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

Abstract

Rationale: Four monocentric studies reported that circadian rhythms can affect left ventricular infarct size after ST-segment-elevation acute myocardial infarction (STEMI).Objective: To further validate the circadian dependence of infarct size after STEMI in a multicentric and multiethnic population. Methods and Results:We analyzed a prospective cohort of subjects with first STEMI from the First Acute Myocardial Infarction study that enrolled 1099 patients (ischemic time <6 hours) in Italy, Scotland, and China. We confirmed a circadian variation of STEMI incidence with an increased morning incidence (from 6:00 am till noon). We investigated the presence of circadian dependence of infarct size plotting the peak creatine kinase against time onset of ischemia. In addition, we studied the patients from the 3 countries separately, including 624 Italians; all patients were treated with percutaneous coronary intervention. We adopted several levels of analysis with different inclusion criteria consistent with previous studies. In all the analyses, we did not find a clear-cut circadian dependence of infarct size after STEMI. Conclusions:

“Summer Shift”: A Potential Effect of Sunshine on the Time Onset of ST‐Elevation Acute Myocardial Infarction

“…In fact, in a study performed in Minnesota, after multivariate adjustment for prehospital delay and door‐to‐balloon time, there was no significant association between circadian patterns of time of onset and in‐hospital death 35. Nevertheless, the issue regarding circadian rhythms, infarct size, and mortality remains a field of open discussion with contrasting reports, probably affected by origin of the study population and other variables 8, 11, 34, 36. Other important issues that need clarification are the genetic and ethnic background, which could influence circadian rhythms and seasonal patterns, even if this study found that the pattern of a summer shift can be observed in different ethnic and genetic backgrounds.…”

“…Therefore, we decided to investigate (Figure 2) whether the clear overall decrease of STEMI onset during summer (summer nadir) would also affect the circadian peak during the diurnal hours (second and third quarter of the day, 6:00 to 18:00) with respect to the nocturnal hours (the fourth and first quarter of the day, 18:00 to 6:00). The choice to select these 2 precise intervals (6:00 to 18:00 and 18:00 to 6:00) was motivated by the fact that this subdivision was largely accepted in previous studies, and in general, higher incidence of STEMI occurs during the second and third quarters of the day 4, 5, 6, 7, 8, 9. Hence, we decided to measure the percentage difference (Δ%) of STEMI onset during the 6:00 to 18:00 (diurnal) interval with respect to the 18:00 to 6:00 (nocturnal) interval using the following formula:$\mathrm{\Delta }\%=\frac{false(\#\text{STEMI in 6 to 18 time interval)}-false(\#\text{STEMI in 18 to 6 time interval)}}{(\#\text{STEMI in 18 to 6 time interval)}}\times 100$ …”

“…Triggers that explain this acute transition from asymptomatic coronary plaques to acute thrombosis and STEMI are still under investigation 2, 3. The fact that onset of STEMI has a circadian rhythm with a peak during diurnal hours has been well described 4, 5, 6, 7, 8, 9, 10, 11, 12. A seasonal pattern13 in the occurrence of STEMI was also found with a salient peak of cases in the winter months and a marked nadir of cases in the summer months 14, 15, 16, 17, 18, 19.…”

Of Mice and Men

“…These results 11,13 are consistent with the observations that the highest incidence of heart failure results from infarctions that occur around midnight. 14 In this issue of Circulation Research, Ammirati et al 15 provide a fourth analysis investigating the possible circadian effects on ischemic tolerance in humans in the setting of STEMI. Their study is unique in that its cohort was derived from a geographically and ethnically diverse group of patients from Italy, Scotland, and China who participated in the First Acute Myocardial Infarction study.…”

Circadian rhythm and cardiovascular disorders

“…[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. This added complexity must be taken into consideration and may require larger cohorts and better designed controls, both of which are extremely challenging in human studies.…”