Elsevier

Clinica Chimica Acta

Volume 412, Issues 1–2, 14 January 2011, Pages 91-97
Clinica Chimica Acta

Clinical implications of the change of cardiac troponin I levels in patients with acute chest pain — An evaluation with respect to the Universal Definition of Myocardial Infarction

https://doi.org/10.1016/j.cca.2010.09.020Get rights and content

Abstract

Background

The Universal Definition of Myocardial Infarction incorporates elevated cardiac troponin levels (> 99th percentile) together with a significant rise/fall of troponins as biochemical criterion. We sought to evaluate the clinical implications of the relative change of cardiac troponin I (cTnI) levels with respect to the Universal Definition in patients with acute chest pain.

Methods

cTnI (Stratus CS) was measured serially in 454 patients within 24 h from admission. Acute myocardial infarction (AMI) was defined using the criteria adapted to the ESC/ACC consensus document, or corresponding to the Universal Definition together with prespecified cTnI changes of ≥ 20%, ≥ 50% and ≥ 100%. Follow-up was completed after 5.8 years.

Results

A peak cTnI level above the 99th percentile together with a cTnI change of ≥ 20% was found in 160 patients of whom 25 did not have AMI according to the ESC/ACC criteria. These 160 patients had a significantly raised mortality (HR 2.5 [95% CI 1.7–3.8]). Higher cTnI deltas were not associated with higher mortalities but identified smaller patient cohorts at risk.

Conclusions

The Universal Definition of AMI together with a ≥ 20% cTnI change appears to improve the discrimination of acute from chronic causes of cTnI release, and allows a reliable identification of patients at risk.

Introduction

Advances in the understanding of the pathobiology of acute coronary syndromes together with the implementation of improved assays for biomarkers of cardiomyocyte necrosis have had considerable implications upon what is regarded as AMI. As a consequence, the 2000 consensus document of the joint ESC/ACC Committee for the Redefinition of Myocardial Infarction recommended the cardiac troponins as biochemical gold standard of myocardial necrosis [1]. As cut-off, the 99th percentile in a healthy reference population was suggested or alternatively, the lowest concentration measurable with a CV < 10% [2].

In 2007, the diagnostic criteria for AMI have been updated in the consensus guidelines from the Global Task Force for the Universal Definition of Myocardial Infarction [3]. According to these guidelines, elevated and significantly changing cardiac troponin levels in a setting suggestive of myocardial ischemia are required as criterion for non procedure-related AMI in conjunction with either typical symptoms, new ECG changes, or imaging evidence of new loss of myocardium. This applies to both underlying unstable coronary artery disease (type 1 AMI) and other conditions causing myocardial damage due to an oxygen supply/demand imbalance (type 2 AMI).

According to the Universal Definition, troponin elevation is defined by the 99th percentile derived from healthy controls. The required degree of a change of troponin levels to fulfill the diagnosis of AMI however, is subject of debate. Considering analytical aspects of currently applied assays, a relative change of at least 20–30% has been recommended [4], [5], [6] whereas recent data on the biologic variability of troponin suggest that higher deltas might be needed [7], [8]. Moreover, there are only sparse data regarding the clinical implications of troponin deltas in patients with chest pain in whom a diagnosis of AMI has not yet been confirmed [6]. In order to investigate these important issues, we conducted a retrospective analysis in a heterogeneous chest pain population in whom cTnI levels had been measured serially.

Section snippets

Study population

This analysis was performed in a pooled population of unique patients included in the FAST II- and FASTER I-studies [9], [10]. The primary aim of both studies was to assess the implications of serial testing for circulating biomarkers of myocardial damage in patients with acute chest pain. Both studies enrolled patients who had been admitted to coronary care units after an initial evaluation at the emergency department. The FAST II-study was conducted between May 2000 and March 2001 at the

Patient characteristics

The population for the present analysis consisted of 454 patients. The median time from onset of chest pain to the first blood sample was 4.5 (3.1–5.9 [25th, 75th percentiles]) hours.

Applying the initial classification that was adapted to the ESC/ACC criteria, AMI was diagnosed in 142 patients (31.3%), unstable angina in 82 patients (18.1%), other cardiac disease in 37 patients (8.2%), non-cardiac disease in 26 patients (5.7%) and unspecified chest pain in 167 patients (36.8%). The cohort with

Discussion

The introduction of the Universal Definition of AMI [3] has been followed by a still ongoing discussion regarding the appropriate degree of troponin change required for the diagnosis of AMI. The underlying issue in this context is the question which troponin delta is needed to distinguish acute from chronic causes of troponin elevation, a problem that is of paramount importance for the correct interpretation of troponin results in clinical situations.

The present analysis sheds new light on this

Limitations

Some limitations of our study warrant consideration. This is a retrospective analysis of patients included into two different studies. The analytical precision of the Stratus CS assay is fairly high [2], [11], [12] but not perfect and could not be validated by duplicate analyses using a highly sensitive troponin assay due to a shortcoming of available samples. The lower analytical sensitivity of the AxSYM assay relative to the Stratus CS [19] may have created a bias towards the classification

Funding

The FAST II-study had been supported by grants from Dade Behring AB, Skärholmen, Sweden (now Siemens Healthcare Diagnostics) and the FASTER I-study by a grant from Cardiological Decision Support Uppsala AB, Uppsala, Sweden.

Conflict of interest

Dr Jaffe is consultant to Siemens Healthcare Diagnostics, Beckman Coulter Inc., Ortho Diagnostics, Singulex and Nanosphere, and has received research funding from Siemens Healthcare Diagnostics and Beckman Coulter Inc. Dr Venge has received research honoraria from Siemens Healthcare Diagnostics, Abbott Diagnostics, Beckman Coulter Inc. and Roche Diagnostics. Dr Lindahl has served as a consultant for Siemens Healthcare Diagnostics, has received honoraria for educational lectures from that

References (19)

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