Predictive value of apoptotic microparticles to mononuclear progenitor cells ratio in advanced chronic heart failure patients

AbstractBackgroundAcutely decompensated chronic heart failure (ADHF) is considered a life-threatening event. Despite contemporary treatment strategies of ADHF, frequent recurrent hospitalizations due to other cardiovascular reasons after discharge of patients from hospital occur. The objective of the study was to examine the prognostic value of circulating endothelial-derived apoptotic microparticles (EMPs) to mononuclear progenitor cells (MPCs) ratio for post-discharge patients with clinical stabilization after ischemic ADHF.MethodsWe consecutively enrolled 136 patients (62 male) with coronary artery disease (CAD) admitted with a primary diagnosis of ADHF. All patients gave written informed consent for participation in the study. At baseline, all enrolled patients were hemodynamically stable and they had New York Heart Association (NYHA) III/IV classes of ischemic chronic heart failure (CHF). Observation period started at discharge from the hospital and was up to 3 years. Flow cytometry analysis for quantifying the number of EMPs and angiogenic MPCs was used.ResultsCalculated EMP to MPC ratios in survivor and dead patient cohort were 8.4 (95% CI=7.6–9.2) and 78.9 (95% CI=53.0–116.6), respectively (p=0.001). MPCs, EMPs, NYHA class, N-terminal pro-brain natriuretic peptide (NT-proBNP) and increased NT-proBNP>30% within 24–84h of admission period remained statistically significant for all-cause mortality, CHF-related death, and CHF-related rehospitalization, whereas left ventricular ejection fraction and high-sensitivity C-reactive protein for all variables did not. We found that the addition of EPMs to MPCs ratio to the ABC model (NT-pro-BNP, increased NT-pro-BNP>30%) improved the relative integrated discrimination indices by 19.6% for all-cause mortality, by 21.7% for CHF-related death, and by 19.5% for CHF-related rehospitalization.ConclusionWe 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

Links between biota and climate-related variables in the Baltic region using Lake Onega as an example**This work was supported by Biodiversity Bioresources Programmes grants from the Russian Academy of Sciences.

AbstractThis paper aims to reveal current changes (recent decades) in regional climatic variables like water temperature (WT), the duration of the ice-free period (ICE-FREE) and the precipitation rate (P), as exemplified by Petrozavodsk Bay (Lake Onega, European Russia), and to analyse their relationships with the global climatic indices NAO, AO and structural characteristics of biota (chlorophyll a concentration (Chl a), phytoplankton and zoobenthos abundance/biomass) in the lake ecosystem, which lies within the Baltic Sea catchment area. Spearman’s rank correlations yielded significant (p<0.05) relationships between the NAO and planktonic Cyanobacteria abundance, and also between NAO, AO, WT, P and the abundance and biomass of zoobenthos. Chl a correlates positively (R=0.66; p=0.03) with WT and negatively with ICE-FREE (R=−0.53; p=0.05). At the same time, multiple regression analysis confirmed that the global climate governs primarily the regional climatic variables and productivity level in the lake’s ecosystem, whereas most of the biotic characteristics respond to variability in the regional climate

Serum Uric Acid Predicts Declining of Circulating Proangiogenic Mononuclear Progenitor Cells in Chronic Heart Failure Patients

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

The predictive role of circulating microparticles in patients with chronic heart failure

Aim: The 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. Methods: The 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. Results: Median 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. Conclusion: Apoptotic phenotype of circulating microparticles may relate 3-year combined clinical outcomes in CHF patients

The association of subclinical hypothyroidism and pattern of circulating endothelial-derived microparticles among chronic heart failure patients

Background: Subclinical hypothyroidism (SH) is diagnosed biochemically by the presence of normal serum free thyroxine concentration, in conjunction with an elevated serum thyroid-stimulating hormone level. Recent studies have demonstrated the frequent association between SH and cardiovascular diseases and risk factors. Objectives: To evaluate the impact of SH on patterns of circulating endothelial-derived microparticles, (EMPs) among chronic heart failure (CHF) patients Patients and Methods: This is a retrospective study involving a cohort of 388 patients with CHF. Fifty-three CHF subjects had SH and 335 patients were free from thyroid dysfunction. Circulating levels of N-terminal-pro brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), thyroid-stimulating hormone (TSH), total and free thyroxine (T4), and triiodothyronine (T3), and endothelial apoptotic microparticles (EMPs), were measured at baseline. SH was defined, according to contemporary clinical guidelines, as a biochemical state associated with an elevated serum TSH level of greater 10 μϋ/L and normal basal free T3 and T4 concentrations. Results: Circulating CD31+/annexin V+ EMPs were higher in patients with SH compared to those without SH. In contrast, activated CD62E+ EMP numbers were not significantly different between both patient cohorts. Using uni (bi) variate and multivariate age- and gender- adjusted regression analysis, we found several predictors that affected the increase of the CD31+/annexin V+ to CD62E+ ratio in the patient study population. The independent impact of TSH per 6.5 μϋ/L (odds ratio [OR] = 1.23, P = 0.001), SH (OR=1.22, P = 0.001), NT-proBNP (OR= 1.19, P = 0.001), NYHA class (OR=1.09, P = 0.001), hs-CRP per 4.50 mg/L (OR = 1.05, P = 0.001), dyslipidemia (OR=1.06, P = 0.001), serum uric acid per 9.5 mmol/L (OR=1.04, P = 0.022) on the increase in the CD31+/annexin V+ to CD62E+ ratio, was determined. Conclusions: We believe that the SH state in CHF patients may be associated with the impaired pattern of circulating EMPs, with the predominantly increased number of apoptotic-derived microparticles

Links between concentrations of serum 25-hydroxyvitamin D3 and the numbers of circulating progenitor mononuclear cells in patients with metabolic syndrome

Background: Evidence points to the pivotal role of vitamin D in the pathogenesis of metabolic syndrome (MetS), including deterioration of the endogenous endothelial repair system. Objectives: This study was conducted to investigate links between serum 25-hydroxyvitamin D3 (25(OH)3D) concentrations and the numbers of circulating progenitor mononuclear cells in MetS individuals. Methods: The cross-sectional study involved 47 patients with MetS. The circulating level of 25(OH)D3 and other biomarkers were measured at the start of the study. The number of mononuclear progenitor cells was determined using the flow cytometric technique (FCT). Results: MetS patients from the entire group of 47 patients were divided into four cohorts depending on 25(OH)D3 levels. The groups comprised patients with 25(OH)D3 levels above 100 nmol/L (n = 10), patients with levels from 50 to 100 nmol/L (n = 12), patients with levels from 30 to 50 nmol/L (n = 14), and patients with levels below 30 nmol/L (n = 11). There were significant differences between the MetS cohorts in terms of haemoglobin A1c (HbA1c) (P = 0.038), the homeostasis model assessment for insulin resistance (HOMA-IR) (P = 0.042), triglycerides (P = 0.044), osteoprotegerin (P=0.028), adiponectin (P = 0.018), high density lipoprotein cholesterol (HDL-C) (P=0.036), and CD14+D309+Tie-2+ cells. Vitamin D deficiency in a multivariate log-linear regression model appeared to be an independent predictor of the numbers of CD14+D309+ Tie-2+ cells (OR 1.12; 95% CI 1.06 to 1.19; P = 0.002). Osteoprotegerin, high sensitivity C-reactive protein (hs-CRP), and adiponectin have been shown to make an independent impact on the numbers of CD14+D309+ Tie-2+ cells. Using C-statistics, we found that the use of three biomarkers (osteoprotegerin, hs-CRP, and adiponectin) can significantly improve a predictive model based on vitamin D deficiency for decreased numbers of CD14+ D309+Tie-2+ cells. Conclusions: We found that low levels of 25(OH)D3 were associated with depleted numbers of proangiogenic progenitor mononuclear cells in MetS patients

Pattern of circulating microparticles in chronic heart failure patients with metabolic syndrome: Relevance to neurohumoral and inflammatory activation

Background: The 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. Methods: The 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. Results: The 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

Data regarding association between serum osteoprotegerin level, numerous of circulating endothelial-derived and mononuclear-derived progenitor cells in patients with metabolic syndrome

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. Keywords: Metabolic syndrome, Osteoprotegerin, Circulating endothelial derived progenitor cells, Mononuclear-derived progenitor cell

Pattern of endothelial progenitor cells and apoptotic endothelial cell-derived microparticles in chronic heart failure patients with preserved and reduced left ventricular ejection fraction

Background: Chronic 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. Methods: One 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. Results: In 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. Conclusion: We 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