High-Sensitivity Troponin T Exhibits a Diurnal Rhythm That Troponin I Does Not
Hourly sampling in 24 healthy individuals revealed that hs-cTnT follows a diurnal pattern, peaking in the morning and reaching a nadir in the evening, while hs-cTnI shows no such rhythm. In a validation cohort of 2,782 chest pain patients, the hs-cTnT rhythm did not meaningfully affect diagnostic accuracy for acute MI (all AUCs above 0.93). However, the rhythm has important implications for hs-cTnT-based screening and population health programs where fixed thresholds are applied.
The original study
Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute Myocardial Infarction.
- Authors
- Klinkenberg LJ, Wildi K, van der Linden N, Kouw IW, Niens M, Twerenbold R, et al.
- Journal
- Clinical chemistry
- Type
- Clinical Trial, Journal Article
- PMID
- 27707754
Original abstract
BACKGROUND: Interpretation of serial high-sensitivity cardiac troponin (hs-cTn) measurements for the diagnosis of acute myocardial infarction (AMI) assumes random fluctuation of hs-cTn around an individual's homeostatic set point. The aim of this study was to challenge this diagnostic concept. METHODS: Study 1 examined the presence of a diurnal hs-cTn rhythm by hourly blood sampling, day and night, in 24 individuals without a recent history of AMI. Study 2 assessed morning vs evening diagnostic accuracy of hs-cTnT and hs-cTnI in a prospective multicenter diagnostic study of 2782 unselected patients, presenting to the emergency department with acute chest pain. RESULTS: In study 1, hs-cTnT, but not hs-cTnI, exhibited a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime, to peak concentrations in the morning (mean 16.2 ng/L at 8:30 AM and 12.1 ng/L at 7:30 PM). In study 2, the hs-cTnT rhythm was confirmed by higher hs-cTnT concentrations in early-morning presenters compared to evening presenters with an adjudicated diagnosis of noncardiac disease. The diagnostic accuracy [area under the receiver-operation characteristics curve (AUC)] of hs-cTnT at presentation, 1 h, and for the combination of absolute changes with presenting concentration, were very high and comparable among patients presenting early morning as compared to evening (all AUC >0.93). hs-cTnI exhibited no diurnal rhythm with no differences in AUC among early-morning and evening presenters. CONCLUSIONS: Rhythmic diurnal variation of hs-cTnT is a general phenomenon that is not seen with hs-cTnI. While the diurnal hs-cTnT rhythm does not seem to affect the diagnostic accuracy of hs-cTnT for AMI, it should be considered when using hs-cTnT for screening purposes. CLINICAL TRIAL REGISTRATION: 1. Circadian Variation of Cardiac Troponin, NCT02091427, www.clinicaltrials.gov/ct2/show/NCT02091427. 2. Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) Study, NCT00470587, www.clinicaltrials.gov/ct2/show/NCT00470587.