Introduction: Defining the 99th percentile upper-reference limit (URL) of cardiac troponin (cTn), the concentration threshold used to support the Universal Definition of Myocardial Infarction is critically important; with challenges in defining normality for subjects used to derive this threshold. With increasing implementation of high sensitivity cTnI (hs-cTnI) and hs-cTnT assays in global clinical practice, our goal was to determine overall and sex-specific 99th percentiles in 6 hs-cTn assays using a universal sample bank.
Methods: Apparently normal subjects were obtained from the American Association of Clinical Chemistry (AACC) Universal Sample Bank, comprised of 423 men and 415 women, screened using a health questionnaire. Hemoglobin A1c (URL 6.5%), NT-proBNP (URL 125 ng/L) and eGFR (60 mL/min), along with statin use, assisted in verifying subject normality, and used as surrogate biomarker exclusion criteria. 99th percentiles were determined by the non-parametric, Harrell-Davis Bootstrap, and Robust methods.
Results: Demographics: ages 19 to 91y; Caucasian 58%, African American 27%, Hispanic 8% Pacific Islander/Asian 11%, other 4%; Hispanic 8%, non-Hispanic 92%. Table 1 shows the 99th percentiles before and after exclusion. The statistical method influenced both the overall and sex-specific 99th percentile, showing substantially different 99th percentiles between assays. For all assays, men had higher 99th percentiles (ng/L) than women, whereas for women, the Roche and Beckman (only after exclusions) assays did not measure cTn ≥LoD in >50%.
Conclusions: Our study has important clinical practice implications, in that a) sex-specific 99th percentiles vary according to the statistical method and hs-assay used, b) not all hs-cTn assays provide measurable concentrations ≥ LoD in >50% for women, and c) surrogate exclusion criteria used to define normality tends to lower 99th percentiles.