Biomarkers in acute myocardial injury

Published:December 09, 2011DOI:
      Acute coronary syndrome (ACS) is a significant cause of morbidity and mortality worldwide. The proper diagnosis of ACS requires reliable and accurate biomarker assays to detect evidence of myocardial necrosis. Currently, troponin is the gold standard biomarker for myocardial injury and is used commonly in conjunction with creatine kinase-MB (CK-MB) and myoglobin to enable a more rapid diagnosis of ACS. A new generation of highly sensitive troponin assays with improved accuracy in the early detection of ACS is now available, but the correct interpretation of assay results will require a careful consideration of assay characteristics and the clinical setting prior to incorporation into routine practice. B-type natriuretic peptides, copeptin, ischemia-modified albumin, heart-type fatty-acid-binding protein, myeloperoxidase, C-reactive protein, choline, placental growth factor, and growth-differentiation factor-15 make up a promising group of other biomarkers that have shown the ability to improve prognosis and diagnosis of ACS compared with traditional markers.


      ACS (acute coronary syndrome), AMI (acute myocardial infarction), BNP (B-type natriuretic peptide), CAD (coronary artery disease), CK-MB (creatine kinase-MB), CRP (C-reactive protein), cTn (troponin), cTnI (troponin I), cTnT (troponin T), CV (coefficient of variation), ECG (electrocardiogram), ED (emergency department), GDF-15 (growth-differentiation factor-15), H-FABP (heart-type fatty-acid-binding protein), hs-Tn (high sensitivity troponin), hs-TnI (high sensitivity troponin I), hs-TnT (high sensitivity troponin T), IMA (ischemia-modified albumin), MI (myocardial infarction), MPO (myeloperoxidase), NPV (negative predictive value), NSTEMI (non-ST-elevation myocardial infarction), NT-proBNP (N-terminal pro-B-type natriuretic peptide), PlGF (placental growth factor), PPV (positive predictive value), ROC AUC (area under the receiver operating characteristic curve), sCD40L (soluble CD40 ligand), STEMI (ST-elevation myocardial infarction)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lee T.H.
        • Rouan G.W.
        • Weisberg M.C.
        • et al.
        Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room.
        Am J Cardiol. 1987; 60: 219-224
        • Pope J.H.
        • Aufderheide T.P.
        • Ruthazer R.
        • et al.
        Missed diagnoses of acute cardiac ischemia in the emergency department.
        N Engl J Med. 2000; 342: 1163-1170
        • Thygesen K.
        • Alpert J.S.
        • White H.D.
        Infarction JEAAWTFftRoM. Universal definition of myocardial infarction.
        J Am Coll Cardiol. 2007; 50: 2173-2195
        • Apple F.S.
        • Jesse R.L.
        • Newby L.K.
        • et al.
        National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: analytical issues for biochemical markers of acute coronary syndromes.
        Circulation. 2007; 115: e352-e355
        • Roberts R.
        • Sobel B.E.
        Ediortial: isoenzymes of creatine phosphokinase and diagnosis of myocardial infarction.
        Ann Intern Med. 1973; 79: 741-743
        • Daubert M.A.
        • Jeremias A.
        The utility of troponin measurement to detect myocardial infarction: review of the current findings.
        Vasc Health Risk Manag. 2010; 6: 691-699
        • Morrow D.A.
        • Cannon C.P.
        • Jesse R.L.
        • et al.
        National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes.
        Clin Chem. 2007; 53: 552-574
        • Gerhardt W.
        • Nordin G.
        • Ljungdahl L.
        Can troponin T replace CK MBmass as "gold standard" for acute myocardial infarction (“AMI”)?.
        Scand J Clin Lab Invest Suppl. 1999; 230: 83-89
        • Higgins J.P.
        • Higgins J.A.
        Elevation of cardiac troponin I indicates more than myocardial ischemia.
        Clin Invest Med. 2003; 26: 133-147
        • Katus H.A.
        • Remppis A.
        • Scheffold T.
        • Diederich K.W.
        • Kuebler W.
        Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction.
        Am J Cardiol. 1991; 67: 1360-1367
        • Freda B.J.
        • Tang W.H.
        • Van Lente F.
        • Peacock W.F.
        • Francis G.S.
        Cardiac troponins in renal insufficiency: review and clinical implications.
        J Am Coll Cardiol. 2002; 40: 2065-2071
        • Diris J.H.
        • Hackeng C.M.
        • Kooman J.P.
        • et al.
        Impaired renal clearance explains elevated troponin T fragments in hemodialysis patients.
        Circulation. 2004; 109: 23-25
        • Tucker J.F.
        • Collins R.A.
        • Anderson A.J.
        • et al.
        Early diagnostic efficiency of cardiac troponin I and Troponin T for acute myocardial infarction.
        Acad Emerg Med. 1997; 4: 13-21
        • Balk E.M.
        • Ioannidis J.P.
        • Salem D.
        • Chew P.W.
        • Lau J.
        Accuracy of biomarkers to diagnose acute cardiac ischemia in the emergency department: a meta-analysis.
        Ann Emerg Med. 2001; 37: 478-494
        • Saenger A.K.
        • Jaffe A.S.
        The use of biomarkers for the evaluation and treatment of patients with acute coronary syndromes.
        Med Clin North Am. 2007; 91: 657-681
        • Wu A.H.
        • Wang X.M.
        • Gornet T.G.
        • Ordóñez-Llanos J.
        Creatine kinase MB isoforms in patients with skeletal muscle injury: ramifications for early detection of acute myocardial infarction.
        Clin Chem. 1992; 38: 2396-2400
        • Puleo P.R.
        • Guadagno P.A.
        • Roberts R.
        • et al.
        Early diagnosis of acute myocardial infarction based on assay for subforms of creatine kinase-MB.
        Circulation. 1990; 82: 759-764
        • Lin J.C.
        • Apple F.S.
        • Murakami M.M.
        • Luepker R.V.
        Rates of positive cardiac troponin I and creatine kinase MB mass among patients hospitalized for suspected acute coronary syndromes.
        Clin Chem. 2004; 50: 333-338
        • Zimmerman J.
        • Fromm R.
        • Meyer D.
        • et al.
        Diagnostic marker cooperative study for the diagnosis of myocardial infarction.
        Circulation. 1999; 99: 1671-1677
        • Jernberg T.
        • Lindahl B.
        • James S.
        • Ronquist G.
        • Wallentin L.
        Comparison between strategies using creatine kinase-MB(mass), myoglobin, and troponin T in the early detection or exclusion of acute myocardial infarction in patients with chest pain and a nondiagnostic electrocardiogram.
        Am J Cardiol. 2000; 86: 1367-1371
        • Ellestad M.H.
        • Startt-Selvester R.
        • Stanton E.
        • et al.
        The utility of four biochemical markers in the triage of chest pain patients.
        Cardiology. 2000; 93: 242-248
        • Saenger A.K.
        A tale of two biomarkers: the use of troponin and CK-MB in contemporary practice.
        Clin Lab Sci. 2010; 23: 134-140
        • Polanczyk C.A.
        • Johnson P.A.
        • Cook E.F.
        • Lee T.H.
        A proposed strategy for utilization of creatine kinase-MB and troponin I in the evaluation of acute chest pain.
        Am J Cardiol. 1999; 83: 1175-1179
        • Mair J.
        • Artner-Dworzak E.
        • Lechleitner P.
        • et al.
        Early diagnosis of acute myocardial infarction by a newly developed rapid immunoturbidimetric assay for myoglobin.
        Br Heart J. 1992; 68: 462-468
        • Melanson S.F.
        • Lewandrowski E.L.
        • Januzzi J.L.
        • Lewandrowski K.B.
        Reevaluation of myoglobin for acute chest pain evaluation: would false-positive results on “first-draw” specimens lead to increased hospital admissions?.
        Am J Clin Pathol. 2004; 121: 804-808
        • de Winter R.J.
        • Koster R.W.
        • Sturk A.
        • Sanders G.T.
        Value of myoglobin, troponin T, and CK-MBmass in ruling out an acute myocardial infarction in the emergency room.
        Circulation. 1995; 92: 3401-3407
        • Gilkeson G.
        • Stone M.J.
        • Waterman M.
        • et al.
        Detection of myoglobin by radioimmmunoassay in human sera: its usefulness and limitations as an emergency room screening test for acute myocardial infarction.
        Am Heart J. 1978; 95: 70-77
        • McCord J.
        • Nowak R.M.
        • Hudson M.P.
        • et al.
        The prognostic significance of serial myoglobin, troponin I, and creatine kinase-MB measurements in patients evaluated in the emergency department for acute coronary syndrome.
        Ann Emerg Med. 2003; 42: 343-350
        • Weber M.
        • Bazzino O.
        • Navarro Estrada J.L.
        • et al.
        Improved diagnostic and prognostic performance of a new high-sensitive troponin T assay in patients with acute coronary syndrome.
        Am Heart J. 2011; 162: 81-88
        • Panteghini M.
        • Pagani F.
        • Yeo K.T.
        • et al.
        Evaluation of imprecision for cardiac troponin assays at low-range concentrations.
        Clin Chem. 2004; 50: 327-332
        • Jaffe A.S.
        • Lindahl B.
        • Katus H.A.
        Sensitive troponin I assay in patients with suspected acute coronary syndrome.
        JAMA. 2011; 306: 488-489
        • Thygesen K.
        • Mair J.
        • Katus H.
        • et al.
        Recommendations for the use of cardiac troponin measurement in acute cardiac care.
        Eur Heart J. 2010; 31: 2197-2204
        • Reichlin T.
        • Hochholzer W.
        • Bassetti S.
        • et al.
        Early diagnosis of myocardial infarction with sensitive cardiac troponin assays.
        N Engl J Med. 2009; 361: 858-867
        • Keller T.
        • Zeller T.
        • Peetz D.
        • et al.
        Sensitive troponin I assay in early diagnosis of acute myocardial infarction.
        N Engl J Med. 2009; 361: 868-877
        • Giannitsis E.
        • Kurz K.
        • Hallermayer K.
        • et al.
        Analytical validation of a high-sensitivity cardiac troponin T assay.
        Clin Chem. 2010; 56: 254-261
        • Giannitsis E.
        • Becker M.
        • Kurz K.
        • et al.
        High-sensitivity cardiac troponin T for early prediction of evolving non-ST-segment elevation myocardial infarction in patients with suspected acute coronary syndrome and negative troponin results on admission.
        Clin Chem. 2010; 56: 642-650
        • Apple F.S.
        • Pearce L.A.
        • Smith S.W.
        • Kaczmarek J.M.
        • Murakami M.M.
        Role of monitoring changes in sensitive cardiac troponin I assay results for early diagnosis of myocardial infarction and prediction of risk of adverse events.
        Clin Chem. 2009; 55: 930-937
        • White H.D.
        Pathobiology of troponin elevations: do elevations occur with myocardial ischemia as well as necrosis?.
        J Am Coll Cardiol. 2011; 57: 2406-2408
        • McDonough J.L.
        • Arrell D.K.
        • Van Eyk J.E.
        Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury.
        Circ Res. 1999; 84: 9-20
        • Hessel M.H.
        • Atsma D.E.
        • van der Valk E.J.
        • et al.
        Release of cardiac troponin I from viable cardiomyocytes is mediated by integrin stimulation.
        Pflugers Arch. 2008; 455: 979-986
        • Hickman P.E.
        • Potter J.M.
        • Aroney C.
        • et al.
        Cardiac troponin may be released by ischemia alone, without necrosis.
        Clin Chim Acta. 2010; 411: 318-323
        • Homma S.
        • Grahame-Clarke C.
        Editorial comment–myocardial damage in patients with subarachnoid hemorrhage.
        Stroke. 2004; 35: 552-553
        • Katz S.D.
        • Hryniewicz K.
        • Hriljac I.
        • et al.
        Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure.
        Circulation. 2005; 111: 310-314
        • Mingels A.
        • Jacobs L.
        • Michielsen E.
        • et al.
        Reference population and marathon runner sera assessed by highly sensitive cardiac troponin T and commercial cardiac troponin T and I assays.
        Clin Chem. 2009; 55: 101-108
        • Mousavi N.
        • Czarnecki A.
        • Kumar K.
        • et al.
        Relation of biomarkers and cardiac magnetic resonance imaging after marathon running.
        Am J Cardiol. 2009; 103: 1467-1472
        • Missov E.D.
        • De Marco T.
        Clinical insights on the use of highly sensitive cardiac troponin assays.
        Clin Chim Acta. 1999; 284: 175-185
        • de Lemos J.A.
        • Drazner M.H.
        • Omland T.
        • et al.
        Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population.
        JAMA. 2010; 304: 2503-2512
        • Wallace T.W.
        • Abdullah S.M.
        • Drazner M.H.
        • et al.
        Prevalence and determinants of troponin T elevation in the general population.
        Circulation. 2006; 113: 1958-1965
        • Daniels L.B.
        • Laughlin G.A.
        • Clopton P.
        • Maisel A.S.
        • Barrett-Connor E.
        Minimally elevated cardiac troponin T and elevated N-terminal pro-B-type natriuretic peptide predict mortality in older adults: results from the Rancho Bernardo Study.
        J Am Coll Cardiol. 2008; 52: 450-459
        • Chenevier-Gobeaux C.
        • Meune C.
        • Blanc M.C.
        • et al.
        Analytical evaluation of a high-sensitivity troponin T assay and its clinical assessment in acute coronary syndrome.
        Ann Clin Biochem. 2011; 48: 452-458
        • Shayanfar N.
        • Bestmann L.
        • Schulthess G.
        • Hersberger M.
        False-positive cardiac troponin T due to assay interference with heterophilic antibodies.
        Swiss Med Wkly. 2008; 138: 470
        • Wu A.H.
        • Lu Q.A.
        • Todd J.
        • Moecks J.
        • Wians F.
        Short- and long-term biological variation in cardiac troponin I measured with a high-sensitivity assay: implications for clinical practice.
        Clin Chem. 2009; 55: 52-58
        • Turer A.T.
        • Addo T.A.
        • Martin J.L.
        • et al.
        Myocardial ischemia induced by rapid atrial pacing causes troponin T release detectable by a highly sensitive assay: insights from a coronary sinus sampling study.
        J Am Coll Cardiol. 2011; 57: 2398-2405
        • Kurz K.
        • Giannitsis E.
        • Zehelein J.
        • Katus H.A.
        Highly sensitive cardiac troponin T values remain constant after brief exercise- or pharmacologic-induced reversible myocardial ischemia.
        Clin Chem. 2008; 54: 1234-1238
        • Sabatine M.S.
        • Morrow D.A.
        • de Lemos J.A.
        • Jarolim P.
        • Braunwald E.
        Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35.
        Eur Heart J. 2009; 30: 162-169
        • Wilson S.R.
        • Sabatine M.S.
        • Braunwald E.
        • et al.
        Detection of myocardial injury in patients with unstable angina using a novel nanoparticle cardiac troponin I assay: observations from the PROTECT-TIMI 30 Trial.
        Am Heart J. 2009; 158: 386-391
        • Needham D.M.
        • Shufelt K.A.
        • Tomlinson G.
        • Scholey J.W.
        • Newton G.E.
        Troponin I and T levels in renal failure patients without acute coronary syndrome: a systematic review of the literature.
        Can J Cardiol. 2004; 20: 1212-1218
        • Antman E.M.
        • Tanasijevic M.J.
        • Thompson B.
        • et al.
        Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes.
        N Engl J Med. 1996; 335: 1342-1349
        • Ohman E.M.
        • Armstrong P.W.
        • Christenson R.H.
        • et al.
        Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators.
        N Engl J Med. 1996; 335: 1333-1341
        • Dokainish H.
        • Pillai M.
        • Murphy S.A.
        • et al.
        Prognostic implications of elevated troponin in patients with suspected acute coronary syndrome but no critical epicardial coronary disease: a TACTICS-TIMI-18 substudy.
        J Am Coll Cardiol. 2005; 45: 19-24
        • Hassan A.K.
        • Bergheanu S.C.
        • Hasan-Ali H.
        • et al.
        Usefulness of peak troponin-T to predict infarct size and long-term outcome in patients with first acute myocardial infarction after primary percutaneous coronary intervention.
        Am J Cardiol. 2009; 103: 779-784
        • Kurz K.
        • Schild C.
        • Isfort P.
        • Katus H.A.
        • Giannitsis E.
        Serial and single time-point measurements of cardiac troponin T for prediction of clinical outcomes in patients with acute ST-segment elevation myocardial infarction.
        Clin Res Cardiol. 2009; 98: 94-100
        • Morrow D.A.
        • Cannon C.P.
        • Rifai N.
        • et al.
        Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial.
        JAMA. 2001; 286: 2405-2412
        • Mills N.L.
        • Churchhouse A.M.
        • Lee K.K.
        • et al.
        Implementation of a sensitive troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome.
        JAMA. 2011; 305: 1210-1216
        • Gattis W.A.
        • O’Connor C.M.
        • Hasselblad V.
        • et al.
        Usefulness of an elevated troponin-I in predicting clinical events in patients admitted with acute heart failure and acute coronary syndrome (from the RITZ-4 trial).
        Am J Cardiol. 2004; 93: 1436-1437
        • Latini R.
        • Masson S.
        • Anand I.S.
        • et al.
        Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure.
        Circulation. 2007; 116: 1242-1249
        • Omland T.
        • de Lemos J.A.
        • Sabatine M.S.
        • et al.
        A sensitive cardiac troponin T assay in stable coronary artery disease.
        N Engl J Med. 2009; 361: 2538-2547
        • Otsuka T.
        • Kawada T.
        • Ibuki C.
        • Seino Y.
        Association between high-sensitivity cardiac troponin T levels and the predicted cardiovascular risk in middle-aged men without overt cardiovascular disease.
        Am Heart J. 2010; 159: 972-978
        • Yasue H.
        • Yoshimura M.
        • Sumida H.
        • et al.
        Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure.
        Circulation. 1994; 90: 195-203
        • Maisel A.S.
        • Krishnaswamy P.
        • Nowak R.M.
        • et al.
        Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.
        N Engl J Med. 2002; 347: 161-167
        • Richards A.M.
        • Nicholls M.G.
        • Espiner E.A.
        • et al.
        B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction.
        Circulation. 2003; 107: 2786-2792
        • de Lemos J.A.
        • 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
        • Januzzi J.L.
        • Camargo C.A.
        • Anwaruddin S.
        • et al.
        The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study.
        Am J Cardiol. 2005; 95: 948-954
        • Eggers K.M.
        • Lagerqvist B.
        • Venge P.
        • Wallentin L.
        • Lindahl B.
        Prognostic value of biomarkers during and after non-ST-segment elevation acute coronary syndrome.
        J Am Coll Cardiol. 2009; 54: 357-364
        • Khan S.Q.
        • Dhillon O.S.
        • O’Brien R.J.
        • et al.
        C-terminal provasopressin (copeptin) as a novel and prognostic marker in acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) study.
        Circulation. 2007; 115: 2103-2110
        • Reichlin T.
        • Hochholzer W.
        • Stelzig C.
        • et al.
        Incremental value of copeptin for rapid rule out of acute myocardial infarction.
        J Am Coll Cardiol. 2009; 54: 60-68
        • Sharma R.
        • Gaze D.C.
        • Pellerin D.
        • et al.
        Evaluation of ischaemia-modified albumin as a marker of myocardial ischaemia in end-stage renal disease.
        Clin Sci (Lond). 2007; 113: 25-32
        • Musso P.
        • Cox I.
        • Vidano E.
        • Zambon D.
        • Panteghini M.
        Cardiac troponin elevations in chronic renal failure: prevalence and clinical significance.
        Clin Biochem. 1999; 32: 125-130
        • Sinha M.K.
        • Gaze D.C.
        • Tippins J.R.
        • Collinson P.O.
        • Kaski J.C.
        Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention.
        Circulation. 2003; 107: 2403-2405
        • Lee Y.W.
        • Kim H.J.
        • Cho Y.H.
        • et al.
        Application of albumin-adjusted ischemia modified albumin index as an early screening marker for acute coronary syndrome.
        Clin Chim Acta. 2007; 384: 24-27
        • Peacock F.
        • Morris D.L.
        • Anwaruddin S.
        • et al.
        Meta-analysis of ischemia-modified albumin to rule out acute coronary syndromes in the emergency department.
        Am Heart J. 2006; 152: 253-262
        • Lin R.M.
        • Fatovich D.M.
        • Grasko J.M.
        • Vasikaran S.D.
        Ischaemia modified albumin cannot be used for rapid exclusion of acute coronary syndrome.
        Emerg Med J. 2010; 27: 668-671
        • Quiles J.
        • Roy D.
        • Gaze D.
        • et al.
        Relation of ischemia-modified albumin (IMA) levels following elective angioplasty for stable angina pectoris to duration of balloon-induced myocardial ischemia.
        Am J Cardiol. 2003; 92: 322-324
        • Sinha M.K.
        • Vazquez J.M.
        • Calvino R.
        • et al.
        Effects of balloon occlusion during percutaneous coronary intervention on circulating Ischemia Modified Albumin and transmyocardial lactate extraction.
        Heart. 2006; 92: 1852-1853
        • Chan D.
        • Ng L.L.
        Biomarkers in acute myocardial infarction.
        BMC Med. 2010; 8: 34
        • Viswanathan K.
        • Kilcullen N.
        • Morrell C.
        • et al.
        Heart-type fatty acid-binding protein predicts long-term mortality and re-infarction in consecutive patients with suspected acute coronary syndrome who are troponin-negative.
        J Am Coll Cardiol. 2010; 55: 2590-2598
        • McMahon C.G.
        • Lamont J.V.
        • Curtin E.
        • et al.
        Diagnostic accuracy of heart-type fatty acid-binding protein for the early diagnosis of acute myocardial infarction.
        Am J Emerg Med. 2011 Jan 3; ([Epub ahead of print])
        • Inoue K.
        • Suwa S.
        • Ohta H.
        • et al.
        Heart fatty acid-binding protein offers similar diagnostic performance to high-sensitivity troponin T in emergency room patients presenting with chest pain.
        Circ J. 2011 Sep 21; ([Epub ahead of print])
        • O’Donoghue M.
        • de Lemos J.A.
        • Morrow D.A.
        • et al.
        Prognostic utility of heart-type fatty acid binding protein in patients with acute coronary syndromes.
        Circulation. 2006; 114: 550-557
        • Kilcullen N.
        • Viswanathan K.
        • Das R.
        • et al.
        Heart-type fatty acid-binding protein predicts long-term mortality after acute coronary syndrome and identifies high-risk patients across the range of troponin values.
        J Am Coll Cardiol. 2007; 50: 2061-2067
        • Bathia D.P.
        • Carless D.R.
        • Viswanathan K.
        • Hall A.S.
        • Barth J.H.
        Serum 99th centile values for two heart-type fatty acid binding protein assays.
        Ann Clin Biochem. 2009; 46: 464-467
        • Mullane K.M.
        • Kraemer R.
        • Smith B.
        Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium.
        J Pharmacol Methods. 1985; 14: 157-167
        • Kalantar-Zadeh K.
        • Brennan M.L.
        • Hazen S.L.
        Serum myeloperoxidase and mortality in maintenance hemodialysis patients.
        Am J Kidney Dis. 2006; 48: 59-68
        • Shao B.
        • Oda M.N.
        • Oram J.F.
        • Heinecke J.W.
        Myeloperoxidase: an inflammatory enzyme for generating dysfunctional high density lipoprotein.
        Curr Opin Cardiol. 2006; 21: 322-328
        • Meuwese M.C.
        • Stroes E.S.
        • Hazen S.L.
        • et al.
        Serum myeloperoxidase levels are associated with the future risk of coronary artery disease in apparently healthy individuals: the EPIC-Norfolk Prospective Population Study.
        J Am Coll Cardiol. 2007; 50: 159-165
        • Brennan M.L.
        • Penn M.S.
        • Van Lente F.
        • et al.
        Prognostic value of myeloperoxidase in patients with chest pain.
        N Engl J Med. 2003; 349: 1595-1604
        • Cavusoglu E.
        • Ruwende C.
        • Eng C.
        • et al.
        Usefulness of baseline plasma myeloperoxidase levels as an independent predictor of myocardial infarction at two years in patients presenting with acute coronary syndrome.
        Am J Cardiol. 2007; 99: 1364-1368
        • Pietilä K.
        • Harmoinen A.
        • Hermens W.
        • et al.
        Serum C-reactive protein and infarct size in myocardial infarct patients with a closed versus an open infarct-related coronary artery after thrombolytic therapy.
        Eur Heart J. 1993; 14: 915-919
        • Kushner I.
        • Rakita L.
        • Kaplan M.H.
        Studies of acute-phase protein. II. Localization of Cx-reactive protein in heart in induced myocardial infarction in rabbits.
        J Clin Invest. 1963; 42: 286-292
        • Diercks D.B.
        • Kirk J.D.
        • Naser S.
        • Turnipseed S.
        • Amsterdam E.A.
        Value of high-sensitivity C-reactive protein in low risk chest pain observation unit patients.
        Int J Emerg Med. 2011; 4: 37
        • Ueda S.
        • Ikeda U.
        • Yamamoto K.
        • et al.
        C-reactive protein as a predictor of cardiac rupture after acute myocardial infarction.
        Am Heart J. 1996; 131: 857-860
        • Lindahl B.
        • Toss H.
        • Siegbahn A.
        • Venge P.
        • Wallentin L.
        Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease.
        N Engl J Med. 2000; 343: 1139-1147
        • de Winter R.J.
        • Bholasingh R.
        • Lijmer J.G.
        • et al.
        Independent prognostic value of C-reactive protein and troponin I in patients with unstable angina or non-Q-wave myocardial infarction.
        Cardiovasc Res. 1999; 42: 240-245
        • Heeschen C.
        • Hamm C.W.
        • Bruemmer J.
        • Simoons M.L.
        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. 2000; 35: 1535-1542
        • Bodí V.
        • Sanchis J.
        • López-Lereu M.P.
        • et al.
        Usefulness of a comprehensive cardiovascular magnetic resonance imaging assessment for predicting recovery of left ventricular wall motion in the setting of myocardial stunning.
        J Am Coll Cardiol. 2005; 46: 1747-1752
        • Correia L.C.
        • Esteves J.P.
        C-Reactive protein and outcomes in acute coronary syndromes: a systematic review and meta-analysis.
        Arq Bras Cardiol. 2011; 97: 76-85
        • Pietilä K.O.
        • Harmoinen A.P.
        • Jokiniitty J.
        • Pasternack A.I.
        Serum C-reactive protein concentration in acute myocardial infarction and its relationship to mortality during 24 months of follow-up in patients under thrombolytic treatment.
        Eur Heart J. 1996; 17: 1345-1349
        • Pfeffer M.A.
        • Braunwald E.
        • Moyé L.A.
        • et al.
        Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators.
        N Engl J Med. 1992; 327: 669-677
        • The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators
        Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure.
        Lancet. 1993; 342: 821-828
        • Ceremuzynski L.
        • Kleczar E.
        • Krzeminska-Pakula M.
        • et al.
        Effect of amiodarone on mortality after myocardial infarction: a double-blind, placebo-controlled, pilot study.
        J Am Coll Cardiol. 1992; 20: 1056-1062
        • Zeisel S.H.
        • da Costa K.A.
        Choline: an essential nutrient for public health.
        Nutr Rev. 2009; 67: 615-623
        • Danne O.
        • Möckel M.
        • Lueders C.
        • et al.
        Prognostic implications of elevated whole blood choline levels in acute coronary syndromes.
        Am J Cardiol. 2003; 91: 1060-1067
        • Apple F.S.
        • Wu A.H.
        • Mair J.
        • et al.
        Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome.
        Clin Chem. 2005; 51: 810-824
        • Heeschen C.
        • Dimmeler S.
        • Fichtlscherer S.
        • et al.
        Prognostic value of placental growth factor in patients with acute chest pain.
        JAMA. 2004; 291: 435-441
        • Glaser R.
        • Peacock W.F.
        • Wu A.H.
        • et al.
        Placental growth factor and B-type natriuretic peptide as independent predictors of risk from a multibiomarker panel in suspected acute coronary syndrome (Acute Risk and Related Outcomes Assessed With Cardiac Biomarkers [ARROW]) study.
        Am J Cardiol. 2011; 107: 821-826
        • Henn V.
        • Steinbach S.
        • Büchner K.
        • Presek P.
        • Kroczek R.A.
        The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40.
        Blood. 2001; 98: 1047-1054
        • Morrow D.A.
        • Sabatine M.S.
        • Brennan M.L.
        • et al.
        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. 2008; 29: 1096-1102
        • Varo N.
        • de Lemos J.A.
        • Libby P.
        • et al.
        Soluble CD40L: risk prediction after acute coronary syndromes.
        Circulation. 2003; 108: 1049-1052
        • Heeschen C.
        • Dimmeler S.
        • Hamm C.W.
        • et al.
        Soluble CD40 ligand in acute coronary syndromes.
        N Engl J Med. 2003; 348: 1104-1111
        • Weber M.
        • Rabenau B.
        • Stanisch M.
        • et al.
        Influence of sample type and storage conditions on soluble CD40 ligand assessment.
        Clin Chem. 2006; 52: 888-891
        • Apple F.S.
        • Pearce L.A.
        • Chung A.
        • Ler R.
        • Murakami M.M.
        Multiple biomarker use for detection of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome.
        Clin Chem. 2007; 53: 874-881
        • Schlittenhardt D.
        • Schober A.
        • Strelau J.
        • et al.
        Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions.
        Cell Tissue Res. 2004; 318: 325-333
        • Kempf T.
        • Eden M.
        • Strelau J.
        • et al.
        The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury.
        Circ Res. 2006; 98: 351-360
        • Xu J.
        • Kimball T.R.
        • Lorenz J.N.
        • et al.
        GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation.
        Circ Res. 2006; 98: 342-350
        • Kempf T.
        • Sinning J.M.
        • Quint A.
        • et al.
        Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease: results from the AtheroGene study.
        Circ Cardiovasc Genet. 2009; 2: 286-292
        • Kempf T.
        • Björklund E.
        • Olofsson S.
        • et al.
        Growth-differentiation factor-15 improves risk stratification in ST-segment elevation myocardial infarction.
        Eur Heart J. 2007; 28: 2858-2865
        • Wollert K.C.
        • Kempf T.
        • Lagerqvist B.
        • et al.
        Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome.
        Circulation. 2007; 116: 1540-1548
        • Tello-Montoliu A.
        • Marín F.
        • Roldán V.
        • et al.
        A multimarker risk stratification approach to non-ST elevation acute coronary syndrome: implications of troponin T, CRP, NT pro-BNP and fibrin D-dimer levels.
        J Intern Med. 2007; 262: 651-658