Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute Myocardial Infarction.

Lieke J J Klinkenberg, Karin Wildi, Noreen van der Linden, Imre W K Kouw, Marijke Niens, Raphael Twerenbold, Maria Rubini Gimenez, Christian Puelacher, Jean Daniel Neuhaus, Petra Hillinger, Thomas Nestelberger, Jasper Boeddinghaus, Karin Grimm, Zaid Sabti, Judith A P Bons, Jeroen D E van Suijlen, Frans E S Tan, Joop Ten Kate, Otto Bekers, Luc J C van Loon, Marja P van Dieijen-Visser, Christian Mueller, Steven J R Meex

Journal: Clinical chemistry 2017;62(12):1602-1611

PMID: 27707754

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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.

Address: Department of Clinical Chemistry, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), the Netherlands.; Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.; Department of Human Movement Sciences, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.; Department of Clinical Chemistry and Laboratory Hematology, Gelre ziekenhuizen, Apeldoorn/Zutphen, the Netherlands.; Department of Clinical Chemistry, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.; Department of Methodology and Statistics, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.; Department of Clinical Chemistry and Hematology, Zuyderland Medical Center, Sittard-Geleen, the Netherlands.; Department of Clinical Chemistry, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands; [email protected].; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), the Netherlands.

DOI: 10.1373/clinchem.2016.257485