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Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction: Analysis of 28 months of follow-up in 196 patients FREE

Jan Ravkilde, MD; Henrik Nissen, MD; Mogens Hørder, MD, DSc; Kristian Thygesen, MD, DSc, FACC
[+] Author Information

This study was supported by a grant from the Danish Heart Foundation, Copenhagen, Denmark. Boehringer Mannheim GmbH, Mannheim, Germany and Novo-Nordisk Bioscience AIS, Copenhagen, Denmark supplied the troponin T and myosin light chain kits, respectively.Address for correspondence: Dr. Jan Ravkilde, Department of MedicineCardiology A, Aarhus Amtssygehus University Hospital, Tage Hansensgade 2, DK-8000 Aarhus C, Denmark.

American College of Cardiology

J Am Coll Cardiol. 1995;25(3):574-581. doi:10.1016/0735-1097(94)00430-X
Published online

Objectives.  We sought to determine the incidence and independent prognostic value of increased serum levels of sensitive serologic markers in patients in whom a conventionally diagnosed acute myocardial infarction had been ruled out.

Background.  Increased serum levels of creatine kinase (CK) isoenzyme MB mass and cardiac troponin T in patients with unstable angina pectoris are associated with a poor prognosis.

Methods.  We analyzed data from 196 consecutive patients with suspected acute myocardial infarction, which was later ruled out in 124. Increased serum levels of CK-MB mass, troponin T and myosin light chains were compared with clinical findings, ST-T wave abnormalities and presence of arrhythmias.

Results.  Of the patients in the noninfarction group, 28% had serum CK-MB mass ≥μg/liter, 20% had troponin T ≥0.20 μg/liter, and 26% had myosin light chains ≥0.4 μg/liter (discrimination limits). The cardiac event rate (cardiac death, nonfatal acute myocardial infarction) within 28 months was significantly higher in patients in the noninfarction group with elevated marker levels (range 22% to 24%) than in patients with values below these discriminators (range 3% to 5%) but was not significantly different from that in patients with a definite diagnosis of acute myocardial infarction (29%). Further, significant predictors of cardiac events were previous myocardial infarction; myocardial infarction or angina pectoris, or both; previous congestive heart failure; ST-T wave abnormalities on admission; a transient ST-T wave shift on serial electrocardiograms (ECGs); recurrent chest pain; and occurrence of supraventricular or ventricular tachycardia, or both, during the 1st 48 h after admission. It was found that all three biochemical markers, in the main, convey independent prognostic information with respect to clinical findings and presence of arrhythmias but not ST-T wave abnormalities on admission or a transient ST-T wave shift on serial ECGs.

Conclusions.  Increased serum levels of CK-MB mass, troponin T and myosin light chains all detect a subgroup of 25% of patients without acute myocardial infarction who have as poor a prognosis as that of patients with a definite diagnosis of acute myocardial infarction. All three biochemical markers provide similar important independent prognostic information with regard to clinical findings and arrhythmias but add no additional prognostic information once ECG ST-T wave changes are considered.

References

Pasternak  RC, Braunwald  E, Sobel  BE; Acute myocardial infarction.Braunwald  E;Heart Disease: A Textbook of Cardiovascular Medicine 1992 Saunders St. Louis:1200-1292.
 Working Group on the Establishment of Ischaemic Heart Disease Registers: Report of the Fifth Working Group. Eur 8201 1971 WHO Philadelphia
Katus  HA, Remppis  A, Neumann  FJ; Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation. 83 1991:902-912.
CrossRef | PubMed
Gerhardt  W, Katus  H, Ravkilde  J; S-Troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentrations of S-creatine kinase isoenzyme MB. Clin Chem. 37 1991:1405-1411.
PubMed
Katus  HA, Yasuda  T, Gold  HK; Diagnosis of acute myocardial infarction by detection of circulating cardiac myosin light chains. Am J Cardiol. 54 1984:964-970.
CrossRef | PubMed
Wang  J, Shi  Q, Wu  T-W, Jackowski  G, Mickle  DAG; The quantification of human ventricular myosin light chain 1 in serum after myocardial necrosis and infarction. Clin Chim Acta. 181 1989:325-336.
CrossRef | PubMed
Ravkilde  J, Bøtker  HE, Søgaard  P; Human ventricular myosin light chain isotype 1 as a marker of myocardial injury. Cardiology. 84 1994:135-144.
CrossRef | PubMed
Chan  DW, Taylor  E, Frye  R, Blitzer  RL; Immunoenzymatic assay for creatine kinase MB with subunit specific monoclonal antibodies compared with an immunochemical method and electrophoresis. Clin Chem. 31 1985:465-469.
PubMed
Jørgensen  PJ, Hørder  M, Selmer  J, Bøtker  HE; Analytical evaluation of a sensitive enzyme immunoassay for determinations of creatine kinase isoenzyme MB. Clin Chem. 36 1990:1502-1505.
PubMed
Adams  JE, Bodor  GS, Dávila-Román  VG; Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation. 88 1993:101-106.
CrossRef | PubMed
Bøtker  HE, Ravkilde  J, Sogaard  P, Jorgensen  PJ, Hørder  M, Thygesen  K; Gradation of unstable angina based on a sensitive immunoassay for serum creatine kinase MB. Br Heart J. 65 1991:72-76.
CrossRef | PubMed
Hamm  CW, Ravkilde  J, Gerhardt  W; The prognostic value of serum troponin T in unstable angina. N Engl J Med. 327 1992:146-150.
CrossRef | PubMed
Ravkilde  J, Hansen  AB, Hørder  M, Jørgensen  PJ, Thygesen  K; Risk stratification in suspected acute myocardial infarction based on a sensitive immunoassay for serum creatine kinase isoenzyme MB. Cardiology. 80 1992:143-151.
CrossRef | PubMed
Pettersson  T, Ohlsson  O, Tryding  N; Increased CK MB (mass concentration) in patients without traditional evidence of AMI. A risk indicator of coronary death.  Eur Heart J. 13 1992:1387-1392.
Ravkilde  J, Hørder  M, Gerhardt  W; Diagnostic performance and prognostic value of serum troponin T in suspected acute myocardial infarction. Scand J Clin Lab Invest. 53 1993:677-685.
CrossRef | PubMed
Stein  W; Laboratory diagnosis of acute myocardial infarction. Using CK and CK MB immunoinhibition 1988 GIT Verlag Copenhagen:30-62.
Gerhardt  W, Waldenström  J, Hörder  M; Creatine kinase and creatine kinase B.subunit activity in serum in cases of suspected myocardial infarction. Clin Chem. 28 1982:277-283.
PubMed
Braunwald  E; Unstable angina: a classification. Circulation. 80 1989:410-414.
CrossRef | PubMed
Horder  M, Gerhardt  W; Diagnostic application of biochemical markers in acute myocardial infarction.Thygesen  K, Kjekshus  J; Myocardial Ischaemia. 1990 Blackwell Scientific Darmstadt, Germany:251-259.
Katus  HA, Looser  S, Hallermayer  K; Development and in vitro characterization of a new immunoassay of cardiac troponin T. Clin Chem. 38 1992:386-393.
PubMed
The Committee on Enzymes of the Scandinavian Society for Clinical Chemistry and Clinical Physiology (SCE); Recommended method for the determination of creatine kinase in blood modified by the inclusion of EDTA. Scand J Clin Lab Invest. 39 1979:1-5.
PubMed
Benedetti  J, Yuen  K, Young  L; Life tables and survivor functions.Dixon  WJ; BMDP Statistical Software. 1990 Univ of California Press Oxford:739-768.
 StatXact Statistical Software. 1991 Cytel Software Corporation Berkeley (CA)
Cairns  JA, Singer  J, Gent  M; One year mortality outcomes of all coronary and intensive care unit patients with acute myocardial infarction, unstable angina or other chest pain in Hamilton, Ontario, a city of 375,000 people. Can J Cardiol. 5 1989:239-246.
PubMed
Betriu  A, Heras  M, Cohen  M, Fuster  V; Unstable angina: outcome according to clinical presentation. J Am Coll Cardiol. 19 1992:1659-1663.
CrossRef | PubMed
Madsen  JK, Thomsen  BL, Sorensen  JN, Kjedgaard  KM, Kromann-Andersen  B; Risk factors and prognosis after discharge for patients admitted because of suspected acute myocardial infarction with and without confirmed diagnosis. Am J Cardiol. 59 1987:1064-1070.
CrossRef | PubMed
Ross  J  Jr, Gilpin  EA, Madsen  EB; A decision scheme for coronary angiography after acute myocardial infarction. Circulation. 79 1989:292-303.
CrossRef | PubMed
Turi  ZG, Rutherford  JD, Roberts  R; Electrocardiographic, enzymatic and scintigraphic criteria of acute myocardial infarction as determined from study of 726 patients (a MILIS study). Am J Cardiol. 55 1985:1463-1468.
CrossRef | PubMed
Ambrose  JA, Hjemdahl-Monsen  CE, Borrico  S, Gorlin  R, Fuster  V; Angiographic demonstration of a common link between unstable angina pectoris and non-Q wave acute myocardial infarction. Am J Cardiol. 61 1988:244-247.
CrossRef | PubMed
Fuster  V, Badimon  L, Badimon  JJ, Chesebro  JH; The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med. 326 1992:242-250.
CrossRef | PubMed

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References

Pasternak  RC, Braunwald  E, Sobel  BE; Acute myocardial infarction.Braunwald  E;Heart Disease: A Textbook of Cardiovascular Medicine 1992 Saunders St. Louis:1200-1292.
 Working Group on the Establishment of Ischaemic Heart Disease Registers: Report of the Fifth Working Group. Eur 8201 1971 WHO Philadelphia
Katus  HA, Remppis  A, Neumann  FJ; Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation. 83 1991:902-912.
CrossRef | PubMed
Gerhardt  W, Katus  H, Ravkilde  J; S-Troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentrations of S-creatine kinase isoenzyme MB. Clin Chem. 37 1991:1405-1411.
PubMed
Katus  HA, Yasuda  T, Gold  HK; Diagnosis of acute myocardial infarction by detection of circulating cardiac myosin light chains. Am J Cardiol. 54 1984:964-970.
CrossRef | PubMed
Wang  J, Shi  Q, Wu  T-W, Jackowski  G, Mickle  DAG; The quantification of human ventricular myosin light chain 1 in serum after myocardial necrosis and infarction. Clin Chim Acta. 181 1989:325-336.
CrossRef | PubMed
Ravkilde  J, Bøtker  HE, Søgaard  P; Human ventricular myosin light chain isotype 1 as a marker of myocardial injury. Cardiology. 84 1994:135-144.
CrossRef | PubMed
Chan  DW, Taylor  E, Frye  R, Blitzer  RL; Immunoenzymatic assay for creatine kinase MB with subunit specific monoclonal antibodies compared with an immunochemical method and electrophoresis. Clin Chem. 31 1985:465-469.
PubMed
Jørgensen  PJ, Hørder  M, Selmer  J, Bøtker  HE; Analytical evaluation of a sensitive enzyme immunoassay for determinations of creatine kinase isoenzyme MB. Clin Chem. 36 1990:1502-1505.
PubMed
Adams  JE, Bodor  GS, Dávila-Román  VG; Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation. 88 1993:101-106.
CrossRef | PubMed
Bøtker  HE, Ravkilde  J, Sogaard  P, Jorgensen  PJ, Hørder  M, Thygesen  K; Gradation of unstable angina based on a sensitive immunoassay for serum creatine kinase MB. Br Heart J. 65 1991:72-76.
CrossRef | PubMed
Hamm  CW, Ravkilde  J, Gerhardt  W; The prognostic value of serum troponin T in unstable angina. N Engl J Med. 327 1992:146-150.
CrossRef | PubMed
Ravkilde  J, Hansen  AB, Hørder  M, Jørgensen  PJ, Thygesen  K; Risk stratification in suspected acute myocardial infarction based on a sensitive immunoassay for serum creatine kinase isoenzyme MB. Cardiology. 80 1992:143-151.
CrossRef | PubMed
Pettersson  T, Ohlsson  O, Tryding  N; Increased CK MB (mass concentration) in patients without traditional evidence of AMI. A risk indicator of coronary death.  Eur Heart J. 13 1992:1387-1392.
Ravkilde  J, Hørder  M, Gerhardt  W; Diagnostic performance and prognostic value of serum troponin T in suspected acute myocardial infarction. Scand J Clin Lab Invest. 53 1993:677-685.
CrossRef | PubMed
Stein  W; Laboratory diagnosis of acute myocardial infarction. Using CK and CK MB immunoinhibition 1988 GIT Verlag Copenhagen:30-62.
Gerhardt  W, Waldenström  J, Hörder  M; Creatine kinase and creatine kinase B.subunit activity in serum in cases of suspected myocardial infarction. Clin Chem. 28 1982:277-283.
PubMed
Braunwald  E; Unstable angina: a classification. Circulation. 80 1989:410-414.
CrossRef | PubMed
Horder  M, Gerhardt  W; Diagnostic application of biochemical markers in acute myocardial infarction.Thygesen  K, Kjekshus  J; Myocardial Ischaemia. 1990 Blackwell Scientific Darmstadt, Germany:251-259.
Katus  HA, Looser  S, Hallermayer  K; Development and in vitro characterization of a new immunoassay of cardiac troponin T. Clin Chem. 38 1992:386-393.
PubMed
The Committee on Enzymes of the Scandinavian Society for Clinical Chemistry and Clinical Physiology (SCE); Recommended method for the determination of creatine kinase in blood modified by the inclusion of EDTA. Scand J Clin Lab Invest. 39 1979:1-5.
PubMed
Benedetti  J, Yuen  K, Young  L; Life tables and survivor functions.Dixon  WJ; BMDP Statistical Software. 1990 Univ of California Press Oxford:739-768.
 StatXact Statistical Software. 1991 Cytel Software Corporation Berkeley (CA)
Cairns  JA, Singer  J, Gent  M; One year mortality outcomes of all coronary and intensive care unit patients with acute myocardial infarction, unstable angina or other chest pain in Hamilton, Ontario, a city of 375,000 people. Can J Cardiol. 5 1989:239-246.
PubMed
Betriu  A, Heras  M, Cohen  M, Fuster  V; Unstable angina: outcome according to clinical presentation. J Am Coll Cardiol. 19 1992:1659-1663.
CrossRef | PubMed
Madsen  JK, Thomsen  BL, Sorensen  JN, Kjedgaard  KM, Kromann-Andersen  B; Risk factors and prognosis after discharge for patients admitted because of suspected acute myocardial infarction with and without confirmed diagnosis. Am J Cardiol. 59 1987:1064-1070.
CrossRef | PubMed
Ross  J  Jr, Gilpin  EA, Madsen  EB; A decision scheme for coronary angiography after acute myocardial infarction. Circulation. 79 1989:292-303.
CrossRef | PubMed
Turi  ZG, Rutherford  JD, Roberts  R; Electrocardiographic, enzymatic and scintigraphic criteria of acute myocardial infarction as determined from study of 726 patients (a MILIS study). Am J Cardiol. 55 1985:1463-1468.
CrossRef | PubMed
Ambrose  JA, Hjemdahl-Monsen  CE, Borrico  S, Gorlin  R, Fuster  V; Angiographic demonstration of a common link between unstable angina pectoris and non-Q wave acute myocardial infarction. Am J Cardiol. 61 1988:244-247.
CrossRef | PubMed
Fuster  V, Badimon  L, Badimon  JJ, Chesebro  JH; The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med. 326 1992:242-250.
CrossRef | PubMed

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