Sex-specific high-sensitivity troponin T cut-points have similar safety but lower efficacy than overall cut-points in a multisite U.S. cohort

Data comparing the performance of sex-specific to overall (non-sex-specific) high-sensitivity cardiac troponin (hs-cTn) cut-points for diagnosing acute coronary syndrome (ACS) are limited. This study aims to compare the safety and efficacy of sex-specific versus overall 99th percentile high-sensitivity cardiac troponin T (hs-cTnT) cut-points. We conducted a secondary analysis of the STOP-CP cohort, which prospectively enrolled emergency department patients ≥ 21 years old with symptoms suggestive of ACS without ST-elevation on initial electrocardiogram across eight U.S. sites (January 25, 2017-September 6, 2018). Participants with both 0- and 1-h hs-cTnT measures less than or equal to the 99th percentile (sex-specific 22 ng/L for males, 14 ng/L for females; overall 19 ng/L) were classified into the rule-out group. The safety outcome was adjudicated cardiac death or myocardial infarction (MI) at 30 days. Efficacy was defined as the proportion classified to the rule-out group. McNemar's test and a generalized score statistic were used to compare rule-out and 30-day cardiac death or MI rates between strategies. Net reclassification improvement (NRI) index was used to further compare performance. This analysis included 1430 patients, of whom 45.8% (655/1430) were female; the mean ± SD age was 57.6 ± 12.8 years. At 30 days, cardiac death or MI occurred in 12.8% (183/1430). The rule-out rate was lower using sex-specific versus overall cut-points (70.6% [1010/1430] vs. 72.5% [1037/1430]; p = 0.003). Among rule-out patients, the 30-day cardiac death or MI rates were similar for sex-specific (2.4% [24/1010]) vs. overall (2.3% [24/1037]) strategies (p = 0.79). Among patients with cardiac death or MI, sex-specific versus overall cut-points correctly reclassified three females and incorrectly reclassified three males. The sex-specific strategy resulted in a net of 27 patients being incorrectly reclassified into the rule-in group. This led to an NRI of -2.2% (95% CI -5.1% to 0.8%). Sex-specific hs-cTnT cut-points resulted in fewer patients being ruled out without an improvement in safety compared to the overall cut-point strategy.