BackgroundChronic heart failure (HF) remains a leading cause of cardiovascular (CV) mortality and morbidity worldwide. The aim of the study was to investigate whether the pattern of angiogenic endothelial progenitor cells (EPCs) and apoptotic endothelial cell-derived microparticles (EMPs) would be able to differentiate HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction.MethodsOne hundred sixty four chronic HF subjects met inclusion criteria. Patients with global left ventricular ejection fraction ≥ 50% were categorized as the HFpEF group (n = 79) and those with ≤ 45% as the HFrEF group (n = 85). Therefore, to compare the circulating levels of biological markers 35 control subjects without HF were included in the study. All control individuals were age- and sex-matched chronic HF patients. The serum level of biomarkers was measured at baseline. The flow cytometric technique was used for predictably distinguishing circulating cell subsets depending on expression of CD45, CD34, CD14, Tie-2, and CD309 antigens and determining endothelial cell-derived microparticles. CD31+/annexin V+ was defined as apoptotic endothelial cell-derived MPs, MPs labeled for CD105+ or CD62E+ were determined as MPs produced due to activation of endothelial cells.ResultsIn multivariate logistic regression model T2DM (R2 = 0.26; P = 0.001), obesity (R2 = 0.22; P = 0.001), previous MI (R2 = 0.17; P = 0.012), galectin-3 (R2 = 0.67; P = 0.012), CD31+/annexin V+ EMPs (R2 = 0.11; P = 0.001), NT-proBNP (R2 = 0.11; P = 0.046), CD14+ CD309+ cells (R2 = 0.058; P = 0.001), and CD14+ СD309+ Tie-2+ cells (R2 = 0.044; P = 0.028) were found as independent predictors of HFpEF. Using multivariate Cox-regression analysis adjusted etiology (previous myocardial infarction), cardiovascular risk factors (obesity, type 2 diabetes mellitus) we found that NT-proBNP (OR 1.08; 95% CI = 1.03–1.12; P = 0.001) and CD31+/annexin V+ EMPs to CD14+ CD309+ cell ratio (OR 1.06; 95% CI = 1.02–1.11; P = 0.02) were independent predictors for HFpEF.ConclusionWe found that CD31+/annexin V+ EMPs to CD14+ CD309+ cell ratio added to NT-proBNP, clinical data, and cardiovascular risk factors has exhibited the best discriminate value and higher reliability to predict HFpEF compared with NT-proBNP and clinical data/cardiovascular risk factors alone.

BackgroundChronic heart failure (CHF) has been remained a leading cause of cardiovascular morbidity and mortaluty. The risk stratification of CHF individuals based on clinical criteria and biomarkers' models may improve medical care and probably increase efficacy of treatment strategy. However, various predictive models approved for CHF patients appear to be distinguished in their prognostications. The study aim was to evaluate whether biomarker risk prediction score is powerful tool for risk assessment of three-year fatal and non-fatal cardiovascular events in CHF patients.MethodsIt was studied prospectively the incidence of fatal and non-fatal cardiovascular events in a cohort of 388 patients with ischemic-induced CHF within 3 years. Circulating biomarkers were collected at baseline of the study.ResultsIndependent predictors of clinical outcomes in patients with CHF were NT-pro-BNP, galectin-3, hs-CRP, osteoprotegerin, CD31+/annexin V+ endothelail-derived microparticles (EMPs) and CD31+/annexin V+ EMPs to CD14+CD309+ monuclear progenitor cells (MPCs) ratio. Index of cardiovascular risk was calculated by mathematical summation of all ranks of independent predictors, which occurred in the patients included in the study. Kaplan-Meier analysis showed that patients with CHF and the magnitude of the risk of less than 4 units have an advantage in survival when compared with patients for whom obtained higher values of cardiovascular risk score ranks.ConclusionBiomarker risk score for cumulative cardiovascular events, constructed by measurement of circulating NT-pro-BNP, galectin-3, hs-CRP, osteoprotegerin, CD31+/annexin V+ EMPs and CD31+/annexin V+ EMPs to CD14+CD309+ MPCs ratio, allowing reliably predict the probability survival of patients with CHF.

AimThe study aim was to evaluate whether circulating microparticles with apoptotic or non-apoptotic phenotypes are useful for risk assessment of 3-year cumulative fatal and non-fatal cardiovascular events in CHF patients.MethodsThe incidence of fatal and non-fatal cardiovascular events, as well as the frequency of occurrence of death from any cause in a cohort of 388 patients with CHF during 3 years of observation was studied prospectively. Circulating levels of NT-pro brain natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), and endothelial apoptotic microparticles (EMPs) were measured at baseline.ResultsMedian follow-up was 2.32 years (IQR = 1.8–3.1). During follow-up, 110 cardiovascular events (including 43 fatal cases) were determined. Additionally, 74 subjects were hospitalized repetitively due to worsening CHF and also 16 subjects were readmitted in the hospital due to other cardiovascular reasons. In the univariate logistic regression analysis, the main factors independently related with cumulative endpoints were creatinine, fasting glucose, HbA1c, total cholesterol, uric acid, various types of EPMs, NT-pro-BNP, hs-CRP, NYHA class, decreased left ventricular ejection fraction (LVEF) less 45%, and type 2 diabetes mellitus. In multivariate model NYHA class, decreased LVEF (less 45%), NT-pro-BNP, hs-CRP, CD144 +/CD31 +/annexin V + EMPs, and CD31 +/annexin V + EMPs remained statistically significant for cumulative endpoint. Adding of CD144 +/CD31 +/annexin V + EMCs and CD31 +/annexin V + EMCs to the standard ABC model may improve the relative IDI for cumulative endpoint by 11.4% and 10.5% respectively.ConclusionApoptotic phenotype of circulating microparticles may relate 3-year combined clinical outcomes in CHF patients.

We demonstrated that EMP to MPC ratio is considered an important indicator of an imbalance between angiogenic and apoptotic responses with possible relation to cardiovascular outcomes in post-discharge patients with clinical stabilization after ischemic ADHF.

BackgroundThe role of pattern of circulating endothelial cell-, platelet-, and monocyte-derived microparticles in metabolic syndrome (MetS) patients with chronic heart failure (CHF) is not still understood.The aim of the study was to investigate a pattern of circulating MPs in MetS patients with CHF in relation to neurohumoral and inflammatory activation.MethodsThe study retrospectively involved 101 patients with MetS (54 subjects with CHF and 47 patients without CHF) without documented coronary artery stenosis > 50% at least of one artery and 35 healthy volunteers. Biomarkers were measured at baseline of the study. Circulating MPs were phenotyped by flow cytometry technique.ResultsThe results of the study have shown that numerous of the circulating platelet-derived and monocyte-derived MPs in subjects with MetS (with or without CHF) were insufficiently distinguished from the level obtained in healthy volunteers. We found an elevated level of CD31 +/annexin V + MPs in association with a lower level of CD62E + MPs. All these led to decreased CD62E + to CD31 +/annexin V + ratio among patients with MetS in comparison with healthy volunteers, as well as in MetS patients with CHF compared with those who did not demonstrated CHF. Therefore, we found that biomarkers of biomechanical stress (NT-proBNP) and inflammation (hs-CRP, osteoprotegerin) remain statistically significant predictors for decreased CD62E + to CD31 +/annexin V + ratio in MetS patients with CHF.In conclusion, decreased CD62E + to CD31 +/annexin V + ratio reflected impaired immune phenotype of MPs may be discuss surrogate marker of CHF development in MetS population.

Metabolic syndrome (MetS) is defined as cluster of multiple metabolic and cardiovascular (CV) abnormalities included abdominal obesity, high-normal blood pressure, dyslipidaemia, and impaired fasting glucose tolerance that exhibits has a growing prevalence worldwide. We investigated whether an elevated level of osteoprotegerin (OPG) predicts imbalance between different phenotypes of circulating endothelial (EPCs) and mononuclear (MPCs) progenitor cells in MetS patients. We have analyzed data regarding dysmetabolic disorder subjects without known CV disease), as well as with known type two diabetes mellitus. All patients have given their informed written consent for participation in the study. This article contains data on the independent predictors of depletion in numerous of circulating EPCs and MPCs in MetS patients. The data are supplemental to our original research article describing detailed associations of elevated OPG level in MetS patients with numerous of EPCs and MPCs beyond traditional CV risk factors.

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Introduction: Serum uric acid (SUA) is considered a marker for natural progression of chronic heart failure (CHF) mediated cardiovascular remodelling. CHF associates with declining of circulating mononuclear progenitor cells (MPCs). The objective of this study was to evaluate the interrelationship between SUA concentrations and proangiogenic MPCs in ischemic CHF patients. Methods: The study population was structured retrospectively after determining the coronary artery disease (CAD) by contrast-enhanced spiral computed tomography angiography in 126 subjects with symptomatic ischemic mild-to-severe CHF and 128 CAD subjects without CHF. Baseline biomarkers were measured in all patients. Cox proportional multivariate hazard ratio was calculated for predictors of MPCs declining in both CHF and non-CHF patient population predictors of MPCs declining in CHF subjects were examined in stepwise logistic regression. C-statistics, integrated discrimination indices (IDI) and net-reclassification improvement were utilized for prediction performance analyses. Results: Cox proportional adjusted hazard ratio analyses for CD14+CD309+ and CD14+CD309+Tie2+ MPCs by SUA has shown that the higher quartiles (Q3 and Q4) of SUA compared to the lower quartiles (Q1 and Q2) are associated with increased risks of depletion of both CD14+CD309+ and CD14+CD309+Tie2+ MPCs. The addition of Q4 SUA to the ABC model improved the relative IDI by 13.8% for depletion of CD14+CD309+ MPCs and by 14.5% for depletion of CD14+CD309+Tie2+ MPCs. Conclusion: Circulating levels of proangiogenic MPCs are declined progressively depending on the levels of SUA in the HF subjects with CHF. We suggest that even mild elevations of SUA might be used to predict of relative depletion of proangiogenic MPCs among chronic HF patients.