Relation Between Troponin T and the Risk of Subsequent Cardiac Events in Unstable Coronary Artery Disease
Background Early risk assessment is important in patients with unstable coronary artery disease, ie, unstable angina or non–Q-wave myocardial infarction. Some previous small studies have indicated that patients with unstable angina and elevation of troponin T (tn-T) have worse short-term and long-term prognoses. In this study, the prognostic value of tn-T was evaluated and compared with other early available risk indicators.
Methods and Results Nine hundred seventy-six patients participating in a randomized study of low-molecular-weight heparin in unstable coronary artery disease were followed for 5 months after the index episode. The risk of cardiac events increased with increasing maximal levels of tn-T obtained in the initial 24 hours. The lowest quintile (<0.06 μg/L) constituted a low-risk group, the second quintile (0.06 to 0.18 μg/L) an intermediate-risk group, and the three highest quintiles (≥0.18 μg/L) a high-risk group, with 4.3%, 10.5%, and 16.1% risk of either myocardial infarction or cardiac death, respectively. Troponin T level was identified together with age, hypertension, number of antianginal drugs, and ECG changes at rest as independent prognostic variables for myocardial infarction or cardiac death in a multivariate analysis. The prognostic value of tn-T was independent of the classification of index event into unstable angina or myocardial infarction.
Conclusions Troponin T determination is an inexpensive and widely applicable method for early risk assessment in patients with unstable coronary artery disease. The maximum tn-T value obtained during the first 24 hours provides independent and important prognostic information.
Patients with UCAD, ie, UA or acute non–Q-wave myocardial infarction (MI), still have an elevated risk for subsequent cardiac events despite the considerable progress in treatment during the last decade.1 2 3 4 However, the UCAD population is heterogeneous regarding both the severity of the underlying coronary artery disease and the prognosis.5 6 7 8 9 Therefore, early assessment of the risk for future cardiac events is important for the selection of appropriate medical treatment and optimal use of invasive procedures.10 During the last years, the new sensitive and specific biochemical markers of myocardial damage, ie, CK-MB (mass), myosin light chains, and tn-T have been found elevated in 30% to 50% of patients with UA.11 12 13 In a few recent small trials, elevation of these markers has been associated with impaired short-term14 15 16 and long-term prognoses17 18 in patients with UA or chest pain with MI ruled out. However, UA and non–Q-MI often have similar pathophysiology and clinical presentation at admission.5 6 Thus, the classification into either group is arbitrary and depends on the diagnostic criteria, mainly which biochemical markers and cutoff levels that are used.
The aim of the present study was to elucidate the prognostic value of tn-T in a large cohort of patients with UCAD and to compare tn-T with other known early and widely available risk indicators.
The study was part of a randomized trial of low-molecular-weight heparin (dalteparin sodium, Fragmin Pharmacia AB, Sweden) in patients with UCAD including 1506 patients at 23 hospitals in Sweden between May 1992 and October 1994. In 15 hospitals, the protocol included a special blood sampling schedule from which the study cohort of 976 patients was recruited. At least one blood sample obtained for analysis of tn-T at inclusion or after 12 hours was required. Eligible for inclusion were men or women aged over 40 years admitted to the hospital because of myocardial ischemia demonstrated both by (a) symptoms, ie, either new-onset angina pectoris the last 2 months, increasing angina pectoris the last 2 months, or ongoing chest pain suggestive of MI with the last episode of chest pain within 72 hours and by (b) signs of myocardial ischemia in 12-lead ECG at rest, ie, in two contiguous leads either ST depression of ≥0.1 mV, T-wave inversion, or both. The exclusion criteria were premenopause in women, indication for thrombolysis (ie, ST elevation or bundle branch block and start of chest pain within the last 12 hours), new Q waves, Q waves in the same leads as ST depression or T-wave inversion, left bundle branch block, pacemaker, suspected myocarditis or pericarditis, septic endocarditis, cardiomyopathy, significant aortic valve disease, uncontrolled hypertension, hypotension, planned percutaneous transluminal coronary angioplasty or coronary artery bypass graft, increased risk of bleeding, anemia, renal failure, hepatic failure, fever ≥39°C, serious intercurrent disease, hypersensitivity to heparin or low-molecular-weight heparin, and unwillingness or inability to participate.
After admission, all patients without contraindications received oral aspirin 75 mg daily and β-blockers and as needed, organic nitrates and calcium antagonists. Double-blind, placebo-controlled randomized treatment with dalteparin sodium/placebo was given as a subcutaneous injection twice daily at a dose of 120 U/kg body wt for the first 5 to 7 days and then daily at a dose of 7500 U for another 5 weeks. Heparin infusion, coronary angiography, and revascularization were recommended in the case of refractory or incapacitating angina despite medical treatment or after signs of severe ischemia at an exercise test. All therapeutic decisions were made without knowledge of the patients’ tn-T levels.
The study was approved by the local ethics committee, and all enrolled patients provided informed consent.
Blood Samples and Laboratory Methods
Venous blood samples for analyses of plasma tn-T were obtained at inclusion and then after 12, 24, 48, and 120 hours. Blood was collected in EDTA-containing tubes and was then centrifuged; plasma was frozen in aliquots and stored for subsequent analysis. Troponin T was determined by the Enzymun-Test system (Boehringer-Mannheim).19 The lower detection limit is 0.04 μg/L according to the manufacturer, and the upper reference level in healthy blood donors is 0.06 μg/L.20 All analyses were performed at one laboratory (Department of Clinical Chemistry, Uppsala) and without knowledge of the patient’s diagnosis and outcome. The between-day coefficient of variation more than 4 months (n=99) at our laboratory was 10.2% and 5.1% at levels of 0.28 and 6.10 μg/L, respectively.
Standard 12-lead ECGs were obtained at inclusion and after 24 hours. All ECGs were interpreted centrally and without knowledge of the patient’s diagnosis and outcome. ST depression was defined as a deflection of the ST segment of ≥0.1 mV, measured 60 ms after the J-point, below the isoelectric line in any lead. T-wave inversion was registered in the case of negative or isoelectric T wave in leads V2-V6, I and II, in aVL if r>.5 mV, and in aVF if QRS was mainly positive.
Evaluation of Index Event and End Points
The episode that qualified a patient for enrollment in the study (index event) was classified retrospectively as acute MI or UA, based on the maximal levels of available cardiac enzymes obtained and analyzed at the local hospital immediately after that episode: CK-MB (mass) determined by the IMx system (Abbot Laboratories), discrimination limit 15 μg/L (n=620) or by the Icon-QSR system (Hybritech, discrimination limit 10 μg/L (n=46); CK (catalytic activity), discrimination limit 2.5 μkat/L for women and 3.0 for men (n=152); CK-MB (catalytic activity), discrimination limit 0.4 μkat/L (n=112), and aspartate-aminotransferase, discrimination limit 0.6 μkat/L for women and 0.8 μkat/L for men (n=45); the three latter enzymes were analyzed according to the IFCC/ECCLS standards.21
The prognostic value of tn-T was evaluated on the basis of the samples obtained during the first 24 hours, and only patients with events occurring 1 day beyond this sampling period were considered in the evaluation of the prognostic value of tn-T in order to avoid confusion between the prognostic and diagnostic capacity of tn-T. Thus, 13 patients with a MI during the sampling period were excluded in the analysis of the prognostic value of tn-T.
All patients were followed while in the hospital and thereafter by outpatient visits after 6 weeks and 5 to 6 months. All primary end points, ie, death and nonfatal MI, were classified by an independent end point committee. MI was defined by conventional WHO criteria22 satisfying two of the following three criteria: (1) severe ischemic chest pain of at least 20 minutes duration, (2) a diagnostic ECG, or (3) an increase of cardiac enzymes above the upper reference level at the local hospital in at least two consecutive samples. Whenever possible, causes of death were based on autopsy findings. Sudden death was considered cardiac.
Differences in proportions were judged by χ2 analysis. A significant difference was considered to exist at the P<.05 level. The cumulative hazard curves were constructed using the Kaplan-Meier method. The end points were cardiac death and cardiac death or nonfatal MI, respectively. Noncardiac death was treated as a censored observation. Statistical assessment was performed using the log-rank test.
To identify variables of prognostic importance, simple and forward stepwise multiple logistic regression analyses were used regarding the predefined end points of cardiac death or MI. Evaluated independent variables were age ≤70/>70 years; sex; smoking habits; history of hypertension, congestive heart failure, diabetes mellitus, or previous MI; duration of angina ≤2/>2 months, crescendo angina ≤1/>1 week; occurrence of rest angina last week; use of digoxin, ACE inhibitor, or aspirin; number of antianginal drugs (β-blockade, calcium inhibitor, and long-acting organic nitrate) at admission; occurrence of ST depression or T-wave inversion or both in 12-lead ECG at inclusion; inclusion diagnosis (non–Q-MI/UA); tn-T maximum during the first 24 hours in quintiles; and serum creatinine at admission.
All statistical analyses were performed by a computer with the SPSS system 6.1 (Statistical Package for the Social Sciences, 1994).
The clinical characteristics at inclusion of the 976 patients with UCAD are shown in Table 1⇓. The study population had a high median age, 70 years, and almost one third had a history of previous MI. Approximately 40% had onset of increasing angina and 50% angina at rest during the preceding week. Sixty percent had chest pain at admission to the hospital. The median time from onset of the last episode of chest pain to admission was 5 hours and to inclusion, 24 hours. ECG at inclusion showed both ST depression and T-wave inversion in 45%, ST depression only in 16%, and T-wave inversion only in 38%. According to the retrospective classification, the index event was UA in 593 (61%) and MI in 382 (39%).
During the 5-month follow-up there were 120 MIs (12.3%), 43 cardiac deaths (4.4%), and 6 other deaths (0.6%). In 358 patients (36.7%), coronary artery bypass grafting or percutaneous transluminal coronary angioplasty was performed, and 397 (41.8%) had a new hospital admission.
Prognostic Value of Troponin T
The median value of tn-T was 0.24 μg/L at inclusion; 77% of the patients had tn-T values ≥0.06 μg/L and 66% ≥0.1 μg/L. The median tn-T maximum was 0.33 μg/L (range, <0.04 to 19.0) during the first 24 hours and was 0.06, 0.18, 0.62, and 2.12 μg/L, respectively, the first, second, third, and fourth quintiles. The addition of samples at 48 and 120 hours, respectively, did not improve the prognostic value of tn-T regarding cardiac death or MI (data not shown). Hence, all of the presented results of the prognostic value of tn-T are based only on samples obtained during the first 24 hours.
There was an increase in the rate of the combined end point MI or cardiac death during the study period from lower to higher quintiles of tn-T (Fig 1⇓), the lowest quintile constituting a low-risk group, the second quintile an intermediate-risk group, and the three highest quintiles a high-risk group, with 4.3%, 10.5%, and 16.1% risk of cardiac death or MI after 5 months, respectively (low versus intermediate risk, P=.02; intermediate versus high risk, P=.05). For cardiac death alone, there was an increase in the risk from the first to the second and third and a further elevation in the two highest quintiles of tn-T (Fig 2⇓). The 5-month risk was 0%, 2.8%, and 8.6%, respectively (first versus second and third quintiles, P=.02; second and third versus two highest quintiles, P=.0005). There was no relation between tn-T and need for revascularization.
Prognostic Value of Troponin T Compared With Other Variables
The prognostic value of tn-T was compared with other early and easily available clinical or laboratory variables, using the univariate and multivariate forward stepwise logistic regression analysis (Table 2⇓). The following five independent prognostic variables for MI or cardiac death at 5 months were identified: tn-T level, number of antianginal drugs at admission, increasing age, ST depression in the 12-lead ECG at inclusion, and hypertension. The inclusion diagnosis (non–Q-MI or UA) did not add any independent prognostic information. The prognostic values for combinations of tn-T and 12-lead ECG are shown in Fig 3⇓.
Comparison With CK-MB (Mass)
In patients (n=620) in whom CK-MB (mass) was analyzed by the IMx method at the local hospital immediately after the index event, the maximal levels of CK-MB were compared with the maximal tn-T levels. The Pearson correlation coefficient was .80 (P<.01). However, in patients with tn-T <0.2 μg/L (n=240), the correlation coefficient was only .27 (P<.01).
The incidence of cardiac death or MI was 8.7% in those with CK-MB below the upper reference limit in healthy persons (6 μg/L), 15.8% in those with CK-MB 6 to 15 μg/L, and 16.9% in those with CK-MB above the discrimination limit for acute MI diagnosis (15 μg/L). In the group of patients with CK-MB <6 μg/L, there was a higher risk of cardiac death or MI (13.0% versus 4.6%, P<.05) among those with tn-T 0.06 to 0.18 μg/L (n=108) compared with those with tn-T <0.06 μg/L (n=109).
Classification of Index Event and Troponin T
In the patients classified retrospectively as MI patients, the median tn-T maximum within 24 hours was 2.0 μg/L (range, <0.04 to 19.0), and 99% and 90% had tn-T maximum ≥0.1 μg/L and >0.5 μg/L, respectively. In the UA group, the median tn-T maximum was 0.1 μg/L (range, <0.04 to 11.3); 78%, 51%, and 34% of the patients had tn-T maximum ≥0.05, ≥0.1, and ≥0.2 μg/L, respectively. There was a considerable overlap in maximal tn-T levels between the two groups in the interval of 0.4 to 2.0 μg/L (Fig 4⇓).
The 5-month risk of cardiac death was five times higher in patients with MI than in patients with UA (7.5% versus 1.5%, P<.001), while the risk of a cardiac death or MI was nearly doubled (17.6 versus 9.5%, P<.001).
Within the UA group, there was a significant increase in the rate of cardiac events (MI or cardiac death) during the 5 months from lower to higher levels of tn-T, whereas this was less obvious in the MI group because the great majority of patients had tn-T >0.62 μg/L. The discriminatory levels of tn-T that best categorized the UA-patients into different risk groups were <0.06, 0.06 to 0.18, and ≥0.18 μg/L, respectively. The 5-month risks of cardiac death and cardiac death/MI, respectively, in relation to index event and tn-T level are shown in Table 3⇓. Using these cutoff levels (but otherwise the same variables as in the whole group) in the forward stepwise multiple logistic regression analyses in the UA group, the following three independent prognostic variables for MI or cardiac death at 5 months were identified: tn-T, changes in the 12-lead ECG at inclusion, and history of hypertension.
In accordance with previous experiences of UCAD,23 24 25 the patients in the present study with advanced age, history of increasing or rest angina pectoris, and ST depression or T-wave inversion in 12-lead ECG had a high risk of subsequent cardiac events−after 5 months, cardiac death or MI in 13% and revascularization in 37%. The risk is most pronounced early after the initial event. In the present study, approximately one fourth of the events occurred during the first 6 days and more than half during the first 6 weeks, which emphasizes the necessity of early risk assessment in order to properly select further investigations and treatment.
The common cause of UCAD, ie, UA and non–Q-MI, is fissuring of atheromatous plaques, activation of platelets, and formation of a thrombus that impairs blood flow in a coronary artery.5 6 The patients are admitted because of chest pain and ischemic ECG changes without ST elevation, bundle branch block, or Q waves in the affected area. Therefore, the distinction between UA and non–Q-MI must be performed retrospectively and depends on an arbitrary choice of biochemical markers and their decision limits, as illustrated by the continuum of tn-T levels between UA and non–Q-MI patients in the present study (Fig 4⇑). The importance of the various cardiospecificities of the biochemical markers used is illustrated by the fact that three patients diagnosed to have acute MI according to the decision limits of the conventional enzymes had tn-T values <0.06 μg/L and thus hardly any sign of irreversible myocardial damage.
Troponin T is a regulatory protein mainly located on the thin filament of the contractile apparatus of the myocyte, but a small free pool exists in the cytosol.26 A transient leakage of the cytosolic pool might occur as the result of loss of cell membrane integrity during severe reversible ischemia, but a prolonged leakage is due to degradation of myofilaments in irreversibly damaged cells.27 The cardiac isoform of tn-T is unique and can be differentiated from the isoforms in the skeletal muscle, leading to a very high specificity for myocardial damage.19 The wide time window, from 3 to 4 hours until up to 3 weeks, and the high sensitivity and specificity make tn-T suitable for detecting myocardial ischemia damage in UCAD patients, with their often fluctuating symptoms. Different discriminator values of tn-T for myocardial injury have been used. The discriminator values have been lowered gradually as the tn-T assay has been improved. In the studies on the prognostic value of tn-T in UA, 0.2 μg/L has been used14 16 18 and recently 0.1 μg/L as a definition of acute MI28 and “ischemic myocardial injury,”29 respectively. Even lower discriminator levels for the detection of myocardial damage might be justified, since the upper reference level in healthy blood donors seems to be 0.06 μg/L.20
In the present study, the risk of subsequent cardiac events was demonstrated to increase gradually with increasing maximal levels of tn-T. A significant increase in the risk was shown at very low levels of tn-T, from 4.3% of cardiac death or MI in patients with tn-T <0.06 μg/L to 10.5% in patients with tn-T between 0.06 to 0.18 μg/L; the increase was in fact evident in patients with tn-T 0.06 to 0.10 μg/L, in whom 11 of 109 (10.1%) suffered an event. On the basis of the tn-T level, it was possible to identify groups with low, intermediate, and high risk of MI or cardiac death. Most of the fatalities were caused by MI. Thus, elevation of tn-T was shown to be associated with an increased risk of MI in accordance with previous findings in some small patient studies.14 16 18 The cause of differences in discriminatory levels between risk of MI and risk of death might be explained by a worse outcome of the next MI in patients with previous larger myocardial damage (as evidenced by higher tn-T levels during the index event). Why, then, is the risk for future myocardial infarctions gradually increased with increasing tn-T levels? It might be hypothesized that the tn-T level reflects the severity of ischemia, as supported by the more frequent occurrence of left ventricular dysfunction during anginal attacks in UA patients with than without tn-T elevation.30 Another possible explanation might be that the tn-T level reflects the liability of thrombus formation at the unstable plaque, leading to occlusion of the coronary artery and thereby explaining the relation to future cardiac events.
Index Events and Prognosis
By analyzing the UA group separately, we found that tn-T levels of <0.06, 0.06 to 0.18, and ≥0.18 μg/L separated the patients into low-, intermediate-, and high-risk groups, respectively. Previous studies have used 0.2 μg/L as the cutoff level,14 16 18 which agrees well with the discrimination between the intermediate- and high-risk groups in the present material. In contrast to a previous small study,14 we did not find any difference regarding in-hospital risk of cardiac death or MI between those with or without elevated tn-T in the UA group. In the previous study,14 the in-hospital incidence of MI and death was extremely high: 5 of 33 with positive tn-T (15%) died and 10 (30%) had MI, whereas only 5 (2.4%) of 209 in the UA group with tn-T ≥0.18 μg/L suffered a cardiac event during hospitalization in the present study. In accordance with a previous study16 of 127 patients with nonacute MI and 9 events, we found a significantly higher risk of cardiac death or MI during the follow-up in UA patients with elevated tn-T, but in addition, we were able to demonstrate higher risk for cardiac death in UA patients with tn-T elevation. These minor differences from previous studies might be explained by somewhat different definitions of UA, whether or not ECG changes were required, and the very careful separation of index and subsequent events in the present study. Patients with a non–Q-MI had elevated tn-T and hence an elevated future risk of cardiac events. However, there was no significant difference in the incidence of cardiac events between those with UA and non–Q-wave MI in the same interval of tn-T elevation (data not shown). Furthermore, in the multivariate analysis, the inclusion diagnosis did not add any independent prognostic information in contrast to the tn-T level, suggesting that the tn-T level gives better prognostic information than the crude separation of UCAD patients into UA or non–Q-wave MI according to conventional criteria.
Comparison With CK-MB
In accordance with previous studies,17 18 a minor increase of CK-MB (mass) indicated a higher risk of subsequent cardiac events in the present study. However, in the group with CK-MB levels below the upper reference limit, it was possible to demonstrate small elevations of tn-T in a large proportion of patients and a significant difference in risk of cardiac events between those with and those without detectable elevations of tn-T. Thus, for identification of a definite low-risk group, tn-T appears to be superior to CK-MB (mass).
Comparison With Other Risk Indicators
To optimize the use of clinical resources and to select appropriate treatment, the risk assessment should be performed as early as possible−ideally the very first day after admission in patients with UCAD. Therefore, the prognostic value of tn-T obtained during the first 24 hours was compared with a number of other early available clinical variables with potential prognostic value (Table 2⇑). In this study, in the multivariate analysis, the tn-T level was a strong, consistent, and independent prognostic variable concerning cardiac death or MI, in contrast to a recent report18 in which tn-T level did not add any independent prognostic information when ST-T abnormalities were present at admission. Other factors of prognostic importance at admission were age and indications of hypertension and severity of ischemia, which are well-established predictors of subsequent cardiac events7 25 31 and hence add important prognostic information to the tn-T level.
Limitations of the Present Study
Patients unable to stabilize during the first hours after admission despite adequate medication might not have been included in the present study because of the need for immediate coronary angiography. However, in those patients there is hardly a need for additional prognostic indicators.
Although patients were admitted to the hospital with a median delay of 5 hours from onset of the last episode of chest pain, the median delay to inclusion (and first blood sample) was 24 hours. Thus, some patients might have had minor, transient elevations of tn-T that had disappeared before the first blood sample was obtained. On the other hand, the delay might have yielded higher tn-T values in some patients than if the sampling period had started immediately at admission, since the tn-T value continues to increase to approximately the third day in patients with persisting coronary occlusion.26
Troponin-T determination is an inexpensive and widely applicable method for early risk assessment in patients with UCAD and appears to be superior to CK-MB (mass) determination. The maximal tn-T value obtained during the first 24 hours provides independent and important prognostic information regardless of whether the patient is classified as having UA or non–Q-wave MI. Patients with low or undetectable tn-T levels, <0.06 μg/L, have a low risk for cardiac death or MI while in the hospital and during the subsequent 5 months and might on appropriate medication be discharged early and followed in the out-patient clinic. When other early available independent prognostic indicators are taken into consideration, eg, the 12-lead ECG at admission, the patients with tn-T levels of 0.06 to 0.18 μg/L might be further separated into a low-risk group that can be treated further and evaluated in the outpatient clinic and into a group with higher risk that needs further evaluation and treatment while still in the hospital. Finally, patients with tn-T levels >0.18 μg/L have a high risk for subsequent cardiac events that warrants further investigations and intense medical and/or interventional treatment while still in the hospital. Thus, by inclusion of tn-T into the strategy for early risk assessment, the handling of patients with UCAD can be improved in efficacy and cost-effectiveness.
Selected Abbreviations and Acronyms
|non–Q-MI||=||non–Q-wave myocardial infarction|
|UCAD||=||unstable coronary artery disease|
Participating Clinical Centers and Investigators of the Research Group on Fragmin During InStability in Coronary Artery Disease (FRISC)
Chairman and coordinator: Lars Wallentin; co-chairman and coordinator: Eva Swahn; steering committee members: Erling Karlsson, Lennart Lundin, Finn Landgren, Helge Sætre, Bertil Andrén, and Jan Ohlsson; participating centers and investigators at Uppsala: Lennart Lundin, Henrik Toss, Bertil Lindahl, Gunilla Lindström, Eva Svensson, and Gerd Ålsjö; Falun: Helge Sætre, Greger Ahlberg, Lars Hagström, Christina Sundqvist, and Eva Pihl; Gävle: Gunnar Gustafsson, Lotta Larsson, Per-Erik Gustavsson, Rurik Löfmark, and Ing-Britt Lundqvist; Bollnäs: Eskil Hammarström, Hamid Bastani, and Erland Eng; Danderyd: Peter Lundin, Nina Rehnqvist, Björn Ambrant, Pia Oblack, and Martin Holmstrand; Mora: Björn Fjelstad, Dic Aronson, and Solveig Östberg; Ludvika: John Eric Frisell, Anders Hedman, and Marianne Sandström; Avesta: Göran Perers, Per Irving, and Irene Andersson; South Hospital, Stockholm: Johan Hulting, Jonas Höjier, Aman Amanullah, Bassem Samad, Ingemar Steinbruck, and Mona Ekblom; Linköping: Eva Swahn, Erling Karlsson, Niels Nielsen, Kåge Säfström, and Elisabeth Logander; Norrköping: Stig-Åke Falk, Jan Fridén, Ove Nilsson, Katarina Rönnhagen, and Lena Abou-Zeid; Oskarshamn: Bo Hedbäck, Joep Perk, and Lotta Ossiansson-Pettersson; Kalmar: Bengt Holmberg, Finn Landgren, Stefan Rydén, and Eva Bjurling; Jönköping: Jan-Erik Karlsson, Claes Malmberg, Olof Svensson, and Eira Svensson; Eksjö: Sten Ekdahl, Ingvar Nyman, and Yvonne Pantzar; end point classification committee: Ebba Enghoff and Torbjörn Lundström; ECG evaluation: Bertil Andrén and Jan Ohlsson; data center: Lars Wallentin and Jan Ohlsson; research nurses and monitors: Gunilla Lindström, Elisabeth Logander, and Eva Svensson.
This study was supported by grants from the Swedish Heart and Lung Foundation; the Selander’s Foundation, Uppsala, Sweden; the Uppsala County Association Against Heart and Lung Diseases, Sweden; Pharmacia Biosensor AB, Uppsala, Sweden; and Pharmacia AB, Stockholm, Sweden. Boehringer Mannheim Scandinavia AB, Bromma, Sweden, provided us generously with the troponin T kits. We wish to thank the clinical staff of each center involved for their skillful assistance.
The FRISC Study Group investigators and their institutions are listed in the “Appendix.”
- Received October 19, 1995.
- Revision received January 11, 1996.
- Accepted January 22, 1996.
- Copyright © 1996 by American Heart Association
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