Skip to main content

Advertisement

SpringerLink
Log in

Inflammatory biomarkers and coronary heart disease: from bench to bedside and back

  • EM - Review
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Inflammation plays a pivotal role in all stages of atherosclerosis from endothelial dysfunction and plaque formation to plaque destabilization and disruption. Inflammatory biomarkers, originally studied to better understand the pathophysiology of atherosclerosis, have generated increasing interest among clinicians, because of their utility in the challenging problems of diagnosis and risk assessment of patients with suspected or proved coronary heart disease. Moreover, in fascinating perspective, they could be used as therapeutic target, counteracting initiation, progression, and development of complications of atherosclerosis. In this review, we will provide an overview of the more promising inflammatory biomarkers, focusing on their utility and limitations in the clinical setting.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Weiner SG, Grossman SA (2006) Cardiac markers in the low-risk chest pain patient. Intern Emerg Med 1:223–228

    Article  PubMed  Google Scholar 

  2. Liuzzo G, Biasucci LM, Trotta G et al (2007) Unusual CD4+ CD28null T lymphocytes and recurrence of acute coronary events. J Am Coll Cardiol 50:1450–1458

    Article  CAS  PubMed  Google Scholar 

  3. Liuzzo G, Biasucci LM, Gallimore JR et al (1994) The prognostic value of C-Reactive Protein and serum amyloid A protein in severe unstable angina. N Engl J Med 331:417–424

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Zethelius B, Berglund L, Sundström J et al (2008) Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 358:2107–2116

    Article  CAS  PubMed  Google Scholar 

  6. Ridker PM, Danielson E, Fonseca FAH et al (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359:2195–2207

    Article  CAS  PubMed  Google Scholar 

  7. The Emerging Risk Factors Collaboration (2009) C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet (Epub ahead of print)

  8. James SK, Armstrong P, Barnathan E et al (2003) Troponin and C-reactive protein have different relation to subsequent mortality and myocardial infarction after acute coronary syndrome: a GUSTO-IV substudy. J Am Coll Cardiol 41:916–924

    Article  CAS  PubMed  Google Scholar 

  9. Heeschen C, Hamm CW, Bruemmer J et al (2000) Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis. CAPTURE Investigators. Chimeric c7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard treatment trial. J Am Coll Cardiol 35:1535–1542

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Morrow DA, Cannon CP, Jesse RL et al (2007) National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Circulation 115:e356–e375

    Article  PubMed  Google Scholar 

  12. Pearson TA, Mensah GA, Alexander RW et al (2003) 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 107:499–511

    Article  PubMed  Google Scholar 

  13. Suleiman M, Khatib R, Agmon Y et al (2006) Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C-reactive protein. J Am Coll Cardiol 47:962–968

    Article  PubMed  Google Scholar 

  14. Sabatine MS, Morrow DA, de Lemos JA et al (2002) Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation 105:1760–1763

    Article  CAS  PubMed  Google Scholar 

  15. Prasad K (2006) C-reactive protein (CRP)-lowering agents. Cardiovasc Drug Rev 24:33–50

    Article  CAS  PubMed  Google Scholar 

  16. Ridker PM, Cannon CP, Morrow D et al (2005) Pravastatin or atorvastatin evaluation and infection therapy—Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators. C-Reactive protein levels and outcomes after statin therapy. N Engl J Med 352:20–28

    Article  CAS  PubMed  Google Scholar 

  17. Vizzardi E, Nodari S, Zanini G et al (2009) High sensitivity C-reactive protein: a predictor for recurrence of atrial fibrillation after successful cardioversion. Intern Emerg Med 4:309–313

    Article  PubMed  Google Scholar 

  18. Pepys MB, Hirschfield GM, Tennent GA et al (2006) Targeting C-reactive protein for the treatment of cardiovascular disease. Nature 440:1217–1221

    Article  CAS  PubMed  Google Scholar 

  19. Biasucci LM, Liuzzo G, Grillo RL et al (1999) Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 99:855–860

    CAS  PubMed  Google Scholar 

  20. Johnson BD, Kip KE, Marroquin OC et al (2004) Serum Amyloid A as a predictor of Coronary Artery Disease and cardiovascular outcome in women: The National Heart, Lung and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE). Circulation 109:726–732

    Article  CAS  PubMed  Google Scholar 

  21. Kosuge M, Ebina T, Ishikawa T et al (2007) Serum Amyloid A is a better predictor of clinical outcome than C-Reactive Protein in Non-ST-segment Elevation Acute Coronary Syndromes. Circ J 71:186–190

    Article  CAS  PubMed  Google Scholar 

  22. Morrow DA, Rifai N, Antman EM et al (2000) Serum Amyloid A predicts early mortality in Acute Coronary Syndromes: a TIMI 11A substudy. J Am Coll Cardiol 35:358–362

    Article  CAS  PubMed  Google Scholar 

  23. Haverkate F, Thompson SG, Pyke SDM et al (1997) Production of C-Reactive Protein and risk of coronary events in stable and unstable angina. Lancet 349:462–466

    Article  CAS  PubMed  Google Scholar 

  24. Harb TS, Zareba W, Moss AJ et al (2002) Association of C-Reactive Protein and Serum Amyloid A with recurrent coronary events in stable patients after healing of acute myocardial infarction. Am J Cardiol 89:216–221

    Article  CAS  PubMed  Google Scholar 

  25. Ridker PM, Rifai N, Stampfer MJ et al (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767–1772

    CAS  PubMed  Google Scholar 

  26. Lindmark E, Diderholm E, Wallentin L et al (2001) Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease. JAMA 286:2107–2113

    Article  CAS  PubMed  Google Scholar 

  27. Biasucci L, Liuzzo G, Fantuzzi G et al (1999) Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events. Circulation 99:2079–2084

    CAS  PubMed  Google Scholar 

  28. Rizzello V, Liuzzo G, Brugaletta S et al (2006) Modulation of CD4(+)CD28null T lymphocytes by tumor necrosis factor-alpha blockade in patients with unstable angina. Circulation 113:2272–2277

    Article  CAS  PubMed  Google Scholar 

  29. Meuwese MC, Stroes ESG, Hazen SL et al (2007) Serum Myeloperoxidase levels are associated with the future risk of Coronary Artery Disease in apparently healthy individuals. The EPIC-Norflok Prospective Population Study. J Am Coll Cardiol 50:159–165

    Article  CAS  PubMed  Google Scholar 

  30. Zhang R, Brennan ML, Fu X et al (2001) Association between Myeloperoxidase levels and risk of Coronary Artery Disease. JAMA 286:2136–2142

    Article  CAS  PubMed  Google Scholar 

  31. Buffon A, Biasucci LM, Liuzzo G et al (2002) Widespread coronary inflammation in unstable angina. N Engl J Med 347:5–12

    Article  PubMed  Google Scholar 

  32. Hamm CW, Heeschen C, Goldmann B et al (1999) Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels: c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators. N Engl J Med 340:1623–1629

    Article  CAS  PubMed  Google Scholar 

  33. Brennan ML, Penn MS, Van Lente F et al (2003) Prognostic value of Myeloperoxidase in patients with chest pain. N Engl J Med 349:1595–1604

    Article  CAS  PubMed  Google Scholar 

  34. Mocatta TJ, Pilbrow AP, Cameron VA et al (2007) Plasma concentrations of Myeloperoxidase predict mortality after Acute Myocardial Infarction. J Am Coll Cardiol 49:1993–2000

    Article  CAS  PubMed  Google Scholar 

  35. Zhou T, Zhou S, Qi S et al (2006) The effect of Atorvastatin on serum Myeloperoxidase and CRP levels in patients with Acute Coronary Syndrome. Clinica Chimica Acta 368:168–172

    Article  CAS  Google Scholar 

  36. Baldus S, Rudolph V, Roiss M et al (2006) Heparins increase endothelial Nitric Oxide bioavailability by liberating vessel-immobilized Myeloperoxidase. Circulation 113:1871–1878

    Article  CAS  PubMed  Google Scholar 

  37. Busti C, Falcinelli E, Momi S et al (2009) Matrix metalloproteinases and peripheral arterial disease. Intern Emerg Med (Epub ahead of print)

  38. Kalela A, Koivu TA, Sisto T et al (2002) Serum matrix metalloproteinase-9 concentration in angiographically assessed coronary artery disease. Scand Clin Lab Invest 62:337–342

    Article  CAS  Google Scholar 

  39. Blankenberg S, Rupprecht HJ, Poirier O et al (2003) Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 107:1579–1585

    Article  CAS  PubMed  Google Scholar 

  40. Hidalgo M, Eckhardt SG (2001) Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 93:178–193

    Article  CAS  PubMed  Google Scholar 

  41. Bayes-Genis A, Conover CA, Overgaard MT et al (2001) Pregnancy-associated plasma protein A as a marker of Acute Coronary Syndrome. N Engl J Med 345:1022–1029

    Article  CAS  PubMed  Google Scholar 

  42. Elesber AA, Conover CA, Denktas AE et al (2006) Prognostic value of circulating Pregnancy-associated plasma protein-A levels in patients with chronic stable angina. Eur Heart J 27:1678–1684

    Article  CAS  PubMed  Google Scholar 

  43. Laterza OF, Cameron SJ, Chappell D et al (2004) Evaluation of pregnancy-associated plasma protein A as a prognostic indicator in acute coronary syndrome patients. Clin Chim Acta 348:163–169

    Article  CAS  PubMed  Google Scholar 

  44. Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez M et al (2005) Circulating Pregnancy-associated plasma protein-A is not an early marker of acute myocardial infarction. Clin Biochem 38:180–182

    Article  CAS  PubMed  Google Scholar 

  45. Santilli F, Basili S, Ferroni P et al (2007) CD40/CD40L system and vascular disease. Intern Emerg Med 2:256–268

    Article  CAS  PubMed  Google Scholar 

  46. Aukrust P, Müller F, Ueland T et al (1999) Enhanced levels of soluble and membrane-bound CD40 Ligand in patients with unstable angina: possible reflection of T Lymphocyte and platelet involvement in the pathogenesis of Acute Coronary Syndromes. Circulation 100:614–620

    CAS  PubMed  Google Scholar 

  47. Heeschen C, Dimmeler S, Hamm CW et al (2003) Soluble CD 40 Ligand in Acute Coronary Syndromes. N Engl J Med 348:1104–1111

    Article  CAS  PubMed  Google Scholar 

  48. Morrow DA, Sabatine MS, Brennan ML et al (2008) Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome: myeloperoxidase and soluble CD40 ligand and the risk of recurrent ischaemic events in TACTICS-TIMI 18. Eur Heart J 29:1096–1102

    Article  CAS  PubMed  Google Scholar 

  49. Rondina MT, Lappé JM, Carlquist JF et al (2008) Soluble CD40L as a predictor of Coronary Artery Disease and long-term clinical outcomes in stable patients undergoing coronary angiography. Cardiology 109:196–201

    Article  CAS  PubMed  Google Scholar 

  50. Kinlay S, Schwartz GG, Olsson AG et al (2004) Effect of atorvastatin on risk of recurrent cardiovascular events after an acute coronary syndrome associated with high soluble CD40 Ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study. Circulation 110:386–391

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Institute of Cardiology, Catholic University of Sacred Heart-Rome, L.go A. Gemelli, 8, 00168, Rome, Italy

    Gina Biasillo, Milena Leo, Roberta Della Bona & Luigi Marzio Biasucci

Authors
  1. Gina Biasillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Milena Leo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberta Della Bona
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luigi Marzio Biasucci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luigi Marzio Biasucci.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Biasillo, G., Leo, M., Della Bona, R. et al. Inflammatory biomarkers and coronary heart disease: from bench to bedside and back. Intern Emerg Med 5, 225–233 (2010). https://doi.org/10.1007/s11739-010-0361-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-010-0361-1

Keywords

Search

Navigation