Is There a Better Time of Day to Have a Heart Attack?

Abstract

It is widely accepted that time influences cardiovascular health and disease, including the time of the day, day of the week, or season of the year. For example, myocardial infarctions occur with greatest incidence early on a Monday morning, in fall/winter. 1 Peak incidence in adverse cardiovascular events, such as acute myocardial infarction, arrhythmias, and sudden cardiac death, has classically been ascribed to temporal changes in extracardiac factors. 1,2 These factors include fluctuations in posture, physical exertion, food consumption, and body temperature over the course of the day contributing toward changes in sympathetic and autonomic activity, numerous endocrine and paracrine factors, as well as thrombolytic factors, ultimately influencing cardiovascular function and/or precipitating an adverse cardiovascular event. [3][4][5][6] Recently, what has become increasingly evident is a significant contribution of intrinsic mechanisms mediating temporal dependence of cardiovascular physiology and pathophysiology. 7-9 For instance, travelers retain time-of-day oscillations in sudden cardiac death, in such a way that the peak incidence is equivalent to the early hours of the morning in the time zone of origin. 10 What might be the nature of an intrinsic mechanism that influences cardiovascular function in a temporal manner? Over the last several decades, multiple laboratories have highlighted the existence of circadian clocks within virtually all mammalian cells, including critical components of the cardiovascular system. 11-15 Circadian clocks are molecular mechanisms residing within individual cells that directly modulate cellular function during the course of the day. This is largely a transcriptionally based mechanism, composed of a series of positive and negative feedback loops made up of more than 13 transcription factors. 16 Scientists studying genetically modified mouse models of altered circadian clock function have recently demonstrated that circadian clock genes contribute very significantly to time-of-day-dependent changes in both heart rate and blood pressure. [17][18][19] This same clock mechanism has also been shown to directly regulate multiple thrombolytic factors, such as PAI-1 and thrombomodulin, raising the possibility that it might also contribute toward temporal oscillations in adverse cardiovascular events. 14,20 In this issue of Circulation Research, Durgan et al sought to test the hypothesis that the time of day at which the heart is subjected to ischemia/reperfusion injury influences subsequent tissue damage and left ventricular contractile function. 21 The study revealed a 3.5-fold oscillation in infarct size, depending on the time-of-day at which the ischemic episode occurred, with the greatest infarct size observed at the sleep-to-wake transition. Interestingly, this is the same time of the day when the incidence of myocardial infarction peaks in humans. The investigators also report that this temporaldependence in ischemia/reperfusion tolerance is absent in a mouse model in which ...

Pyridostigmine prevents haemodynamic alterations but does not affect their nycthemeral oscillations in infarcted mice

“…There are abundant reports of the circadian influence on the expression and severity of cardiovascular diseases (Bonney et al, 2013;Lefer, 2010;Martino and Sole, 2009;Takeda and Maemura, 2011). However, the impact of cardiovascular diseases on the nycthemeral, or daily, variation of arterial pressure and heart rate has not been examined in mice, although huge amounts of data are available in humans (Caruana et al, 1988;Giles et al, 1996;Shaw et al, 2001) and rats (Zhou et al, 2011).…”

NK1-receptor-expressing paraventricular nucleus neurones modulate daily variation in heart rate and stress-induced changes in heart rate variability

“…Neurones in this area have cyclically changing membrane potentials which allow general changes in activity on a 24-h rhythm (Belle et al 2009). Studies show that this is paralleled by changes in rodent heart rate (Nunn et al 2013) and we find that this involves PVN NK1 neurones, since their lesion significantly alters the rhythm, shifting it by approximately 3 h. This is potentially of huge medical relevance, since in humans, hypertension is strongly linked to sympathetic activity (Mancia and Grassi 2014) and circadian variation in cardiovascular control is strongly linked to a spate of heart attacks that occurs in the morning (Muller et al 1989;Spielberg et al 1996;Lefer 2010).…”

Circadian rhythms in ischaemic heart disease: key aspects for preclinical and translational research: position paper of the ESC working group on cellular biology of the heart

“…To better assess direct causal relationships between circadian rhythmicity and infarct size, mouse models of AMI have been instrumental. 61 Animal and in vitro models also help understand the processes involved in diurnal variation of AMI outcome. In support of a possible role for circadian clocks in ischaemic damage, genetic disruption of clock genes leads to an altered infarct size in mice.…”