title: Myocardial infarct size and mortality depend on the time of day-a large multicenter study.
abstract: BACKGROUND
  Different studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry.
  
  
  METHODS
  This retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods.
  
  
  RESULTS
  6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00.
  
  
  CONCLUSIONS
  As a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction.
authors.affiliation: Department of Cardiology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: Stephane
authors.initials: S
authors.lastname: Fournier
authors.affiliation: Institute for Social and Preventive Medicine, Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Taffé
authors.affiliation: AMIS Plus Data Center, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Dragana
authors.initials: D
authors.lastname: Radovanovic
authors.affiliation: Institute for Social and Preventive Medicine, Lausanne, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: Von Elm
authors.affiliation: Department of Cardiology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: Beata
authors.initials: B
authors.lastname: Morawiec
authors.affiliation: Department of Cardiology, Fribourg Hospital, Fribourg, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Stauffer
authors.affiliation: AMIS Plus Data Center, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
authors.affiliation: Department of Cardiology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Beggah
authors.affiliation: Department of Cardiology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Monney
authors.affiliation: Department of Cardiology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Pascale
authors.affiliation: Department of Cardiology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: Juan-Fernando
authors.initials: JF
authors.lastname: Iglesias
authors.affiliation: Department of Cardiology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Eeckhout
authors.affiliation: Department of Cardiology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Muller
mesh_terms: D002940:Circadian Rhythm; D003402:Creatine Kinase / Q000378:metabolism*; D017052:Hospital Mortality; D006801:Humans; D007297:Inpatients; D009203:Myocardial Infarction / Q000201:enzymology / Q000401:mortality* / Q000503:physiopathology*; D011379:Prognosis; D012042:Registries; D012044:Regression Analysis; D012189:Retrospective Studies; D013557:Switzerland / Q000453:epidemiology; D013997:Time Factors
chemical_list: D003402:Creatine Kinase