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

Abstract

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.

Serum uric acid as a metabolic regulator of endothelial function in heart failure

“…Consequently, uric acid may consider as an endogenous regulator of vascular repair system that undoubtedly opens new sign on the role of uric acid metabolism as integrative asset explaining an impact of various comorbidities on a risk of HF manifestation. As an evidence of the opinion it has been allowed presenting data, which confi rm higher predictive value of elevated SUA in HF patients beyond etiology of disease, cardiac pump function, traditional risk factors and estimated glomerular fi ltration rate [24][25][26]. Interestingly, large numbers of clinical and observational studies have shown that elevated SUA levels are associated with reduced survival in in-patients and outpatients with several phenotypes of chronic HF, as well as in acute / actually decompensated HF [27][28][29].…”

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“…Acting through several intracellular pro-survival regulators (hypoxia induced factor-1α, Akt / eNOS signaling) EPC-depending cytokines are able mediate cytoprotective effects on the target cells in injured tissues [9]. In this context, CV risk factors including diabetes, obesity, impaired fasting glucose, hypothyroidism, hyperurikemia may induce EPC dysfunction determined as lowering EPC number and weak their functionality [10][11][12][13]. As a result EPC dysfunction may precedes manifesting endothelial dysfunction and CV diseases through worsening vascular repair capability [9,14].…”

“…In this context, CV risk factors including diabetes, obesity, impaired fasting glucose, hypothyroidism, hyperurikemia may induce EPC dysfunction determined as lowering EPC number and weak their functionality [10][11][12][13]. As a result EPC dysfunction may precedes manifesting endothelial dysfunction and CV diseases through worsening vascular repair capability [9,14]. On the other hand, EPC dysfunction could preview CV diseases and even CV risk factors, although there is no a clear explanation of the phenomenon [14][15][16].…”

“…As a result EPC dysfunction may precedes manifesting endothelial dysfunction and CV diseases through worsening vascular repair capability [9,14]. On the other hand, EPC dysfunction could preview CV diseases and even CV risk factors, although there is no a clear explanation of the phenomenon [14][15][16]. Probably epigenetic dysregulation is a main cause leading to both lowered number and weak function of EPCs prior to influencing traditional CV risk factors [17].…”

“…Consequently, early outgrow EPCs may produce slightly broad spectrum of pro-angiogenic and angiopoetic cytokines including VEGF and interleukin (IL)-6 [19,20]. Indeed, an exhaustion of circulating number of EPCs labeled as CD34+ and / or CD133+, AC133+, endothelial cell markers (CD309, CD31, CD 144) was found in patient with atherosclerosis, cardiac dysfunction, myocardial infarction / acute coronary syndrome, hypertension, diabetes mellitus, thyroid dysfunction [14,15,[23][24][25]. However, there are several controversies regarding the role of different immune phenotypes of EPCs in tissue reparation.…”