Implementation of a Sensitive Troponin I Assay and Risk of Recurrent Myocardial Infarction and Death in Patients With Suspected Acute Coronary Syndrome

Nicholas L. Mills, Antonia M. D. Churchhouse, Kuan Ken Lee, Atul Anand, David Gamble, Anoop S. V. Shah, Elspeth Paterson, Margaret MacLeod, Catriona Graham, Simon Walker, Martin A. Denvir, Keith A. A. Fox, David E. Newby

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Although troponin assays have become increasingly more sensitive, it is unclear whether further reductions in the threshold of detection for plasma troponin concentrations will improve clinical outcomes in patients with suspected acute coronary syndrome (ACS).To determine whether lowering the diagnostic threshold for myocardial infarction (MI) with a sensitive troponin assay could improve clinical outcomes.
All consecutive patients admitted with suspected ACS to the Royal Infirmary of Edinburgh, Edinburgh, Scotland, before (n=1038; February 1-July 31, 2008, during the validation phase) and after (n=1054; February 1-July 31, 2009, during the implementation phase) lowering the threshold of detection for myocardial necrosis from 0.20 to 0.05 ng/mL with a sensitive troponin I assay were stratified into 3 groups (<0.05 ng/mL, 0.05-0.19 ng/mL, and ≥0.20 ng/mL). During the validation phase, only concentrations above the original diagnostic threshold of 0.20 ng/mL were reported to clinicians.
Event-free survival (recurrent MI and death) at 1 year in patients grouped by plasma troponin concentrations.
Plasma troponin concentrations were less than 0.05 ng/mL in 1340 patients (64%), 0.05 to 0.19 ng/mL in 170 patients (8%), and 0.20 ng/mL or more in 582 patients (28%). During the validation phase, 39% of patients with plasma troponin concentrations of 0.05 to 0.19 ng/mL were dead or had recurrent MI at 1 year compared with 7% and 24% of those patients with troponin concentrations of less than 0.05 ng/mL (P<.001) or 0.20 ng/mL or more (P=.007), respectively. During the implementation phase, lowering the diagnostic threshold to 0.05 ng/mL was associated with a lower risk of death and recurrent MI (from 39% to 21%) in patients with troponin concentrations of 0.05 to 0.19 ng/mL (odds ratio, 0.42; 95% confidence interval, 0.24-0.84; P=.01).
In patients with suspected ACS, implementation of a sensitive troponin assay increased the diagnosis of MI and identified patients at high risk of recurrent MI and death. Lowering the diagnostic threshold of plasma troponin was associated with major reductions in morbidity and mortality.

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Recent reports have indicated that the latest generation of sensitive troponin assays can increase diagnostic performance and improve the early diagnosis of myocardial infarction (MI).1-2 Lowering the threshold for detecting cardiac troponin is a highly controversial issue among clinicians with cardiologists, physicians, and clinical biochemists uncertain as to whether the benefits of small improvements in sensitivity will outweigh the problems that may arise as a result of reduced specificity. Furthermore, whether lowering the threshold for detection of plasma troponin improves clinical outcomes in patients with suspected acute coronary syndrome (ACS) is unknown.

Following improvements in assay performance, a more sensitive troponin I assay was introduced into our institution. During the validation phase of the assay, only values at or above the diagnostic threshold of 0.20 ng/mL from the previous generation of assay were reported to clinicians. The validation and subsequent implementation of this assay provided a unique opportunity to assess in patients presenting with suspected ACS (1) the effect of this sensitive assay on the rate of diagnosis of MI, (2) whether small increases in plasma troponin concentrations would predict the future risk of adverse clinical outcome, and (3) how lowering the diagnostic thresholds would affect clinical outcomes.

Original languageEnglish
Pages (from-to)1210-1216
Number of pages7
JournalJournal of the American Medical Association
Issue number12
Publication statusPublished - 23 Mar 2011

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