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Received on August 29, 2003
Accepted on November 20, 2003
Proteomics and Protein Markers |
1 Division of Cardiology, Department of Medicine, University of Minnesota Medical School
2 Department of Laboratory Medicine and Pathology, Hennepin County Medical Center, Minneapolis, MN.and
University of Minnesota, Minneapolis, MN.
3 Department of Laboratory Medicine and Pathology, Hennepin County Medical Center, Minneapolis, MN
4 Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN.
* To whom correspondence should be addressed. E-mail: luepker{at}epi.umn.edu.
Background: Cardiac troponin I (cTnI) is a more specific and sensitive biomarker than creatine kinase MB (CKMB) for detection of myocardial damage. We report the prevalence of positive cTnI and CKMB mass among patients hospitalized with suspected acute coronary syndrome (ACS) and the potential impact of use of different reference cutoffs, particularly those proposed by European Society of Cardiology/American College of Cardiology (ESC/ACC) consensus guidelines, on rates of diagnosis of acute myocardial infarction (AMI).
Methods: We analyzed 1719 consecutive patients with suspected ACS admitted to an urban acute care hospital over a 6-month period. Patients (
18 years of age) had at least two separate sets of plasma biomarkers (cTnI and CKMB) measured more than 12-24 h after admission to determine the potential rates of AMI based on different biomarker cutoff concentrations.
Results: The prevalence of cTnI-positive cases ranged from 10.6%, based on a cutoff of twice the ROC curve (cTnI 
1.2 µg/L), to 25.0%, using the ESC/ACC-recommended 99th percentile cutoff (cTnI <0.1 µg/L). The prevalence of CKMB-positive cases ranged from 10.4%, with the cutoff of twice the ROC curve (CKMB 10.0 µg/L) to 21.7%, with the 99th percentile cutoff (CKMB <3.9 µg/L). Use of the 10% CV cutoff (cTnI 0.3 µg/L and CKMB <3.9 µg/L) instead of the ROC cutoff produced a 26% increase in all cTnI-positive cases. Use of the 99th percentile reference cutoff instead of the ROC curve-derived cutoff produced an 85% increase in all cTnI-positive cases. A substantial proportion of the increase in total cTnI-positive cases was derived from cTnI-positive/CKMB-negative cases: 71 (4.1%), 73 (4.2%), 98 (5.7%), and 209 (12.2%) of cTnI-positive cases were CKMB-negative, as determined by the twice the ROC, ROC, 10% CV, and 99th percentile reference cutoffs, respectively. At the 99th percentile cutoffs, 8.8% of cases were CKMB-positive/cTnI-negative.
Conclusions: Use of lower reference cutoffs for plasma biomarkers, as recommended by ESC/ACC guidelines, markedly increases the rates of cTnI-positive cases overall. A substantial proportion of the increase in total cTnI-positive cases was derived from the creation of additional cTnI-positive/CKMB-negative cases. CKMB-positive/cTnI-negative cases are likely false positive for myocardial injury.© 2004 American Association for Clinical Chemistry
The following articles in journals at HighWire Press have cited this article:
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  F. S. Apple A New Season for Cardiac Troponin Assays: It's Time to Keep a Scorecard Clin. Chem., July 1, 2009; 55(7): 1303 - 1306. [Full Text] [PDF]
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F. S. Apple, S. W. Smith, L. A. Pearce, and M. M. Murakami Assessment of the Multiple-Biomarker Approach for Diagnosis of Myocardial Infarction in Patients Presenting with Symptoms Suggestive of Acute Coronary Syndrome Clin. Chem., January 1, 2009; 55(1): 93 - 100. [Abstract] [Full Text] [PDF]
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 A. K. Saenger and A. S. Jaffe Requiem for a Heavyweight: The Demise of Creatine Kinase-MB Circulation, November 18, 2008; 118(21): 2200 - 2206. [Full Text] [PDF]
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 A. V. G. Edwards, M. Y. White, and S. J. Cordwell The Role of Proteomics in Clinical Cardiovascular Biomarker Discovery Mol. Cell. Proteomics, October 1, 2008; 7(10): 1824 - 1837. [Abstract] [Full Text] [PDF]
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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]
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 H. D White Evolution of the definition of myocardial infarction: what are the implications of a new universal definition? Heart, June 1, 2008; 94(6): 679 - 684. [Full Text] [PDF]
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F. S. Apple, L. A. Pearce, A. Chung, R. Ler, and M. M. Murakami Multiple Biomarker Use for Detection of Adverse Events in Patients Presenting with Symptoms Suggestive of Acute Coronary Syndrome Clin. Chem., May 1, 2007; 53(5): 874 - 881. [Abstract] [Full Text] [PDF]
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 P Wong, S Murray, A Ramsewak, A Robinson, C van Heyningen, and E Rodrigues Raised cardiac troponin T levels in patients without acute coronary syndrome Postgrad. Med. J., March 1, 2007; 83(977): 200 - 205. [Abstract] [Full Text] [PDF]
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P. A. Kavsak, A. R. MacRae, G. E. Palomaki, A. M. Newman, D. T. Ko, V. Lustig, J. V. Tu, and A. S. Jaffe Health Outcomes Categorized by Current and Previous Definitions of Acute Myocardial Infarction in an Unselected Cohort of Troponin-Naive Emergency Department Patients Clin. Chem., November 1, 2006; 52(11): 2028 - 2035. [Abstract] [Full Text] [PDF]
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 F. S. Apple Clinical Biomarkers of Cardiac Injury: Cardiac Troponins and Natriuretic Peptides Toxicol Pathol, January 1, 2006; 34(1): 91 - 93. [Abstract] [Full Text] [PDF]
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 V. L. Roger Invited Commentary: Will Heart Attacks Be "Gone with the Century"? Am. J. Epidemiol., December 15, 2004; 160(12): 1147 - 1149. [Full Text] [PDF]
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F. S. Apple and M. M. Murakami Serum 99th Percentile Reference Cutoffs for Seven Cardiac Troponin Assays Clin. Chem., August 1, 2004; 50(8): 1477 - 1479. [Full Text] [PDF]
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