title: Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute Myocardial Infarction.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.|Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), the Netherlands.
authors.forename: Lieke J J
authors.initials: LJ
authors.lastname: Klinkenberg
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Wildi
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.|Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), the Netherlands.
authors.forename: Noreen
authors.initials: N
authors.lastname: van der Linden
authors.affiliation: Department of Human Movement Sciences, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.
authors.forename: Imre W K
authors.initials: IW
authors.lastname: Kouw
authors.affiliation: Department of Clinical Chemistry and Laboratory Hematology, Gelre ziekenhuizen, Apeldoorn/Zutphen, the Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Niens
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Twerenbold
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Rubini Gimenez
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Puelacher
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Jean
authors.initials: J
authors.lastname: Daniel Neuhaus
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Hillinger
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nestelberger
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Jasper
authors.initials: J
authors.lastname: Boeddinghaus
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Grimm
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Sabti
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.
authors.forename: Judith A P
authors.initials: JA
authors.lastname: Bons
authors.affiliation: Department of Clinical Chemistry and Laboratory Hematology, Gelre ziekenhuizen, Apeldoorn/Zutphen, the Netherlands.
authors.forename: Jeroen D E
authors.initials: JD
authors.lastname: van Suijlen
authors.affiliation: Department of Methodology and Statistics, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.
authors.forename: Frans E S
authors.initials: FE
authors.lastname: Tan
authors.affiliation: Department of Clinical Chemistry and Hematology, Zuyderland Medical Center, Sittard-Geleen, the Netherlands.
authors.forename: Joop
authors.initials: J
authors.lastname: Ten Kate
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.|Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), the Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Bekers
authors.affiliation: Department of Human Movement Sciences, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.
authors.forename: Luc J C
authors.initials: LJ
authors.lastname: van Loon
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.|Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), the Netherlands.
authors.forename: Marja P
authors.initials: MP
authors.lastname: van Dieijen-Visser
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands; steven.meex@mumc.nl.|Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), the Netherlands.
authors.forename: Steven J R
authors.initials: SJ
authors.lastname: Meex
mesh_terms: D000208:Acute Disease; D000368:Aged; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis*; D019210:Troponin I / Q000097:blood; D020107:Troponin T / Q000097:blood*
chemical_list: D019210:Troponin I; D020107:Troponin T