Abstract Body (Do not enter title and authors here): Introduction: The circadian variation of high-sensitivity cardiac troponin has been established, but whether sex-based differences in these rhythms affect early acute coronary syndrome risk evaluation remains unknown.
Research Questions: The research examines whether high-sensitivity cardiac troponin I (hs-cTnI) displays distinct diurnal patterns between men and women and investigates if these differences affect the prediction of 30-day major adverse cardiac events (MACE) for patients suspected of acute coronary syndrome independently.
Methods: The RACE-IT stepped-wedge randomized trial underwent secondary analysis in nine Michigan emergency departments from July 2020 to April 2021. Our analysis included patients from the primary trial who had recorded an hs-cTnI value among 32,609 participants. All the hs-cTnI samples received timestamp data and measurements fell between 2–18 ng/L using the Beckman-Coulter assay. We used Cosinor regression models to assess diurnal variation and Cox proportional hazards models to examine the relationship with 30-day MACE while controlling for cardiovascular risk factors. Our study presented Midline Estimating Statistic Of Rhythm (MESOR) values, which show the average level of hs-cTnI throughout the day.
Results: The participants had an average age of 57 years, 42% were male, and 32% were Black. Mesor hs-cTnI measurements were higher among men (6.3 ng/L versus 5.5 ng/L; p < 0.001) while their diurnal amplitude was also greater (β = 0.21 versus 0.13; p < 0.001). Peak concentrations occurred at ~06:00 h in both sexes (Figure 1). The multivariable analysis identified male sex (HR = 2.35; 95% CI: 1.67–3.31) and presentation time near midnight (per 6-hour interval HR = 0.65; 95% CI: 0.54–0.79) as independent factors predicting 30-day MACE. When hs-cTnI levels rose by 1 ng/L, patients experienced a 7% higher MACE risk, reflected by an HR of 1.07 (95% CI: 1.03–1.12). The research findings remained consistent when data were stratified by age, and patients with previous cardiovascular disease were excluded from the analysis.
Conclusions: Men exhibit stronger diurnal hs-cTnI rhythms while sex and time of presentation provide separate prognostic insights. Using sex- and time-specific hs-cTnI thresholds can refine early acute coronary syndrome risk assessment and identify patients who require enhanced monitoring or treatment. Prospective studies integrating circadian biomarker patterns into diagnostic algorithms are warranted.