Independent association between symptom onset time and infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Karim D. Mahmoud, Maarten W. Nijsten, Wouter G. Wieringa, Jan P. Ottervanger, David Holmes, Hans L. Hillege, Arnoud W. Van 'T Hof, Erik Lipsic

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)468-477
Number of pages10
JournalChronobiology International
Volume32
Issue number4
DOIs
StatePublished - May 1 2015

Fingerprint

Percutaneous Coronary Intervention
Creatine Kinase
Myocardial Infarction
Confidence Intervals
Reperfusion Injury
Registries
ST Elevation Myocardial Infarction
Mortality

Keywords

  • Angioplasty
  • Circadian rhythm
  • Infarct size
  • Ischemia/reperfusion
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Independent association between symptom onset time and infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. / Mahmoud, Karim D.; Nijsten, Maarten W.; Wieringa, Wouter G.; Ottervanger, Jan P.; Holmes, David; Hillege, Hans L.; Van 'T Hof, Arnoud W.; Lipsic, Erik.

In: Chronobiology International, Vol. 32, No. 4, 01.05.2015, p. 468-477.

Research output: Contribution to journalArticle

Mahmoud, Karim D. ; Nijsten, Maarten W. ; Wieringa, Wouter G. ; Ottervanger, Jan P. ; Holmes, David ; Hillege, Hans L. ; Van 'T Hof, Arnoud W. ; Lipsic, Erik. / Independent association between symptom onset time and infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. In: Chronobiology International. 2015 ; Vol. 32, No. 4. pp. 468-477.
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AB - 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.

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