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

Alexander E. Berezin 1 , Alexander A. Kremzer 2 , Giovanni Cammarota 3 , Anthony Zulli 4 , Daniel Petrovic 5 , Nieves Martell-Claros 6 , Jan Sabo 7 , and Peter Kruzliak
  • 1 Internal Medicine Department, State Medical University, Zaporozhye, Ukraine
  • 2 Clinical Pharmacology Department, State Medical University, Zaporozhye, Ukraine
  • 3 Division of Internal Medicine and Gastroenterology, Catholic University of Sacred Heart, A. Gemelli Medical School, Rome, Italy
  • 4 The Centre for Chronic Diseases (CCD), College of Health and Biomedicine, Victoria University, St Albans, Australia
  • 5 Faculty of Medicine, Institute of Histology and Embryology, University of Ljubljana, Ljubljana, Slovenia
  • 6 Unit of Hypertension, Área de Prevención Cardiovascular, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
  • 7 Faculty of Medicine, Department of Medical Physics and Biophysics, Pavol Jozef Safarik University, Kosice, Slovak Republic
  • 8 2nd Department of Internal Medicine, St. Anne’s University Hospital and Masaryk University, Brno, Czech Republic
  • 9 2nd Department of Surgery, St. Anne’s University Hospital and Masaryk University, Brno, Czech Republic
Alexander E. Berezin, Alexander A. Kremzer, Giovanni Cammarota, Anthony Zulli, Daniel Petrovic, Nieves Martell-Claros, Jan Sabo and Peter Kruzliak

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.

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