Implications of lowering threshold of plasma troponin concentration in diagnosis of myocardial infarction: cohort studyBMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e1533 (Published 15 March 2012) Cite this as: BMJ 2012;344:e1533
- Nicholas L Mills, BHF intermediate clinical research fellow1,
- Kuan Ken Lee, medical student1,
- David A McAllister, clinical lecturer in public health2,
- Antonia M D Churchhouse, foundation year doctor1,
- Margaret MacLeod, specialist nurse in cardiology3,
- Mary Stoddart, advanced biomedical scientist4,
- Simon Walker, consultant in clinical biochemistry4,
- Martin A Denvir, consultant cardiologist1,
- Keith A A Fox, professor of cardiology1,
- David E Newby, professor of cardiology1
- 1BHF/University Centre for Cardiovascular Science, Edinburgh University, Edinburgh EH16 4SU, UK
- 2Public Health Sciences, Edinburgh University, Edinburgh EH8 9AG
- 3Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA
- 4Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA
- Correspondence to: N L Mills, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Chancellor’s Building, Edinburgh, EH16 4SB
- Accepted 19 January 2012
Objective To assess the relation between troponin concentration, assay precision, and clinical outcomes in patients with suspected acute coronary syndrome.
Design Cohort study.
Setting Tertiary centre in Scotland.
Participants 2092 consecutive patients admitted with suspected acute coronary syndrome were stratified with a sensitive troponin I assay into three groups (<0.012, 0.012-0.049, and ≥0.050 µg/L) based on the 99th centile for troponin concentration (0.012 µg/L; coefficient of variation 20.8%) and the diagnostic threshold (0.050 µg/L; 7.2%).
Main outcome measure One year survival without events (recurrent myocardial infarction, death) in patients grouped by troponin concentration.
Results Troponin I concentrations were <0.012 µg/L in 988 patients (47%), 0.012-0.049 µg/L in 352 patients (17%), and ≥0.050 µg/L in 752 patients (36%). Adoption of the 99th centile would increase the number of people receiving a diagnosis of myocardial infarction from 752 to 1104: a relative increase of 47%. At one year, patients with troponin concentrations of 0.012-0.049 µg/L were more likely to be dead or readmitted with recurrent myocardial infarction than those with troponin concentrations <0.012 µg/L (13% v 3%, P<0.001; odds ratio 4.7, 95% confidence interval 2.9 to 7.9). Compared with troponin ≥0.050 µg/L, patients with troponin 0.012-0.049 µg/L had a higher risk profile but were less likely to have a diagnosis of, or be investigated and treated for, acute coronary syndrome.
Conclusion Lowering the diagnostic threshold to the 99th centile and accepting greater assay imprecision would identify more patients with acute coronary syndrome at risk of recurrent myocardial infarction and death but would increase the diagnosis of myocardial infarction by 47%. It remains to be established whether reclassification of these patients and treatment for myocardial infarction would improve outcome.
Contribution: NLM, SW, MAD, KAAF, and DEN conceived and designed the study. KKL, AMDC, MM, and MS acquired the data. KKL, NLM, and DAM analysed and interpreted the data. NLM and DEN drafted the initial manuscript. KKL, DAM, AMDC, MM, MS, SW, MAD, KAAF, and DEN made critical revisions of the manuscript for important intellectual content. MAD, KAAF, and DEN contributed equally to this work. All authors approved the final version. NLM is guarantor.
Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. NLM is supported by an intermediate clinical research fellowship from the British Heart Foundation (BHF) (FS/10/024/28266). KAAF and DEN are supported by BHF Chair Awards (CH/92010/6773 and CH/09/002/26360, respectively).
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; NLM and SW have specified relationships with Abbott Diagnostics that might have an interest in the submitted work in the previous three years.
Ethical approval: Not required. The study protocol was reviewed by the Chairman and Scientific Advisor of the Lothian research ethics committee, who advised that the proposed study represented clinical audit and service evaluation and therefore did not require approval. Data collection and record linkage were performed with permission from the Caldicott Guardian.
Data sharing: No additional data available.
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