. MUDr. Dušan Dobrota, CSc. 2
Published in: Vnitř Lék 2013; 59(12): 1057-1064
Category: Review


Atherosclerosis is being nowadays defined as chronic subclinical inflammatory disease. Recently published clinical and laboratory studies have shown that subclinical inflammation represents main role in initiation of creation, in progress and destabilization of atherosclerotic plaque. Screening including traditional cardiovascular risk factors fails in identification in more than 50% of individuals with later development of acute coronary syndrome. According to above mentioned reason indicators are being searched for, which would be usable to monitor the activity of atherosclerotic process. According to role of subclinical inflammatory process in pathogenesis of atherosclerosis, the determination of C-reactive protein using ultrasensitive method is being showed as perspective marker. Ultrasensitive C-reactive protein represents a strong, independent predictor of future cardiovascular events in apparently heal­thy individuals and has also prognostic utility in patients with acute coronary syndromes. Predictive capacity of C-reactive protein determination is independent of traditional risk factors and offers prognostic advantage as opposed to determination of lipids alone. The paper provides a review of currently available knowledge of possibilities for utilization of C-reactive protein laboratory assessment, as the main representative of acute phase proteins, in monitoring of creation and severity of coronary atherosclerosis, in possibilities of the disease prognosis determination and prediction of its acute complications, and also in prediction of prognosis in patient with already existing acute complication.

Key words:
ultrasensitive C-reactive protein – coronary atherosclerosis – myocardial infarction


1. Ross R. Atherosclerosis an inflammatory di­sease. N Engl J Med 1999; 340: 115–126.

2. Hansson GK, Berne GP. Atherosclerosis and the immune system. Acta Paediatr Suppl 2004; 93: 63–69.

3. Libby P. Inflammation in atherosclerosis. Natu­­re 2002; 420: 868–874.

4. Davies MJ. Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995. Circulation 1996; 94: 2013–2020.

5. Dollery CM, Libby P. Atherosclerosis and proteinase activation. Cardiovasc Res 2006; 69: 625–635.

6. Dvořáková A, Poledne R. Ultrasenzitivně měřený C-reaktivní protein – nový parametr kardiovaskulárního rizika. Vnitř Lék 2004; 50: ­852–857.

7. Ošťádal P. C-reaktivní protein – molekula, která změnila kardiologii. Editorial k článku Dvořáková et al Ultrasenzitivně měřený C-reaktivní protein – nový parametr kardiovaskulárního rizika. Vnitř Lék 2004; 50: 809–811.

8. Pullmann R, Pavlovič M. Laboratórne nálezy a ich klinická interpretácia. Bratislava: Raabe 2007.

9. Meško D, Pullmann R, Nosáľová G. Vademékum klinickej biochémie. Martin: Osveta 1998.

10. Špirková Z, Daňová K, Pecháň I et al. Kardiomarkery. Bratislava: Phonec agency 2003.

11. Ridker PM, Hennekens CH, Buring JE et al. ­C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: ­836–843.

12. Rifai N, Tracy RP, Ridker PM. Clinical efficacy of an automated high-sensitivity C-reactive protein assay. Clin Chem 1999; 45: 2136–2141.

13. Ess SM, Szucs TD. Medical-economical aspects of high sensitivity C-reactive protein assay for the prediction of coronary heart dis­ease. An analysis in Germany and Italy. Ital Heart J 2001; 2: 181–188.

14. Ridker PM, Morrow DA. C-reactive protein, inflammation, and coronary risk. Cardiol Clin 2003; 21: 315–325.

15. Zakynthinos E, Pappa N. Inflammatory biomarkers in coronary artery disease. J Cardiol 2009; 53: 317–333.

16. Ridker PM, Macfadyen JG, Nordestgaard BG et al. Rosuvastatin for primary prevention among individuals with elevated high-sensitivity C-reactive protein and 5% to 10% and 10% to 20% 10-year risk. Implications of the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial for “intermediate risk”. Circ Cardiovasc Qual Outcomes 2010; 3: 447–452.

17. Schnell-Inderst P, Schwarzer R, Göhler A at al. Prognostic value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein as a marker for major cardiac events in asymptomatic individuals: a health technology assessment report. Int J Technol Assess Health Care 2010; 26: 30–39.

18. Choudhry NK, Patrick AR, Glynn RJ et al. The cost-effectiveness of C-reactive protein testing and rosuvastatin treatment for patients with normal cholesterol levels. J Am Coll Cardiol 2011; 57: 784–791.

19. Wijns W, Kohl P, Danchin N et al. Guidelines on myocardial revascularization. Eur Heart J 2010; 31: 2501–2555.

20. Perk J, De Backer G, Gohlke H et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J 2012; 33: 1635–1701.

21. Stone JA, Arthur HM. Canadian Guidelines for cardiac rehabilitation and cardiovascular disease prevention, second edition, 2004: executive summary. Can J Cardiol 2005; 21 (Suppl D): 3D–19D.

22. Veselka J, Procházková S, Duchonová R et al. Relationship of C-reactive protein to presence and severity of coronary atherosclerosis in patients with stable angina pectoris or a pathological exercise test. Coron Artery Dis 2002; 3: ­151–154.

23. Zairis MN, Papadaki OA, Manousakis SJ et al. C-reactive protein and multiple complex coronary artery plaques in patients with primary unstable angina. Atherosclerosis 2002; 164: 355–359.

24. Noto D, Cottone S, Baldassare Cefalù A et al. Interleukin 6 plasma levels predict with high sensitivity and specificity coronary stenosis detected by coronary angiography. Thromb Hae­most 2007; 98: 1362–1367.

25. Piechota W, Piechota W. Correlation of high-sensitivity CRP concentration with the extent of coronary atherosclerosis in men with symptoms of ischemic heart disease. Pol Merkur Lekarski 2005; 18: 511–515.

26. Liang KW, Sheu WH, Lee WL et al. Coronary artery disease progression is associated with ­C-reactive protein and conventional risk factors but not soluble CD40 ligand. Can J Cardiol 2006; 22: 691–696.

27. Sukhija R, Fahdi I, Garza L et al. Inflammatory markers, angiographic severity of coronary artery disease, and patient outcome. Am J Cardiol 2007; 99: 879–884.

28. Ulucay A, Demirbag R, Yilmaz R et al. The relationship between plasma C-reactive protein levels and presence and severity of coronary stenosis in patients with stable angina. Angiology 2007; 58: 657–662.

29. Paniugova EV, Aleksandrova EN, Nasonov EL et al. Atherosclerotic lesion of the vessels in patients with stable coronary artery disease: relations with concentration of C-reactive protein. Kardiologiia 2009; 49: 40–45.

30. Auer J, Rammer M, Berent R et al. Relation of C-reactive protein levels to presence, extent, and severity of angiographic coronary artery disease. Indian Heart J 2002; 54: 284–288.

31. Kazanis K, Dalamaga M, Nounopoulos C et al. Ischemia modified albumin, high-sensitivity C-reactive protein and natriuretic peptide in patients with coronary atherosclerosis. Clin Chim Acta 2009; 408: 65–69.

32. Momiyama Y, Ohmori R, Fayad ZA et al. Associations between plasma C-reactive protein levels and the severities of coronary and aortic atherosclerosis. J Atheroscler Thromb 2010; 17: 460–467.

33. Gotsman I, Stabholz A, Planer D et al. Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden? Isr Med Assoc J 2008; 10: ­494–498.

34. Mori T, Sasaki J, Kawaguchi H et al. Serum glycoproteins and severity of coronary atherosclerosis. Am Heart J 2010; 129: 234–238.

35. Samoš M, Funiak S, Karaffová N et al. Indikátory zápalu u koronarografovaných pacientov. Ateroskleróza 2012; 16: 279–284.

36. 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.

37. 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.

38. 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.

39. Doggen CJ, Berckmans RJ, Sturk A et al. ­C-reactive protein, cardiovascular risk factors and the association with myocardial infarction in men. J Intern Med 2008; 248: 406–414.

40. Speidl WS, Graf S, Hornykewycz S et al. High-sensitivity C-reactive protein in the prediction of coronary events in patients with premature coronary artery disease. Am Heart J 2002; 144: 449–455.

41. Roubille F, Cayla G, Picot MC et al. C-reactive protein (CRP) after revascularized STEMI: is CRP a prognostic factor? Rev Med Interne 2008; 29: 868–874.

42. Fisman EZ, Benderly M, Esper RJ et al. Inter­leukin-6 and the risk of future cardiovascular events in patients with angina pectoris and/or healed myocardial infarction. Am J Cardiol 2006; 98: 14–18.

43. Karpiński L, Płaksej R, Kosmala W et al. Serum levels of interleukin-6, interleukin-10 and C-reactive protein in relation to left ventricular function in patients with myocardial infarction treated with primary angioplasty. Kardiol Pol 2008; 66: 1279–1285.

44. Akkus MN, Polat G, Yurtdas M et al. Admis­sion levels of C-reactive protein and plasminogen activator inhibitor-1 in patients with acute myocardial infarction with and without cardiogenic shock or heart failure on admission. Int Heart J 2009; 50: 33–45.

45. Kohno T, Anzai T, Naito K et al. Impact of serum C-reactive protein elevation on the left ventricular spherical change and the develop­ment of mitral regurgitation after anterior acute myocardial infarction. Cardiology 2007; 107: 386–394.

46. Anzai T, Yoshikawa T, Shiraki H et al. C-reactive protein as a predictor of infarct expansion and cardiac rupture after a first Q-wave acute myocardial infarction. Circulation 1997; 96: 778–784.

47. Celik T, Iyisoy A, Kursaklioglu H et al. The impact of admission C-reactive protein levels on the development of poor myocardial perfusion after primary percutaneous intervention in pa­tients with acute myocardial infarction. Coron Artery Dis 2005; 16: 293–299.

48. Gedikli O, Orem C, Baykan M et al. Association between serum C-reactive protein elevation and atrial fibrillation after first anterior myocardial infarction. Clin Cardiol 2008; 31: 482–487.

49. Kaneko H, Anzai T, Naito K et al. Role of ischemic preconditioning and inflammatory response in the development of malignant ventricular arrhythmias after reperfused ST-elevation myocardial infarction. J Card Fail 2009; 15: ­775–781.

50. Tanaka A, Shimada K, Sato T et al. Multiple plaque rupture and C-reactive protein in acute myocardial infarction. J Am Coll Cardiol 2005; 45: 1594–1599.

51. Kuch B, von Scheidt W, Kling B et al. Differential impact of admission C-reactive protein levels on 28-day mortality risk in patients with ST-elevation versus non-ST-elevation myocardial infarction (from the Monitoring Trends and Determinants on Cardiovascular Diseases ­[MONICA]/Cooperative Health Research in the Region of Augsburg [KORA] Augsburg Myocardial Infarction Registry). Am J Cardiol 2008; 102: 1125–1130.

52. Möckel M, Heller G Jr, Müller C et al. C-reactive protein as an independent marker of prognosis in acute coronary syndrome: comparison with troponin T. Z Kardiol 2000; 89: 658–666.

53. Berton G, Cordiano R, Palmieri R et al. Comparison of C-reactive protein and albumin excretion as prognostic markers for 10-year mortality after myocardial infarction. Clin Cardiol 2010; 33: 508–515.

54. Foussas SG, Zairis MN, Makrygiannis SS et al. The significance of circulating levels of both cardiac troponin I and high-sensitivity ­C-reactive protein for the prediction of intravenous thrombolysis outcome in patients with ­ST-segment elevation myocardial infarction. Heart 2007; 93: 952–956.

55. Kuklinska AM, Sobkowicz B, Mroczko B et al. Prognostic significance of the admission plasma B-type natriuretic peptide measurement in pa­tients with first ST-elevation myocardial infarction in comparison with C-reactive protein and TIMI risk score. Clin Chim Acta 2007; 382: 106–11.

56. Brodov Y, Behar S, Goldenberg I et al. Usefulness of combining serum uric acid and C-reactive protein for risk stratification of patients with coronary artery disease (Bezafibrate Infarction Prevention [BIP] study). Am J Cardiol 2009; 104: 194–198.

57. Raposeiras-Roubin S, Barreiro Paradal C, Rodino Janeiro B et al. High-sensitivity C-reactive protein is a predictor of in-hospital cardiac events in acute myocardial infarction independently of GRACE risk score. Angiology 2012; 63: 30–34.

58. Bazzino O, Fuselli JJ, Botto F et al. Relative value of N-terminal probrain natriuretic peptide, TIMI risk score, ACC/AHA prognostic classification and other risk markers in patients with non-ST-elevation acute coronary syndromes. Eur Heart J 2004; 25: 859–866.

59. Roubille F, Samri A, Cornillet L et al. Routinely-feasible multiple biomarkers score to predict prognosis after revascularized STEMI. Eur J Intern Med 2010; 21: 131–136.

60. Beijk MA, Koch KT, Tijssen JG et al. A retrospective analysis of consecutive patients under­going nonurgent percutaneous coronary intervention comparing bare metal stents with drug-eluting stents using the National Institute for Clinical Excellence criteria. Coron Artery Dis 2011; 22: 32–39.

61. Razzouk L, Muntner P, Bansilal S et al. C-reactive protein predicts long-term mortality independently of low-density lipoprotein cholesterol in patients undergoing percutaneous coronary intervention. Am Heart J 2009; 158: 277–283.

62. Choi DH, Park KW, Yang HM et al. Renal dysfunction and high levels of hsCRP are additively associated with hard endpoints after percutaneous coronary intervention with drug eluting stents. Int J Cardiol 2011; 149: 174–181.

63. Fournier JA, Delgado-Pecellín C, Cayuela A et al. The high-sensitivity C-reactive protein level one month after bare-metal coronary stenting may predict late adverse events. Rev Esp Cardiol 2008; 61: 313–316.

64. Iijima R, Byrne RA, Ndrepepa G et al. Pre-procedural C-reactive protein levels and clinical outcomes after percutaneous coronary interventions with and without abciximab: pooled analysis of four ISAR trials. Heart 2009; 95: 107–112.

65. Gach O, Legrand V, Biessaux Y et al. Long-term prognostic significance of high-sensitivity C-reactive protein before and after coronary angioplasty in patients with stable angina pectoris. Am J Cardiol 2007; 99: 31–35.

66. Karha J, Bavry AA, Rajagopal V et al. Relation of C-reactive protein level and long-term risk of death or myocardial infarction following percutaneous coronary intervention with a sirolimus-eluting stent. Am J Cardiol 2006; 98: ­616–618.

67. Ishii H, Toriyama T, Aoyama T et al. Prognostic values of C-reactive protein levels on clinical outcome after implantation of sirolimus-eluting stents in patients on hemodialysis. Circ Cardiovasc Interv 2009; 2: 513–518.

68. Hoshida S, Nishino M, Takeda T et al. A persistent increase in C-reactive protein is a risk factor for restenosis in patients with stable angina who are not receiving statins. Atherosclerosis 2004; 173: 285–290.

69. Grander W, Dichtl W, Prokop W et al. ­C-reactive protein plasma levels but not factor VII activity predict clinical outcome in pa­tients undergoing elective coronary intervention. Clin Cardiol 2004; 27: 211–216.

70. Saleh N, Tornvall P. Serum C-reactive protein response to percutaneous coronary intervention in patients with unstable or stable angina pectoris is associated with the risk of clinical restenosis. Atherosclerosis 2007; 195: 374–378.

71. Jeong WK, Jeong MH, Kim KH et al. An elevated value of C-reactive protein is the only predictive factor of restenosis after percuta­neous coronary intervention. Korean J Intern Med 2003; 18: 154–160.

72. Žurakowski A, Wojakowski W, Dzielski T et al. Plasma levels of C-reactive protein and interleukin-10 predict late coronary in-stent restenosis 6 months after elective stenting. Kardiol Pol 2009; 15: 623–630.

73. Vaněk I et al. Kardiovaskulární chirurgie. Praha: Karolinum 2003.

74. Biancari F, Lahtinen J, Lepojärvi S et al. Pre­operative C-reactive protein and outcome after coronary artery bypass surgery. Ann Thorac Surg 2003; 76: 2007–2012.

75. Kangasniemi OP, Biancari F, Luukkonen J et al. Preoperative C-reactive protein is predictive of long-term outcome after coronary artery bypass surgery. Eur J Cardiothorac Surg 2006; 29: 983–985.

76. Balciunas M, Bagdonaite L, Samalavicius R et al. Pre-operative high sensitive C-reactive protein predicts cardiovascular events after coronary artery bypass grafting surgery: a prospective observational study. Ann Card Anaesth 2009; 12: 127–132.

77. Perry TE, Muehlschlegel JD, Liu KY et al. CABG Genomics Investigators: Preoperative ­C-reactive protein predicts long-term mortality and hospital length of stay after primary, nonemergent coronary artery bypass grafting. Anesthesiology 2010; 112: 607–613.

78. Ishida K, Kimura F, Imamaki M et al. Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting. Eur J Cardiothorac Surg 2006; 29: ­501–505.

79. Kaireviciute D, Blann AD, Balakrishnan B et al. Characterisation and validity of inflammatory biomarkers in the prediction of post-operative atrial fibrillation in coronary artery disease patients. Thromb Haemost 2010; 104: 122–127.

80. Ziabakhsh-Tabari S. Can perioperative ­C-reactive protein and interleukin-6 levels predict atrial fibrillation after coronary artery bypass surgery? Saudi Med J 2008; 29: 1429–1431.

Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue 12

2013 Issue 12

Most read in this issue

This topic is also in:

Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account