ISSN 0326-646X





Sumario Vol. 43 - Nº 1 Enero - Marzo 2014

Is the Time of Day Critical in the Development of Myocardial Infarction?

Stella M. Macin

Instituto de Cardiología JF Cabral.
Bolivar 1334 (3400) Corrientes, Argentina
E mail

Recibido 17-ENE-14 – ACEPTADO 31-ENERO-2014.

The author declare not having conflicts of interest.

Rev Fed Arg Cardiol. 2013; 42(4): 1-2
Editorials reflect the opinion of authors, not necessarily 
those of the Editorial Board of the FAC Journal


Print version Imprimir sólo la columna central


In spite of the significant decrease in the mortality rate of acute myocardial infarction in developed countries, coronary artery disease (CAD) is still an important cause of death and disability [1,2].

Although numerous modifiable and non-modifiable risk factors have been associated to an increase in the risk of CAD, over the last twenty five years, the periodicity of infarctions has been reported. Thus, cardiovascular events have been observed as displaying a time variability, and that myocardial ischemia events are distributed irregularly over time, with a greater incidence during certain times in the day, at given days in the week, or even months of the year, and in work days in regard to weekends [3,4].

Most cardiovascular risk factors predispose individuals to develop an acute coronary syndrome. Many of them can be used as prognostic indicators in patients who suffered an infarction [3].

Although myocardial ischemia may occur at any time during the day, a circadian rhythm has been confirmed related to the appearance of it, already in the MILIS study, published more than 20 years ago. Later, other studies have confirmed these results, although with slight variations in regard to the onset and end of the peak of incidence, influenced by the different risk factors [5]. Thus, the onset of infarction increases between 06.00 and 12.00. These responses may be related to an increase in sympathetic activity, after individuals wake up in the morning, the interaction between catecholamines and platelet aggregation affecting the atherosclerotic plaque, as well as variations in relation to hemodynamic responses, including blood pressure, myocardial blood flow, heart rate, fibrinogen plasma concentration and coagulation factors and fibrinolytic system activity [6].

Aroche R, et al [7], in the paper published in this issue of the FAC Journal, confirmed the circadian variation of the onset of infarction, and the significance of risk factors at the time of the onset of symptoms, with a circadian behavior with acrophase at 11:08, with peaks between 9:00-11:59 and 24:00-02:59, and adjusted curve of sinusoidal aspect, similar in all patients. The parameter was only modified in diabetic individuals, with history of stroke and smokers, in whom another night time peak was obtained, between 24:00 and 02:59, matching other published papers. See the paper published.

In regard to the influence of risk factors, the ISIS-2 study (Second International Study of Infarct Survival) [8] reported the absence of a circadian rhythm in infarction in diabetic patients, while other authors record circadian variations in the same type of patient, with a peak of incidence between 6:00 and 12:00. Other series showed that individuals older than 70 years, smokers and female, revealed a bimodal distribution of ischemic episodes in the morning and night peaks. Thus, the paper presented in this Journal by Aroche R et al, in agreement with previous papers, showed a curve with a bimodal aspectin smokers and diabetic patients [7]. Instead, other authors have reported the absence of a circadian rhythm in regard to the time of appearance of infarction symptoms in diabetes. The methodology used to analyze the careful periodicity in these studies, and the small population may be a reason for this [9,10].

Smokers present a circadian rhythm different from non-smokers. The curve adjusted by smokers shows a circadian rhythm of smaller widths and a double peak of incidence during the day, one in the morning and the other, less prominent, around 16:00 [1]. In the paper by Aroche R et al, the subset of smokers showed the same peak of daily incidence in the morning and low night point, as mentioned previously [7]. Smoke may increase platelet aggregation. Indeed, there is a relation between smoking a cigarette and the activation of sympathetic mechanisms in the autonomous nervous system. Spacing in smoking during the day may favor an attenuation in the morning peak, and the appearance of a plateau-like incidence during the night [11].

The time of appearance of symptoms of infarction follows a sinusoidal curve with a peak in the morning and an early channel in the morning, which yields the appearance of these symptoms of a circadian rhythm. This morning pattern with sinusoidal peak is maintained regardless of age and gender, in patients who suffered a previous stroke and those that have a family history of ischemic heart disease. People with hypertension and dyslipidemia also show this pattern. However, patients with diabetes, who smoke or suffer a reinfarction, show a double peak of incidence in their curves [7].

In some series, dyslipidemia affected the onset of symptoms in a similar manner to hypertension. Once again, the curve was similar to the standard curve for all the population, with a peak in the morning.

The findings in the paper by Aroche R et al, allow us to know the circadian rhythm in acute myocardial infarction and the relation of risk factors to mortality [7]. One may wonder then, whether time is critical in infarction. We know that a greater frequency occurs between eight in the morning and three in the afternoon, with a greater lethality at noon; second, the time of onset of infarction is related to the delay to consult. The present paper does not report the delay, but the fact that the greatest mortality was at noon, leads us to consider that different elements than time may be involved, such as age and the reperfusion strategy choice. Often, the scenario may be different according to the time of onset of symptoms and the delay to consult, and some series show that the time of onset is related to the magnitude of it, and this with a greater mortality [1,8,10,11-13].

The paper by Aroche R et al, has weak points. The high rate of lethality of infarction, which was 15.6%, is in contrast with other clinical trials that report lower mortalities as 4-6% and registries of 8-10% [1,2,14]. Although it is true that the goal of the study was not to analyze mortality, maybe it could be explained by the period of time when the study was conducted, since 2005 to 2009; besides, not all patients could receive primary angioplasty, or could delay their arrival to the ER, to undergo reperfusion strategies. Another complicated issue is related to the selection of cases, since this is a registry of 1432 patients with a diagnosis of acute infarction, and the sample selected randomly is not representative of the population, or the average age of the population.

Finally, the existence of circadian clocks in the components of the cardiovascular system has long term implications, which extend beyond the clinical environment. Given the diversity of daily variations of the intrinsic properties of the cardiovascular system, extreme caution is required when investigation studies are designed, since they may be affected by circadian variations; so, taking into account the time of day may be significant when designing investigation experiments. Performing experiments in an inappropriate time of day or omitting the proper time may lead to mistaken conclusions or uninterpretable data. Such time considerations would help to reduce the discrepancies between the studies made in different populations.

In spite of these precautions, the scenario of mortality of 15.5% yielded by the work by Aroche R et al, should be taken into account, as the authors comment, for a proper supply of the therapy based on evidence, with the aim of reducing mortality [6,15].



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Publication: March 2014

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