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

 

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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.

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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 3 Hamm C W, Braunwald E. A classification of unstable angina revisited.  Circulation . 2000;  102 118-122
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 43 Gabay C, Kushner I. Acute phase proteins and other systemic responses to inflammation.  N Engl J Med . 1999;  340 448-454
  CrossrefPubMedGoogle Scholar
• 44 Biasucci L M, Vitelli A, Liuzzo G. et al . Elevated levels of interleukin-6 in unstable angina.  Circulation . 1996;  94 874-877
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 63 Albert M A, Glynn R J, Ridker P M. Alcohol consumption and plasma concentration of C-reactive protein.  Circulation . 2003;  107 443-447
  CrossrefPubMedGoogle Scholar
• 64 Bhatt D L, Topol E J. Need to test the arterial inflammation hypothesis.  Circulation . 2002;  106 136-140
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar