Circadian variations of ischemic burden among patients with myocardial infarction undergoing primary percutaneous coronary intervention

Abstract

Background Several parameters of cardiovascular physiology and pathophysiology exhibit circadian rhythms.Recently, a relation between infarct size and the time of day at which it occurs has been suggested in experimental models of myocardial infarction. The aim of this study is to investigate whether circadian rhythms could cause differences in ischemic burden in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).Methods In 353 consecutive patients with STEMI treated by PPCI, time of symptom onset, peak creatine kinase (CK), and follow-up at 30 days were obtained. We divided 24 hours into 4 time groups based on time of symptom onset (00:00-05:59, 06:00-11:59, 12:00-17:59, and 18:00-23:59).Results There was no difference between the groups regarding baseline patients and management's characteristics. At multivariable analysis, there was a statistically significant difference between peak CK levels among patients with symptom onset between 00:00 and 05:59 when compared with peak CK levels of patients with symptom onset in any other time group (mean increase 38.4%, P b .05). Thirty-day mortality for STEMI patients with symptom onset occurring between 00:00 and 05:59 was significantly higher than any other time group (P b .05). ConclusionThis study demonstrates an independent correlation between the infarct size of STEMI patients treated by PPCI and the time of the day at which symptoms occurred. These results suggest that time of the day should be a critical issue to look at when assessing prognosis of patients with myocardial infarction.

Questing for Circadian Dependence in ST-Segment–Elevation Acute Myocardial Infarction

“…6 Earlier, 3 other independent monocentric studies by Suárez-Barrientos et al, 7 by Arroyo Ucar et al 8 (both from Spain), and by Fournier et al 9 (from Switzerland) confirmed a circadian variation of infarct size in humans.…”

“…This further challenges the circadian dependence of infarct size after STEMI. It is interesting to note that in Figure 2A and 2B, although not statistically significant, peak infarct size occurred near the same time point (1:00 am) as described by Reiter et al 6 and by Fournier et al 9 Thus, we performed a second analysis of the STEMI cohort of 624 Italian patients, which was broken down by 4 time intervals (6 hours each), according to the time of infarct onset. We investigated whether the CK peak level was higher in a specific quarter of the day.…”

Mechanism of the circadian clock in physiology

“…This effect was lost in CCM mice, demonstrating a role for the circadian clock in the regulation of this process. This effect was mirrored in two human studies (39,115), which showed that infarct size and myocardial injury displayed circadian oscillations, with highest injury occurring during the early morning hours (5:00 -6:00 AM). Hypoxiainducible factor-1␣ (HIF-1␣) is involved in enhancing the ischemic adaptation of the heart, through the enrichment of the glycolytic capacity of the heart.…”

Circadian rhythm and cardiovascular disorders

“…Two retrospective studies and one prospective study have independently demonstrated that a larger infarct size, estimated by biomarker release, in patients with ST-elevation MI undergoing primary percutaneous coronary intervention is associated with onset of symptoms in the sleep-wake transition. [53][54][55] However, a recent prospective multicenter, multiethnic cohort study did not find a clear circadian dependence of infarct size either in the entire data set or in each of the three participating countries separately. 56 Unlike symptoms of ischemia, infarct size is influenced not only by the circadian biology of the patient, but also by the circadian biology of their health care providers, who are shift workers themselves and under different levels of stress in a time-of-day-dependent manner.…”