Circadian variations of infarct size in acute myocardial infarction

Abstract

Background: The circadian clock influences a number of cardiovascular (patho)physiological processes including the incidence of acute myocardial infarction. A circadian variation in infarct size has recently been shown in rodents, but there is no clinical evidence of this finding. Objective: To determine the impact of time-of-day onset of ST segment elevation myocardial infarction (STEMI) on infarct size. Methods: A retrospective single-centre analysis of 811 patients with STEMI admitted between 2003 and 2009 was performed. Infarct size was estimated by peak enzyme release. The relationship between peak enzyme concentrations and time-of-day were characterised using multivariate regression splines. Time of STEMI onset was divided into four 6-hour periods in phase with circadian rhythms. Results: Model comparisons based on likelihood ratio tests showed a circadian variation in infarct size across time-of-day as evaluated by peak creatine kinase (CK) and troponin-I (TnI) concentrations (p=0.015 and p=0.012, respectively). CK and TnI curves described similar patterns across time, with a global maximum in the 6:00 - noon period and a local minimum in the noon - 18:00 period. Infarct size was largest in patients with STEMI onset in the dark-to-light transition period (6:00 - noon), with an increase in peak CK and TnI concentrations of 18.3% (p=0.031) and 24.6% (p=0.033), respectively, compared with onset of STEMI in the 18:00 - midnight period. Patients with anterior wall STEMI also had significantly larger infarcts than those with STEMI in other locations. Conclusions: Significant circadian oscillations in infarct size were found in patients according to time-of-day of STEMI onset. The infarct size was found to be significantly larger with STEMI onset in the dark-to-light transition period (6:00 - noon). If confirmed, these results may have a significant impact on the interpretation of clinical trials of cardioprotective strategies in STEMI.