The CirculatingVE-catherin as Predictor of Poor Outcomes in Patients with Ischemic Chronic Heart Failure

Review Article

J Dis Markers. 2015;2(1): 1017.

The CirculatingVE-catherin as Predictor of Poor Outcomes in Patients with Ischemic Chronic Heart Failure

Alexander E Berezin1*, Alexander A Kremzer2, Yulia V Martovitskaya3, Tatayna A Samura2 and Tatyana A Berezina4

1State Medical University, Internal Medicine Department, Zaporozhye, Ukraine

2State Medical University, Clinical Pharmacology Department, Zaporozhye, Ukraine

3State Medical University, Pathology Department, Zaporozhye, Ukraine

4Private center “VITA CENTER”, Zaporozhye, Ukraine

*Corresponding author: Alexander E Berezin, Internal Medicine Department, State Medical University, Ukraine

Received: December 27, 2014; Accepted: January 27, 2015; Published: January 29, 2015


Aim: To evaluate the predictive value of circulating VE-catherin for cumulative cardiovascular outcomes in patients with chronic heart failure (CHF).

Methods: A total of 388 patients with CHF were enrolled in the study on discharge from the hospital. Observation period was up to 3 years. Blood samples for biomarkers measurements were collected. ELISA method for measurements of circulating level of CD144 (VE-catherin) was used. Concentrations of VEcatherin for cumulative cardiovascular outcomes were tested.

Results: Median follow-up was of 2.32 years (IQR=1.8-3.0). During followup, 110 cardiovascular events (including 43 fatal cases) were determined. Thirty five patients were died due to advance of CHF, and eight cases of death were related with suddenly death, fatal myocardial infarction, and systemic thromboembolism. Therefore, 74 subjects were readmitted in the hospital due to worsening CHF and 16 subjects were readmitted due to other cardiovascular reasons. Medians of circulating levels of VE-catherin in both patient cohorts (without and with experienced clinical outcomes) were 0.63 ng/mL (iterquartile range [IQR] = 0.55-0.64 ng/mL) and 1.03 ng/ml (IQR = 0.97-1.07 ng/mL) (P<0.001). Receive Operation Curve analysis has shown that the best balanced the cut-off of VE-catherin concentration for combined cardiovascular events was 0.755ng/ml. A significantly divergence of Kaplan-Meier curves in high VE-catherin patients (>0.755ng/ml) and low VE-catherin (<0.755 ng/ml) was reported. Multivariate age-adjusted Cox regression shown that NYHA class, VEcatherin, NT-pro-BNP and LVEF remained independent predictors for combined cardiovascular events, whereasT2DM and hs-CRP did not.

Conclusion: We found that increased circulating VE-catherin associated with increased three-year combined cardiovascular events among patients with CHF. Adding VE-catherin level to NT-pro BNP and NYHA class sufficient improve the prediction of standard model of CHF.

Keywords: VE-catherin; Chronic heart failure; Cardiovascular outcomes; Prognosis


Chronic heart failure (CHF) is considered a leading cause of morbidity and mortality worldwide [1]. Nature evolution of CHF associates with endothelial dysfunction that is result in shear stress disorders on endothelium. However, several factors, such as angiotensin-aldosterone system activation, oxidative stress, inflammatory response, exaggerated extracellular matrix remodelling in vasculature, degradation of vasodilators, etc. are referred as causality modulator of endothelial dysfunction [2]. There are evidences regarding pivotal role of endothelial dysfunction in cardiovascular mortality in patients with CHF especially ischemic origin [3]. Therefore endothelial dysfunction predicts cardiovascular outcomes independent of conventional cardiovascular risk factors [3]. Mechanical interaction of endothelial cells (ECs) mediated by blood flow may lead to junction of vascular remodelling [4]. Particularly this phenomenon is realized by involvement of junctional protein vascular endothelial-cadherin (VE-cadherin) that is essential for supporting endothelial function [5]. Currently VE-cadherin is considered a component of endothelial cell-to-cell adherence junctions and it has a key role in the maintenance of vascular integrity [6]. The mechanisms of action of VE-cadherin are complex and include reshaping and organization of the ECs cytoskeleton and modulation of gene transcription [6]. Therefore, VE-cadherin mediates cell adhesion and monolayer integrity, regulates angiogenesis and actin-driven to be support a mechanical capacity of endothelium after activation by soluble vascular cell adhesion molecules [7]. There is currently evidence affected VE-cadherin as a marker of endothelial dysfunction in several settings including CHF [8]. Therefore, several factors may modulate CHF evolution, such as ischemia. We tested hypothesis that VE-cadherin added to traditional biomarkers may improve a risk stratification of the patients with ischemic-induced CHF, although VE-cadherin alone probably has not a predictive value. However, the prognostic value of circulating VE-catherin in CHF has not defined. The objective of this study was to evaluate the prognostic value of circulating VE-catherin for combined cardiovascular events in patients with chronic heart failure.


The study population consisted of 388 consecutive patients with CHF who were reposted myocardial infarction or underwent quantitative coronary artery angiography or PCI between April 2010 to June 2014 (Figure 1). All these patients were selected after reviewing 1427 discharge reports obtained from persons who were treated in Zaporozhye Regional Hospital, City Hospital #6, City Hospital #10, Zaporozhye Regional Center of Cardiovascular Diseases and Private center “VITA CENTER” with primary diagnosis ischemic heart disease. One hundred fifthly five subjects were excluded due incompliance of the study protocol because of no documented ischemic heart disease was presented, which was determined when exiting myocardial infarction and/ or stenosis of coronary arteries were found. Among 1272 discharge reports were enrolled data regarding 388 patients with ischemic-induced CHF diagnosed according to current clinical guidelines [8]. Patients with severe kidney and liver diseases; malignancy; creatinine plasma level above 440μmol/L; estimated GFR index< 35 ml/min/м2; brain injury within 3 months before the enrollment; pulmonary edema; tachyarrhythmia; valvular heart disease; thyrotoxicosis; ischemic stroke; intracranial hemorrhage; acute infections; surgery; trauma; all the ischemic events within 3 previous months; inflammations within a previous month; pregnancy; implanted pacemaker, any disorder that may discontinue patient’s participation in the study according to investigators were excluded from the study.