**5. Myocardial infarction**

Myocardial infarction is the leading cause of mortality in developed countries and developing countries. It can be caused and triggered by different pathophysiological processes. Myocardial infarction is an inflammatory disease due to the death of myocardial cells because of complete coronary circulation interruption, which is in most cases a consequence of thrombotic occlusion of the coronary artery at the site of the activated atherosclerotic plaque. An electrocardiogram (ECG) of the ST elevation is only an indirect indicator of the fact that ischemia affects all three layers of cardiac muscle (endocardium, myocardium, and epicardium) [50].

ST-elevation myocardial infarction (STEMI) is the most severe form of acute coronary syndrome. Myocardial infarction is accompanied by increased cellular oxidative stress in the pericardial cavity [51]. The primary cause of infarction is platelet aggregation in the coronary artery. The platelet activity is the highest in the morning. Also, in the morning hours, mental and physical activity increase due to cortisol and catecholamine elevation, which increases cardiac output [45]. The biochemical markers of myocardial damage are cardiac troponin T or troponin I in serum. These biochemical markers are more reliable than those previously used, such as measurement of creatine kinase (CK). The initial increase in troponin in peripheral blood in patients with infarction occurs over 3–4 hours with a permanent increase for up to 2 weeks after infarction. In order to confirm or exclude myocardial damage, troponin T serum levels are repeated in the first 6–12 hours after severe chest pain [52].

The classification of myocardial infarction in five types was introduced in 2007 and established the clinical criteria for its exact differentiation [50]. Type 1 is related to a coronary plaque rupture, fissuring, or dissection with resulting intraluminal thrombosis. Type 2 myocardial infarction is secondary to myocardial ischemia resulting from increased oxygen demand or decreased supply. Type 3 myocardial infarction is linked to unexpected cardiac death when cardiac biomarkers are unavailable. Types 4 and 5 myocardial infarction are procedure related [53].

In the study of Saaby et al., [54] it was shown that the most significant number of patients with myocardial infarction come under Type 1 (72%). In patients with Type 1 myocardial infarction, changes in the ECG are seen either as the elevation or depression of the ST segment; the troponin T level also increases in the blood and serves as a diagnostic marker. The troponin T level in the blood is higher in patients with Type 1 myocardial infarction than Type 2 [55].

For manifestation of infarction, apart from lifestyle, a genetic background of myocardial infarction is also essential. A positive family history of myocardial infarction is a major cardiovascular risk factor [56]. Coronary artery disease and myocardial infarction have a genetic background in 50–60% of cases. Many genes are found in the genetic background of myocardial infarction. Whole genome association studies have revealed many variants of genes associated with increased risk for myocardial infarction [56]. So far the most frequently explored genes with increased risk for myocardial infarction are involved in the metabolic pathways of lipid metabolism and development of type 2 diabetes. The relationship between the circadian rhythm genes and the onset of myocardial infarction will be discussed below.

**27**

*Myocardial Infarction and Circadian Rhythm DOI: http://dx.doi.org/10.5772/intechopen.83393*

**6. Myocardial infarction and circadian rhythm**

clocks control tissue-specific expression [27].

before bedtime reduced blood pressure [3].

of myocardial infarction [57, 61].

Many cardiovascular events and diseases have a circadian pattern of appearance. The normal circadian blood pressure shows the two highest values during the day, around 9 am and 7 pm, while there is a slight decrease around 3 pm. It is considered that circadian variations in the tone of coronary vessels and endothelial function play an essential role in the onset of myocardial infarction. As myocardial infarction is significant medical stress, it causes increased cortisol levels in plasma [3]. In the acute phase of myocardial infarction, the phase of the circadian clock in the ischemic part of the heart differs from the non-ischemic part of the heart. The arrhythmia may occur because of the difference in the phase of the rhythm, or different expressions of the circadian clock genes. The loss of synchronization of the circadian rhythm between organs or tissues occurs more often than we would expect [4]. Circadian regulation of physiological processes is regulated locally. Peripheral tissue

Homeostatic changes, gene expression changes, and external triggers can cause a stressful environment and cause damage to the atherosclerotic plaque in the coronary arteries in the morning, when prothrombin is increased [57]. Many intrinsic vasoactive and cardioactive substances, such as angiotensin II, melatonin, plasminogen activator inhibitor 1 (PAI-1), glucocorticoids, epinephrine, norepinephrine, and nitrogen oxide, show a specific circadian pattern. The fibrinolytic system, which regulates PAI-1, shows a circadian pattern of occurrence in both healthy patients and those with ischemic heart disease. The concentration and activity of PAI-1 depend on the circadian rhythm and are the highest in the morning [28]. CLIF (Cycle-Like Factor) expression in endothelial cells creates heterodimers with CLOCK protein, and binds to the E-box of the *PAI-1* gene promoter and promotes its expression, while PER2 and CRY1 inhibit expression of *PAI-1* by blocking heterodimer CLOCK-CLIF. CLIF controls the circadian rhythm of PAI-1 in endothelial cells, which might explain the higher incidence of myocardial infarction in the morning [26, 58]. As a result of this, the fibrinolytic system in patients with MI might be a potential goal for chronotherapy, to treat acute cardiovascular events. The circadian clock regulates the endothelial response to vascular injury. The main factor that can be affected by potential chronotherapy is PAI-1 because it is a crucial fibrinolysis inhibitor [59]. Chronotherapy includes the accurate timing of drug taking and can improve the therapeutic efficacy of the drug, while limiting its toxicity [41]. That is why many studies support chronotherapy for cardiovascular disease by limiting pathogenesis and improving treatment after the occurrence of acute cardiovascular events [59]. It is known that melatonin levels decrease during the night in coronary heart disease and infarction. Melatonin is an antioxidant that can inhibit the action of reactive oxygen radicals during heart ischemia. It also plays a vital role in regulating blood pressure, depending on the circadian rhythm. Animal studies have shown that animals with the pineal gland removed develop hypertension. Clinical examinations have shown that in patients with hypertension melatonin drugs taken daily

The appearance of myocardial infarction has two peaks during the day. The highest incidence of myocardial infarction is during the morning, and the second peak occurs late at night [60]. The beta blockers prevent increased sympathetic activity, catecholamine concentration, heart rate, blood pressure and lack of oxygen in the heart, and these are the physiological reasons for the existence of two peaks

Ischemia occurs in the morning due to increased oxygen demand, whereas in the evening it is due to decreased coronary blood flow. The appearance of myocardial infarction depends on ethnic origin, and the British differ from Asians in the

*Visions of Cardiomyocyte - Fundamental Concepts of Heart Life and Disease*

[32, 48, 49].

**5. Myocardial infarction**

severe chest pain [52].

mechanisms of insulin resistance and risk factors for cardiovascular diseases, such as metabolic syndrome. Excessive weight plays a significant role because fatty tissue becomes an active endocrine organ that secretes low-level inflammation mediators, and these stimulate the development of metabolic syndrome and vascular diseases

Myocardial infarction is the leading cause of mortality in developed countries and developing countries. It can be caused and triggered by different pathophysiological processes. Myocardial infarction is an inflammatory disease due to the death of myocardial cells because of complete coronary circulation interruption, which is in most cases a consequence of thrombotic occlusion of the coronary artery at the site of the activated atherosclerotic plaque. An electrocardiogram (ECG) of the ST elevation is only an indirect indicator of the fact that ischemia affects all three layers

ST-elevation myocardial infarction (STEMI) is the most severe form of acute coronary syndrome. Myocardial infarction is accompanied by increased cellular oxidative stress in the pericardial cavity [51]. The primary cause of infarction is platelet aggregation in the coronary artery. The platelet activity is the highest in the morning. Also, in the morning hours, mental and physical activity increase due to cortisol and catecholamine elevation, which increases cardiac output [45]. The biochemical markers of myocardial damage are cardiac troponin T or troponin I in serum. These biochemical markers are more reliable than those previously used, such as measurement of creatine kinase (CK). The initial increase in troponin in peripheral blood in patients with infarction occurs over 3–4 hours with a permanent increase for up to 2 weeks after infarction. In order to confirm or exclude myocardial damage, troponin T serum levels are repeated in the first 6–12 hours after

The classification of myocardial infarction in five types was introduced in 2007 and established the clinical criteria for its exact differentiation [50]. Type 1 is related to a coronary plaque rupture, fissuring, or dissection with resulting intraluminal thrombosis. Type 2 myocardial infarction is secondary to myocardial ischemia resulting from increased oxygen demand or decreased supply. Type 3 myocardial infarction is linked to unexpected cardiac death when cardiac biomarkers are unavailable. Types 4 and 5 myocardial infarction are procedure related [53].

In the study of Saaby et al., [54] it was shown that the most significant number of patients with myocardial infarction come under Type 1 (72%). In patients with Type 1 myocardial infarction, changes in the ECG are seen either as the elevation or depression of the ST segment; the troponin T level also increases in the blood and serves as a diagnostic marker. The troponin T level in the blood is higher in patients

For manifestation of infarction, apart from lifestyle, a genetic background of myocardial infarction is also essential. A positive family history of myocardial infarction is a major cardiovascular risk factor [56]. Coronary artery disease and myocardial infarction have a genetic background in 50–60% of cases. Many genes are found in the genetic background of myocardial infarction. Whole genome association studies have revealed many variants of genes associated with increased risk for myocardial infarction [56]. So far the most frequently explored genes with increased risk for myocardial infarction are involved in the metabolic pathways of lipid metabolism and development of type 2 diabetes. The relationship between the circadian rhythm

genes and the onset of myocardial infarction will be discussed below.

with Type 1 myocardial infarction than Type 2 [55].

of cardiac muscle (endocardium, myocardium, and epicardium) [50].

**26**
