Z. Bilous1, О. Abrahamovych1, N. Mazur2, S. Ryabokon2, N. Ilenkiv2, N. Bevza2
1Danylo Halytsky Lviv National Medical University
2Clinical Hospital “Lviv Railway”, branch of the health care center on transport of PJSC “Ukrzaliznytsia”
Introduction. Despite the significant advances in the study of pathogenesis, clinics, diagnostics and treatment of acute coronary syndrome (ACS), it remains one of the most common cardiovascular diseases, the severity of which is complicated by concomitant type 2 diabetes mellitus, since atherosclerosis in patients with type 2 diabetes develops 10-15 years earlier than in the general population, and it is characterized by accelerated damage of large subepicardial vessels, its severity increases faster and more often leads to complications. Diabetes mellitus almost doubles the risk of death from cardiovascular diseases, which is comparable to the risk after transferred myocardial infarction, because there is a high frequency of multiple damage of the coronary vessels, increased activation of intra-vascular inflammation on the background of hyperglycemia and hyperinsulinemia, increased activity of all parts of the hemostasis system. There is a marked increase in the risk of cardiovascular death, not only in case of true diabetes, but also in case of its subclinical forms, glucose intolerance. In case of diabetes mellitus, high mortality rate is also high, and its percentage increases in the next 1-5 years after the myocardial infarction. Therefore, patients with type 2 diabetes mellitus remain the most vulnerable group, as their mortality rate decrease is negligible.
The results of the study have shown that intensive glycemic control significantly reduces the risk of microvascular complications of diabetes, but does not significantly affect the macrovascular complications and overall mortality.
The aim of the study. To make a review of the literature and a description of the clinical case in order to clarify the peculiarities of the clinical condition and pathogenesis of acute coronary syndrome in patients with type 2 diabetes.
Materials and methods. Cochrane Library, Research Gate for the key words: GKS, diabetes, acute coronary syndrome, diabetes mellitus, hypercholesterolemia, dyslipidemia, insulin resistance, hyperglycemia. 130 sources were analyzed in the English and Ukrainian languages. Sources are selected, which highlight the clinical and pathogenetic features of ACS in patients with type 2 diabetes. A clinical case is described.
Results. ACS in patients with diabetes mellitus often occurs with less severe pain syndrome (often complete absence of typical pain syndrome), shortness of breath while walking, palpitations. The frequency of asymptomatic ischemia is 2.0-4.0 % in the general population of patients with type 2 diabetes mellitus and in 30.0-50.0 % of patients with type 2 diabetes mellitus with ischemic heart disease. The absence of pain in the cardiac area is due to the neuropathy of the nerves branched out in the cardiac muscle, and the absence of an initial irritation signal during ischemia, as well as myocardial infarction with necrosis of the sensitive receptors. The absence of pain means the loss of the limiting factor of physical activity, which, accordingly, increases the risk of acute myocardial infarction and sudden cardiogenic death in diabetic patients.
The main mechanisms of vascular lesions in patients with diabetes mellitus: mechanical obstruction (atherosclerotic plaque), dynamic obstruction (spasm of normal or atherosclerotically changed arteries), microvascular dysfunction. Specific risk factors for vascular damage in the presence of type 2 diabetes mellitus include: hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia.
Pathologic mechanisms that underlie diabetes mellitus and its macrovascular complications include oxidative stress and inflammation. According to modern presentations, diabetes is considered a condition of acute inflammation with prothrombogenic changes in hemostasis and fibrinolysis, which increases the risk of vascular damage. Proinflammatory cytokines in patients with diabetes mellitus affect not only the formation of insulin resistance of peripheral tissues, but also play an important role in reducing the insulin-producing capacity of the pancreas.
The main mechanisms for the implementation of the effect of hyperglycemia include: activation of the polyolic pathway of glucose metabolism (sorbitol/aldose reductase); glycosylation of proteins; the effect of oxidative stress; increase of the role of diacylglycerols and activation of protein kinase isoforms as a result of enhanced formation of superoxide radical by inflammatory blood cells, smooth muscle cells, endothelial cells. In patients with diabetes mellitus the glycosylation of lipoproteins with the acquisition of proatherogenic properties is present. The process of glycosylation of proteins, especially apo-proteins of very low density and low density lipoproteins, arises as a result of the ability of glucose to non-enzymatically attach to them, which complicates the recognition of these modified lipoproteins by tissue B, E-receptors, causes inhibition of their elimination from the blood and enhanced capture by macrophages, followed by the formation of foam cells. In addition, glucose is capable of auto-oxidation and activation of free radical processes, which is one of the most important mechanisms of modification of lipoproteins.
When combined ACS with type 2 diabetes mellitus there is a sharp decline in functional activity of the endothelium of the vascular wall: flow-dependent vasodilation, anticoagulant, antiplatelet and anti-fibrinolytic activity, which correlate with the severity of carbohydrate metabolism violations. The pathogenetic mechanisms of endothelial damage on the background of insulin resistance contribute to the prevalence of thromboembolic complications, threatening arrhythmias, and the development of congestive heart failure precisely in patients with acute myocardial infarction with concomitant type 2 diabetes mellitus.
It is known that in case of hyperglycemia the structure of the intercellular matrix and the basal membrane are violated. The reason of this is the development of insulin resistance, which causes the activation of components of the extracellular matrix: MMP and TIMMP, which leads to remodeling of the basal membrane in case of type 2 diabetes mellitus and, as a consequence, contributes to heart failure severity increase.
Conclusions. Consequently, the key problems in managing the patients with ACS and diabetes mellitus are timely and accurate diagnosis, risk assessment, disease prognosis and the adequate treatment algorithm administering.
In view of this, it is important to consider the peculiarities of the connections between the individual pathogenetic mechanisms of accelerated atherogenesis in patients with diabetes, which will expand the therapeutic potential of these processes. The role of insulin resistance, endothelial dysfunction, disorders in the system of metalloproteinases and cytokines, immunoinflammatory markers of adipose tissue in the destabilization of the atherosclerotic process and the correlation of these factors with lipid disorders are still insufficiently studied. The problem of the influence of insulin resistance on the system of extracellular matrix is controversial. The effect of each individual pathogenic marker on the clinical course and complications of these patients remains undetermined; therefore, the study of the clinical course of ACS with comorbid type 2 diabetes mellitus and the prediction of complications are important for improving the prognosis in these patients.
Therefore, a detailed study of the pathogenetic foundations, mechanisms, and approaches to timely diagnosis can not only reduce the risk but also lead to a qualitatively new strategic position in the prevention and treatment of such patients.
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