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Sumario Vol. 43 - Nº 1 Enero - Marzo 2014

Cardiovascular risk factors in the circadian rhythm
of myocardial infarction

Ronald Aroche (1), Adrián A. Naranjo,
Ángel Y. Rodríguez, Rosa E. Llera (2)

Docente Abel Santamaría. Pinar del Río, Cuba.
(1)
Centro de Investigaciones Médico Quirúrgico. CIMEQ. La Habana. Cuba.
(2) Universidad de Ciencias Médicas de Pinar del Río Cuba. Hospital General
E mail

Recibido 05-DIC-13 – ACEPTADO después de revisión 31-ENERO-2014.

The authors declare not having a conflict of interest.

Rev Fed Arg Cardiol. 2013; 43(1): 32-37


Print version Imprimir sólo la columna central

 

SUMMARY

Objective: Characterizing the time of beginning of the symptoms of myocardial infarction in patients hospitalized during five years.
Methods: Cross-sectional descriptive study. The universe was constituted by the 1432 patients assisted in the Educational General Hospital Abel Santamaria Cuadrado of Pinar del Río, Cuba among the years 2005 and 2009. The sample included 340 patients that were selected in an aleatory way. Using absolute and relative frequencies, the variables hour of beginning of the symptoms, the age, the sex, the habit of smoking, the personal history of arterial hypertension and diabetes mellitus as well as mortality were described. The curve of hour of beginning of the symptomswas adjustedwith the Cosinorpattern.
Results: The hour of beginning of the myocardial infarction shows a circadian rhythm with peaks between 9:00-11:59 h and 24:00-02:59 h. In all the groups of ages a circadian rhythm was found, with an adjusted curve of sinusoidal aspect. In the smoking patients the curve adopts a bimodal aspect. Myocardial infarction mortalitywas of 15.6%.
Conclusions: The hour of beginning of myocardial infarction behaves with circadian rhythm. In the smoking patients, contrary to those with hypertension and diabetes, there are variations in the beginninghour. Mortality is superior in the patients that suffered myocardial infarction at midday.

Key words: Myocardial Infarction. Circadian rhythm. Chronobiology.

 

INTRODUCTION
Acute coronary syndromes are a major public health problem in all the world. In recent years, important advancements were made in the knowledge of its epidemiology, pathophysiology and treatment. The impact of management guidelines and the prognosis of these patients has been remarkable [1].

In Cuba, the incidence and prevalence of coronary heart diseases is high, and constitutes one of the main causes of death in both genders. In 2010, the mortality rate by ischemic heart disease was 146.3/100,000 inhabitants and there was a total of 16,435 deaths by this cause. This highlights the increase in mortality over the last 4 decades and in comparison to year 2009 [2].

Time is a determining factor, it is a factor to beat [3], is “saved muscle” in the management of acute coronary syndromes with ST segment elevation [4]. The optimization of the diagnostic and therapeutic opportunities offered to the patient, in such scenario, constitute a key factor [5]. In Cuba, in spite of the continuing sanitary education and the cultural level of the population, 20% or more deaths occur by extra-institutional infarction [6].

The investigation of biological clocks contributes new parameters to take into account in the daily practice, in the pattern of medication prescription. The usual practice of prescribing some medications three times a day along with food or at regular intervals along the day, could be not just inefficient, but also harmful [7].

The advancement in the chronobiological methodology experienced during recent years, has allowed learning about new aspects of the behavior of rhythmic phenomena in the different cardiovascular risk factors that were not considered previously [8]. The circadian variation in the operation of the cardiovascular system explains the evident fact that the greatest incidence of cardiovascular events occur during the morning. Blood pressure, plasma levels of catecholamines and cortisol, platelet aggregation and the fibrinolytic system action, are the mechanisms involved most frequently [7].

In recent years, it was possible to verify that the presentation of acute coronary syndromes (ACS) along the day is not uniform, but rather experiences rhythmic variations. It has been clearly shown that the onset of acute myocardial infarction (AMI) happens more frequently in the early morning. Numerous authors have attempted to define the causes of this circadian distribution, as well as its clinical and therapeutic implications [9].

Most cardiovascular risk factors are predisposing for the different presentations of acute coronary syndrome. Many of these risk factors also behave as prognostic factors for the evolution of patients that suffered AMI. The presence of some given factors seems to modify the circadian rhythm (CR) characteristic of the onset of infarction in the general population and induces, in patients with such factors, the clinical presentation of AMI in a different time range [9].

In Cuba, some investigations were made in the province of Camagüey [10] and in Pinar del Río [11] on this topic, with publications about it, besides other researches not yet published. The previous investigations, however, did not approach the search for factors related to the circadian variability of AMI; from there the question: The time of onset of the symptoms in the patients that suffered acute myocardial infarction, could be related to different modifications that may produce cardiovascular risk factors?

Motivated by this issue, the present investigation has the goal of analyzing the influence of cardiovascular risk factors in the circadian rhythm of presentation of acute myocardial infarction in patients cared for at the Hospital General Docente Abel Santamaría in the 2005-2009 term.

 

MATERIAL AND METHODS
A cross-sectional study was made including the patients admitted in the Hospital General Docente Abel Santamaría Cuadrado from Pinar del Río, Cuba since January 1st, 2005 to December 31st, 2009.

The universe included 1432 patients with diagnosis of acute myocardial infarction in the mentioned term. The sample was constituted by 340 patients selected by simple random sampling.


Methods and instruments to gather data
The information was gathered by the authors from the clinical histories and entered into a worksheet designed with such purpose; it included the following variables: time of onset of symptoms, gender age groups, vital state at discharge, history of diabetes mellitus, hypertension, ischemic heart disease, stroke and smoking.


Processing and analysis of data
The MatLab platform was used, both to estimate the existence of rhythm and for the comparison between groups, where a level of significance (α) of 0.05 was accepted. In the characterization of the sample being studied, basic descriptive statistics was used: average, standard deviation, as well as absolute and relative frequencies distribution. To analyze the presence of circadian rhythm in each variable and the comparison according to its presence or not, the sample was classified in different subsets according to the presence or absence of the variable to be analyzed. Statistical hypothesis testing or goodness of fit for a variable was used, and it was attempted to prove whether the distribution of frequencies of the episodes in each group follow a given “law”; i.e. if it follows an expected distribution of frequencies. Also, a mathematical function was used to analyze and describe the time rhythm of the appearance of symptoms in infarction, of a trigonometric basis, called cosinor model. The simple cosinor model allows, by null amplitude test, confirming the existence of the rhythm and by the acrophase amplitude test, comparing different rhythms between themselves. This is based on adjusting a cosine curve to the data, using the method of least squares to make the adjustment.

 

RESULTS
In the group of patients studied, the male gender was predominant (66.5%). The average age was 69.9±11.9 years. In the female gender, the average age was greater than that found in the male gender: 70.5±11.2 and 65.11±11.8 respectively.

The distribution of age by groups showed that the appearance of AMI was more frequent in >50 years. We should highlight that 33.3% of the patients studied presented history of ischemic heart disease (Table 1).

Variable

n

%

Overall

340

100

Sex

 

 

  • Male

226

66.5

  • Female

114

33.5

Age

 

 

  • <50 years

25

7.4

  • >50 years

315

92.6

Previous ischemic heart disease

113

33.2

State at discharge from the coronary unit

 

 

  • Alive

287

84.4

  • Deceased

53

15.6

Source: copyright
Table 1. General characteristics of the sample studied.
Hospital Abel Santamaría. 2005-2009

 

The most prevalent risk factor was hypertension (59.7%). We should highlight that 85.6% of the population studied, presented some cardiovascular risk factor (Table 2).

Risk factors

n

%

Overall

291

85.6

No risk factors

49

14.4

Stroke

10

2.9

Previous ischem heart disease

113

33.2

Hypertension

203

59.7

Diabetes Mellitus

79

23.2

Smoking

81

23.8

Source: copyright
Table 2. Distribution of cardiovascular risk factors

 

Figure 1 shows the rhythmic pattern of occurrence of acute myocardial infarction, with an acrophase between 10 and 15 hours.

Figure 1. Rhythmic pattern of overall distribution of acute myocardial infarction

 

Tables 3 and 4 show the acrophase and batiphase estimated according to the presence or not of the risk factors considered. Check that globally, there are significant differences in the absence and presence of the risk factors considered.

Variables

Circadian rhythm

 

Acrophase

Batiphase

Overall

11.08

23.08

No risk factors

11.00

23.00

Risk factors

9.25

21.25

Sex

 

 

  • Male

9.39

21.39

  • Female

11.36

23.36

Age

 

 

  • <50 years

0.23

12.23

  • >50 years

11.45

23.45

Stroke

 

 

  • Yes

2.10

14.00

  • No

11.50

23.50

Source: copyright
Table 3. Descriptive parameters of circadian rhythm in the population according to non-modifiable cardiovascular risk factors.

 

Variables

Circadian rhythm

 

Acrophase

Batiphase

Hypertension

 

 

  • Yes

9.50

21.50

  • No

11.55

23.55

Diabetes Mellitus

 

 

  • Yes

1.30

13.30

  • No

11.22

23.22

Smoking

 

 

  • Yes

9.40

21.40

  • No

11.12

23.12

Previous ischemic heart disease

 

 

  • Yes

11.17

23.17

  • No

9.08

21.08

CV: cardiovascular
Table 4. Comparative analysis of circadian rhythm according
to the different CV risk factors.

 

Figures 2, 3 and 4 show the time distribution patterns obtained, after applying the cosinor model, according to the presence or not of the mentioned cardiovascular risk factors.

Figure 2. Pattern of AMI distribution with HTN and DM according to the implementation or not of the cosinor model. HTN: Hypertension; DM: Diabetes mellitus.

 

Figure 3. Pattern of AMI distribution with previous IHD and Smoking according
to the implementation or not of the cosinor method. IHD: Ischemic heart disease.

 

Figure 4. Pattern of AMI distribution with previous stroke according to the implementation or not of the cosinor method.

 

DISCUSSION
In Cuba, ischemic heart disease represents since several years the first cause of death [12]. This pathology is responsible of almost 25% of the mortality rate of the country, so its demographic, sanitary and social impact is crucial, and it is expected to increase over the next few decades, not just in Cuba, but also in Spain [13] and the rest of the world [14,15].

In the present study, more than 50% of the mortality rate is located within the age groups included from 50 years of age, a fact that coincides with what was reported in the previously quoted investigations. At a greater age, the greater the risk of myocardial infarction complications, especially heart failure and arrhythmias, mainly AV block, a fact that is frequently associated to the development of complex atherosclerotic disease [16].

The occlusion of the coronary arteries, with the subsequent reduction in coronary flow usually leads to the complication of an atherosclerotic plaque (vulnerable plaque) (rupture and/or erosion) with the formation of an overaggregated (partial or total) occlusive thrombus. Vasoconstriction and the concomitant coronary microembolization that affects coronary microcirculation may also be responsible for the acute coronary event [17]. The formation of overlapping thrombi over a vulnerable plaque by erosion of the fibroatheroma layer, and not by rupture, is less frequent. The underlying inflammatory process has become an important motor for plaque rupture and thrombosis [18].

The prevalence of hypertension for Cuba is 202.7 per each 1000 inhabitants, almost exceeding by 5 times that of diabetes mellitus of 40.4 per each 1000 inhabitants; proportions similar to these are present in the province of Pinar del Río, where the rates are 221.1 and 34.6 respectively [2].

Between the main causal risk factors for ACS, the following stood out: smoking, hypertension and diabetes mellitus, risk factors also very prevalent in the population that eventually suffered a myocardial infarction. In the present investigation, the behavior of these risk factors was similar to what was described, positioning hypertension as the predominant risk factor, highlighting then the history of ischemic heart disease as one of the most prevalent risk factors.

In the term between 2005 and 2009, the group of cases analyzed to evaluate the influence of risk factors on circadian rhythm indeed showed the presence of a circadian rhythm at the time of onset of AMI symptoms, in the different subsets stratified according to the different risk factors. The onset of the symptoms of AMI and their behavior according to risk factors followed a circadian pattern with a similar behavior for these factors, a pattern that was only modified in diabetic individuals, in those with history of stroke and in smokers, in whom another peak in the night time was obtained between 24:00 and 02:59. In other areas of the world, there are periodical variations that show significant differences in regard to daily, monthly and seasonal patterns of ST elevation myocardial infarction presentation [19].

The investigations made by Tartabull et al [10] and by López Mesa et al [8] pose that the personal history of hypertension as cardiovascular risk factor is associated to a morning pattern with a single peak; unlike what happens with history of smoking that relates to a pattern of double morning peak. These authors also propose that the patients with history of diabetes mellitus present a behavior similar to that of patients with history of smoking, a result that was not obtained in the present investigation, with diabetes mellitus being out of phase in regard to the overall circadian rhythm.

The present investigation corroborated the greater morning incidence of myocardial infarction, with a tendency to a marked increase of the onset of symptoms in the first hours of the morning (24:00 – 02:59 h). The cosinor method supported the behavior described, finding an acrophase at 11:08 h.

The patients that presented encephalic vascular accident prior to the AMI episode, in the period analyzed, did not show a standard circadian rhythm (CR), although there was a more marked peak of incidence in the first hours of the morning. This could be attributed, besides the possible association between the pharmacotherapy used in these patients and its possible influence on circadian rhythm, to the possibility that in some cases, the ischemic accident could affect the brain connections of the hypothalamic nucleus. Thus, the most common manifestation of CR in AMI could be altered, although this hypothesis could not be corroborated to this date in electrophysiology or chronobiopathological studies.

In diabetic patients, a CR was observed with a bimodal circadian pattern with a double peak: in the morning and the night (Figures 3 and 4), an assessment different from that published by other authors that considered there is no significant variation in the onset of myocardial infarction in individuals with type 2 diabetes [20].

López Mesa attributes this bimodal behavior with a double morning peak, to the influence of autonomic deregulation suffered by diabetic patients. The factors intimately related to the pathogenesis of thrombotic episodes of AMI would suffer alterations both in their circadian variability and their intensity. The circadian variability of heart rate would decrease, the night decrease of blood pressure would be attenuated, the threshold of morning platelet aggregation would increase, fibrinolytic activity would decrease and vascular thrombogenicity would increase during the day, among others. The loss of synchronicity between the central and peripheral biological clock contributes to the loss of homeostasis, the pathogenesis of cardiovascular disease, and the progression of it [21].

We may infer that the alteration that occurs in the autonomic regulation of the vegetative nervous system in diabetic patients could be one of the main causes for the loss of the standard pattern of CR in them. The presence of a double morning peak could be a reflection of such alteration, along with a greater sensibility of the adrenergic receptors outside the morning time of a maximal incidence, described in other subsets. Besides, the frequent association between diabetes and other cardiovascular risk factors should be taken into account, since they may display frequent interactions between such variables and the pharmacological treatments associated to controlling other cardiovascular risk factors.

 

CONCLUSIONS
The onset of the symptoms of acute myocardial infarction presented a circadian behavior with acrophase at 11:08 h. This pattern changes in patients with history of diabetes mellitus and cerebrovascular accident, cardiovascular risk factors that modified the time of appearance of acute myocardial infarction in the population studied.

 

BIBLIOGRAPHY

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Publication: March 2014

 
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