title: Independent association between symptom onset time and infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.
abstract: Recent studies have reported on circadian variation in infarct size in ST-elevation myocardial infarction (STEMI) patients. Controversy remains as to whether this finding indicates circadian dependence of myocardial tolerance to ischemia/reperfusion injury or that it can simply be explained by confounding factors such as baseline profile and ischemic time. We assessed the clinical impact and independent association between symptom onset time and infarct size, accounting for possible subgroup differences. From a multicenter registry, 6799 consecutive STEMI patients undergoing primary percutaneous coronary intervention (PCI) between 2004 and 2010 were included. Infarct size was measured using peak creatine kinase (CK). Infarct size exhibited circadian variation with largest infarct size in patients with symptom onset around 03:00 at night (estimated peak CK 1322 U/l; 95% confidence interval (CI): 1217-1436) and smallest infarct size around 11:00 in the morning (estimated peak CK 1071 U/l; 95% CI: 1001-1146; relative reduction 19%; p = 0.001). Circadian variation in infarct size followed an inverse pattern in patients with prior myocardial infarction (p-interaction <0.001) and prior PCI (p-interaction = 0.006), although the later did not persist in multivariable analysis. Symptom onset time remained associated with infarct size after accounting for these interactions and adjusting for baseline characteristics and ischemic time. Symptom onset time did not predict one-year mortality (p = 0.081). In conclusion, there is substantial circadian variation in infarct size, which cannot be fully explained by variations in baseline profile or ischemic time. Our results lend support to the hypothesis of circadian myocardial ischemic tolerance and suggest a different mechanism in patients with prior myocardial infarction.
authors.affiliation: Department of Cardiology, Thorax Center, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands .
authors.forename: Karim D
authors.initials: KD
authors.lastname: Mahmoud
authors.forename: Maarten W
authors.initials: MW
authors.lastname: Nijsten
authors.forename: Wouter G
authors.initials: WG
authors.lastname: Wieringa
authors.forename: Jan P
authors.initials: JP
authors.lastname: Ottervanger
authors.forename: David R
authors.initials: DR
authors.lastname: Holmes
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.forename: Arnoud W
authors.initials: AW
authors.lastname: van 't Hof
authors.forename: Erik
authors.initials: E
authors.lastname: Lipsic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002940:Circadian Rhythm / Q000502:physiology*; D003331:Coronary Vessels / Q000601:surgery; D003402:Creatine Kinase / Q000378:metabolism; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D062645:Percutaneous Coronary Intervention; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003402:Creatine Kinase
keywords: Angioplasty; circadian rhythm; infarct size; ischemia/reperfusion; myocardial infarction