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Recently, the 'normal' range for cardiac troponin I (TnI) has been changed following the introduction of newer, more sensitive tests. The universal definition of myocardial infarction (MI) specifies diagnostic criteria for MI as the detection of increasing or decreasing cardiac biomarkers (preferably cardiac troponin) with one or more values above the 99th percentile for the population, together with either clinical symptoms, new ischaemic electrocardiographic changes or typical imaging findings. 1 However, concerns about diagnostic specificity and test performance have raised doubts about the validity of low level elevations in clinical practice. 2 3 Some authors have suggested that a threshold level of two to five times the upper limit of normal (ULN) should be used to guide therapeutic intervention. 3
Previous research has found that levels of TnI greater than 2.0 ng/ml are associated with adverse events, but that levels between 0.5 and 2 ng/ml have only a weak association. 4 A more recent small study reported that TnI levels between 0.08 and 0.79 ng/ml are associated with an increased risk of adverse events, reporting a rate of 44% versus 24% for the comparator group (TnI <0.08 ng/ml) for a composite endpoint. 5 Interpreting these findings is difficult as the sample includes patients with TnI levels that would now be defined as clearly indicative of MI. The sample size was also relatively small and the rate of adverse events was unexpectedly high.
There are several reasons for a TnI level in the so-called 'grey' zone. It may be the early phase of a 'true' troponin elevation indicative of acute myocardial injury. In this case, further testing will reveal a typical rise and then fall of TnI levels. It has been hypothesised that it could indicate a 'leak' due to myocardial strain; for example, related to an episode of rapid atrial fibrillation or strenuous exercise. 6 If this is the case, repeat testing will show an early fall in the TnI level back towards normal. It could be indicative of a chronic elevation of TnI as may be seen in conditions such as chronic renal failure and congestive cardiac failure (among others) without new acute myocardial injury. 6 If this is so, repeat testing will reveal a chronic elevation of TnI without the rise and fall...