- Email: [email protected]
The twilight zone of troponins
The Twilight
Zone of Troponins
Hendrik
Zimmet,
MBBS
Epworth Hospital, Melbourne,
Australia
Since its introduction into the clinical environment in the early nineties, the cardiac enzyme troponin has significantly changed the way we diagnose and manage acute coronary syndromes. Troponin I is a biochemical marker of myocardial injury with a high level of specificity and sensitivity. It has been demonstrated that as ischaemia progresses, troponin I is degraded predictably into smaller and smaller fragments that can be detected in the blood-stream. This may eventually allow more accurate determination of the duration of ischaemia and the Lung and Circulafion 2003; 12: S90-S94) 1ikClihood of myocardial salvage and recovery. (Heart,
S
ince its introduction into the clinical environment in the early nineties, the cardiac enzyme troponin has significantly changed the way we diagnose and manage acute coronary syndromes. As with any new technology, it has provided some answers and raised many questions. Troponin I is a biochemical marker of myocardial injury with a high level of specificity and sensitivity.l Both troponin I and troponin T are structural proteins that regulate the calcium-modulated interaction of actin and myosin filaments in myocardial cells? (Fig. 1). Troponin I is not found outside heart muscle at any stage of human development.3,4 The Troponin Complex consists of three components that all interact - Troponin C, Troponin I and Troponin T. Troponin C (C for calcium) binds intercellular calcium that results in the Troponin I (I for inhibiting) shifting and exposing the binding site, Troponin T (T for tropomyosin) where myosin and actin crosslink (Fig. 2). -
tropomyosin
Troponin C
Troponin T
Figure 2. The troponin troponin
complex (troponin C, troponin T); (zuhite circles) actin; (grey line) tropomyosin.
myosin binding site
troponin complex Correspondence: Hendrik Zimmet, Flinders Drv, Bedford Park, South Email: [email protected]
Troponin I
Flinders Australia
Medical Centre, 5042, Australia.
Figure 1. Myocardial (white circles) actin.
actin filament
1,
Heart,
Lung
and
Circulation
2003; 12
H. Zimmet The twi/i,ght
Pathophysiology Release
of Ischaemic Troponin
Troponin exists in two major forms in the cardiac myocyte - cytosolic and structural.5,6 The cytosolic troponin floats freely in cytoplasm of the myocyte. The structural troponin is bound in complex form in actual myofilaments. When ischaemia occurs the integrity of the cell membrane is compromised and cytosolic troponin leaks out first causing the initial rise in serum troponin levels. A later result of the ischaemia is degradation of myofilaments causing the second characteristic rise in serum troponin levels7 (Figs 3 and 4). Serum troponin levels are first detectable by current conventional assays 4-6 h following the onset of ischaemia. Levels peak at around 18-24 h and then remain elevated for up to 10 days. 8 The release kinetics make
s91
of troponins
troponin an excellent biomarker for detection of myocardial ischaemia during the early, intermediate and late phases of an ischaemic event.
Comparison Enzymes
of Troponifi
and Other Cardiac
Prior to the routine use of troponin in the clinical setting, serum levels of creatinine kinase (CK) and its myocardial isoforms (CKMB), asparatate aminotransferase (AST) and lactate dehydrogenase (LDH) were used to determine the presence of myocardial infarction. Following a myocardial infarction, myoglobin levels become elevated first, followed by a rise in CK, followed by AST and finally LDH.? The combined assessment of the various levels of these biomarkers would allow estimation of when the myocardial infarction most likely occurred. If one considers the release kinetics of the various cardiac biomarkers, it is evident that troponin, alone, provides most of the information that the other cardiac biomarkers can only provide in combination.
Clinical
Figure 3. Two major forms of troponin 1 - cytosolic and structural.
zom
Application
Troponin I is not only of diagnostic but is also of highlevel prognostic significance in the setting of acute coronary syndromes. lo-l6 TroponinT shows similar properties in this regard.17 In acute coronary syndromes, troponin elevation predicts which patients are more likely to benefit from various treatments such as administration of low molecular weight heparin and inhibitors platelet glycoprotein _ -IIb/IIIa.18-21 Furthermore, there is emerging data to suggest that troponin levels may indicate which patients benefit from early invasive strategies. ZJInitial evidence also suggests that troponin elevation following percutaneous intervention23 or coronary artery bypass surgery24 may signify patients at higher risk of subsequent cardiac events.
New Definition of Acute Myocardial Infarction (AMI)
0
12
3
4
5
6
710
Days After Onset of AMI Figure 4. Troponin 1 releasekinetics. Blood level in days after onset of acute myocardial infarction.
The specificity and sensitivity of the troponin determination has led to a new joint European Society of Cardiology and American College of Cardiology recommendation for definition of AM1 that relies on the elevation of the cardiac marker in the first instan& (see Table 1). Even minor elevations of troponin define AMI. As a consequence, many patients with normal CK levels, who previously were diagnosed with unstable angina, now are considered to have suffered a myocardial infarction.
S92
H. Zimmet The twilight
Heart,
Lung
and Circulation
2003;
12
zone of troponins
Table 1. ESC/ACC Redefinition of AMP5 Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following: a. ischemic symptoms; b. development of pathologic Q waves; c. ECG changes indicative of ischemia (ST segment elevation or depression; d. coronary artery intervention Pathologic findings of AM1
The greater sensitivity and specificity that troponin provides in detecting myocardial ischaemia now lays before us a clearer picture of the ischaemic spectrum, from minimal myocardial damage, to unstable angina and myocardial infarction. The term acute coronary syndrome goes some way to encompassing these entities and recognising their continuity.
The Perfect Test? Initially, troponin seemed to be the perfect biochemical test for myocardial ischaemia. However, troponin rises have been reported in the setting of tachyarrhythmias, myocarditis, severe congestive cardiac failure, pulmonary embolism, severe sepsis, use of cardiotoxic chemo(see therapy drugs, cirrhosis and renal failur$632 Table 2). Interestingly, in patients with renal failure and cirrhosis, where troponin levels are elevated, left ventricular function, assessed by echocardiography, was significantly reduced compared to similar patients with normal troponin levels. The exact pathophysiologic mechanisms of troponin elevation outside the setting of myocardial ischaemia remains unclear. At present, the majority of studies considering the prognostic significance of troponins have focused on patients who present with an acute coronary syndrome. There is limited data in regard to patients with elevated Table 2. Conditions associated with elevated Troponin levels Acute coronary syndromes Post-PCI/Post-CABG Tachyarrhythmias Severe Congestive Heart Failure Cardiac contusion Myocarditis Cardiotoxic chemotherapy Pulmonary Embolism Severe Sepsis Cirrhosis Renal Failure
troponin levels without an acute coronary syndrome or in those presenting with symptoms of other diseases.33-36 The significance of Troponin elevation in the absence of other features of an acute coronary syndrome is unknown. We do not know whether these patients are at increased risk of death or cardiac events. We do not know whether they should be admitted to hospital or to what extent they should be investigated for cardiac disease. Currently, many of these patients are admitted to hospital in the absence of any major body of clinical evidence to support such decisions. This results in significant financial burden to the healthcare system, as well as the personal stress involved for the patient. Further research will provide some answers to these questions.
Future Directions It has been demonstrated that as ischaemia progresses, troponin I is degraded predictably into smaller and smaller fragments that can be detected in the bloodstream.37 This may eventually allow more accurate determination of the duration of ischaemia and the likelihood of myocardial salvage and recovery. The use of troponin in combination with other new cardiac biomarkers is an appealing prospect. High sensitivity C-reactive peptide (hs-CRP), an inflammatory marker, has been shown to synergistically complement the prognostic utility of troponin.38 Brain natriuretic peptide (BNP), a marker of left ventricular dysfunction, may complement these other markers in signifying the functional consequences of the ischaemic insult.39 Biomarkers of coronary plaque instability are also being sought and have been reported.40 Perhaps detectable rises in these may portend ischaemic events, even before they occur, providing new possibilities in ‘pre-emptive’ intervention.
References 1. Adams JE III, Bodor GS, Davilla-Roman ponin I: A marker with high specificity lation 1993; 88: 101-6.
VG et al. Cardiac for cardiac injury.
TroCircu-
Heart,
Lung
and Circulation
2003;
12 The twilight
2. Tobacman LS. Thin filament-mediated regulation of cardiac contraction. Annu. Rev. Physiol. 1996; 58: 447-81. 3. Adams JE III, Bodor GS, Davilla-Roman VG et al. Cardiac troponin I. A marker with high specificity for cardiac injury. CircuL&ion 1993; 88: 101. 4. Bodor GS, Porterfield D, Voss EM, Smith S, Apple FS. Cardiac troponin I is not expressed in fetal and healthy or diseased adult human skeletal muscle tissue. Clin. Chem. 1995; 41: 1710-5. 5. 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. 6. Adams JE III, Schechtman KB, Landt Y et al. Comparable detection of acute myocardial infarction by creatine kinase MB isoenzyme and cardiac troponin I. Clin. Chem. 1994; 40: 1291. 7. Wu AH. Biochemical markers of cardiac damage: from traditional enzymes to cardiac-specific proteins. IFCC Subcommittee on Standardization of Cardiac Markers (S-SCM). Stand. 1. Clin. Laboratory Invest. Suppl. 1999; 230: 74-82. 8. Jaffe AS. Troponins, creatinine kinase, and CK isoforms as biomarkers of cardiac injury. UpToDate Online 2002. Available from URL: www.uptodate.com 9. Adams JE III, Abendschein DR, Jaffe AS. Biochemical markers of myocardial injury. Is MB creatine kinase the choice for the 199Os? Circulation 1993; 88: 750. 10. Hamm CW, Ravkilde J, Gerhardt W et al. The prognostic value of serum troponin T in unstable angina. N. En@ J Med. 1992; 327: 146-50. 11. Antman EM, Tanasijevic MJ, Thompson B et nl. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N. Engl. 1. Med. 1996; 335: 1342-9. 12. Galvani M, Ottani F, Ferrini D et al. Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina. Circulation 1997; 95: 2053-9. 13. Luscher MS, Thygesen K, Ravkilde J, Heichendorff L. Applicability of cardiac troponin T and I for early risk stratification in unstable coronary artery disease. Circulation 1997; 96: 2578-85. 14. Ohman EM. Troponin and other cardiac markers: role in management of acute coronary syndromes. Aust. NZ 1. Med. 1999; 29: 43643. 15. Lindahl B, Toss H, Siegbahn A, Venge I’, Wallentin L. Markers of myocardial damage and inflammation in relation to longterm mortality in unstable coronary artery disease. Fragmin in Unstable Coronary Disease (FRISC) Study Group. N. En,@. 1. Med. 2000; 343: 113947. 16. Ottani F, Galvani M, Nicolini FA et al. Elevated cardiac troponin levels predict the risk of adverse outcome in patients with acute coronary syndromes. Am. Heart I.2000; 140: 917-27. 17. Olatidoye AG, Wu AH, Feng YJ, Waters D. Prognostic role of troponin T versus troponin I in unstable angina pectoris for cardiac events with meta-analysis comparing published studies. Am. 1, Cardiol. 1998; 81: 1405-10. 18. Lindahl B, Venge P, Wallentin L. Troponin T identifies patients with unstable coronary disease who benefit from long-term antithrombotic protection. FRlSC Group. J. Am. Co/l. Cardiol. 1997; 29: 43-S. 19. Hamm CW, Heeschen C, Goldmann B et ~2. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. C7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators. N. En@. 1. Med. 1999; 340: 1623-9.
H. Zimmet zone of troponins
s93
20. Heeschen C, Hamm CW, Goldmann B, Deu A, Langebrink L, White HD. Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban. PRISM Study Investigators. Plntelet Receptor Inhibition lschaemic Syndrome Manage. Lancet 1999; 354: 1757-62. 21. Morrow DA, Antman EM, Tanasijevic M et al. Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-IIB substudy. J. Am. Coil. Cnrdiol. 2000; 36: 1812-7. 22. Morrow DA, Cannon CP, Rifai N, Frey MJ 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: 2405-12. 23. Ricchiuti V, Shear WS, Henry TD, Paulsen PR, Miller EA, Apple FS. Monitoring plasma cardiac troponin I for the detection of myocardial injury after percutaneous transluminal coronary angioplasty. Clin. Chim Acta 2000; 302: 161-70. 24. Eigel I’, van Ingen G, Wagenpfeil S. Predictive value of perioperative cardiac troponin I for adverse outcome in coronary artery bypass surgery. Eur. J. Cnrdiothoruc. Surg. 2001; 20: 544-9. 25. The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined - A consensus document of the Joint European Sociey of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. 1. Am. Coil. Cardiol. 2000; 36: 957-8. 26. Smith SC, Ladenson JH, Mason JW, Jaffe AS. Elevations of cardiac troponin I associated with myocarditis. Experimental and clinical correlates. Circulation 1997; 95 (1): 163-8. 27. Missov E, Calzolari C, Pau B. Circulating cardiac troponin I in severe congestive heart failure. Circulation 1997; 96 (9): 2953-8. 28. Giannitsis E, Muller-Bardorff M, Kurowski V, Weidtmann B, Wiegand U, Kampmann M, Katus HA. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism. Circulation 2000; 102 (2): 211-7. 29. Spies C, Haude V, Fitzner R et al. Serum cardiac troponin T as a prognostic marker in early sepsis. Chest 1998; 113: 1055-63. 30. Missov E, Calzolari C, Pau 8. Increased levels of cardiac troponin I in cancer patients. J Am. Coil. CurdioL 1997; 29: 321A. 31. Pateron D, Beyne I’, Laperche T et al. Elevated circulating cardiac troponin I in patients with cirrhosis. Hepatology 1999; 29: 640-3. 32. Roppolo LP, Fitzgerald R., Dillow J, Ziegler T, Rice M, Maisel A. A comparison of troponin T and troponin I as predictors of cardiac events in patients undergoing chronic dialysis at a Veteran’s Hospital: a pilot study. J. Am. Coil. Cardiol. 1999; 34: 4%54. 33. Barasch E, Kaushik V, Gupta R., Ronen I’, Hartwell B. Elevated cardiac troponin levels do not predict adverse outcomes in hospitalised patients without clinical manifestation of acute coronary syndromes. Cardiology 2000; 93: l-6. 34. Khan IA, Tun A, Wattanasauwan N et al. Elevation of serum cardiac troponin I in noncardiac and cardiac diseases other than acute coronary syndromes. Am. 1. Emerg. Med. 1999; 17: 225-9. 35. Guest TM, Ramanathan AV, Tuteur PG, Schechtmann KB, Ladenson JH, Jaffe AS. Myocardial injury in critically ill patients - a frequency unrecognised complication. JAMA 1995; 273: 1945-9. 36. Wright SA, Sawyer DB, Sacks DB, Chyu S, Goldhaber SZ. Elevation of troponin I levels in patients without evidence of myocardial injury. ]AMA 1997; 278: 2144.
s94
H. Zimmet The twilight
Heart, zone
Lung
and Circulation
2003; 12
of troponins
37. McDonough JL, Arrell DK, Van Eyk JE. Troponin I degradation and covalent complex formation accompanies myocardial ischaemia/reperfusion injury. Circ. Res. 1999; 84: 9-20. 38. Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L, The FRISC Study Group. Markers of Myocardial Damage and Inflammation in Relation to Long-Term Mortality in Unstable Coronary Artery Disease. N. En@. J. Med. 2000; 343: 1139-47.
39. de Lemos JA, Morrow DA, Bentley JH et ~2. The prognostic value of B-Type natriuretic peptide in patients with acute coronary syndromes. N. Engl. J. Med. 2001; 345: 1014-21. 40. Bayes-Genis A, Conover CA, Overgaard MT et a/. Pregnancyassociated plasma protein A as a marker of acute coronary syndromes. N. En@. 1. Med. 2001; 345: 1022-9.
Zone of Troponins
Hendrik
Zimmet,
MBBS
Epworth Hospital, Melbourne,
Australia
Since its introduction into the clinical environment in the early nineties, the cardiac enzyme troponin has significantly changed the way we diagnose and manage acute coronary syndromes. Troponin I is a biochemical marker of myocardial injury with a high level of specificity and sensitivity. It has been demonstrated that as ischaemia progresses, troponin I is degraded predictably into smaller and smaller fragments that can be detected in the blood-stream. This may eventually allow more accurate determination of the duration of ischaemia and the Lung and Circulafion 2003; 12: S90-S94) 1ikClihood of myocardial salvage and recovery. (Heart,
S
ince its introduction into the clinical environment in the early nineties, the cardiac enzyme troponin has significantly changed the way we diagnose and manage acute coronary syndromes. As with any new technology, it has provided some answers and raised many questions. Troponin I is a biochemical marker of myocardial injury with a high level of specificity and sensitivity.l Both troponin I and troponin T are structural proteins that regulate the calcium-modulated interaction of actin and myosin filaments in myocardial cells? (Fig. 1). Troponin I is not found outside heart muscle at any stage of human development.3,4 The Troponin Complex consists of three components that all interact - Troponin C, Troponin I and Troponin T. Troponin C (C for calcium) binds intercellular calcium that results in the Troponin I (I for inhibiting) shifting and exposing the binding site, Troponin T (T for tropomyosin) where myosin and actin crosslink (Fig. 2). -
tropomyosin
Troponin C
Troponin T
Figure 2. The troponin troponin
complex (troponin C, troponin T); (zuhite circles) actin; (grey line) tropomyosin.
myosin binding site
troponin complex Correspondence: Hendrik Zimmet, Flinders Drv, Bedford Park, South Email: [email protected]
Troponin I
Flinders Australia
Medical Centre, 5042, Australia.
Figure 1. Myocardial (white circles) actin.
actin filament
1,
Heart,
Lung
and
Circulation
2003; 12
H. Zimmet The twi/i,ght
Pathophysiology Release
of Ischaemic Troponin
Troponin exists in two major forms in the cardiac myocyte - cytosolic and structural.5,6 The cytosolic troponin floats freely in cytoplasm of the myocyte. The structural troponin is bound in complex form in actual myofilaments. When ischaemia occurs the integrity of the cell membrane is compromised and cytosolic troponin leaks out first causing the initial rise in serum troponin levels. A later result of the ischaemia is degradation of myofilaments causing the second characteristic rise in serum troponin levels7 (Figs 3 and 4). Serum troponin levels are first detectable by current conventional assays 4-6 h following the onset of ischaemia. Levels peak at around 18-24 h and then remain elevated for up to 10 days. 8 The release kinetics make
s91
of troponins
troponin an excellent biomarker for detection of myocardial ischaemia during the early, intermediate and late phases of an ischaemic event.
Comparison Enzymes
of Troponifi
and Other Cardiac
Prior to the routine use of troponin in the clinical setting, serum levels of creatinine kinase (CK) and its myocardial isoforms (CKMB), asparatate aminotransferase (AST) and lactate dehydrogenase (LDH) were used to determine the presence of myocardial infarction. Following a myocardial infarction, myoglobin levels become elevated first, followed by a rise in CK, followed by AST and finally LDH.? The combined assessment of the various levels of these biomarkers would allow estimation of when the myocardial infarction most likely occurred. If one considers the release kinetics of the various cardiac biomarkers, it is evident that troponin, alone, provides most of the information that the other cardiac biomarkers can only provide in combination.
Clinical
Figure 3. Two major forms of troponin 1 - cytosolic and structural.
zom
Application
Troponin I is not only of diagnostic but is also of highlevel prognostic significance in the setting of acute coronary syndromes. lo-l6 TroponinT shows similar properties in this regard.17 In acute coronary syndromes, troponin elevation predicts which patients are more likely to benefit from various treatments such as administration of low molecular weight heparin and inhibitors platelet glycoprotein _ -IIb/IIIa.18-21 Furthermore, there is emerging data to suggest that troponin levels may indicate which patients benefit from early invasive strategies. ZJInitial evidence also suggests that troponin elevation following percutaneous intervention23 or coronary artery bypass surgery24 may signify patients at higher risk of subsequent cardiac events.
New Definition of Acute Myocardial Infarction (AMI)
0
12
3
4
5
6
710
Days After Onset of AMI Figure 4. Troponin 1 releasekinetics. Blood level in days after onset of acute myocardial infarction.
The specificity and sensitivity of the troponin determination has led to a new joint European Society of Cardiology and American College of Cardiology recommendation for definition of AM1 that relies on the elevation of the cardiac marker in the first instan& (see Table 1). Even minor elevations of troponin define AMI. As a consequence, many patients with normal CK levels, who previously were diagnosed with unstable angina, now are considered to have suffered a myocardial infarction.
S92
H. Zimmet The twilight
Heart,
Lung
and Circulation
2003;
12
zone of troponins
Table 1. ESC/ACC Redefinition of AMP5 Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following: a. ischemic symptoms; b. development of pathologic Q waves; c. ECG changes indicative of ischemia (ST segment elevation or depression; d. coronary artery intervention Pathologic findings of AM1
The greater sensitivity and specificity that troponin provides in detecting myocardial ischaemia now lays before us a clearer picture of the ischaemic spectrum, from minimal myocardial damage, to unstable angina and myocardial infarction. The term acute coronary syndrome goes some way to encompassing these entities and recognising their continuity.
The Perfect Test? Initially, troponin seemed to be the perfect biochemical test for myocardial ischaemia. However, troponin rises have been reported in the setting of tachyarrhythmias, myocarditis, severe congestive cardiac failure, pulmonary embolism, severe sepsis, use of cardiotoxic chemo(see therapy drugs, cirrhosis and renal failur$632 Table 2). Interestingly, in patients with renal failure and cirrhosis, where troponin levels are elevated, left ventricular function, assessed by echocardiography, was significantly reduced compared to similar patients with normal troponin levels. The exact pathophysiologic mechanisms of troponin elevation outside the setting of myocardial ischaemia remains unclear. At present, the majority of studies considering the prognostic significance of troponins have focused on patients who present with an acute coronary syndrome. There is limited data in regard to patients with elevated Table 2. Conditions associated with elevated Troponin levels Acute coronary syndromes Post-PCI/Post-CABG Tachyarrhythmias Severe Congestive Heart Failure Cardiac contusion Myocarditis Cardiotoxic chemotherapy Pulmonary Embolism Severe Sepsis Cirrhosis Renal Failure
troponin levels without an acute coronary syndrome or in those presenting with symptoms of other diseases.33-36 The significance of Troponin elevation in the absence of other features of an acute coronary syndrome is unknown. We do not know whether these patients are at increased risk of death or cardiac events. We do not know whether they should be admitted to hospital or to what extent they should be investigated for cardiac disease. Currently, many of these patients are admitted to hospital in the absence of any major body of clinical evidence to support such decisions. This results in significant financial burden to the healthcare system, as well as the personal stress involved for the patient. Further research will provide some answers to these questions.
Future Directions It has been demonstrated that as ischaemia progresses, troponin I is degraded predictably into smaller and smaller fragments that can be detected in the bloodstream.37 This may eventually allow more accurate determination of the duration of ischaemia and the likelihood of myocardial salvage and recovery. The use of troponin in combination with other new cardiac biomarkers is an appealing prospect. High sensitivity C-reactive peptide (hs-CRP), an inflammatory marker, has been shown to synergistically complement the prognostic utility of troponin.38 Brain natriuretic peptide (BNP), a marker of left ventricular dysfunction, may complement these other markers in signifying the functional consequences of the ischaemic insult.39 Biomarkers of coronary plaque instability are also being sought and have been reported.40 Perhaps detectable rises in these may portend ischaemic events, even before they occur, providing new possibilities in ‘pre-emptive’ intervention.
References 1. Adams JE III, Bodor GS, Davilla-Roman ponin I: A marker with high specificity lation 1993; 88: 101-6.
VG et al. Cardiac for cardiac injury.
TroCircu-
Heart,
Lung
and Circulation
2003;
12 The twilight
2. Tobacman LS. Thin filament-mediated regulation of cardiac contraction. Annu. Rev. Physiol. 1996; 58: 447-81. 3. Adams JE III, Bodor GS, Davilla-Roman VG et al. Cardiac troponin I. A marker with high specificity for cardiac injury. CircuL&ion 1993; 88: 101. 4. Bodor GS, Porterfield D, Voss EM, Smith S, Apple FS. Cardiac troponin I is not expressed in fetal and healthy or diseased adult human skeletal muscle tissue. Clin. Chem. 1995; 41: 1710-5. 5. 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. 6. Adams JE III, Schechtman KB, Landt Y et al. Comparable detection of acute myocardial infarction by creatine kinase MB isoenzyme and cardiac troponin I. Clin. Chem. 1994; 40: 1291. 7. Wu AH. Biochemical markers of cardiac damage: from traditional enzymes to cardiac-specific proteins. IFCC Subcommittee on Standardization of Cardiac Markers (S-SCM). Stand. 1. Clin. Laboratory Invest. Suppl. 1999; 230: 74-82. 8. Jaffe AS. Troponins, creatinine kinase, and CK isoforms as biomarkers of cardiac injury. UpToDate Online 2002. Available from URL: www.uptodate.com 9. Adams JE III, Abendschein DR, Jaffe AS. Biochemical markers of myocardial injury. Is MB creatine kinase the choice for the 199Os? Circulation 1993; 88: 750. 10. Hamm CW, Ravkilde J, Gerhardt W et al. The prognostic value of serum troponin T in unstable angina. N. En@ J Med. 1992; 327: 146-50. 11. Antman EM, Tanasijevic MJ, Thompson B et nl. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N. Engl. 1. Med. 1996; 335: 1342-9. 12. Galvani M, Ottani F, Ferrini D et al. Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina. Circulation 1997; 95: 2053-9. 13. Luscher MS, Thygesen K, Ravkilde J, Heichendorff L. Applicability of cardiac troponin T and I for early risk stratification in unstable coronary artery disease. Circulation 1997; 96: 2578-85. 14. Ohman EM. Troponin and other cardiac markers: role in management of acute coronary syndromes. Aust. NZ 1. Med. 1999; 29: 43643. 15. Lindahl B, Toss H, Siegbahn A, Venge I’, Wallentin L. Markers of myocardial damage and inflammation in relation to longterm mortality in unstable coronary artery disease. Fragmin in Unstable Coronary Disease (FRISC) Study Group. N. En,@. 1. Med. 2000; 343: 113947. 16. Ottani F, Galvani M, Nicolini FA et al. Elevated cardiac troponin levels predict the risk of adverse outcome in patients with acute coronary syndromes. Am. Heart I.2000; 140: 917-27. 17. Olatidoye AG, Wu AH, Feng YJ, Waters D. Prognostic role of troponin T versus troponin I in unstable angina pectoris for cardiac events with meta-analysis comparing published studies. Am. 1, Cardiol. 1998; 81: 1405-10. 18. Lindahl B, Venge P, Wallentin L. Troponin T identifies patients with unstable coronary disease who benefit from long-term antithrombotic protection. FRlSC Group. J. Am. Co/l. Cardiol. 1997; 29: 43-S. 19. Hamm CW, Heeschen C, Goldmann B et ~2. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. C7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators. N. En@. 1. Med. 1999; 340: 1623-9.
H. Zimmet zone of troponins
s93
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