Key result
Men evaluated for suspected acute coronary syndrome exhibited a higher 24-hour mean hs-cTnI level and greater diurnal amplitude than women, and male sex independently predicted 30-day MACE (aOR 2.37).
Why the study?
Although hs-cTn exhibits circadian variation, whether these variations differ by sex and affect early risk stratification for suspected ACS remains uncertain.
Does high-sensitivity cardiac troponin I exhibit sex-specific circadian variation, and do these variations influence 30-day MACE risk in patients with suspected acute coronary syndrome?
Observational (n=23,803)
Yes
Does high-sensitivity cardiac troponin I exhibit sex-specific circadian variation, and do these variations influence 30-day MACE risk in patients with suspected acute coronary syndrome?
High-sensitivity cardiac troponin I exhibits sex-specific circadian patterns with men showing higher baseline levels and greater diurnal fluctuations, suggesting that time- and sex-adjusted thresholds could improve early risk stratification for suspected ACS.
Sex- and time-adjusted hs-cTnI thresholds may refine ED ACS risk stratification; extends circadian variation data to independent MACE prediction.[[1]](https://link.springer.com/article/10.
High-sensitivity cardiac troponin (hs-cTn) exhibits circadian variation, yet whether these variations differ by sex and influence early risk stratification for suspected acute coronary syndrome (ACS) is uncertain. We performed a secondary analysis of the RACE-IT stepped-wedge randomized trial across nine Michigan emergency departments (July 2020–April 2021). From the 32,609 patients in the primary trial, we analyzed those with available hs-cTnI values, time-stamped, that fell within the indeterminate range (4–18 ng/L) and were performed with the Beckman Coulter assay. We performed cosinor regression models to evaluate diurnal variation and multivariable logistic regression to analyze the association with 30-day major adverse cardiac events (MACE) after adjusting for cardiovascular risk factors. Median age was 57 years; 42% were men. Men showed a higher Midline Estimating Statistic of Rhythm (MESOR) hs-cTnI (6.3 ng/L vs 5.5 ng/L; p < 0.001) and greater diurnal amplitude ( β = 0.21 vs 0.13; p < 0.001). Peak concentrations occurred at 6:06 AM in both sexes. In multivariable analysis, male sex (adjusted odds ratio [aOR] 2.37, 95% CI 1.68–3.34) and earlier presentation time (per 6-h interval closer to midnight: aOR 0.65, 95% CI 0.54–0.79) independently predicted 30-day MACE. Each 1 ng/L increase in hs-cTnI conferred a 7% higher MACE risk (OR 1.07, 95% CI 1.03–1.12). hs-cTnI exhibits sex-specific circadian patterns with independent prognostic significance. These findings support the potential for time- and sex-adjusted hs-cTnI thresholds to improve early risk stratification in emergency care.
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Emakhu et al. (2026) conducted an observational in Suspected acute coronary syndrome (n=23,803). Male sex vs. Female sex was evaluated on Midline Estimating Statistic of Rhythm (MESOR) hs-cTnI (p=<0.001). Men evaluated for suspected acute coronary syndrome exhibited a higher 24-hour mean hs-cTnI level and greater diurnal amplitude than women, and male sex independently predicted 30-day MACE (aOR 2.37).
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