Patients with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) have high risk of microcirculation complications and microangiopathies. An increase in thrombogenic risk is associated with platelet hyperaggregation, hypercoagulation, and hyperfibrinolysis. Factors leading to platelet activation in MetS and T2DM comprise insulin resistance, hyperglycemia, non-enzymatic glycosylation, oxidative stress, and inflammation. This review discusses the role of nitric oxide (NO) in the regulation of platelet adhesion and aggregation processes. Nitric oxide is synthesized both in endotheliocytes, smooth muscle cells, macrophages, and platelets. Modification of platelet NO-synthase (NOS) activity in MetS patients can play a central role in the manifestation of platelet hyperactivation. Metabolic changes, accompanying T2DM, can lead to an abnormal NOS expression and activity in platelets. Hyperhomocysteinemia, often accompanying T2DM, is a risk factor for cardiovascular accidents. Homocysteine can reduce NO production by platelets. This review provides data on the insulin effects in platelets. Decrease in a number and sensitivity of the insulin receptors on platelets in T2DM can cause platelet hyperactivation. Various intracellular mechanisms of anti-aggregating insulin effects are discussed. Anti-aggregating effects of insulin are mediated by a NO-induced elevation of cGMP and upregulation of cAMP- and cGMP-dependent pathways. The review presents data suggesting an ability of platelets to synthesize humoral factors stimulating thrombogenesis and inflammation. Proinflammatory cytokines are considered as markers of T2DM and cardiovascular complications and are involved in the development of dyslipidemia and insulin resistance. The article provides an evaluation of NO-mediated signaling pathway in the effects of cytokines on platelet aggregation. The effects of the proinflammatory cytokines on functional activity of platelets are demonstrated.

Coronary artery disease (CAD) is the primary risk factor for heart failure (HF) development. Coronary artery bypass graft (CABG) surgery remains the gold-standard treatment for multivessel coronary artery disease. The purpose of this study was to identify predictors of cardiovascular events in patients after CABG by looking at clinical parameters, examining biomarkers of inflammation and fibrosis, and assessing patients’ adherence to heart failure therapy before CABG. The prospective observational study included consecutively hospitalized patients with HF and CAD eligible for CABG (n = 82). The study’s primary endpoint was a combination (MACE) of cardiac death, hospitalization with HF, acute ischemic events requiring unplanned revascularization, or stroke. The enzyme-linked immunosorbent assay was performed to assess serum levels of NGAL, GDF-15, NTproBNP, TGF beta, and hsCRP. The participants’ medication adherence level was assessed using the Morisky–Green scale. A total of 37 events were registered (45.1%) at follow-up (36 (26; 43) months). All patients were divided into two groups: Group 1 (n = 45) comprised patients without the combined endpoint, and Group 2 (n = 37) comprised patient who suffered adverse cardiovascular events. A high GDF-15 level and low adherence based on the Morisky–Green scale were independent predictors of a MACE at follow-up. The median time before the development of the MACE which was predicted based on Kaplan–Meier analysis in the group with a GDF-15 value less than 2064 pg/mL was 64 (50; 80) months, and in the group with a GDF-15 value more than or equal to 2064 pg/mL, it was 40 (34; 46) months (p < 0.001). Higher GDF-15 values and poor adherence to treatment are associated with adverse cardiovascular events in patients with HF and CAD who have undergone CABG. However, further studies are needed to support the use of GDF-15 as a prognostic marker in real-life clinical practice.

Background/Objectives: Biological aging phenotypes in coronary artery disease (CAD) include coronary atherosclerosis, vascular aging, and endothelial dysfunction. The aim of the present study was to investigate the potential links between aging phenotypes, regulatory immune cells, and features of the thymus in patients with CAD. Methods: A single-center, cross-sectional, comparative study was conducted. Patients were stratified according to the severity of coronary atherosclerosis: patients with a Gensini score ≥ 65 points and patients with a Gensini score < 65 points. Peripheral blood and thymus biopsy were obtained. Imaging flow cytometry, ELISA, and immunohistochemical analysis were used for analysis. Results: Thymic morphology ranged from total fatty involution to a preserved structure of the thymus (20–80% area in 31% of obtained samples) but was not associated with the severity of atherosclerosis. Meanwhile, patients with a Gensini score ≥ 65 had impaired thymus cellular composition compared to patients with a Gensini score < 65 points; increased frequency of CD8+ T lymphocytes and NK cells; and decreased frequency of CD4 + CD8+ T lymphocytes. In peripheral blood, the main determinants of a Gensini score ≥ 65 points were low absolute counts of eMDSCs and CD25^low Tregs with FoxP3 nuclear translocation, while advanced vascular aging was associated with elevated eMDSC absolute counts. Advanced coronary atherosclerosis was also associated with decreased numbers of endothelial progenitor cells in circulation. Conclusions: Thymus dysfunction accompanies CAD progression and is manifested in changes in cellular composition rather than morphology. In CAD patients, MDSC and Treg lymphocytes are equally involved in the progression of coronary atherosclerosis, which is aggravated by the decreased regulatory potential of the endothelium. Vascular aging represents a distinct phenotype of biological aging in CAD patients, characterized by the expansion of eMDSCs.

Возможности клинического применения нового биомаркера ST2 у больных с хронической сердечной недостаточностью ишемического генеза: тест с физической нагрузкой

Aim. To analyze the prognostic significance of clinical, anamnestic and paraclinical parameters in patients with heart failure with preserved ejection fraction (HFpEF) and non-obstructive coronary artery disease.Material and methods. The study included 54 patients. Cardiac and lung ultrasound was performed. In addition, the level of N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin-1β, interleukin-18, growth differentiation factor 15 (GDF-15), and cryopyrin was determined. The level of quality of life, anxiety and depression, and adherence to treatment were analyzed.Results. The patients were divided into 2 following groups: group 1 (n=22) with an unfavorable course and group 2 (n=32) with a favorable disease course. Basic echocardiographic parameters, as well as the number of B-lines in lungs, were comparable in both groups. An unfavorable HFpEF course was associated with a longer history of hypertension — 17,5 [10;20] and 7 [5;15] years (p=0,03), smoking — 36,4 and 9,4% (p=0,035), impaired carbohydrate metabolism — 54,5 and 15,6% (p=0,003) and lower adherence to treatment (p=0,02). In group 1, GDF-15 levels were higher than in group 2 — 1841 [1237;3552] vs 1709,5 [1158;2492] pg/ml (p=0,026).Conclusion. Low-intensity subclinical inflammation, the predisposing factors of which are smoking, impaired carbohydrate metabolism, and a long history of hypertension, is associated with higher GDF-15 values in patients with HFpEF and, along with low patient adherence to treatment, has an adverse effect on the clinical course of heart failure.

Aim.The purpose of this study was to examine the association of increasing concentrations of endothelin-1 and soluble forms of ST2 protein (sST2) in the blood plasma of patients with chronic heart failure (CHF) who underwent implantation of a cardioverter-defibrillator, with the development of cardiovascular events (death from cardiovascular diseases, decompensated CHF, acute coronary syndrome or acute ischemic stroke) to determine whether these biomarkers can be used as predictors of an unfavorable course of the disease.Material and methods. A 6-month cohort study included 40 patients with CHF who received an ICD 4-12 weeks before their inclusion in the study. At the beginning of the study the concentrations of endothelin-1 and sST2 in plasma by ELISA were analyzed, along with conventional diagnostic techniques typical of a specialized cardiology clinic.Results.Phenotype with a favorable course of the disease was identified in 21 patients (group 1), and with a unfavorable course was seen in 19 (group 2). The concentration of endothelin-1 and sST2 in the blood plasma of the 2nd group patients was higher than in patients of the 1st group. The link of cardiovascular events with high levels of soluble ST2 protein and endothelin-1 in blood plasma has been identified. Variation of the decision rule threshold on the ROC-curve has allowed sST2 concentration of 34.93 ng/ml to be determined as a cutoff point. Accuracy of two-class classification (determination of the posterior probability of cardiovascular events) after identifying such cut-off point was characterized by 93% sensitivity and 72% specificity (area under ROC-curve – 0.87). If the value of the plasma concentrations of sST2 more 34.93 ng/ml the relative risk of cardiovascular events was 4.4 (95% CI 1.7–11.1). The use of endothelin-1 surplus in plasma (cut-off point – 0.34 fmol/ml) in predicting cardiovascular events was lower: the sensitivity – 88%, specificity – 68% (area under ROC-curve – 0.74). When the concentration of endothelin-1 in blood plasma was more than 0.34 fmol/ml the relative risk of cardiovascular events was 2.7 (95% CI 1.2–6.3).Conclusion.The increase in the sST2 and endothelin-1 concentration in blood plasma may be considered as a predictor of cardiovascular events in CHF patients after implantation of cardioverter-defibrillator.