Circadian rhythms are a natural phenomenon in which oscillations occur in various biological processes, including the sleep cycle [1]. These rhythms are controlled by two types of clocks: a central one located in the suprachiasmatic nucleus of the hypothalamus [2], and others present in different tissues at the genetic level [3]. The existence of a diurnal rhythm affecting the incidence of an acute myocardial infarction (AMI) has been known since the middle of the last century [4]. Numerous studies have shown an increase during the morning [4, 5, 6, 7, 8]. Regional, cultural and perhaps ethnic variations in this rhythm have also been described [9, 10]. The main determinant of the rhythm set by the central nervous system is thought to be light [11]. Light affects the frequency of neuronal discharges and modifies both the expression of circadian genes [12] and the activity of the autonomic nervous system, thereby altering fundamental factors of circulatory regulation such as blood pressure, endothelial response, and platelet aggregation [11]. The activation of the autonomic nervous system during waking hours may explain the increased incidence of AMI in the morning. There are other factors that influence the regulation of circadian rhythms and can cause circadian disruption, in particular changes in physical activity [13], stress, and mealtimes. In mammals, there is a daily rhythm of increased activity that precedes the availability of food, called the food-entrainable oscillator or food-anticipatory activity [14]. Disruption of the circadian rhythm by these factors modifies circulatory variables [15] and could act as a trigger for cardiovascular events such as AMI, both through changes in heart rate and vascular reactivity or through rupture of the atheroma plaque [11]. Previous studies have demonstrated a diurnal cycle in AMI, but there is limited evidence in relation to type I infarctions due to atheroma plaque rupture [16] and the potential relation of circadian patterns with seasons and months.

The aim of this study is to observe possible variations in the hourly incidence of AMI throughout the year, based on the hypothesis that the main determinant of the circadian rhythm affecting the incidence of AMI is the habits of the subjects, rather than the light cycles. In order to analyze a unique pathophysiological phenomenon, only cases of type I ST-segment elevation myocardial infarction (STEMI) were included.

During the 5-year study period, the registry recorded 6765 cases of STEMI with an identified culprit plaque. Of these, 5238 (77.4%) were men. The mean age of the sample was 63.2 years (range 17–101, SD 13.667), of which 2801 (41.9%) were 65 years or older. Events were more frequent in winter and less common in summer (Fig. 1A), with January, February and March being the months with the highest incidence (Fig. 1B).

The number of daily events was similar across the seven days of the week, with a range from 13.3% of episodes occurring on Fridays and 15.3% on Sundays (p not significant). STEMI tended to occur 20 minutes later on Sundays than on weekdays (12:20:59 PM vs 12:01:36 PM, p not significant). The hourly distribution of infarctions followed a fixed daily pattern throughout the year, and were more frequent between 6 AM and 4 PM, with a peak around 1 PM and a valley between 10 PM and 6 AM (Fig. 2).

The mean time of presentation of STEMI did not change throughout the year, always around 12:00 PM (p = 0.134, ANOVA, Fig. 3). When the mean time to system activation was compared between months with more and less sunlight (July and December, respectively), no significant difference was found, although a tendency to delay the time was observed in the month of July (12:40 PM vs 12:02 PM, p = 0.098). No differences in presentation were found when men and women were analyzed separately, nor when patients older and younger than 65 years were compared (Figs. 4,5).

There was a close correlation between the total number of events per month and the number of events attended during the periods defined as daytime (6 AM to 6 PM, r = 0.988, p = 0.001) and nighttime (6 PM to 6 AM, r = 0.944, p 0.001). We found a clear difference in the slope of the regression lines as the total incidence increased, with a maximum in January and a minimum in May and August (t-test, p 0.001, Fig. 6), so that the difference between day-night events increased with the total incidence.

Our study shows the existence of a circadian rhythm in type I STEMI. The incidence of these events is highest around midday and lowest at night, with no variation in this pattern throughout the months of the year. Winter months have the highest incidence. When the incidence increases, it does so both in the morning and at night, but mainly during the day.

The existence of a circadian rhythm in the incidence of AMI has been described in several studies since the middle of the last century [4] and also affects other clinical manifestations closely related to acute coronary syndrome, such as sudden death [20]. However, the different manifestations of acute coronary syndrome are due to different pathophysiological phenomena, which may follow different rhythms. Whereas vasospasm tends to be a predominantly nocturnal phenomenon [21], thrombotic phenomena tend to occur preferentially in the morning [22]. This may contribute to the finding of different patterns in different studies. A study of 7032 cases of acute coronary syndrome showed a bimodal pattern with morning and evening peaks [23], which may be explained by the inclusion of a heterogeneous group in which predominantly thrombotic and predominantly spastic phenomena are mixed. The same reasons may have caused the bimodal patterns found in studies in which AMI was defined solely by elevations in biomarkers [7], thus including infarcts with potentially different pathophysiological etiologies [16]. Studies based on a population selected for treatment with primary angioplasty usually show a single peak [24]. This is the case in our study, where patients were selected on the basis of the presence of a plaque responsible for type I STEMI.

The fundamental role of light as a regulator of the circadian rhythm [11, 12] may suggest that variations in the number of daylight hours during the seasons should affect the presentation of AMI. We are aware of only one other study that has considered this possibility [19]. Cannistraci et al. [19] described a possible shift in the incidence of AMI towards the evening hours during the summer months, which they relate to sunlight hours and serum vitamin D concentration. Using the same time intervals and considering all months of the year, our study shows the same circadian rhythm pattern in the distribution of the peak incidence and mean alert activation time. When the incidence of infarction increases, it does so both during the day and at night, but much more during the day. This phenomenon, which to our knowledge has not been previously described, explains the apparent nocturnal shift in incidence during the months with fewer infarctions. Our interpretation is that, in a relatively fixed circadian pattern, infarct triggers such as influenza and cold weather [25] find a patient more vulnerable during the day due to increased physical activity, feeding rhythms, and cycles of sympathetic and cortisol activation [11, 13, 14, 15], although they also cause an increase in events during the night.

There is a circadian pattern in the presentation of type-I STEMI, that is not influenced by sex and age. The different incidence of STEMI at different times of the year does not affect the circadian pattern in terms of the shape of the curve or the mean time of presentation, although diurnal events increase more than nocturnal events, suggesting that triggers are most likely to occur during vulnerable periods determined by a circadian-based rhythm.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

JCDP, CTG, AGL and MMS designed the research study. AGL and JAM provided the raw data for the study and obtained the ethical committee approval. ALB, ARS and EGS generated the databases and performed the statistical analysis. All authors contributed to redaction of the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The Research Ethics Committee of one of the hospitals included in the registry granted the approval for the study, including the exemption to request informed consent. The protocol was approved by the Ethics Committee of the Hospital Universitario Príncipe de Asturias (approval number: OE 10/2017).

Not applicable.

This research received no external funding.

The authors declare no conflict of interest. Manuel Martínez-Sellés is serving as one of the Editorial Board members/Guest editors of this journal. We declare that Manuel Martínez-Sellés has no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Fabio Angeli.