In addition to their antithrombotic and antiatherosclerotic effects, they also play a role in the repair of fibrinolytic balance, exerted in part via the bradykinin-dependent (nitric oxide [NO]) processes, which can be considered a particular home of ACEIs [28, 31C33]. risk. Key Points The majority of coronary events generally happen at dawn and in the early morning, a timing that may also be relevant to their prevention. The risk of acute myocardial events is definitely significantly affected by prothrombotic, hormonal, and hemodynamic processes that happen in the body relating to circadian rhythms.While the blood pressure-lowering effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARBs) should be considered, so too should all other differences that may protect against a plaque rupture leading to myocardial infarction. Open in a separate window Intro Ischemic heart disease is one of the most frequent diseases worldwide, and cardiovascular (CV) diseases are among the best causes of death in developed industrial countries [1, 2]. Progressive coronary atherosclerosis is the main pathological foundation of ischemic heart disease, eventually resulting in overt disease. Two main forms of its manifestation are differentiated in medical practice: stable coronary artery disease (SCAD) and acute coronary syndrome (ACS), which includes unstable angina (UA) pectoris and various forms of myocardial infarction (MI) such as ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) . As we know, most acute coronary events are underlain by rupture or erosion of plaques, which block the blood supply at given myocardial areas by thrombus formation. In patients who have experienced an acute MI (AMI), the incidence of plaque rupture (70C75?%) is definitely higher than that of plaque erosion (20C25?%) [3, 4]. The mechanisms leading Cefotaxime sodium to unstable plaques Cefotaxime sodium are complex, and several local and systemic factors play a part . However, the majority of coronary events happen at dawn and in the early hours of the morning, which may also become of substantial relevance in terms of prevention . The development Cefotaxime sodium of acute MI  and the closely related mortality shows a significant peak primarily in the period between 6 a.m. and 8 a.m. ; the risk of developing events then decreases to the early afternoon (Fig.?1). Open in a separate windows Fig.?1 Circadian rhythm of coronary heart disease mortality and acute myocardial infarction that shows a significant maximum primarily in the period between 6 a.m. and 8 a.m. [6C8]. coronary heart disease Importance of Dawn and the Early Morning Hours and Roles of the Acute Risk Factors Although the development of unstable atherosclerotic lesions is regarded as a key step in the initiation of ACS, the mechanism leading to it is only partly recognized, IL22R but can be concretized with difficulty by highlighting some of its major elements [5, 9]. Plaque instability is determined mainly by a complex of inflammatory processes and immune system activation in the plaque, as well as thrombogenic factors in the circulating blood . In the presence of a vulnerable plaque, the prothrombotic processes that lead to the rupture of the plaque may be induced by stressors of a physical (e.g., excessive exercise), mental (e.g., place of work stress, panic, anger), or chemical (e.g., alcohol, narcotic) nature . However, these risks are characteristic of the active morning and even afternoon parts of the day and don’t explain why acute conditions maximum with dawn and in the early hours of the morning. Nevertheless, the development of ACS may be significantly Cefotaxime sodium determined by transient biological/physiological changes that follow a circadian rhythm and predominate in the early morning . In addition to the improved sympathetic tonus, the prothrombotic response may be augmented from the dawn increase in blood pressure, platelet activation, and coagulability, and disrupted fibrinolysis balance. These changes acting on the short term are the acute risk factors that represent the final impetus in the process leading to plaque instability and rupture, and may therefore increase the risk of CV events developing . The early morning increase in blood pressure and heart rate enhance myocardial oxygen demand while coronary circulation is decreased . The number and activity of circulating platelets may also fluctuate relating to circadian rhythms, where catecholamines may also play a role [15, 16]. The activation of coagulation factors (e.g., Element VII, fibrinogen, prothrombin), and the decreased morning activity of fibrinolytic system elements (plasminogen activator inhibitor-1 [PAI-1] and cells plasminogen activator [t-PA]) also adhere to a circadian rhythm [15C18] (Fig.?2). The variations between the two main processes of cardiac oxygen demand/supply and coagulation/fibrinolytic systems may underlie the development of morning ACS [17, 18]. Results of intravascular ultrasonography (IVUS) angiographies performed prior to coronary interventions demonstrate the circadian rhythm of AMI can.