Circadian Dependence of Infarct Size and Acute Heart Failure in ST Elevation Myocardial Infarction

Abstract

ObjectivesThere are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI.MethodsWe studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight–6:00 A.M., 6:00 A.M.–noon, noon–6:00 P.M. and 6:00 P.M.–midnight. We used peak creatine kinase as a surrogate marker of infarct size.ResultsMidnight–6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight–6:00 A.M. patients and lowest among 6:00 A.M.–noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight–6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.–noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001).ConclusionWe observed a circadian peak and nadir in infarct size during STEMI onset from midnight–6:00A.M and 6:00A.M.–noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian pattern of infarct size and acute heart failure.

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

“…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. Discovering molecular pathways associated with diseases plays a pivotal role in understanding the relation between cardiological pathologies and genetic factors.…”

“…Furthermore, we did not record diabetic status, renal function, which can affect the levels of vitamin D, and if any subjects were taking vitamin D supplements or other drugs that could potentially affect the results, such as β‐blockers (populations of our study where these data were available accounted for <15%) and aspirin 32, 33. However, contrasting findings were reported regarding diabetic status and the absence of circadian rhythm, in particular the absence of an increased morning peak of STEMI incidence in diabetic patients 32, 33, 34. Finally, in our study we address STEMI incidence but not outcome (eg, death), which might be another interesting variable to consider.…”

“…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.…”

“…32,33 However, contrasting findings were reported regarding diabetic status and the absence of circadian rhythm, in particular the absence of an increased morning peak of STEMI incidence in diabetic patients. [32][33][34] Finally, in our study we address STEMI incidence but not outcome (eg, death), which might be another interesting variable to consider. However, it must be noted that outcome after a STEMI can be affected by several other confounding variables (in particular different health systems with different availability to primary coronary intervention) that could mask any effect of seasonal/circadian influence.…”

Circadian clocks: from stem cells to tissue homeostasis and regeneration

“…Circadian rhythms have also been shown to play a major role in heart pathophysiology. This is illustrated by increased incidence of myocardial infarction in the morning compared to the evening [77][78][79], and a correlation between infarct size and the time of the day at which it occurs is noted [80][81][82]. Mice that overexpress a dominantnegative form of the CLOCK protein in cardiomyocytes specifically (CCM) show abolished rhythmicity in cardiac CCG expression, which results in an abrogated circadian response in infarct size after ischemia/reperfusion [36].…”