Key result
Sex-specific hs-cTn thresholds achieve >99% sensitivity for ruling out MI, shifting rule-out rates by sex.
Why the study?
Sex-specific diagnostic thresholds for hs-cTn assays are recommended by guidelines for MI diagnosis, but their performance as single-sample rule-out thresholds in the emergency department needed evaluation.
Do sex-specific high-sensitivity cardiac troponin thresholds improve safety and efficiency for rule-out of non-ST-elevation myocardial infarction compared to uniform thresholds in patients presenting with suspected MI?
Cohort (n=3,844)
Yes
Do sex-specific high-sensitivity cardiac troponin thresholds improve safety and efficiency for rule-out of non-ST-elevation myocardial infarction compared to uniform thresholds in patients presenting with suspected MI?
Sex-specific high-sensitivity cardiac troponin thresholds achieve >99% sensitivity for MI, improving safety in females and efficiency in males compared to uniform thresholds.
Sex-specific hs-cTn thresholds achieve >99% sensitivity for MI rule-out; leaves open whether they improve outcomes versus uniform cutoffs.
Background Sex-specific diagnostic thresholds for high-sensitivity cardiac troponin (hs-cTn) assays are recommended by international guidelines for the diagnosis of myocardial infarction (MI). We assessed the performance of sex-specific single-sample rule-out thresholds for identifying low-risk patients in the emergency department. Methods The derivation cohort comprised patients ≥18 years presenting with suspected MI to 2 Norwegian hospitals between 2015 and 2020 with 0-hour hs-cTnT (Roche) and high-sensitivity cardiac troponin I (Abbott and Siemens) measurements available. The primary endpoint was type 1 MI at index encounter. Diagnoses were adjudicated using assay-specific criteria per the Fourth Universal Definition of Myocardial Infarction. Sex-specific single-sample rule-out thresholds were derived, compared with guideline-recommended uniform thresholds, and externally validated in an independent and comparable British cohort. Results Among 1896 patients [median age 62 (25th–75th percentile 52–72) years; 39% female], MI occurred in 12.5%–12.8% males and 8.8%–9.2% females, depending on the adjudication assay. For each assay, more females had hs-cTn concentrations below the uniform single-sample thresholds, yet these thresholds did not achieve >99% sensitivity in females. Sex-specific adjustment achieved >99% sensitivity at cutoffs of <4 and <7 ng/L (Roche); <1 and <6 ng/L (Abbott); <2 and <7 ng/L (Siemens) for females and males, respectively. Sex-specific thresholds reduced rule-out proportions in females (from 29%–60% to 10%–32%) and increased them in males (from 17%–53% to 45%–64%). Trends were similar in the validation cohort of 1948 patients. Conclusions Uniform single-sample rule-out thresholds reveal marked sex differences in MI risk stratification. Sex-specific hs-cTn thresholds could improve safety in females and efficiency in males. ClinicalTrials.gov Registration Numbers NCT02620202; NCT01852123.
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Restan et al. (2026) conducted a cohort in Suspected myocardial infarction (n=3,844). Sex-specific single-sample rule-out thresholds vs. Uniform single-sample rule-out thresholds was evaluated on Type 1 MI at index encounter. Sex-specific hs-cTn thresholds achieved >99% sensitivity for ruling out MI, reducing rule-out proportions in females (to 10%-32%) and increasing them in males (to 45%-64%).
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