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.