What is the clinical evidence from this study?

Study design: Observational. Population: Suspected acute coronary syndrome (n=23803). Intervention: Male sex vs. Female sex. Primary outcome: Midline Estimating Statistic of Rhythm (MESOR) hs-cTnI (p=<0.001).

What question did this study set out to answer?

To investigate circadian variations in high-sensitivity cardiac troponin and their sex-specific implications for risk stratification in acute coronary syndrome.

April 18, 2026Internal and Emergency Medicine0 citationsOpen Access

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

Q: What are the key findings of this study?

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).

Q: What question did this study set out to answer?

To investigate circadian variations in high-sensitivity cardiac troponin and their sex-specific implications for risk stratification in acute coronary syndrome.

JEJoshua EmakhuHenry Ford Health System SSSana SomanHenry Ford Health System KHKegham HawatianHenry Ford Health System

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).

Key Points

To investigate circadian variations in high-sensitivity cardiac troponin and their sex-specific implications for risk stratification in acute coronary syndrome.
Secondary analysis of the RACE-IT trial data from Michigan emergency departments.
Analysis focused on patients with hs-cTnI values in the indeterminate range.
Utilized cosinor regression models for diurnal variation and multivariable logistic regression for MACE associations.
Adjusted for cardiovascular risk factors.
Men exhibited higher hs-cTnI levels and greater diurnal amplitudes compared to women.
Peak hs-cTnI levels were observed at 6:06 AM for both sexes.
Male sex and closer presentation times to midnight independently predicted higher 30-day MACE risk.
Each 1 ng/L increase in hs-cTnI was associated with a 7% increase in MACE risk.

Study Design

Type

Observational (n=23,803)

Multicenter

Yes

Structured PICO

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?

Population

23,803 patients presenting with suspected acute coronary syndrome (ACS) to 9 emergency departments in Michigan, USA. Mean age 57.5 years, 42.5% male, 32.7% Black, 53.7% White. Key inclusion: available time-stamped hs-cTnI values in the indeterminate range (4-18 ng/L) measured with the Beckman Coulter assay. Key exclusion: STEMI presentation, incomplete data on presentation time or unavailable hs-cTnI levels.

Intervention

Exposure to different times of presentation (morning, afternoon, evening, night) and biological sex (male vs female) to evaluate diurnal variation of high-sensitivity cardiac troponin I (hs-cTnI).

Comparator

Comparisons made between male and female patients, and across four 6-hour presentation time intervals (morning 6:00-11:59, afternoon 12:00-17:59, evening 18:00-23:59, night 00:00-05:59).

Outcome

Daily hs-cTnI level changes and sex-based differences in these patterns (diurnal variation), quantified using cosinor regression.surrogate

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.

Main Result

Absolute Event Rate: 6.26% vs 5.52%

p-value: p=<0.001

Limitations

Retrospective design and focus on ED patients limits causal inference and generalizability to non-clinical populations
Transient non-ischemic conditions known to influence troponin concentrations were not excluded
Time of symptom onset relative to troponin measurement was not available
Did not account for potential factors related to night-shift work among participants
Inter-laboratory calibration differences could contribute to random measurement variability

Abstract

Abstract 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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