Key result
Reclassification using sex-specific high-sensitivity troponin I upper reference limits independently predicted a 52.5% lower hazard of major adverse cardiac events over time (P=0.016).
Why the study?
The long-term benefit of sex-specific 99th percentile upper reference limits in conjunction with high-sensitivity cardiac troponin assays for suspected ACS is emerging.
Does reclassification using sex-specific 99th percentile URLs for hs-cTnI predict long-term MACE in ED patients with suspected ACS?
Observational (n=1,486)
Does reclassification using sex-specific 99th percentile URLs for hs-cTnI predict long-term MACE in ED patients with suspected ACS?
Integration of sex-specific URLs for hs-cTnI identifies patients at increased cardiovascular risk but is associated with a lower hazard of long-term MACE.
Hypothesis-generating for troponin reclassification in MACE risk assessment; prospective trials needed before clinical adoption.[[1]](https://academic.oup.com/jalm/advance-article/doi/10.
BACKGROUND: The long-term benefit of sex-specific 99th percentile upper reference limits (URLs) in conjunction with high-sensitivity cardiac troponin assays for suspected acute coronary syndrome (ACS) are emerging. We evaluated the long-term outcomes of patients reclassified by this approach using the Beckman Coulter Access high-sensitivity troponin I (hs-cTnI) assay. METHODS: A retrospective observational study evaluated 1486 emergency department (ED) patients with hs-cTnI results for 3 years and 80 days. Patients whose values exceeded the sex-specific URL but remained below the conventional URL were identified and compared with non-reclassified controls. RESULTS: Reclassification occurred 30% more frequently in women (7.6%, 68/893) compared to men (5.7%, 34/593) and demonstrated higher rates of major adverse cardiac events (MACEs), coronary artery disease, and cerebrovascular disease. Among reclassified men, myocardial infarction (MI) was more often followed by death. Among women, reclassification was associated with MI or death, but rarely both. Time to first post-ED MACE was significantly longer in reclassified patients. In a Cox regression model, reclassification independently predicted a 52.5% lower hazard of MACE over time (P = 0.016). The regression model also described Class 1 obesity as protective, with a 68.2% hazard reduction vs normal weight (P < 0.001). CONCLUSIONS: Integration of sex-specific URLs and a hs-cTnI assay identified patients at increased cardiovascular risk, yet was associated with improved long-term outcomes, suggesting potential clinical value. Findings also reinforce the obesity paradox, with Class 1 obesity linked to reduced MACE risk.
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Steiner et al. (2026) conducted an observational in Suspected acute coronary syndrome (ACS) (n=1,486). Reclassification using sex-specific 99th percentile upper reference limits for hs-cTnI vs. Non-reclassified controls was evaluated on Major adverse cardiac events (MACE) (52.5% lower hazard, p=0.016). Reclassification using sex-specific high-sensitivity troponin I upper reference limits independently predicted a 52.5% lower hazard of major adverse cardiac events over time (P=0.016).
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