
Zusammenfassung
Gut etabliert für Diagnose und Klassifikation von akuten Koronarsyndromen sind derzeit die kardialen Troponine. Sie sind bereits in der neuen Definition des akuten Myokardinfarkts und den Behandlungsrichtlinien für Patienten mit akutem Koronarsyndrom ohne ST-Streckenhebung implementiert. Sind die Troponinwerte erhöht, steigt auch das Risiko, ein kardiovaskuläres Ereignis zu erleiden, und die Patienten mit erhöhten Werten profitieren besonders von einem Einsatz von Glykoprotein-IIb/IIIa-Inhibitoren vor einem frühinvasiven Eingriff. Erst kürzlich wurden einige neue Biomarker identifiziert, die noch früher auf Ischämien und Nekrosen hinweisen und damit eine bessere Risikostratifizierung ermöglichen könnten. Erste Daten lassen vermuten, dass diese Marker unser Verständnis der komplexen Pathophysiologie des akuten Koronarsyndroms verbessern. Sie können so dazu beitragen, Patienten mit hohem von solchen mit geringem Risiko zu unterscheiden. Bislang sind diese neuen Risikomarker jedoch noch nicht ausreichend validiert. Bis dieses Problem gelöst und ein Evidenzgrad erreicht ist, der es erlaubt, die neuen Biomarker in die Leitlinienempfehlungen aufzunehmen, bleiben die kardialen Troponine daher der Goldstandard für Diagnose und Akutmanagement von Patienten mit akutem Koronarsyndrom.
Summary
Currently, cardiac troponins are well established for diagnosis and classification of acute coronary syndromes (ACS) and have been implemented in the new definition of acute myocardial infarction and management guidelines for patients with an acute coronary syndrome without ST-segment elevation. Elevated cardiac troponins predict higher cardiac event rates and identify patients who benefit most from an upstream use of GP IIb/IIIa inhibitors followed by early invasive strategy. More recently, several new biomarkers have been introduced for earlier detection of ischemia or necrosis and for improved risk stratification. Preliminary data suggest that these marker will improve our understanding of the complex pathophysiology inherent in acute coronary syndromes and might be helpful for discrimination of patients at high risk from those at very low risk. However, currently most markers are neither available for measurement on an automated platform nor have these markers been validated prospectively. Until the level of evidence for single new marker or implementation of multiple marker concepts has been obtained to allow for a guideline recommendation, cardiac troponins will remain the gold standard for diagnosis and acute management of patients with acute coronary syndrome.
Key words
acute coronary syndrome - troponins - novel biomarker - acute risk
Literatur
-
1
ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina).
Circulation.
2002;
106
1893-1900
-
2
Antman EM, Braunwald E, Wybenga D. 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
-
3
Antman EM, Cohen M, Bernink PJ. et al. .
The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making.
JAMA.
2000;
284
835-842
-
4
Apple FS, Murakami MM.
Cardiac troponin and creatine kinase MB monitoring during in-hospital myocardial reinfarction.
Clin Chem 2004.
5;
51
460-463
-
5
Apple FS, Quist HE, Otto AP. et al. .
Release characteristics of cardiac biomarkers and ischemia-modified albumin as measured by the albumin cobalt-binding test after a marathon race.
Clin Chem.
2002;
48
1097-1100
-
6
Autiero M, Luttun A, Tjwa M, Carmeliet P.
Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders.
J Thromb Haemost.
2003;
1
1356-1370
-
7
Baldus S, Heeschen C, Meinertz T. et al. .
Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes.
Circulation.
2003;
108
1440-1445
-
8
Bar-Or D, Winkler JV, VanBenthuysen K. et al. .
Reduced albumin-cobalt binding with transient myocardial ischemia after elective percutaneous transluminal coronary angioplasty: a preliminary comparison to creatine kinase-MB, myoglobin, and troponin I.
Am Heart J.
2001;
141
985-991
-
9
Bayes-Genis A, Conover CA, Overgaard MT. et al. .
Pregnancy-associated plasma protein A as a marker of acute coronary syndromes.
N Engl J Med.
2001;
345
1022-1029
-
10
Beaudeux JL, Burc L, Imbert-Bismut F. et al. .
Serum plasma pregnancy-associated protein A: a potential marker of echogenic carotid atherosclerotic plaques in asymptomatic hyperlipidemic subjects at high cardiovascular risk.
Arterioscler Thromb Vasc Biol.
2003;
23
7-10
-
11
Borderie D, Allanore Y, Meune C. et al. .
High ischemia-modified albumin concentration reflects oxidative stress but not myocardial involvement in systemic sclerosis.
Clin Chem.
2004;
50
2190-2193
-
12
Brennan ML, Penn MS, Van F Lente. et al. .
Prognostic value of myeloperoxidase in patients with chest pain.
N Engl J Med.
2003;
349
1595-1604
-
13
Cannon CP, Weintraub WS, Demopoulos LA. et al. .
Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.
N Engl J Med.
2001;
344
1879-1887
-
14
Chair B, Simoons ML, Fox KA. et al. .
Management of acute coronary syndromes: 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
-
15
Chan CP, Sanderson JE, Glatz JF. et al. .
A superior early myocardial infarction marker. Human heart-type fatty acid-binding protein.
Z Kardiol.
2004;
93
388-397
-
16
Eggers KM, Oldgren J, Nordenskjold A, Lindahl B.
Diagnostic value of serial measurement of cardiac markers in patients with chest pain: limited value of adding myoglobin to troponin I for exclusion of myocardial infarction.
Am Heart J.
2004;
148
574-581
-
17
Frey N, Dietz A, Kurowski V, Giannitsis E. et al. .
Angiographic correlates of a positive troponin T test in patients with unstable angina.
Crit Care Med.
2001;
29
1130-1136
-
18
Ghani F, Wu AH, Graff L. et al. .
Role of heart-type fatty acid-binding protein in early detection of acute myocardial infarction.
Clin Chem.
2000;
46
718-719
-
19
Gibler WB, Hoekstra JW, Weaver WD. et al. .
A randomized trial of the effects of early cardiac serum marker availability on reperfusion therapy in patients with acute myocardial infarction: the serial markers, acute myocardial infarction and rapid treatment trial (SMARTT).
J Am Coll Cardiol.
2000;
36
1500-1506
-
20
Goetze JP, Christoffersen C, Perko M. et al. .
Increased cardiac BNP expression associated with myocardial ischemia.
FASEB J.
2003;
17
1105-1107
-
21
Hamm CW.
Leitlinien: akutes Koronarsyndrom (ACS) Teil 1: ACS ohne persistierende ST-Hebung.
Z Kardiol.
2004;
93
72-90
-
22
Hamm CW, Giannitsis E, Katus HA.
Cardiac troponin elevations in patients without acute coronary syndrome.
Circulation.
2002;
106
2871-2872
-
23
Hamm CW, Ravkilde J, Gerhardt W. et al. .
The predictive value of serum troponin T in unstable angina.
N Engl J Med.
1992;
327
146-150
-
24
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
-
25
Heeschen C, Dimmeler S, Hamm CW. et al. .
Serum level of the antiinflammatory cytokine interleukin-10 is an important prognostic determinant in patients with acute coronary syndromes.
Circulation.
2003;
107
2109-2114
-
26
Heeschen C, Dimmeler S, Hamm CW. et al. .
Soluble CD40 ligand in acute coronary syndromes.
N Engl J Med.
2003;
348
1104-1111
-
27
Heeschen C, Hamm C, Mitrovic V. et al. .
N-terminal pro-B-type natriuretic peptide levels for dynamic risc stratification of patients with acute conorary syndromes.
Circulation.
2004;
110
3206-3212
-
28
Heeschen C, van MJ Den Brand, Hamm CW, Simoons ML.
Angiographic findings in patients with refractory unstable angina according to troponin T status.
Circulation.
1999;
100
1509-1514
-
29
Jaffe AS, Katus H.
Acute coronary syndrome biomarkers: the need for more adequate reporting.
Circulation.
2004;
110
104-106
-
30
James SK, Lindahl B, Siegbahn A. et al. .
N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease.
Circulation.
2003;
108
275-281
-
31
Jernberg T, Lindahl B, James S. et al. .
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
-
32
Jernberg T, Lindahl B, Siegbahn A. et al. .
N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease.
J Am Coll Cardiol.
2003;
42
1909-1916
-
33
Katus HA, Remppis A, Scheffold T. et al. .
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
-
34
Kleiman NS, Lakkis N, Cannon CP. et al. .
TACTICS-TIMI 18 Investigators. Prospective analysis of creatine kinase muscle-brain fraction and comparison with troponin T to predict cardiac risk and benefit of an invasive strategy in patients with non-ST-elevation acute coronary syndromes.
J Am Coll Cardiol.
2002;
40
1044-1050
-
35
Kontos MC, Fritz LM, Anderson FP. et al. .
Impact of the troponin standard on the prevalence of acute myocardial infarction.
Am Heart J.
2003;
146
446-452
-
36
Lindahl B, Toss H, Siegbahn A. et al. .
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
-
37
Liuzzo G, Biasucci LM, Gallimore JR. 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
-
38
Lund J, Qin QP, Ilva T. et al. .
Circulating pregnancy-associated plasma protein a predicts outcome in patients with acute coronary syndrome but no troponin I elevation.
Circulation.
2003;
108
1924-1926
-
39
Luttun A, Tjwa M, Carmeliet P.
Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders.
Ann NY Acad Sci.
2002;
979
80-93
-
40
Luttun A, Tjwa M, Moons L. et al. .
Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1.
Nat Med.
2002;
8
831-840
-
41
McCord J, Nowak RM, McCullough PA. et al. .
Ninety-minute exclusion of acute myocardial infarction by use of quantitative point-of-care testing of myoglobin and troponin I.
Circulation.
2001;
104
1483-1488
-
42
Morrow DA, JA Lemos de, MS Sabatine. et al. .
Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation MI: BNP and prognosis in TACTICS-TIMI 18.
J Am Coll Cardiol.
2003;
41
1264-1272
-
43
Ohman EM, Armstrong PW, Christenson RH. et al. .
Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators.
N Engl J Med.
1996;
335
1333-1341
-
44
Okamatsu K, Takano M, Sakai S. et al. .
Elevated troponin T levels and lesion characteristics in non-ST-elevation acute coronary syndromes.
Circulation.
2004;
109
465-470
-
45
Okamoto F, Sohmiya K, Ohkaru Y. et al. .
Human heart-type cytoplasmic fatty acid-binding protein (H-FABP) for the diagnosis of acute myocardial infarction. Clinical evaluation of H-FABP in comparison with myoglobin and creatine kinase isoenzyme MB.
Clin Chem Lab Med.
2000;
38
231-238
-
46
Omland T, Persson A, Ng L. et al. .
N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes.
Circulation.
2002;
106
2913-2918
-
47
Ottani F, Galvani M.
Prognostic role of hemostatic markers in acute coronary syndromes patients.
Clin Chim Acta.
2001;
311
33-39
-
48
Ross R.
Atherosclerosis - an inflammatory disease.
N Engl J Med.
1999;
340
115-126
-
49
Roy D, Quiles J, Sharma R. et al. .
Ischemia-modified albumin concentrations in patients with peripheral vascular disease and exercise-induced skeletal muscle ischemia.
Clin Chem.
2004;
50
1656-1660
-
50
Roy D, Quiles J, Sinha M, Floros D. et al. .
Effect of radiofrequency catheter ablation on the biochemical marker ischemia modified albumin.
Am J Cardiol.
2004;
94
234-236
-
51
Sabatine MS, McCabe CH, Morrow DA. et al. .
Identification of patients at high risk for death and cardiac ischemic events after hospital discharge.
Am Heart J.
2002;
143
966-970
-
52
Sabatine MS, Morrow DA, de JA Lemos. et al. .
Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia.
J Am Coll Cardiol.
2004;
44
1988-1995
-
53
Sabatine MS, Morrow DA, de Lemos JA. 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
-
54
Sinha MK, Gaze DC, Tippins JR. et al. .
Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention.
Circulation.
2003;
107
2403-2405
-
55
Smith DA, Irving SD, Sheldon J. et al. .
Serum levels of the antiinflammatory cytokine interleukin-10 are decreased in patients with unstable angina.
Circulation.
2001;
104
746-749
-
56
The Joint European Society of Cardiology/American College of Cardiology Committee. .
Myocardial infarction redefined - A consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction.
Eur Heart J.
2000;
21
1502-1513
-
57
Varo N, de JA Lemos, Libby P. et al. .
Soluble CD40L: risk prediction after acute coronary syndromes.
Circulation.
2003;
108
1049-1052
-
58
Weber M, Dill T, Arnold R. et al. .
N-terminal B-type natriuretic peptide predicts extent of coronary artery disease and ischemia in patients with stable angina pectoris.
Am Heart J.
2004;
148
612-620
1 chimeric 7E3 antiplatelet therapy in unstable angina refractory to standard treatment
Anschrift für die Verfasser
PD Dr. Evangelos GiannitsisMD, FESC
Abteilung Innere Medizin III
Medizinische Klinik
Universitätsklinikum Heidelberg
Im Neuenheimer Feld 410
69120 Heidelberg