[Content of circulating endothelial progenitor cells in patients with chronic ischemic heart failure with preserved left ventricular ejection fraction].

PURPOSE: To assess content of various subpopulations of endothelial progenitor cells (EPC) with CD45-CD34+, CD14+CD309+ and CD14+CD309+Tie2+ phenotypes in patients with chronic heart failure (CHF) of ischemic origin with preserved left ventricular ejection fraction. MATERIAL AND METHODS: We included into the study 126 patients (54 men) aged 48-62 years with angiographically confirmed ischemic heart disease (IHD) and 25 healthy volunteers. Eighty two (65%) patients had NYHA class I-II CHF. Phenotyping of populations of mononuclear cells was performed by flow cytometry with the use of fluorochrome-labeled monoclonal antibodies. Circulating EPC were determined as CD45-CD34+. For identification of subpopulations of EPC coexpressing CD14 antigen we determined CD309(VEGFR2) and Tie2 antigens. RESULTS: In the group of patients with IHD level of circulating proatherogenic mononuclear cells of CD14+CD309+ and CD14+CD309+Tie2+ phenotype depended more on the presence of CHF and number of risk factors of cardiovascular complications (CVC) but not on severity and extent of coronary atherosclerosis. Most important independent predictors of lowering of circulating EPC with CD14+CD309+Tie2+ phenotype were CHF (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.12 to 1.88, p = 0.004), type 2 diabetes (OR 1.21, 95% Cl 1.10 to 1.40; p = 0.008), NT-proBNP > 154 rg/ml (OR 1.13, 95% Cl 1.04 to 1.18, p = 0.003), hyperlipidemia (OR 1.12, 95% CI 1.05 to 1.23, p = 0.005), and presence of ± 3 traditional cardiovascular risk factors (OR 1.31, 95% CL 1.12 to 1.49, p = 0.008). CONCLUSION: Negative impact of factors of risk of CVC relative to manifestation of ischemic CHF might by mediated by deficit of nonhemopoetic circulating EPC, mobilization of which from peripheral tissues if reduced at early stages of formation of myocardial dysfunction.

Impaired immune phenotype of circulating endothelial-derived microparticles in patients with metabolic syndrome and diabetes mellitus.

INTRODUCTION: Type two diabetes mellitus (T2DM) remains a leading contributor to cardiovascular mortality worldwide. This study was conducted to investigate the pattern of circulating EMPs in T2DM patients in comparison with MetS subjects. METHODS: The study retrospectively included 101 patients (54 subjects with T2DM and 47 patients with MetS) and 35 healthy volunteers. All the patients gave written informed consent for participation in the study. Biomarkers were measured at baseline of the study. RESULTS: There is a significant difference between healthy subjects and patients regarding CD31+/annexin V+ EMPs to CD62E+ EMPs ratio, which reflects impaired phenotype of EMPs. Therefore, CD31+/annexin V+ EMPs to CD62E+ EMPs ratio was found to be higher in the T2DM patients compared to MetS patients. Using multivariate linear regression analyses, independent impact of T2DM (r = 0.40, P = 0.003), OPG (r = 0.37, P = 0.001), hs-CRP (r = 0.347, P = 0.001), and adiponectin (r = 0.33, P = 0.001) on increased CD31+/annexin V+ to CD62E+ ratio of EMPs was determined. Using C-statistics, we found that inflammatory biomarkers (hs-C-reactive protein, osteoprotegerin and adiponectin) added to the base model (T2DM) improved the relative IDI by 12.6 % for increased CD31+/annexin V+ EMPs to CD62E+ EMPs ratio. CONCLUSION: We found that patients with T2DM and MetS may be distinguished by predominantly appearing phenotypes of circulating EMPs associated with pro-inflammatory cytokine overproduction. Elevated CD31+/annexin V+ EMPs to CD62E+ EMPs ratio is an indicator of impaired immune phenotype of EMPs, which allows determining the pattern of EMPs in dysmetabolic disorder patients.

Circulating osteopontin as a marker of early coronary vascular calcification in type two diabetes mellitus patients with known asymptomatic coronary artery disease.

OBJECTIVE: To evaluate the interrelation between circulating osteopontin (OPN) and coronary atherosclerosis and calcification in type 2 diabetes mellitus patients (T2DM). DESIGN AND METHODS: 126 subjects (46 patients with T2DM) with previously documented asymptomatic coronary artery disease (CAD) were enrolled in the study. CAD was determined by contrast multispiral CT-angiography. OPN plasma levels were measured by ELISA. RESULTS: Analysis of the results showed that in a patient cohort the mean value of circulating OPN was 43.55 ng/mL (95% CI = 31.5-57.0 ng/mL). OPN plasma levels were correlated with Agatston score index (r = 0.418, P = 0.009), T2DM (r = 0.411, P = 0.006), gender (r = 0.395, P < 0.001 for male), TC (r = 0.405, P = 0.006), hsC-RP (r = 0.368, P = 0.008), age (r = 0.256, P = 0.001), smoking (r = 0.255, P = 0.001) and inversely to LVEF (r = -0.579, P = 0.001). Cox-regression analyzes showed that in T2DM patients upper quartile OPN compared with the lowest quartile are associated with Agatston score index (adjusted OR = 3.23, 95% CI = 1.09-5.20; P = 0.044), numerous of damaged coronary arteries (adjusted OR = 2.60, 95% CI = 1.10-9.20, P = 0.005). The findings suggest that the predictive power of the model for asymptomatic CAD patients with T2DM, the estimated AUC (area under curve) was 0.788. In this case, the concentration of OPN that had the best predict potential on the risk of coronary atherosclerosis was 48.5 ng/mL. In conclusions, we believe that elevated OPN in plasma can be considered as an independent predictor of coronary calcification in T2DM patients with known CAD.

Serum uric Acid as a marker of coronary calcification in patients with asymptomatic coronary artery disease with preserved left ventricular pump function.

Objective. To evaluate the interrelation between serum uric acid and artery calcification in asymptomatic coronary artery disease subjects. Design and Methods. 126 subjects with previously documented asymptomatic coronary artery disease were enrolled in the study. Results. Mean value of serum uric acid level was 23.84 mmol/L (95% confidence interval (CI) = 15.75-31.25 mmol/L). In multivariate Cox regression analysis, the results showed that serum uric acid levels (odds ratio (OR) = 1.42, 95% CI = 1.20-1.82; P < 0.001), osteopontin (OR = 1.14, 95% CI = 1.12-1.25; P < 0.001), osteoprotegerin (OR = 1.45, 95% CI = 1.20-1.89; P < 0.001), type 2 diabetes mellitus (OR = 1.41, 95% CI = 1.20-1.72; P < 0.001), and total cholesterol (OR = 1.13, 95% CI = 1.10-1.22; P < 0.001) were factors that independently associated with coronary artery calcification. The Cox models suggested that high quartile of serum uric acid level is very significant in predicting Agatston score index. In conclusion, we suggested that high quartile of serum uric acid level (cutoff point equaled 35.9 mmol/L) was a very significant predictor of coronary calcification examined by Agatston score index in subjects with asymptomatic coronary artery disease.