Clinical Use of High-sensitivity Cardiac Troponin in Patients With Suspected Myocardial Infarction

Raphael Twerenbold, MD; Jasper Boeddinghaus, MD; Thomas Nestelberger, MD; Karin Wildi, MD; Maria Rubini Gimenez, MD; Patrick Badertscher, MD; Christian Mueller, MD


J Am Coll Cardiol. 2017;70(8):996-1012. 

In This Article

Uniform Versus Sex-specific Cutoff Levels

In patients presenting with suspected MI, beyond the presence or absence of MI, 4 clinical variables seem to impact on hs-cTn concentrations: age, sex, renal dysfunction, and time from chest pain onset.[68–77] Accordingly, 3 strategies can be considered:

  1. First, a sophisticated one individualizing hs-cTn cutoff levels in the ED for all 4 confounders. Once automatized with a laboratory software tool, this approach may be feasible and could present a valid alternative to the current way of using 1 uniform cutoff value.

  2. Second, using sex-specific cutoff levels, but ignoring the possibly larger confounding effect of age and renal dysfunction. Recent studies have highlighted that women presenting with suspected MI are on average 5 to 8 years older than men presenting with suspected MI.[77–82] The higher age of female patients associated with higher hs-cTn levels seemed to well compensate the effect of female sex, which per se is associated with lower hs-cTn levels, obviating the need to adjust cutoff values. Accordingly, the use of sex-specific cutoff levels was associated with only a negligible number of patients reclassified as compared with the use of a uniform cutoff level.[68–77,82] In the largest and methodologically most robust study, including 2,734 patients, the use of sex-specific cutoff values of hs-cTnT resulted in only an upgrade of 2 women from UA to NSTEMI and a downgrade of 1 man from NSTEMI to UA.[77] Identical findings emerged from a second large diagnostic study using hs-cTnT.[82] By contrast, controversies remain for hs-cTnI,[71,79,81] which seem at least in part related to its rather high uniform 99th percentile recommended by the manufacturer.[83] Clearly, further studies are necessary to elucidate benefits and/or harms of sex-specific cutoff levels in the diagnosis of MI. The use of lower hs-cTn cutoff levels in women would invariably increase the number of women classified as MI. The resulting impact of the obligatory drop in specificity and the associated increased rate of elevated hs-cTn levels in absence of myocardial ischemia in women, as well as the corresponding lower number of men detected with MI by using higher hs-cTn cutoff levels in men, requires more in-depth analyses.

  3. Third, the traditional one using a uniform cutoff value. Given the uncertainties and obvious limitations of the second option, the preference of the current ESC guidelines is to continue using uniform cutoff levels.[27] Because increased complexity in the ED is closely linked with an increased rate of errors, the simplest option of continuing to use uniform cutoff levels at this point in time seems also the safest.[27]

It is important to highlight that the possible clinical use of hs-cTn is currently explored in several additional indications beyond the diagnosis of MI and that pros and cons of using sex-specific cutoff values may differ in other emerging indications.