CLINICAL STUDY: ACUTE CORONARY SYNDROMES
Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy
David A. Morrow, MDa,
Elliott M. Antman, MD, FACCa,
Milenko Tanasijevic, MDb,
Nader Rifai, PhDc,
James A. de Lemos, MDa,
Carolyn H. McCabe, BSa,
Christopher P. Cannon, MD, FACCa and
Eugene Braunwald, MD, FACCa
a Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
b Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
c Department of Laboratory Medicine, Children’s Hospital, Boston, Massachusetts, USA
Manuscript received December 30, 1999;
revised manuscript received May 8, 2000,
accepted June 28, 2000.
Reprint requests and correspondence: Dr. David A. Morrow, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115
damorrow{at}bics.bwh.harvard.edu
 |
Abstract
|
|---|
Objectives
We sought to evaluate cardiac troponin I (cTnI) for predicting early clinical outcomes and the efficacy of enoxaparin among patients with non–ST segment elevation acute coronary syndrome (ACS) and negative creatine kinase, MB fraction (CK-MB) levels.
Background
Cardiac TnI identifies patients with unstable angina who are at higher risk of death or myocardial infarction (MI) by 30 days. The utility of cTnI for predicting very early clinical events, including recurrent ischemia, and the efficacy of enoxaparin are not yet established.
Methods
At baseline and 12 h to 24 h after enrollment in the Thrombolysis in Myocardial Infarction (TIMI)-11B trial, samples were collected for cTnI determination.
Results
Among 359 patients with negative serial CK-MB values, 50.1% had a cTnI result  0.1 ng/ml within the first 24 h. Patients with elevated cTnI were at higher risk of death or MI at 48 h (3.9 vs. 0%, p = 0.01) and 14 days (13.9 vs. 2.2%, p < 0.0001). Elevated cTnI also correlated with higher risk of recurrent ischemia requiring urgent revascularization by 48 h (10.0 vs. 1.7%, p = 0.001) and 14 days (20.6 vs. 5.6%, p  0.0001). Enoxaparin had a greater benefit among patients with elevated vs. normal cTnI (p = 0.03), achieving a 47% reduction in the risk of death, MI or urgent revascularization by 14 days in cTnI-positive patients (p = 0.007).
Conclusions
Elevation of cTnI among patients with non–ST segment elevation ACS and negative levels of CK-MB identifies those at higher risk for very early adverse outcomes, including severe recurrent ischemia. Treatment with enoxaparin reduces the risk associated with elevated cTnI.
|
Abbreviations and Acronyms
| | ACS | = acute coronary syndrome | | CABG | = coronary artery bypass graft surgery | | CI | = confidence interval | | CK-MB | = creatine kinase, MB fraction | | cTnI | = cardiac troponin I | | MI | = myocardial infarction | | PTCA | = percutaneous transluminal coronary angioplasty | | TIMI | = Thrombolysis in Myocardial Infarction | | UFH | = unfractionated heparin | | ULN | = upper limit of normal |
|
Patients with unstable angina are heterogeneous with respect to prognosis and present a particular challenge for early risk assessment and triage (1,2), compared with patients with elevated levels of creatine kinase, MB fraction (CK-MB), who may be recognized as being at higher risk (3). Cardiac-specific troponin I (cTnI) is a highly sensitive and specific marker of myocardial necrosis (4) that has demonstrated prognostic utility among the substantial proportion of patients with non–ST segment elevation acute coronary syndrome (ACS) who have no elevation of CK-MB (5–8). We have shown previously that elevation of cTnI 0.4 ng/ml at the time of presentation identifies patients with ischemic symptoms and normal CK-MB who are at higher risk of death by 42 days (5). Other clinical studies have demonstrated that elevated levels of cTnI are associated with a higher incidence of death or myocardial infarction (MI) by 30 days among patients with chest pain suspicious for angina (9) and documented unstable coronary disease (6–8). However, data evaluating the relation between cTnI and the occurrence of refractory angina, as well as the need for revascularization, have been inconclusive (6,7). Furthermore, published data regarding the prognostic utility of cTnI for predicting the risk of clinical events at very early time points (e.g., 48 h) in patients with unstable angina are limited. Finally, current generation cTnI assays offer greater analytic sensitivity than previous versions and have created the need for clinical evaluation of lower cTnI thresholds for risk assessment in ACS (10).
Given increasing economic pressure to constrain the duration of inpatient management and to target more expensive and aggressive therapies, the ability to identify at presentation those patients with ischemic symptoms and negative CK-MB who are at higher risk for early adverse outcomes has taken on particular clinical importance. In addition, data documenting an association between elevation of cardiac troponin T and enhanced efficacy of specific medical therapies (11–14) have demonstrated the potential for the cardiac troponins in guiding early management decisions. Thus, we have evaluated cTnI at a threshold of 0.1 ng/ml, using a current generation assay (Dimension RxL, Dade Behring, Newark, Delaware), for the purpose of predicting early adverse cardiac events, including recurrent ischemia necessitating urgent revascularization by 48 h and 14 days, among patients with unstable angina enrolled in Thrombolysis in Myocardial Infarction (TIMI)-11B Trial. In addition, we tested for any interaction between cTnI results and the efficacy of enoxaparin over unfractionated heparin (UFH) therapy.
|
Methods
|
|---|
Patients.
Men and women with unstable angina enrolled at any of 63 North or South American centers participating in the biomarker protocol of TIMI-11B were eligible for this substudy. The diagnosis of the presenting ischemic syndrome was made by the local investigator on the basis of World Health Organization criteria for MI, using local serial measurements of CK or CK-MB as defined in the TIMI-11B protocol (15) and collected on the Initial Hospitalization Case Report Form. Patients presenting with an ischemic syndrome without acute MI were diagnosed with unstable angina.
TIMI-11B was a randomized, double-blind, parallel group trial of the low molecular weight heparin, enoxaparin, as compared with UFH, for the treatment of high risk patients presenting with non–ST segment elevation ACS. The trial design and inclusion and exclusion criteria of TIMI-11B have been published previously (15). Participants were required to have symptoms at rest within the previous 24 h and evidence of ischemic heart disease (15). Exclusion criteria included plans for revascularization in the first 24 h, regardless of the initial response to medical therapy, coronary artery bypass graft surgery (CABG) within the previous two months or percutaneous transluminal coronary angioplasty (PTCA) within six months and renal insufficiency (serum creatinine >2.0 mg/dl). The TIMI-11B protocol, including the biomarker substudy, was approved by the institutional Committee on Human Research at each of the participating centers.
During the acute phase of TIMI-11B, patients were treated with either intravenous UFH (n = 190) or weight-adjusted dosing of subcutaneous enoxaparin (n = 169). The median duration of treatment with intravenous UFH and acute-phase subcutaneous enoxaparin in the substudy group was 3.0 and 3.5 days, respectively. Patients eligible for the chronic-term phase (e.g., no bleeding or CABG) were then administered fixed-dose subcutaneous enoxaparin or placebo for an additional 35 days (59% of patients in the enoxaparin group and 52% in the UFH/placebo group), starting at the time of discharge or day 8, whichever occurred first.
Blood sampling and measurement of serum markers.
The serum marker protocol specified that on enrollment and 12 h to 24 h later, venous blood samples be drawn and serum stored at –20°C or colder at the enrolling site until shipped to the Core Laboratory at Children’s Hospital Medical Center (Boston, Massachusetts), where they were stored at –80°C until analyzed.
Cardiac TnI results were determined in the Chemistry Laboratory at Brigham and Women’s Hospital (Boston, Massachusetts) on thawed sera using the Dimension RxL cTnI assay (Dade Behring). All operators had no knowledge of patient treatment or clinical outcomes. The day-to-day precision of this assay in the Brigham and Women’s Hospital laboratory, at cTnI concentrations of 0.57 ng/ml, 2.58 ng/ml and 12.22 ng/ml, is reflected by coefficients of variation of 8.8%, 3.1% and 1.5%, respectively. The minimal detectable concentration is 0.04 ng/ml. The 97.5 percentile for 197 healthy blood donors tested in our laboratory was determined to be 0.1 ng/ml. In its "Standards of Laboratory Practice: Recommendations for the Use of Cardiac Markers" the National Academy of Clinical Biochemistry has recommended that the low abnormal decision limit for cardiac troponins in ACS be guided by the 97.5 percentile among normal control subjects (16). Consistent with this recommendation and clinical experience in our laboratory, we used a level of 0.1 ng/ml as the cTnI threshold for analyses in this substudy.
Definitions.
The clinical end point of MI in TIMI-11B was restricted to a new MI occurring after the qualifying ischemic event and included either new diagnostic Q waves or left bundle branch block not present on the enrollment electrocardiogram (ECG) or enzyme evidence of a new infarction (15). Elevation of CK-MB above the upper limit of normal (ULN) and at least 50% over the previous value or, if the CK-MB value was unavailable, elevation of total CK above two times the ULN and 25% of the previous value was necessary to meet enzymatic criteria for a new MI. For patients within 24 h of PTCA or CABG, total CK and CK-MB values were required to be 50% of the previous value and three and five times the ULN, respectively (15). Participants were determined to have recurrent ischemia requiring urgent revascularization if they had either recurrent angina prompting the performance of coronary revascularization during the same hospital stay or an episode of unstable angina after discharge, resulting in repeat hospital admission and coronary intervention. All clinical end points in TIMI-11B, including recurrent ischemia requiring urgent revascularization, were adjudicated by an independent Clinical Endpoints Committee, which had no knowledge of treatment assignment, incorporating a detailed review of relevant ECGs, serum marker data, angiographic findings and a narrative summary.
Statistical analysis.
Statistical comparison of baseline characteristics and clinical outcomes were performed using the chi-square or Fisher exact test for dichotomous variables and either the Wilcoxon rank-sum or two-sample t test for continuous variables. Multivariate analyses were performed using a logistic regression model incorporating recognized cardiovascular risk factors (age, gender, history of coronary artery disease, diabetes, hypertension, tobacco use, ST segment deviation and presence of congestive heart failure at presentation). Testing for a significant interaction between categoric cTnI results and treatment arm was performed using the Breslow-Day test for homogeneity. Data analyses were performed using SAS statistical software (version 6.12, SAS Institute, Cary, North Carolina). All statistical comparisons were two-tailed, and p < 0.05 was considered to indicate statistical significance.
|
Results
|
|---|
Baseline characteristics.
This substudy of TIMI-11B included 359 patients with unstable coronary disease and negative serial CK-MB measurements who had serum samples obtained at baseline or 12 h to 24 h after enrollment, or both, available for determination of cTnI values in our laboratory. Demographic characteristics of patients eligible for this serum marker substudy showed higher rates of hypertension, previous angina and CABG, but were otherwise representative of those in the overall trial (Table 1), with a profile typical of patients presenting with severe unstable ischemic heart disease, including high rates of previous coronary artery disease (46%) and ST segment changes on presentation (81%). Patients in the substudy with a positive cTnI value (0.1 ng/ml) were more likely to be male and were slightly older (Table 1).
Cardiac TnI and clinical outcomes.
Three hundred and forty-one patients with negative CK-MB values had pre-enrollment cTnI determinations, with 155 (45.5%) showing elevated baseline cTnI levels. Of the 359 patients with samples from either time point, 180 (50.1%) had a positive cTnI result within the first 24 h after enrollment. There were 13 deaths (3.6%) by 14 days in the substudy group. Twenty-three patients (6.4%) had a MI after the qualifying index event, and 47 (13.1%) had severe recurrent ischemia requiring urgent revascularization.
Patients with an elevated cTnI value during the first 24 h were at significantly increased risk for adverse clinical events by as early as 48 h, as well as by 14 and 43 days (Table 2). An elevated cTnI value identified patients at a 6% higher absolute risk of death and a fourfold (95% confidence interval [CI] 2.5 to 7.7) higher risk of death, nonfatal MI or urgent revascularization (p < 0.0001) by two weeks after presentation. Moreover, patients with an abnormal cTnI value demonstrated a nearly sixfold higher risk of severe ischemia requiring urgent revascularization by 48 h after enrollment (p < 0.001), with a greater than 14% absolute risk difference at both 14 and 43 days (p 0.0001) (Table 2). Although utilization of the 12- to 24-h measurements added to the strength of the prognostic relation, baseline measurements alone were also highly predictive of each component of the composite end point by 14 days (Fig. 1), as well as severe recurrent ischemia requiring revascularization by 48 h (10.3 vs. 1.6%, p = 0.0005).
View larger version (21K):
[in this window]
[in a new window]
|
Figure 1 Clinical outcomes at 14 days stratified by baseline cTnI results (n = 341). D/MI/UR = death, MI or urgent revascularization.
|
|
In a multivariate model including major clinical risk factors (age, gender, diabetes, tobacco use, history of coronary artery disease, hypertension), as well as the presence of ST segment deviation (depression or transient elevation) on the qualifying ECG, a cTnI level 0.1 ng/ml was an independent predictor of adverse clinical outcomes at 14 days (Table 3). Furthermore, baseline elevation of cTnI was independently associated with a higher risk of severe recurrent ischemia necessitating urgent revascularization at 48 h (p = 0.005) and 14 days (p = 0.003).
Cardiac TnI and enoxaparin treatment.
Consistent with the superior efficacy of enoxaparin over UFH in patients in the main TIMI-11B trial (15), patients in the cTnI substudy treated with enoxaparin had fewer adverse clinical events (death, MI or urgent revascularization) by 14 days (relative risk 0.65, 95% CI 0.40 to 0.97). Stratification of the substudy group by cTnI results from 0 to 24 h revealed a greater relative benefit of enoxaparin therapy among patients with an abnormal cTnI value (Breslow-Day test, p = 0.03, indicating heterogeneity of the treatment effect of enoxaparin vs. UFH with respect to death, MI or urgent revascularization). Patients with an elevated cTnI value experienced a 17% absolute reduction in the risk of severe recurrent ischemia prompting revascularization and nearly half the risk of death, MI or urgent revascularization by 14 days (Fig. 2).
View larger version (26K):
[in this window]
[in a new window]
|
Figure 2 Clinical outcomes at 14 days for patients treated with enoxaparin versus UFH stratified by 0- to 24-h cTnI results. CI = confidence interval; D/MI/UR = death, MI or urgent revascularization; RR = relative risk of the outcome for patients treated with enoxaparin versus UFH.
|
|
|
Discussion
|
|---|
In this substudy of patients with unstable coronary syndromes and negative serial CK-MB measurements enrolled in TIMI-11B, elevated levels of cTnI (0.1 ng/ml) soon after presentation were strongly associated with very early adverse clinical outcomes, including a sixfold higher risk of recurrent ischemia requiring urgent revascularization by as early as 48 h after the initiation of study medication. Notably, an abnormal cTnI value identified patients who were at higher risk for each component of the composite end point (death, MI and recurrent ischemia prompting urgent revascularization) at 14 days. Consistent with previous observations, although elevated baseline levels of cTnI were highly correlated with recurrent cardiac events, repeat determination 12 h to 24 h after presentation added to the prognostic capacity of the marker. Furthermore, cTnI offered prognostic information independent of established clinical risk markers, including age and ST segment deviation on the presenting ECG, and identified higher risk patients who demonstrated particular benefit from enoxaparin versus UFH therapy.
Cardiac TnI and prognosis in unstable angina.
A number of previous studies have evaluated the prognostic capacity of cTnI in patients with suspected ischemic syndromes but no elevation of CK-MB. Among 948 patients with non–ST segment elevation ACS and negative CK-MB enrolled in TIMI-IIIB, elevation of baseline cTnI 0.4 ng/ml, as measured with an earlier generation assay (Stratus II, Dade Behring), was associated with a threefold higher mortality risk at six weeks (5). Galvani et al. (6) made similar observations regarding the prognostic capacity of cTnI with respect to death and nonfatal MI at 30 days and one year among 91 patients with Braunwald class IIIB unstable angina. Data from the ThRombin Inhibition In Myocardial ischemia (TRIM) investigators (7) demonstrated that cTnI levels 2.0 ng/ml (Opus, Behring Diagnostics) were associated with higher 30-day mortality among 309 patients with unstable angina. A meta-analysis including each of these studies showed a cumulative odds ratio of 4.2 (95% CI 2.7 to 6.4) for death or MI over a mean follow-up period of 42 days after presentation with unstable angina and elevated cTnI (8).
Data from TIMI-11B—clinical implications.
Our current report expands on previous studies in several areas of clinical importance. Although the predictive capacity of cTnI with respect to death and MI at four to six weeks after presentation with unstable angina is well documented (5–8), data regarding earlier clinical outcomes are limited. In addition, although several previous investigations have directly explored the relation between cTnI levels and the incidence of recurrent ischemia or revascularization, or both, the data from these studies have been inconclusive (6,7,17). Our report addresses each of these areas that impact decisions regarding the early management of patients with non–ST segment elevation ACS and negative CK-MB values, who might otherwise be considered at lower short-term risk for poor outcomes. These data also suggest that angiographic observations of an association between troponin elevation and thrombus burden/lesion complexity (18) may have immediate clinical relevance with respect to the patient’s risk of early recurrent ischemic events.
Cardiac TnI and therapeutic decision-making.
Given that economic and safety considerations are likely to prohibit the uniform use of expensive pharmacologic and invasive therapies, the identification of patients with non–ST segment elevation ACS who will benefit most from these interventions has become central to the care of this group of patients. Our report suggests that cTnI levels measured soon after presentation are useful in selecting patients with negative CK-MB values who are at higher risk for early adverse outcomes, including severe recurrent ischemia, and who might therefore be considered candidates for more aggressive medical therapy or an early invasive intervention. Our findings also offer evidence that treatment with enoxaparin, a low molecular weight heparin with demonstrated superiority over UFH (15), reduces the risk of poor outcomes associated with an abnormal cTnI level. As such, our data indicate that cTnI, like cardiac troponin T (11,13), may be useful in targeting new antithrombin and antiplatelet (12,14) therapies.
Study limitations.
The TIMI-11B substudy enrolled a high risk group of patients with non–ST segment elevation ACS. One must maintain some caution in extrapolating our data on patients with evidence of ischemic heart disease to more heterogeneous populations with chest symptoms. Furthermore, a number of factors contribute to analytic variability between cTnI methods, as reflected in the diversity of decision limits used in clinical laboratories and reported in the literature (19–21). Thus, although our results provide an evidenced-based guide for the clinical use of a current generation assay (Dimension RxL), one should be wary of generalizing the threshold used in this study to other cTnI assays. Nevertheless, it is interesting to note that in a diverse group of patients with chest pain, a bedside device with a detection limit of 0.1 ng/ml (Spectral Diagnostics; Toronto, Canada) reliably identified patients at higher risk for cardiac death or nonfatal MI over a follow-up of 30 days (9).
Although during the period of this study, few centers participating in TIMI-11B were measuring cardiac troponins in their local laboratories, we cannot exclude the possibility that in few cases, local marker results might have influenced the investigator’s decisions regarding revascularization. However, the end point of severe recurrent ischemia prompting urgent revascularization was carefully adjudicated by an independent Clinical Events Committee and required evidence that both an episode of recurrent ischemia had occurred and the recurrent ischemia had prompted revascularization. Furthermore, given that treatment allocation was blinded, there is no reason to expect systematic bias in the interpretation of any local laboratory measurements with respect to the treatment arm.
Conclusions.
This cTnI substudy from TIMI-11B demonstrates a consistent and significant increase in the risk of early adverse cardiovascular outcomes associated with abnormal levels of cTnI among patients with non–ST segment elevation ACS and negative values of CK-MB. The predictive capacity of cTnI is evident as early as 48 h after presentation and is independent of multiple, well-described clinical risk factors, including age and ST segment deviation. Moreover, an elevated cTnI value identifies patients who may derive particular benefit from enoxaparin therapy.
|
Footnotes
|
|---|
This study was supported by Dade Behring, Newark, Delaware, and Rhone-Poulenc Rorer, Collegeville, Pennsylvania.
|
References
|
|---|
1. Braunwald E. Unstable angina: an etiologic approach to management. Circulation. 1998;98:2219–2222[Free Full Text]
2. Theroux P, Fuster V. Acute coronary syndromes: unstable angina and non–Q-wave myocardial infarction. Circulation. 1998;97:1195–1206[Free Full Text]
3. Braunwald E, Mark D, Jones R, et al. Unstable Angina: Diagnosis and Management. Clinical Practice Guidline Number 10. AHCPR Publication No. 94-0602. Rockville, MD: Agency for Health Care Policy and Research and the National Heart, Lung, and Blood Institute, Public Health Service, U.S. Department of Health and Human Services, 1994:154.
4. Bodor GS, Porter S, Landt Y, Ladenson JH. Development of monoclonal antibodies for an assay of cardiac troponin-I and preliminary results in suspected cases of myocardial infarction. Clin Chem. 1992;38:2203–2214[Abstract/Free Full Text]
5. Antman EM, Tanasijevic MJ, 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[Abstract/Free Full Text]
6. Galvani M, Ottani F, Ferrini D, et al. Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina. Circulation. 1997;95:2053–2059[Abstract/Free Full Text]
7. ThRombin Inhibition In Myocardial ischemia (TRIM) Study GroupLuscher MS, Thygesen K, Ravkilde J, Heickendorff L. Applicability of cardiac troponins T and I for early risk stratification in unstable coronary artery disease. Circulation. 1997;96:2578–2585[Abstract/Free Full Text]
8. 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 J Cardiol. 1998;81:1405–1410[CrossRef][Medline]
9. Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med. 1997;337:1648–1653[Abstract/Free Full Text]
10. Morrow DA, Rifai N, Tanasijevic MJ, Wybenga DR, de Lemos JA, Antman EM. Clinical efficacy of three assays for cardiac troponin I for risk stratification in acute coronary syndromes: a Thrombolysis In Myocardial Infarction (TIMI) 11B substudy. Clin Chem. 2000;46:453–460[Abstract/Free Full Text]
11. Fragmin in Unstable Coronary Artery Disease (FRISC) Study GroupLindahl B, Venge P, Wallentin L. Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. J Am Coll Cardiol. 1997;29:43–48[Abstract]
12. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study InvestigatorsHamm CW, Heeschen C, Goldmann B, et al. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. N Engl J Med. 1999;340:1623–1629[Abstract/Free Full Text]
13. FRISC II Investigators. Long-term low-molecular-mass heparin in unstable coronary artery disease: FRISC II prospective randomised multicentre study. Lancet. 1999;354:701–707[CrossRef][Medline]
14. Heeschen C, Hamm CW, Goldmann B, Deu A, Langenbrink L, White HD. Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban. Lancet. 1999;354:1757–1762[CrossRef][Medline]
15. Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non–Q wave myocardial infarction: results of the TIMI 11B trial. Circulation. 1999;100:1593–1601[Abstract/Free Full Text]
16. Wu A, Apple F, Gibler W, Jesse R, Warshaw M, Valdes R. National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for the use of cardiac markers in coronary artery diseases. Clin Chem. 1999;45:1104–1121[Abstract/Free Full Text]
17. GUSTO-IIa InvestigatorsChristenson RH, Duh SH, Newby LK, et al. Cardiac troponin T and cardiac troponin I: relative values in short-term risk stratification of patients with acute coronary syndromes. Clin Chem. 1998;44:494–501[Abstract/Free Full Text]
18. Heeschen C, van Den Brand MJ, Hamm CW, Simoons ML. Angiographic findings in patients with refractory unstable angina according to troponin T status. Circulation. 1999;100:1509–1514[Abstract/Free Full Text]
19. Wu AH, Feng YJ, Moore R, et al. Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I: American Association for Clinical Chemistry Subcommittee on cTnI Standardization. Clin Chem. 1998;44:1198–1208[Abstract/Free Full Text]
20. Katrukha AG, Bereznikova AV, Esakova TV, et al. Troponin I is released in bloodstream of patients with acute myocardial infarction not in free form but as complex. Clin Chem. 1997;43:1379–1385[Abstract/Free Full Text]
21. Apple FS. Clinical and analytical standardization issues confronting cardiac troponin I. Clin Chem. 1999;45:18–20[Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
T. Reichlin, W. Hochholzer, S. Bassetti, S. Steuer, C. Stelzig, S. Hartwiger, S. Biedert, N. Schaub, C. Buerge, M. Potocki, et al.
Early Diagnosis of Myocardial Infarction with Sensitive Cardiac Troponin Assays
N. Engl. J. Med.,
August 27, 2009;
361(9):
858 - 867.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Damman, J. Tijssen, R. de Winter, B. Rathod, A. Cequier, J. A. Gomez-Hospital, J. Gonzalez-Costello, S. Shojai, S. R. Mehta, S. Yusuf, et al.
Acute Coronary Syndromes
N. Engl. J. Med.,
August 27, 2009;
361(9):
925 - 927.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Rohatgi and J. A. de Lemos
The Report Card on Growth Differentiation Factor 15: Consistent Marks But Not Yet Ready for Promotion
Circ Cardiovasc Genet,
June 1, 2009;
2(3):
209 - 211.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Halim, J. Mulgund, A. Y. Chen, M. T. Roe, E. D. Peterson, W. B. Gibler, E. M. Ohman, and L. K. Newby
Use of Guidelines-Recommended Management and Outcomes Among Women and Men With Low-Level Troponin Elevation: Insights From CRUSADE
Circ Cardiovasc Qual Outcomes,
May 1, 2009;
2(3):
199 - 206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S Alpert, K. Thygesen, A. Jaffe, and H. D White
The universal definition of myocardial infarction: a consensus document
Heart,
October 1, 2008;
94(10):
1335 - 1341.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Bonaca and D. A. Morrow
Defining a Role for Novel Biomarkers in Acute Coronary Syndromes
Clin. Chem.,
September 1, 2008;
54(9):
1424 - 1431.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C D Miller, G J Fermann, C J Lindsell, K W Mahaffey, W F Peacock, C V Pollack, J E Hollander, D B Diercks, W B Gibler, and J W Hoekstra on behalf of the EMCREG-International
Initial risk stratification and presenting characteristics of patients with evolving myocardial infarctions
Emerg. Med. J.,
August 1, 2008;
25(8):
492 - 497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
NACB WRITING GROUP MEMBERS, D. A. Morrow, C. P. Cannon, R. L. Jesse, L. K. Newby, J. Ravkilde, A. B. Storrow, A. H.B. Wu, and R. H. Christenson
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes
Circulation,
April 3, 2007;
115(13):
e356 - e375.
[Full Text]
[PDF]
|
|
|
|
|
|
|
NACB WRITING GROUP MEMBERS, D. A. Morrow, C. P. Cannon, R. L. Jesse, L. K. Newby, J. Ravkilde, A. B. Storrow, A. H.B. Wu, R. H. Christenson, NACB COMMITTEE MEMBERS, et al.
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes
Clin. Chem.,
April 1, 2007;
53(4):
552 - 574.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Jaffe, L. Babuin, and F. S. Apple
Biomarkers in Acute Cardiac Disease: The Present and the Future
J. Am. Coll. Cardiol.,
July 4, 2006;
48(1):
1 - 11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. K. Newby, M. T. Roe, A. Y. Chen, E. M. Ohman, R. H. Christenson, C. V. Pollack Jr, J. W. Hoekstra, W. F. Peacock, R. A. Harrington, R. L. Jesse, et al.
Frequency and Clinical Implications of Discordant Creatine Kinase-MB and Troponin Measurements in Acute Coronary Syndromes
J. Am. Coll. Cardiol.,
January 17, 2006;
47(2):
312 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Part 5: Acute Coronary Syndromes
Circulation,
November 29, 2005;
112(22_suppl):
III-55 - III-72.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Babuin and A. S. Jaffe
Troponin: the biomarker of choice for the detection of cardiac injury
Can. Med. Assoc. J.,
November 8, 2005;
173(10):
1191 - 1202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S. Ginsburg, M. P. Donahue, and L. K. Newby
Prospects for Personalized Cardiovascular Medicine: The Impact of Genomics
J. Am. Coll. Cardiol.,
November 1, 2005;
46(9):
1615 - 1627.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Roe, E. D. Peterson, Y. Li, C. V. Pollack Jr, R. H. Christenson, W. F. Peacock, F. M. Fesmire, L. K. Newby, R. L. Jesse, J. W. Hoekstra, et al.
Relationship Between Risk Stratification by Cardiac Troponin Level and Adherence to Guidelines for Non-ST-Segment Elevation Acute Coronary Syndromes
Arch Intern Med,
September 12, 2005;
165(16):
1870 - 1876.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C-K Wong and H D White
Implications of the new definition of myocardial infarction
Postgrad. Med. J.,
September 1, 2005;
81(959):
552 - 555.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Blazing, J. A. de Lemos, H. D. White, K. A. A. Fox, F. W. A. Verheugt, D. Ardissino, P. M. DiBattiste, J. Palmisano, D. W. Bilheimer, S. M. Snapinn, et al.
Safety and Efficacy of Enoxaparin vs Unfractionated Heparin in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Who Receive Tirofiban and Aspirin: A Randomized Controlled Trial
JAMA,
July 7, 2004;
292(1):
55 - 64.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. E. Ross, F. N. Bever, Z. Uddin, L. Devireddy, and J. M. Gardin
Common Scenarios to Clarify the Interpretation of Cardiac Markers
J Am Osteopath Assoc,
April 1, 2004;
104(4):
165 - 176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Kontos, R. Shah, L. M. Fritz, F. P. Anderson, J. L. Tatum, J. P. Ornato, and R. L. Jesse
Implication of different cardiac troponin I levels for clinical outcomes and prognosis of acute chest pain patients
J. Am. Coll. Cardiol.,
March 17, 2004;
43(6):
958 - 965.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Wiviott, C. P. Cannon, D. A. Morrow, S. A. Murphy, C. M. Gibson, C. H. McCabe, M. S. Sabatine, N. Rifai, R. P. Giugliano, P. M. DiBattiste, et al.
Differential Expression of Cardiac Biomarkers by Gender in Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18) Substudy
Circulation,
February 10, 2004;
109(5):
580 - 586.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. D. White and J. K. French
Use of brain natriuretic peptide levels for risk assessment in non-ST-elevation acute coronary syndromes
J. Am. Coll. Cardiol.,
December 3, 2003;
42(11):
1917 - 1920.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Jaffe
A small step for man, a leap forward for postoperative management
J. Am. Coll. Cardiol.,
November 5, 2003;
42(9):
1555 - 1557.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lund, Q.-P. Qin, T. Ilva, K. Pettersson, L.-M. Voipio-Pulkki, P. Porela, and K. Pulkki
Circulating Pregnancy-Associated Plasma Protein A Predicts Outcome in Patients With Acute Coronary Syndrome but No Troponin I Elevation
Circulation,
October 21, 2003;
108(16):
1924 - 1926.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. L Williams, B. Noronha, and A. G Zaman
Review: The management of acute myocardial infarction in patients with diabetes mellitus
The British Journal of Diabetes & Vascular Disease,
September 1, 2003;
3(5):
319 - 324.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. P. Cannon and A. G.G. Turpie
Unstable Angina and Non-ST-Elevation Myocardial Infarction: Initial Antithrombotic Therapy and Early Invasive Strategy
Circulation,
June 3, 2003;
107(21):
2640 - 2645.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. K. Newby, B. U. Goldmann, and E. M. Ohman
Troponin: an important prognostic marker and risk-stratification tool in non-ST-segment elevation acute coronary syndromes
J. Am. Coll. Cardiol.,
February 19, 2003;
41(4_Suppl_S):
31S - 36S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Blake and P. M. Ridker
C-reactive protein and other inflammatory risk markers in acute coronary syndromes
J. Am. Coll. Cardiol.,
February 19, 2003;
41(4_Suppl_S):
37S - 42S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Topol
A guide to therapeutic decision-making in patients with non-ST-segment elevation acute coronary syndromes
J. Am. Coll. Cardiol.,
February 19, 2003;
41(4_Suppl_S):
123S - 129S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Bertrand, M. L. Simoons, K. A.A. Fox, L. C. Wallentin, C. W. Hamm, E. McFadden, P. J. De Feyter, G. Specchia, and W. Ruzyllo
Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation
Eur. Heart J.,
December 1, 2002;
23(23):
1809 - 1840.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. P. Cannon
Evidence-Based Risk Stratification to Target Therapies in Acute Coronary Syndromes
Circulation,
September 24, 2002;
106(13):
1588 - 1591.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. de Lemos, D. A. Morrow, C. M. Gibson, S. A. Murphy, M. S. Sabatine, N. Rifai, C. H. McCabe, E. M. Antman, C. P. Cannon, and E. Braunwald
The prognostic value of serum myoglobin in patients with non-ST-segment elevation acute coronary syndromes: Results from the TIMI 11B and TACTICS-TIMI 18 studies
J. Am. Coll. Cardiol.,
July 17, 2002;
40(2):
238 - 244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Hamm
Acute coronary syndrome: the struggle for the best in risk stratification and therapy
Eur. Heart J.,
July 2, 2002;
23(14):
1074 - 1076.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Antman
Decision Making with Cardiac Troponin Tests
N. Engl. J. Med.,
June 27, 2002;
346(26):
2079 - 2082.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E.M. Antman, M. Cohen, C. McCabe, S.G. Goodman, S.A. Murphy, and E. Braunwald
Enoxaparin is superior to unfractionated heparin for preventing clinical events at 1-year follow-up of TIMI 11B and ESSENCE
Eur. Heart J.,
February 2, 2002;
23(4):
308 - 314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D.A. Morrow, E.M. Antman, S.M. Snapinn, C.H. McCabe, P. Theroux, and E. Braunwald
An integrated clinical approach to predicting the benefit of tirofiban in non-ST elevation acute coronary syndromes. Application of the TIMI Risk Score for UA/NSTEMI in PRISM-PLUS
Eur. Heart J.,
February 1, 2002;
23(3):
223 - 229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Morrow, C. P. Cannon, N. Rifai, M. J. Frey, R. Vicari, N. Lakkis, D. H. Robertson, D. A. Hille, P. T. DeLucca, P. M. DiBattiste, 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,
November 21, 2001;
286(19):
2405 - 2412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. de Lemos, D. A. Morrow, J. H. Bentley, T. Omland, M. S. Sabatine, C. H. McCabe, C. Hall, C. P. Cannon, and E. Braunwald
The Prognostic Value of B-Type Natriuretic Peptide in Patients with Acute Coronary Syndromes
N. Engl. J. Med.,
October 4, 2001;
345(14):
1014 - 1021.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E.M. Antman, R. Corbalan, K. Huber, and A.S. Jaffe
Issues in early risk stratification for UA/NSTEMI
Eur. Heart J. Suppl.,
August 1, 2001;
3(suppl_J):
J6 - J14.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J.S. Alpert, A.J. Budaj, E.P. Gurfinkel, and T.D. Henry
Issues in antithrombin therapy for UA/NSTEMI
Eur. Heart J. Suppl.,
August 1, 2001;
3(suppl_J):
J15 - J23.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. P. Cannon, W. S. Weintraub, L. A. Demopoulos, R. Vicari, M. J. Frey, N. Lakkis, F.-J. Neumann, D. H. Robertson, P. T. DeLucca, P. M. DiBattiste, 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.,
June 21, 2001;
344(25):
1879 - 1887.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
Top
Abstract
Methods