Exploring Sex-Specific High-Sensitivity Cardiac Troponin Thresholds for Rule-Out of Non-ST-Elevation Myocardial
Ingar Ziad Restan1, Yong Yong Tew2, Ole-Thomas Steiro3
1Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
Clinical Chemistry
|May 14, 2026
Summary
Sex-specific thresholds for high-sensitivity cardiac troponin (hs-cTn) improve myocardial infarction (MI) risk stratification. Developing sex-specific hs-cTn thresholds enhances diagnostic accuracy and efficiency for both female and male patients.
Area of Science:
- Cardiology
- Biomarkers
- Diagnostic Accuracy
Background:
- International guidelines recommend sex-specific thresholds for high-sensitivity cardiac troponin (hs-cTn) assays in myocardial infarction (MI) diagnosis.
- Current uniform thresholds may not optimally identify low-risk patients in emergency settings.
- Assessing the performance of sex-specific single-sample rule-out thresholds is crucial for refining MI diagnosis.
Purpose of the Study:
- To evaluate the effectiveness of sex-specific single-sample rule-out thresholds for hs-cTn assays.
- To compare the performance of sex-specific thresholds against guideline-recommended uniform thresholds.
- To determine if sex-specific thresholds improve MI risk stratification in emergency department patients.
Main Methods:
- A derivation cohort of patients suspected of MI from Norwegian hospitals (2015-2020) was analyzed.
- hs-cTnT (Roche) and hs-cTnI (Abbott, Siemens) measurements were used, with type 1 MI as the primary endpoint.
- Sex-specific single-sample rule-out thresholds were derived and externally validated in a British cohort.
Main Results:
- Uniform thresholds showed marked sex differences in MI risk stratification, with more females below uniform cutoffs.
- Sex-specific thresholds achieved >99% sensitivity at lower cutoffs for females (<4-7 ng/L) and males (<1-7 ng/L) depending on the assay.
- Sex-specific thresholds decreased rule-out proportions in females (10%-32%) and increased them in males (45%-64%), with similar trends in validation.
Conclusions:
- Uniform single-sample rule-out thresholds for hs-cTn assays demonstrate significant sex-based disparities in MI risk stratification.
- Implementing sex-specific hs-cTn thresholds can enhance diagnostic safety for females and improve clinical efficiency for males.
- Sex-specific thresholds represent a promising strategy for optimizing MI diagnosis in diverse patient populations.
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