Association of high-sensitivity cardiac troponin I concentration with cardiac outcomes in patients with suspected acute coronary syndrome

Andrew R. Chapman, Kuan Ken Lee, David A. McAllister, Louise Cullen, Jaimi H. Greenslade, William Parsonage, Andrew Worster, Peter A. Kavsak, Stefan Blankenberg, Johannes Neumann, Nils A. Söerensen, Dirk Westermann, Madelon M. Buijs, Gerard J.E. Verdel, John W. Pickering, Martin P. Than, Raphael Twerenbold, Patrick Badertscher, Zaid Sabti, Christian MuellerAtul Anand, Philip Adamson, Fiona E. Strachan, Amy Ferry, Dennis Sandeman, Alasdair Gray, Richard Body, Brian Keevil, Edward Carlton, Kim Greaves, Frederick K. Korley, Thomas S. Metkus, Yader Sandoval, Fred S. Apple, David E. Newby, Anoop S.V. Shah, Nicholas L. Mills

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

IMPORTANCE: High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5 ng/L identifies patients at presentation as low risk, but the optimal threshold is uncertain. OBJECTIVE: To evaluate the performance of a cardiac troponin I threshold of 5 ng/L at presentation as a risk stratification tool in patients with suspected acute coronary syndrome. DATA SOURCES: Systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases from January 1, 2006, to March 18, 2017. STUDY SELECTION: Prospective studies measuring high-sensitivity cardiac troponin I concentrations in patients with suspected acute coronary syndrome in which the diagnosis was adjudicated according to the universal definition of myocardial infarction. DATA EXTRACTION AND SYNTHESIS: The systematic review identified 19 cohorts. Individual patient-level data were obtained from the corresponding authors of 17 cohorts, with aggregate data from 2 cohorts. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random-effects model. MAIN OUTCOMES AND MEASURES: The primary outcome was myocardial infarction or cardiac death at 30 days. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data. RESULTS: Of 11 845 articles identified, 104 underwent full-text review, and 19 cohorts from 9 countries were included. Among 22 457 patients included in the meta-analysis (mean age, 62 [SD, 15.5] years; n = 9329 women [41.5%]), the primary outcome occurred in 2786 (12.4%). Cardiac troponin I concentrations were less than 5 ng/L at presentation in 11 012 patients (49%), in whom there were 60 missed index or 30-day events (59 index myocardial infarctions, 1 myocardial infarction at 30 days, and no cardiac deaths at 30 days). This resulted in a negative predictive value of 99.5% (95% CI, 99.3%-99.6%) for the primary outcome. There were no cardiac deaths at 30 days and 7 (0.1%) at 1 year, with a negative predictive value of 99.9% (95% CI, 99.7%-99.9%) for cardiac death. CONCLUSIONS AND RELEVANCE: Among patients with suspected acute coronary syndrome, a high-sensitivity cardiac troponin I concentration of less than 5 ng/L identified those at low risk of myocardial infarction or cardiac death within 30 days. Further research is needed to understand the clinical utility and cost-effectiveness of this approach to risk stratification.

Original languageEnglish (US)
Pages (from-to)1913-1924
Number of pages12
JournalJAMA - Journal of the American Medical Association
Volume318
Issue number19
DOIs
StatePublished - Nov 21 2017

Bibliographical note

Funding Information:
completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Chapman has received honoraria from Abbott Diagnostics and AstraZeneca. Dr Cullen has received funding from Abbott Diagnostics, Roche, Alere, Siemens, and Radiometer Pacific for research on diagnostic protocols and from Alere, Boehringer-Ingelheim, Pfizer, AstraZeneca, Abbott Diagnostics, and Radiometer Pacific for speaking and education. Dr Parsonage has received funding from Abbott Diagnostics, Roche, Alere, and Beckmann Coulter for research on diagnostic protocols, honoraria, travel expenses, and consultancy fees from Abbott, AstraZeneca, Hospira, and Sanofi-Aventis; and travel, accommodation, consulting fees, or honoraria from Abbott Laboratories. Dr Metkus performs consulting unrelated to this subject matter for BestDoctors Inc and Oakstone/EBIX and receives royalties for a textbook publication for McGraw-Hill publishing unrelated to this subject matter. Dr Kavsak has received grants, reagents, consultancy, advisory fees, and honoraria from Abbott Laboratories, Abbott Point of Care, Abbott Diagnostics Division Canada, Beckman Coulter, Ortho Clinical Diagnostics, Randox Laboratories, Roche Diagnostics, and Siemens Healthcare Diagnostics. In addition, McMaster University has filed patents with Dr Kavsak listed as an inventor in the acute cardiovascular biomarker field. Dr Anand has received honoraria from Abbott Diagnostics. Dr Carlton has undertaken research under collaborative agreements with Abbott Diagnostics and Randox. Dr Apple has acted as a consultant for Phillips Healthcare Incubator and Metanomics Healthcare, is on the board of directors at HyTest Ltd, has received honoraria from Instrumentation Laboratory and Abbott POC, has been a research principal investigator through the Minneapolis Medical Research Foundation, and has had nonsalaried relationships with Abbott Diagnostics, Roche Diagnostics, Siemens Healthcare, Alere, Ortho-Clinical Diagnostics, Nanomix, Becton Dickinson, and Singulex. Dr Than has accepted travel, accommodation, consulting fees, or honoraria from Abbott Laboratories. Dr Shah has received honoraria from Abbott Diagnostics. Dr Mills has acted as a consultant for Abbott Diagnostics, Beckman-Coulter, Roche, and Singulex. No other disclosures were reported.

Funding Information:
Funding/Support: This research was funded by the British Heart Foundation (SP/12/10/29922 and PG/15/51/31596). Drs Chapman and Mills are supported by a Clinical Research Training Fellowship (FS/16/75/32533) and the Butler Senior Clinical Research Fellowship (FS/16/14/32023), respectively, from the British Heart Foundation. Dr McAllister is supported by an Intermediate Clinical Fellowship (and Beit Award; 201492/Z/16/Z) from the Wellcome Trust.

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