Disorders in the blood coagulation system play an important role in the development of cardiovascular pathology in diabetes. Factors that cause them are hyperglycemia, insulin deficiency, insulin resistance, dyslipidemia, oxidative stress. The most significant changes are observed in the vascular-platelet link of hemostasis. Diabetes is characterized by morphological and functional changes in the endothelium of blood vessels. The activity of platelets increases, which is manifested by their high level of spontaneous aggregation and increased sensitivity to the action of activating factors. The role in the disturbance of hemostasis is played by increasing the activity of the von Willebrand factor, reflecting damage to endothelial cells. Diabetes is characterized by an increase in the activity of plasma clotting factors (I, II, III, VII, VIII, IX, XI, XII and XIII), activation of the callicrein-kinin system. In some cases, this correlates with the development of complications of diabetes. Characteristic disorders in the coagulation inhibition system are a decrease in the activity of antithrombin III, reduced formation of thrombin-antithrombin complexes, reduction of thrombomodulin and protein C. In diabetes, there is a decrease in fibrinolysis, due to a decrease in the expression of tissue activator plasminogen and an increase in the level of the inhibitor of the activator plasminogen. The possibilities of drug correction of hypercoagulation factors in diabetes are to achieve glycemic control with sugar-reducing drugs and elimination of dyslipidemia through hypolipidemic therapy. The most well-studied sugar-lowering drug that improves the state of the blood clotting system is metformin. The system of hemostasis in diabetic patients is positively affected by statins both due to the direct hypolipidemic effect, and by improving endothelial function and increasing fibrinolysis.

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The main pathogenetic mechanisms of hypercoagulation in diabetes and the possibility of its drug correction

Aim . To assess the individual and complex prognostic value of various blood biochemical parameters (biomarkers) in the non-invasive diagnosis of coronary artery (CA) atherosclerosis. Material and methods . The study included 216 patients (men, 115; women, 101) aged 24 to 87 years (mean age, 61,5±10,7 years), who underwent indicated coronary angiography. All patients underwent a biochemical blood tests to determine the parameters of lipid, carbohydrate and nitrogen metabolism, the hemostatic system, inflammatory markers, as well as the creatinine level as an indicator of renal function. Results . Analysis revealed biomarkers, the deviations in the level of which contribute to the diagnosis and determination of the coronary involvement. These biomarkers include glucose, creatinine, C-reactive protein, and adiponectin. Using these biochemical parameters, a multivariate model (MVM) was constructed, which was significant for the diagnosis of coronary atherosclerosis and determination of its severity. With the help of ROC-analysis, the cutoff point of MVM of 2 was found. MVM >2 with a sensitivity of 72% indicate CA atherosclerosis of any severity, as well as with a specificity of 62,5%, it can be ruled out. Using MVM data and a cutoff point of 2, a binary logistic regression model was built, according to which, with a MVM >2, the odds for detecting CA atherosclerosis of any degree is 2,1 times higher (95% confidence interval (CI), 1,2-3,8; p=0,010), severe CA — 4,7 times (95% CI, 1,9-12,0; p=0,001) compared with individuals with MVM ≤2, who have 2,8 times (95% CI, 1,4-4,9; p=0,002) a higher chance of detecting intact CAs. Conclusion . Thus, the total MVM score of 0-2 indicates the absence of coronary atherosclerosis, while 3-4 points -CA atherosclerosis of any severity.

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Биохимические маркеры коронарного атеросклероза: построение моделей и оценка их прогностической значимости для верификации выраженности поражения

Aim. To assess the association of glycemic control (achievement of an individual target glycated hemoglobin level) with the outcomes of elective percutaneous coronary interventions in patients with type 2 diabetes (T2D).Material and methods. This cohort observational study included 74 patients with a median age of 61 (57; 64) years. There were 49% of men with a previously established T2D, who had indications for elective primary percutaneous coronary intervention (PCI) for stable coronary artery disease. At inclusion in the study and after 1 month, the concentration of fasting blood glucose, glycated hemoglobin (HbA1c), fructosamine, and serum creatinine were determined. Plasma glucose levels were determined using the hexokinase method. HbA1c level was determined by immunoturbidimetry on a Konelab 30i chemistry analyzer. The concentration of fructosamine was determined by the kinetic colorimetric assay on a Konelab 30i chemistry analyzer. Statistical processing was carried out using the Statistica 10.0 program from StatSoft, Inc. (USA).Results. At the time of enrollment, 31% of participants had not achieved the target glycated hemoglobin level against the background of nonoptimal hypoglycemic therapy in most cases. A total of 18 (25%) following adverse cardiovascular events were registered within 12 months after PCI: 11 (15%) patients developed acute coronary syndrome; among them, 6 (8%) patients had stent restenosis according to coronary angiography, 4 (6%) patients — progression of atherosclerosis, which required repeated PCI with stenting of another vessel, 2 (3%) patients — cerebrovascular accident, and 3 (4%) patients were hospitalized due to de compensated heart failure. According to multivariate logistic regression, only the HbA1c level was a predictor of adverse outcomes during the year after PCI — a 1% increase in HbA1c level increased the risk of adverse outcomes by 1,79 times (odds ratio, 1,79, 95% confidence interval, 1,06-3,02, p=0,028). Poor glycemic control 1 month before PCI increased the risk of cardiovascular events by 4,04 times over the next year, while non-target HbA1c level immediately before PCI increased the risk of adverse outcomes by 4,7 times, and 5 months after PCI, by 7,34 times.Conclusion. The significance of non-target glycated hemoglobin level for adverse outcomes during the year after elective PCI against the background of T2D was established with an increase in the negative effect as long-term (after myocardial revascularization) maintenance of poor glycemic control.

Role of glycemic control in elective percutaneous coronary interventions in patients with type 2 diabetes

Aim      To evaluate cardiometabolic effects of empagliflozin in patients with ischemic heart disease and type 2 diabetes mellitus (DM) following elective percutaneous coronary intervention (PCI).Materials and methods Patients meeting the inclusion/non-inclusion criteria were randomized into two groups of equal number using simple randomization with successively assigned numbers. Group 1 included 37 patients (18 men and 19 women) who gave their consent for the treatment with empagliflozin 10 mg/day in addition to their previous hypoglycemic therapy. The drug administration started one month prior to the elective PCI and continued for the next 11 months (treatment duration, 12 months). Group 2 (comparison group) consisted of age- and DM duration-matched patients (37 patients; 18 men and 19 women) who continued on their hypoglycemic therapy previously prescribed by endocrinologists during the entire study period. Before the study, 36.11 % patients of the empagliflozin group and 27.03 % of the comparison group had unsatisfactory glycemic control as shown by the level of glycated hemoglobin (HbA1c).Results At 6 and 12 months of the study, fasting glycemia and HbA1c were significantly lower in the empagliflozin treatment group. The groups were comparable by the incidence of adverse outcomes: 8 (22.24 %) patients in the empagliflozin group and 10 (27.04 %) patients in the comparison group (р=0.787). The 12-month empagliflozin treatment reduced total cholesterol (C) by 5.56 % (p<0.05), low density lipoprotein (LDL) C by 3.67 % (p<0.05), visceral adipose tissue area (VATA) by 5.83 % (p<0.05), and subcutaneous adipose tissue area (SATA) by 3.54 % (p<0.05).Conclusion      The empagliflozin treatment for 30 days prior to and after elective PCI can enhance the effectiveness of myocardial revascularization due to the demonstrated beneficial cardiometabolic effects.

Cardiometabolic Effects of Empagliflozin in Patients Undergoing Elective Percu-taneous Coronary Intervention for Type 2 Diabetes Mellitus.

Insulin resistance, which is a fundamental pathogenetic factor of prediabetes, is closely associated with abdominal obesity on the one hand and the development of cardiovascular diseases, heart failure (HF), on the other. The pathogenetic role of insulin resistance is multifaceted and consists in the acceleration of atherosclerosis, the formation of left ventricular myocardial hypertrophy, including through mechanisms that do not depend on blood pressure, as well as the development of its diastolic dysfunction. The latter is the starting point for starting HF with preserved ejection fraction (HFpEF).Compared with patients with HF with reduced ejection fraction, the presence of HFpEF determines a higher frequency of hospitalizations not due to decompensation of heart failure, but due to concomitant diseases, such as destabilization of the course of arterial hypertension, decompensation of type 2 diabetes mellitus, curation of which, in general, has a greater impact in terms of improving prognosis. Thus, in patients with prediabetes and HFpEF, the correction of insulin resistance as the underlying cause and trigger of cardiometabolic disorders can potentially improve not only insulin-glucose homeostasis, but also the parameters of myocardial diastolic function. This literature review is devoted to the accumulated experience of using metformin as a «strategic» antidiabetic drug in HFpEF and considering potential new points of its application as a protector of the cardiovascular system.

Insulin resistance and heart failure with preserved ejection fraction. Pathogenetic and therapeutic crossroads

The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)

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D. C. Wheeler

Papers

2019 Рекомендации ЕSC/EASD по сахарному диабету, предиабету и сердечно-сосудистым заболеваниям