[Biomarkers of Inflammation in Predicting the Outcomes of Heart Failure of Ischemic Etiology: the Results of Factor Analysis].

AIM: To study the prognostic significance of inflammatory biomarkers in patients with chronic heart failure (CHF) and stenotic multivessel coronary atherosclerosis, with determination of the biomarker separate set that reflects subclinical inflammation and is associated with the development of cardiovascular complications during prospective observation. MATERIAL AND METHODS: A prospective observational study was conducted that included 80 patients with CHF and ischemic heart disease who were scheduled for coronary artery bypass grafting (CABG) during their current hospitalization. In addition to routine clinical laboratory tests, coagulation parameters were evaluated and the following inflammatory biomarkers were determined: neutrophil gelatinase-associated lipocalin (NGAL), growth/differentiation factor 15 (GDF-15), fibroblast growth factor 23 (FGF-23), transforming growth factor beta-1 (TGF-ß1), and high-sensitivity C-reactive protein. Also, the calculated neutrophil-to-lymphocyte ratio (N LR) was included in the analysis. Follow-up duration was at least 12 months (median 16 [13, 22] months). Statistical analysis of the data was performed with the IBM SPSS Statistics 21 software. RESULTS: The study presented results of a factor analysis of 10 inflammatory biomarkers in patients who were scheduled for CABG. One of the factors identified by the analysis included the levels of NGAL and GDF-15, N LR, and the level of fibrinogen in the blood in CHF patients with stenotic coronary atherosclerosis and was significantly associated with the death rate during prospective observation. Furthermore, this association remained significant even after adjustments for age, glomerular filtration rate, severity of heart and coronary insufficiency, and the presence of diabetes mellitus. CONCLUSION: In patients with CHF and stenotic coronary atherosclerosis, a set of inflammatory markers, including blood NGAL, GDF-15, N LR, and fibrinogen, can be combined into one factor reflecting subclinical inflammation. The value of this factor can be used to predict cardiovascular death in the long term after surgical myocardial revascularization.

Heart failure with preserved left ventricular ejection fraction in patients with obstructive sleep apnea syndrome: prognostic value of biomarkers.

Aim      To study the role of soluble ST2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), and С-reactive protein (CRP) in patients with chronic heart failure and preserved left ventricular ejection fraction (CHF with pLVEF) and syndrome of obstructive sleep apnea (SOSA) in stratification of the risk for development of cardiovascular complications (CVC) during one month of a prospective observation.Material and methods  The study included 71 men with SOSA with an apnea/hypopnea index (AHI) >15 per hour, abdominal obesity, and arterial hypertension. Polysomnographic study and echocardiography according to a standard protocol with additional evaluation of left ventricular myocardial fractional changes and work index were performed for all patients at baseline and after 12 months of observation. Serum concentrations of sST2 , NT-proBNP, and CRP were measured at baseline by enzyme-linked immunoassay (ELISA).Results The ROC analysis showed that the cutoff point characterizing the development of CVC were sST2 concentrations ≥29.67 ng/l (area under the curve, AUC, 0.773, sensitivity 65.71 %, specificity 86.11 %; p<0.0001) while concentrations of NT-proBNP (AUC 0.619; p=0.081) and CRP (AUC 0.511; р=0.869) were not prognostic markers for the risk of CVC. According to data of the ROC analysis, all patients were divided into 2 groups based on the sST2 cutoff point: group 1 included 29 patients with ST2 ≥29.67 ng/l and group 2 included 42 patients with ST2 <29.67 ng/l. The Kaplan-Meyer analysis showed that the incidence of CVC was higher in group 1 than in group 2 (79.3 and 28.6 %, respectively, p<0.001). The regression analysis showed that adding values of AHI and left ventricular myocardial mass index (LVMMI) to sST2 in the model increased the analysis predictive significance.Conclusion      Measuring sST2 concentration may be used as a noninvasive marker for assessment of the risk of CVC development in patients with CHF with pLVEF and SOSA within 12 months of observation. Adding AHI and LVMMI values to the model increases the predictive significance of the analysis.

Predictive value of laboratory markers in the development of cardiac events in patients with stable coronary artery disease after elective endovascular revascularization.

Aim      To reveal a relationship between preprocedural laboratory data and adverse cardiac outcomes (CO) in patients with stable ischemic heart disease (IHD) following elective endovascular revascularization (ER).Material and methods  This study included 225 patients with IHD admitted for treatment to the Research Institute of Cardiology of the Tomsk National Research Medical Center. The study included patients with documented IHD and hemodynamically significant coronary stenoses requiring elective ER. Patients were divided into groups based on the presence of complications: group 1, 98 patients with adverse CO and group 2, 127 patients without adverse CO. Besides evaluation of complaints, history, and objective status, general clinical and biochemical tests were performed for all patients. Concentration of glycated hemoglobin (НbА1с) was measured by immunoturbidimetry (DiaSys Diagnostic Systems). Serum concentrations of insulin, interleukin-6 (IL-6), endothelin 1 (ET-1), and homocysteine were measured by enzyme immunoassay. Blood lipid profile was determined by enzymatic colorimetry (DiaSys). Content of non-high-density lipoprotein (non-HDL) cholesterol (CS) was calculated as: CS - HDL CS. Insulin resistance (IR) was assessed by the HOMА-IR index. IR was diagnosed at the index of 2.77. Statistical analyses were performed with Statistica 10.0 and Medcalc 19.2.6 software.Results A one-way regression analysis identified predictors for adverse CO following ER. The most significant predictors were fibrinogen (odds ratio (OR), 1.430; 95 % confidence interval (CI), 1.027-1.990), HbA1c (OR 1.825; 95 % CI, 1.283-2.598), homocysteine (OR, 1.555; 95 % CI, 1.348-1.794), ET-1 (OR, 94.408; 95 % CI, 16.762-531.720), triglycerides (TG)/glucose ratio (OR 1.815; 95 % CI, 1.155-2.853). Based on selected factors, logistic regression models were constructed. However, not all models had a high prognostic power. Only concentrations of ET-1 and homocysteine showed a high prognostic capability in respect of the adverse outcome (88.3 and 85.7 %, respectively).Conclusion      For patients with IHD, the prognostic capability of ET-1 and homocysteine with respect of the risk for adverse CO following ER was the highest compared to other markers. The results of the study are completely consistent with data of literature and can be successfully used in clinical practice for optimizing the medical care of patients after elective ER.

Growth differentiation factor 15 associations with clinical features of chronic heart failure with midrange ejection fraction and preserved ejection fraction depending on the history of myocardial infarction.

Aim    To analyze associations between levels of the inflammatory marker, growth differentiation factor 15 (GDF-15), and echocardiographic indexes in CHF patients with mid-range and preserved left ventricular ejection fraction (LV EF) depending on the history of myocardial infarction (MI).Material and methods    This study included 34 CHF patients with preserved and mid-range LV EF after MI (group 1, n=19) and without a history of MI (group 2, n=15). Serum concentration of GDF-15 was measured with enzyme immunoassay (BioVendor, Czech Republic). Statistical analysis was performed with STATISTICA 10.0.Results    Patients of the study groups were age-matched [62 (58;67) and 64 (60;70) years, p=0.2] but differed in the gender; group 1 consisted of men only (100 %) whereas in group 2, the proportion of men was 53.3 % (p=0.001). Median concentration of GDF-15 was 2385 (2274; 2632.5) and 1997 (1534;2691) pg/ml in groups 1 and 2, respectively (p=0.09). Patients without MI showed a moderate negative correlation between LV EF and GDF-15 concentration (r= - 0.51, p=0.050) and a pronounced correlation between GDF-15 and LV stroke volume (r= -0.722, p=0.002). For patients after MI, a correlation between the level of GDF-15 and the degree of systolic dysfunction was not found (р>0.05).Conclusion    Blood concentration of the inflammatory marker, GDF-15, correlates with LV EF and stroke volume in CHF patients with preserved or mid-range LV EF and without a history of MI while no such correlations were observed for patients with a history of MI.

Research of spontaneous and stimulated functional activity of platelets in patients with different types of atrial fibrillation.

Platelet function testing is widely used to diagnose disorders of the cellular link of hemostasis. The study of platelet aggregation activity is relevant for the prevention of thromboembolic complications in atrial fibrillation and monitoring the effectiveness and safety of therapy. In this study, a comparative analysis of spontaneous and stimulated platelet aggregation in groups of patients with two types of atrial fibrillation was performed - paroxysmal and persistent. The effect of ß-adrenoblocker therapy on platelet aggregation activity in patients with atrial fibrillation was also studied. Platelet aggregation activity was studied using the method of G. Born in the modification of Z.A. Gabbasov on a two-channel laser analyzer "Biola". Collagen at a concentration of 2 mg / ml and adrenaline in a concentration range of 2.5-10 µg / ml were used as aggregation-promoting agents. It has been established that spontaneous aggregation potential and collagen-induced platelet aggregation depend on the type of atrial fibrillation, as well as on the presence or absence of ß-blockers in therapy. The response of platelets to stimulation with adrenaline depends, first of all, on the type of atrial fibrillation and the concentration of adrenaline in the reaction medium. The most significant changes were noted in the group of patients with a paroxysmal form atrial fibrillation, taking ß-blockers in therapy.

Prognostic role of ST2 in patients with chronic heart failure of ischemic etiology and carbohydrate metabolism disorders.

AIM: To study the role of soluble ST2 (sST2) in patients with coronary artery disease (CAD) and chronic heart failure (CHF) associated with carbohydrate metabolism disorders (impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) in risk stratification of adverse cardiovascular events (ACE) for 12 months of follow-up. MATERIALS AND METHODS: We enrolled 118 patients with CAD and CHF I-III FC (NYHA) with the ejection fraction of left ventricular of 60 [46; 64] % aged 62.5 [57; 68] years. Serum sST2 levels were measured by enzyme immunoassay. RESULTS: Depending on the presence of carbohydrate metabolism disorders (CMD), the patients were divided into 3 groups: group 1 (n=65) included patients without CDM, group 2 (n=30) included with IGT, and group 3 (n=23) included with type 2 DM. Serum levels of sST2 in patients with CMD were significantly (p=0.011) higher than in patients without CMD, but in subgroups of patients with IGT and type 2 DM, the concentrations of sST2 did not differ. In group 1 sST2 levels were 30.51 [26.38; 37.06] ng/ml, and in group 2 and 3 - 37.97 [33.18; 47.48] and 41.45 [35.27; 50.37] ng/ml, respectively. There were statistically significant differences in the rate of adverse ACE in relation to sST2 levels: in spite of CMD, in subgroups with biomarker overexpression adverse CCC occurred more often (p<0.01). According to the ROC analysis, the sST2 level of 33.14 ng/ml with the sensitivity of 73.3% and the specificity of 75.0% can be considered as a marker of ACE development within 12 months of follow-up (AUC=0.77, 95% CI 0.59-0.89, p=0.002). CONCLUSION: In patients with CHF of ischemic etiology, the prognostic significance of sST2 are established as a biomarker of ACE development. In patients with CDM, sST2 levels are significantly higher than in those without CDM that is associated with a higher rate of ACE within 12 months of follow-up.

[Role of ST2 biomarker for the evaluation of myocardial remodeling in patients with ischemic heart failure with preserved ejection fraction].

AIM: 1) To study the role of soluble ST2 (sST2) in evaluation of left ventricular (LV) myocardial remodeling and 2) to evaluate the predictive value of sST2 for development of adverse cardiovascular events (CVE) during 12 months following myocardial revascularization in patients with ischemic heart disease (IHD) and chronic heart failure (CHF) with preserved LV ejection fraction (EF). MATERIALS AND METHODS: The study included 55 patients (42 men) with IHD and NYHA FC I-III CHF with LV EF 63 [59; 65] % aged 65 [58; 69] who were scheduled for myocardial revascularization. Echocardiographic evaluation of myocardial stress and myocardial remodeling indexes was performed for all patients. Content of sST2 was measured using enzyme immunoassay. RESULTS: Group 1 included patients with sST2 overexpression (≥35 ng/ml) (n=26; sST2-43.75 ng/ml) and group 2 - patients with the sST2 expression.

Effect of insulin on NO production by monocytes from patients with metabolic cardiovascular syndrome.

Basal and insulin-induced production of NO by monocytes significantly increased in patients with metabolic cardiovascular syndrome. Plasma insulin concentration in these patients was below the control. No intergroup differences were found in C-peptide concentration. A negative correlation was revealed between insulin-induced NO production by monocytes and C-peptide/insulin ratio in patients. The role of monocytes on the regulation of vascular tone via NO production in patients with metabolic cardiovascular syndrome is discussed.