Circadian troponin dynamics reveal sex-specific signals for acute coronary syndrome evaluation

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.