• acute coronary syndromes
• acute myocardial infarction

Cardiac troponin is the most established biomarker for acute cardiac care and recommended for the diagnosis of acute myocardial infarction (MI).1 2 Cardiac troponin concentrations above the 99th percentile are defined as pathological and indicate myocardial injury, not necessarily caused by underlying acute or chronic ischaemia.3 The 99th percentile itself is determined in a healthy population, whereas elevated troponin concentrations above this cut-off are regarded as abnormal. A multitude of comorbidities and conditions other than myocardial ischaemia can influence troponin concentrations in the acute or chronic setting. This includes, among many others, age, sex, renal dysfunction and prevalent cardiovascular diseases.1 4 Such confounders are frequent bystanders in the setting of an acute MI and can complicate the diagnostic evaluation. Peak cardiac troponin concentrations correlate with infarct size in imaging modalities and thereby contain strong prognostic information. How peak cardiac troponin concentrations in patients with MI are influenced by comorbidities has been poorly explored. In their present Heart manuscript, Sundaram and colleagues5 investigated the association of peak cardiac troponin concentrations with various comorbidities in a very large registry data set. Between 2003 and 2013, data from more than 330 000 patients with MI were collected within the UK-wide Myocardial Ischemia National Audit Project registry. The observed peak cardiac troponin I and T concentrations were higher in patients with reduced kidney function and lower in patients with a history of MI, heart failure or obstructive pulmonary disease, compared with patients without the respective comorbidity. All of these comorbidities remained independent predictors of 180-day mortality also after adjustment for peak cardiac troponin concentrations.

These findings further contribute to the existing body of evidence indicating a close correlation of several comorbidities and cardiac troponin, also in the acute setting of myocardial infarction. Nevertheless, despite the high prognostic value of peak cardiac troponin concentrations, individual mortality risk cannot fully be depicted by cardiac troponin alone, as additional clinical factors such as comorbidities still provide incremental prognostic information beyond troponin.

However, there are several aspects that merit consideration and should be carefully taken into account when interpreting the results of the present study.

First, the vast majority of patients was enrolled before the clinical introduction of high-sensitivity cardiac troponin assays. Accordingly, this study mostly investigated less sensitive cardiac troponin assays, which do no longer reflect the current state of the art of clinical practice in Europe. Following current guidelines recommendations, most hospitals have meanwhile switched to high-sensitivity cardiac troponin assays.2 6 With the use of high-sensitivity assays, already mild cardiac troponin elevations around the 99th percentile of a healthy reference population became accurately detectable, while most non-sensitive assays cannot reliably detect cardiac troponin concentrations as low as the 99th percentile. Numerous studies have shown that even mild troponin elevations above the assay-specific 99th percentile, mostly prevalent in non-ST-elevation MI (NSTEMI) patients, are associated with poor outcome.7–9 The present study could not identify such patients as they were missed by the use of mostly non-sensitive assays, which might result in a systematic underestimation of the prognostic value of cardiac troponin when using high-sensitivity cardiac troponin.

Second, several manufacturers provide cardiac troponin I assays exist with substantial differences regarding analytical test characteristics between the assays. Standardisation between these assays is very poor, and particularly a 1:1 conversion is not possible. However, as information on type of cardiac troponin I assay was not available in the MINAP registry, the authors lumped all cardiac troponin I concentrations together, assuming a perfect 1:1 standardisation, which would be highly inappropriate in clinical practice.

Third, these analyses are based on registry data without a standardised timing of serial cardiac troponin sampling for determination of the peak cardiac troponin concentrations and without an adjudicated final diagnosis. Both factors limit the validity of the reported findings, particularly as some patients in the present manuscript are classified as NSTEMI or even ST-elevation MI despite a very low peak cardiac troponin concentration of less than 0.01 ng/mL, which is clinically implausible. In addition, the term of ‘myocardial injury’ was introduced in the third version of the Universal Definition of MI for those patients with elevated troponin concentration in absence of signs for myocardial ischaemia. Probably, several of these patients, which are classified as MI in the present manuscript, would now be classified as myocardial injury due to chronic elevation of cardiac troponin. This could explain the unexpected finding that patients with prevalent cardiovascular disease had lower troponin concentrations compared with patients without the prevalent disease. Some of these patients might not actually have an acute MI but myocardial injury due to their comorbidities.

As always, cardiac troponin concentrations should never be interpreted in isolation but always within the respective clinical context. While this is fairly evident for the diagnostic assessment of patients with suspected myocardial infarction, which also integrates electrocardiography, chest pain characteristics, clinical assessment and patients’ history including comorbidities, it may be less clear when interpreting peak cardiac troponin concentrations. This work helps to identify and consider relevant comorbidities when using peak cardiac troponin concentrations for estimation of midterm mortality in patients with MI.