• 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 Sörensen, Dirk Westermann, Madelon M Buijs, Gerard J E Verdel, John W Pickering, Martin P Than, Raphael Twerenbold, Patrick Badertscher, Zaid Sabti, Christian Mueller, Atul 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, ShahAnoop S VASVBHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland., and Nicholas L Mills.
• BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland.
• JAMA. 2017 Nov 21; 318 (19): 191319241913-1924.

ImportanceHigh-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.ObjectiveTo 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 SourcesSystematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases from January 1, 2006, to March 18, 2017.Study SelectionProspective 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 SynthesisThe 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 MeasuresThe 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.ResultsOf 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 RelevanceAmong 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.

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