C-Reactive Protein and Other Inflammatory Biomarkers as Predictors of Outcome Following Acute Coronary Syndromes

ABSTRACT

Despite diagnostic and therapeutic advances, the rate of event recurrence is still relatively high and short- and long-term prediction of risk is necessary although extremely challenging to provide optimal treatment to patients with acute coronary syndromes. Available data recommend the use of C-reactive protein (CRP) as a prognostic marker in patients with acute coronary syndromes in addition to other prognostic factors including troponin levels. Evaluation of CRP levels at time of admission should be included in the evaluation of the patient's risk profile, including clinical data, associated diseases, markers of myocardial necrosis (especially troponin levels), left ventricle performance, and age. A cutoff level of 10 mg/L for CRP may be used as a marker of higher risk for death and possibly myocardial infarction in acute coronary syndromes, and a cutoff of 3 mg/L identifies a group of patients with intermediate risk and a high rate of recurrent events.

KEYWORDS

Inflammation - acute coronary syndromes - C-reactive protein

REFERENCES

• 1 Wallentin L, Lagerqvist B, Husted S, for the FRISC II investigators. et al . Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial.  Lancet . 2000;  356 9-16
• 2 Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM- PLUS) Study Investigators. Inhibition of the platelet IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction.  N Engl J Med . 1998;  338 1488-1497
• 3 Hamm C W, Braunwald E. A classification of unstable angina revisited.  Circulation . 2000;  102 118-122
• 4 Patel D J, Gomma A H, Knight C J. et al . Why is recurrent myocardial ischaemia a predictor of adverse outcome in unstable angina?.  Eur Heart J . 2001;  22 1991-1996
• 5 Dangas G, Mehran R, Wallenstein S. et al . Correlation of angiographic morphology and clinical presentation in unstable angina.  J Am Coll Cardiol . 1997;  29 519-525
• 6 Vetrovec G W, Cowley M J, Overton H, Richardson D W. Intracoronary thrombus in syndromes of unstable myocardial ischemia.  Am Heart J . 1981;  102 1202-1208
• 7 Heeschen C, van Den Brand J M, Hamm C W, Simoons M L. Angiographic findings in patients with refractory unstable angina according to troponin T status.  Circulation . 1999;  100 1509-1514
• 8 Hamm C W, Heeschen C, Goldmann B. et al . Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels.  N Engl J Med . 1999;  340 1623-1629
• 9 Lenderink T, Boersma E, Heeschen C. et al . Elevated troponin T and C-reactive protein predict impaired outcome for 4 years in patients with refractory unstable angina, and troponin T predicts benefit of treatment with abciximab in combination with PTCA.  Eur Heart J . 2003;  24 77-85
• 10 van der Wal C A, Becker A E, van der Loos M C, Das P K. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology.  Circulation . 1994;  89 36-44
• 11 Arbustini E, Grasso M, Diegoli M. et al . Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study.  Am J Cardiol . 1991;  68(suppl) 36B-50B
• 12 DiSciascio G, Cowley M J, Goudreau E, Vetrovec G W, Johnson D E. Histopathologic correlates of unstable ischemic syndromes in patients undergoing directional coronary atherectomy: in vivo evidence of thrombosis, ulceration, and inflammation.  Am Heart J . 1994;  128 419-426
• 13 Buffon A, Biasucci L M, Liuzzo G, D'Onofrio G, Crea F, Maseri A. Widespread coronary inflammation in unstable angina.  N Engl J Med . 2002;  347 5-12
• 14 Biasucci L M, Liuzzo G, Colizzi C, Rizzello V. Clinical use of C-reactive protein for the prognostic stratification of patients with ischemic heart disease.  Ital Heart J . 2001;  2 164-171
• 15 Liuzzo G, Biasucci L M, Gallimore J R. 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
• 16 Ferreiros E R, Boissonnet C P, Pizarro R. et al . Independent prognostic value of C-reactive protein in unstable angina.  Circulation . 1999;  100 1958-1963
• 17 Oltrona L, Ardissino D, Merlini P A. et al . C-reactive protein elevation and early outcome in patients with unstable angina pectoris.  Am J Cardiol . 1997;  80 1002-1006
• 18 Morrow D A, Rifai N, Altman E M. 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 11A.  J Am Coll Cardiol . 1998;  31 1460-1465
• 19 Benamer H, Steg P G, Benessiano J. et al . Comparison of the prognostic value of C-reactive protein and troponin I in patients with unstable angina pectoris.  Am J Cardiol . 1998;  82 845-850
• 20 Biasucci L M, Meo A, Buffon A. et al . Independent prognostic value of C-reactive protein levels for in-hospital death and myocardial infarction in unstable angina.  Circulation . 2000;  102 (suppl II) 140
• 21 Verheggen P H M W, de Maat P M M, Manger Cats V. et al . Inflammatory status as a main determinant of outcome in patients with unstable angina, independent of coagulation activation and endothelial cell function.  Eur Heart J . 1999;  20 567-574
• 22 Mueller C, Buettner H J, Hodgson J M. 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
• 23 Biasucci L M, Liuzzo G, Grillo R L. et al . Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability.  Circulation . 1999;  99 855-860
• 24 Toss H, Lindhal B, Siegbahn A, Wallentin L, for the FRISC Study Group. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease.  Circulation . 1997;  96 4204-4210
• 25 Lindhal B, Toss H, Siegbahn A, for the FRISC Study Group. et al . Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease.  N Engl J Med . 2000;  343 1139-1147
• 26 Cannon C P, Weintraub W S, Demopoulos L. et al . High-sensitivity C-reactive protein (hs-CRP) to predict 6 month mortality and relative benefit of invasive vs.  conservative strategy in patients with unstable angina: primary results of the TACTICS-TIMI 18 C-reactive protein substudy. J Am Coll Cardiol . 2001;  37(suppl A) 315A
• 27 Bazzino O, Ferreiros E R, Pizarro R, Corrado G. C-reactive protein and the stress tests for risk stratification of patients recovering from unstable angina pectoris.  Am J Cardiol . 2001;  87 1235-1239
• 28 Koukkenen H, Penttilä K, Kemppainen A. et al . C-reactive protein, fibrinogen, interleukin-6 and tumor necrosis factor-α in the prognostic classification of unstable angina pectoris.  Ann Med . 2001;  33 37-47
• 29 Rebuzzi A, Quaranta G, Liuzzo G. et al . Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris.  Am J Cardiol . 1998;  82 715-719
• 30 Haverkate F, Thompson S G, Pyke S D, Gallimore J R, Pepys M B. 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
• 31 Heeschen C, Hamm C W, Bruemmer J, for the CAPTURE Investigators. et al . Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis.  J Am Coll Cardiol . 2000;  35 1535-1542
• 32 Buffon A, Liuzzo G, Biasucci L M. 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
• 33 Chew D P, Bhatt D L, Robbins M A. 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
• 34 Versaci F, Gaspardone A, Tomai F. et al . Predictive value of C-reactive protein in patients with unstable angina pectoris undergoing coronary artery stent implantation.  Am J Cardiol . 2000;  85 92-95
• 35 Walter D H, Fichtlscherer S, Sellwig M. et al . Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation.  J Am Coll Cardiol . 2001;  37 839-846
• 36 de Winter J R, Heyde G S, Koch K T. et al . The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty.  Eur Heart J . 2002;  23 960-966
• 37 Ellis S G, Chew D, Chan A, Whitlow P L, Schneider J P, Topol E J. Death following creatine kinase-MB elevation after coronary intervention.  Circulation . 2002;  106 1205-1210
• 38 Versaci F, Gaspardone A, Tomai F. et al . Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS Study).  J Am Coll Cardiol . 2002;  40 1935-1942
• 39 de Lemos A J, Morrow D A, Bentley J H. et al . The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes.  N Engl J Med . 2001;  345 1014-1021
• 40 de Lemos A J, Morrow D A, Bentley J H. et al . The prognostic value of B-type natriuretic peptide and acute coronary syndromes.  N Engl J Med . 2001;  345(14) 1014-1021
• 41 Sabatine M S, Morrow D A, de Lemos A J. et al . 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 . 2002;  105 1760-1763
• 42 Zebrack J S, Muhlestein J B, Horne B D, Anderson J L, for the Intermountain Heart Collaboration Study Group. C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina.  J Am Coll Cardiol . 2002;  39 632-637
• 43 Gabay C, Kushner I. Acute phase proteins and other systemic responses to inflammation.  N Engl J Med . 1999;  340 448-454
• 44 Biasucci L M, Vitelli A, Liuzzo G. et al . Elevated levels of interleukin-6 in unstable angina.  Circulation . 1996;  94 874-877
• 45 Biasucci L M, Liuzzo G, Fantuzzi G. et al . 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 . 1999;  99 2079-2084
• 46 Koukkunen H, Penttilä K, Kemppainen A. et al . C-reactive protein, fibrinogen, interleukin-6 and tumor necrosis factor-α in the prognostic classification of unstable angina pectoris.  Ann Med . 2001;  33 37-47
• 47 Liuzzo G, Kopecky S L, Frye R L. et al . Perturbation of the T-cell repertoire in patients with unstable angina.  Circulation . 1999;  100 2135-2139
• 48 Thompson S G, Kienast J, Pyke S D. et al . Hemostatic factors and of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.  N Engl J Med . 1995;  332 635-641
• 49 Wallen N H, Held C, Rehnqvist N, Hjemdhal P. Elevated serum intercellular adhesion molecule-1 and vascular adhesion molecule-1 among patients with stable angina pectoris who suffer cardiovascular death or non-fatal myocardial infarction.  Eur Heart J . 1999;  20 1039-1043
• 50 Mulvihill N T, Foley J B, Murphy R T, Curtin R, Crean P A, Walsh M. Risk stratification in unstable angina and non-Q wave myocardial infarction using soluble cell adhesion molecules.  Heart . 2001;  85 623-627
• 51 Ridker P M, Rifai N, Pfeffer M. et al . Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction.  Circulation . 2000;  101 2149-2153
• 52 Abbate A, Vecile E, Fiotti N. et al . Plasma concentrations of interleukin-2 soluble receptor in mild ischaemic left ventricular dysfunction.  Eur J Heart Fail . 2003;  5 23-25
• 53 Patti G, Di Sciascio G, D'Ambrosio A, Dicuonzo G, Abbate A, Dobrina A. Prognostic value of interleukin-1 receptor antagonist in patients undergoing percutaneous coronary intervention.  Am J Cardiol . 2002;  89 372-376
• 54 Blankenberg S, Tiret L, Bickel C. et al . Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina.  Circulation . 2002;  105 143-149
• 55 Biasucci L M, Santamaria M, Angiolillo D J. et al . Interleukin-18 levels suggest different inflammatory pathways in unstable angina-18.  J Am Coll Cardiol . 2003;  41(6 Suppl B) 363
• 56 Ridker P M, Rifai N, Clearfield M. >for the Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. et al. Measurement of C-reactive protein for targeting of statin therapy in the primary prevention of acute coronary events.  N Engl J Med . 2001;  344 1959-1965
• 57 Kennon S, Price C P, Mills P G. et al . The effect of aspirin on C-reactive protein as a marker of risk in unstable angina.  J Am Coll Cardiol . 2001;  37 1266-1270
• 58 Chew D P, Bhatt D L, Robbins M A. et al . Effect of clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein.  Am J Cardiol . 2001;  88 672-674
• 59 Buffon A, Liuzzo G, Angiolillo D J. et al . Abciximab decreases cytokine production by circulating monocytes in patients with unstable angina and elevated inflammatory markers.  J Am Coll Cardiol . 2001;  37 (suppl A) 818A
• 60 Lincoff A M, Kereiakes D J, Mascelli M A. et al . Abciximab depresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization.  Circulation . 2001;  104 163-167
• 61 Jialal I, Stein D, Balis D. et al . Effect of hydroxymethyl glutaryl coenzyme A reductase inhibitor therapy on high sensitive C-reactive protein levels.  Circulation . 2001;  103 1933-1935
• 62 Ottenvanger J P, Armstrong P, Barnathan E S. et al . Long-term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina.  Circulation . 2003;  107 437-442
• 63 Albert M A, Glynn R J, Ridker P M. Alcohol consumption and plasma concentration of C-reactive protein.  Circulation . 2003;  107 443-447
• 64 Bhatt D L, Topol E J. Need to test the arterial inflammation hypothesis.  Circulation . 2002;  106 136-140
• 65 Pearson T A, Mensah G A, Alexander R W. et al . Markers of inflammation and cardiovascular disease. Application to clinical and public health practice.  Circulation . 2003;  107 499-511
• 66 Bertrand M E, Simoons M L, Fox K AA. et al . Management of acute coronary syndromes without persistent ST segment elevation. Recommendations of the Task Force of the European Society of Cardiology.  Eur Heart J . 2000;  21 1406-1432
• 67 Horne B D, Muhlestein J B, Carlquist J F. et al . Statin therapy, lipid levels, C-reactive protein and the survival of patients with angiographically severe coronary artery disease.  J Am Coll Cardiol . 2000;  36 1774-1780
• 68 Zebrack J S, Anderson J L, Maycock C A. et al . Usefulness of high-sensitivity C-reactive protein in predicting long-term risk of death or acute myocardial infarction in patients with unstable or stable angina pectoris or acute myocardial infarction.  Am J Cardiol . 2002;  89 145-149