Exploring Sex-Specific High-Sensitivity Cardiac Troponin Thresholds for Rule-Out of Non-ST-Elevation Myocardial...

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.

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.

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.

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.

NCT02620202; NCT01852123.