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Circulating endothelial-derived apoptotic microparticles and insulin resistance in non-diabetic patients with chronic heart failure

  • Alexander E. Berezin , Alexander A. Kremzer , Giovanni Cammarota , Anthony Zulli , Daniel Petrovic , Nieves Martell-Claros , Jan Sabo and Peter Kruzliak EMAIL logo

Abstract

Background: The objective of this study was to assess the relationship between insulin resistance and apoptotic endothelial-derived microparticles (EMPs) in patients with chronic heart failure (CHF).

Methods: The study involved 300 CHF patients (186 males) aged 48–62 years with angiographically proven coronary artery disease and/or previously defined myocardial infarction. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). EMPs phenotype was determined by flow cytofluorometry.

Results: Depending on HOMA-IR cut-off point (over and <2.77 mmol/L×μU/mL) all patients were divided into two cohorts with (n=171) or without (n=129) IR, respectively. Circulating EMPs were higher in CHF patients with IR than in patients without IR. Interestingly, EMPs were directly related to NYHA functional class of CHF, HOMA-IR, NT-pro-BNP, hs-CRP and BMI. There was a significant association between the level of EMPs and HbA1c, gender (r=0.318, p<0.001 for male), age and smoking. On univariate and multivariate regression analysis we found that the NYHA class of CHF,NT-pro-BNP, hs-CRP, and left ventricular ejection fraction (LVEF) appeared to be independent predictors of increased circulatory apoptotic EMPs. The addition of HOMA-IR to the standard model (NYHA class CHF) improved the relative IDI by 19.9% for increased EMPs. For category-free NRI, 10% of events and 24% of non-events were correctly reclassified by the addition of HOMA-IR to the standard model for increased circulating EMPs.

Conclusions: IR may be a contributing factor increasing circulating levels of apoptotic EMPs in non-diabetic CHF patients.


Corresponding author: Dr. Peter Kruzliak, Faculty of Medicine, Department of Medical Physics and Biophysics, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovak Republic, E-mail: ; 2nd Department of Internal Medicine, St. Anne’s University Hospital and Masaryk University, Brno, Czech Republic; and 2nd Department of Surgery, St. Anne’s University Hospital and Masaryk University, Brno, Czech Republic

Acknowledgments

We thank all patients for their participation in the investigation, staff of the Regional Zaporozhye Hospital (Ukraine) and the doctors, nurses, and administrative staff in City Hospital #6 (Zaporozhye, Ukraine), general practices, and site-managed organizations that assisted with the study.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests:The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Ethical principles: All patients have given their written informed consent for participation in the study. The investigators strictly followed all the requirements for clinical trials in accordance with the World Medical Association Declaration of Helsinki, 1964, good clinical practice provided by the International Conference on Harmonisation, Council of Europe Convention for the Protection of Human Rights and Dignity of the Human Being in view of using achievements in biology and medicine, the convention on Human Rights and Biomedicine, including Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Biomedical Research, and legislation of Ukraine.

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Received: 2015-6-26
Accepted: 2015-10-17
Published Online: 2015-12-10
Published in Print: 2016-7-1

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