Troponins

Dr Chris Vorster

PATHCHAT NO 14: EVOLVING ROLE OF TROPONINS

Background

Troponin measurement has been available for almost 15 years, and was initially used as an additional test to the existing cardiac profile. Today, troponins should be used as the sole marker for the diagnosis, prognosis and detection of reinfarction or post intervention infarction.¹Regardless of this fact however, the accuracy of the clinician's diagnosis depends largely on the correct application of the diagnostic criteria for an acute myocardial infarction (AMI), which is the focus of this article.

In 2000 the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) defined the role of biomarkers of myocardial necrosis as evidence of an AMI in the clinical setting of ischaemia. ²Based on the ESC/ACC definition, the American Heart Association (AHA) in 2003 published specific criteria to standardize the case definition of an AMI:

Two measurements of an adequate marker, at least 6 hours apart, that differ by more than 20%, and of which at least one is above the 99 percentile of the reference range of a reference population

PLUS

A setting of ischaemia (clinical and/or ECG findings)

The main difference between the ESC/ACC and AHA definition is that the AHA quantifies the difference required between the two measurements whereas the ESC/ACC simply states that the two values should be rising or falling. Careful consideration of the definition reveals the following critical aspects:

a) Adequate marker

According to the National Academy of Clinical Biochemistry (NACB) and the International Federation of Clinical Chemistry (IFCC) guidelines on the use of biomarkers of myocardial necrosis in 2007 , troponin is the preferred marker while CK-MB is an acceptable alternative only when troponin is not available. Prior to the development of troponin assays with very low detection limits, myoglobin was used as early marker of myocardial damage despite its low specificity , whereas troponin was used as a highly specific although-later rising marker. CK-MB was perceived to rise earlier than the troponins (although less specific), but later than myoglobin (although more specific). Newer troponin assays have much lower detection limits and are now well established to be the earliest indicators of myocardial necrosis.

All of these markers reflect myocardial necrosis and will increase in a setting of ischaemia, excessive myocardial stress or direct trauma. Furthermore, numerous conditions that induce myocardial toxins can also lead to elevated concentrations. Causes of an elevated troponin concentration of origin other than an AMI are listed in Box 1. It is therefore critical that an increased concentration be confirmed to be of an evolving nature and that the clinical setting is judged appropriately as ischaemia.

b) Two measurements…6hrs apart

In the setting of classical symptoms, ECG ST segment elevation and greatly elevated cardiac markers, the clinician may not want to delay treatment to meet the criteria. When the diagnosis is less certain two measurements will be required. The rationale behind this requirement when the first measurement is negative is that myocardial damage may be too early to be detected by any marker. On the other hand, if the first value is positive it may simply be due to a non-ischaemic cause, and establishing that necrosis is evolving with a second measurement will improve specificity. While an interval of at least 6 hours is required to establish this evolving pattern the clinician may want to do a serial measurement earlier than this if clinically justified. The patient should not be discharged unless repeat measurements, at least six hours apart, show a change of less than 20% between the two measurements.

c) The 99 percentile

A discussion of the issues surrounding the 99 percentile cut-off is a discussion of troponin test quality. Let it be stated clearly and without ambiguity: All troponin assays are not equal! Test quality may not be the only consideration in selecting a troponin assay for a specific location: other aspects such as the required turnaround time and expected test volume also have to be taken into account. All too often customer preference predominate the selection process, and such preferences are not always grounded in sound scientific principles but rather in inaccurate perceptions that may result from marketing campaigns. Such campaigns may emphasize distinguishing features which are pseudo-advantages and have not always struck at the heart of the matter. Thus, in order to be able to select the correct troponin assay, an understanding of the test quality is essential. 99% of healthy individuals have a troponin value less than the 99^thpercentile value and only 1% exceeds it.

Read the full article here.

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Troponins