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.
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.
1. Santulli G. Epidemiology of cardiovascular disease in the 21st century: updated numbers and updated facts. JCvD 2013;1:1–2.Search in Google Scholar
3. Hertelyova Z, Salaj R, Chmelarova A, Dombrovsky P, Dvorakova MC, Kruzliak P. The association between lipid parameters and obesity in university students. J Endocrinol Invest 2015 Jan 20. [Epub ahead of print]10.1007/s40618-015-0240-8Search in Google Scholar PubMed
4. Bastien M, Poirier P, Lemieux I, Després JP. Overview of epidemiology and contribution of obesity to cardiovascular disease. Prog Cardiovasc Dis 2014;56:369–81.10.1016/j.pcad.2013.10.016Search in Google Scholar PubMed
6. Berezin AE, Kremzer AA. Relationship between circulating endothelial progenitor cells and insulin resistance in non-diabetic patients with ischemic chronic heart failure. Diabetes Metab Syndr 2014;8:138–44.10.1016/j.dsx.2014.07.001Search in Google Scholar PubMed
7. Berezin A, Zulli A, Kerrigan S, Petrovic D, Kruzliak P. Predictive role of circulating endothelial-derived microparticles in cardiovascular diseases. Clin Biochem 2015;48:562–810.1016/j.clinbiochem.2015.02.003Search in Google Scholar PubMed
8. Kruzliak P, Pechanova O, Kara T. New perspectives of nitric oxide donors in cardiac arrest and cardiopulmonary resuscitation treatment. Heart Fail Rev 2014;19:383–90.10.1007/s10741-013-9397-4Search in Google Scholar PubMed PubMed Central
9. Oka T, Akazawa H, Naito AT, Komuro I. Angiogenesis and cardiac hypertrophy: maintenance of cardiac function and causative roles in heart failure. Circ Res 2014;114:565–71.10.1161/CIRCRESAHA.114.300507Search in Google Scholar PubMed
10. Ingelsson E, Sundström J, Arnlöv J, Zethelius B, Lind L. Insulin resistance and risk of congestive heart failure. J Am Med Assoc 2005;294:334–41.10.1001/jama.294.3.334Search in Google Scholar PubMed
11. Ingelsson E, Arnlöv J, Sundström J, Zethelius B, Vessby B, Lind L. Novel metabolic risk factors for heart failure. J Am Coll Cardiol 2005;46:2054–60.10.1016/j.jacc.2005.07.059Search in Google Scholar PubMed
12. Tuunanen H, Engblom E, Naum A, Scheinin M, Någren K, Airaksinen J, et al. Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: evidence of relationship with insulin resistance and left ventricular dysfunction. J Card Fail 2006;12:644–52.10.1016/j.cardfail.2006.06.005Search in Google Scholar
13. Shimizu I, Yoshida Y, Katsuno T, Tateno K, Okada S, Moriya J, et al. p53-induced adipose tissue inflammation is critically involved in the development of insulin resistance in heart failure. Cell Metab 2012;15:51–64.10.1016/j.cmet.2011.12.006Search in Google Scholar
14. Arnlöv J, Lind L, Zethelius B, Andreґn B, Hales CN, Vessby B, et al. Several factors associated with the insulin resistance syndrome are predictors of left ventricular systolic dysfunction in a male population after 20 years of follow-up. Am Heart J 2001;142:720–4.10.1067/mhj.2001.116957Search in Google Scholar
15. Markiewicz M, Richard E, Marks N, Ludwicka-Bradley A. Impact of endothelial microparticles on coagulation, inflammation, and angiogenesis in age-related vascular diseases. J Aging Res 2013;2013:734509.10.1155/2013/734509Search in Google Scholar
16. Montoro-García S, Shantsila E, Tapp LD, López-Cuenca A, Romero AI, Hernández-Romero D, et al. Small-size circulating microparticles in acute coronary syndromes: relevance to fibrinolytic status, reparative markers and outcomes. Atherosclerosis 2013;227:313–22.10.1016/j.atherosclerosis.2013.01.028Search in Google Scholar
17. Habek JC, Lakusic N, Kruzliak P, Sikic J, Mahovic D, Vrbanic L. Left ventricular diastolic function in diabetes mellitus type 2 patients: correlation with heart rate and its variability. Acta Diabetol 2014;51:999–1005.10.1007/s00592-014-0658-zSearch in Google Scholar
18. Berezin AE, Kremzer AA, Samura TA, MartovitskayaYu A. Apoptotic microparticles to progenitor mononuclear cells ratio in heart failure: relevance of clinical status and outcomes. JCvD 2014;2:1.Search in Google Scholar
19. Berezin AE, Kremzer AA, Samura TA, Berezina TA, Kruzliak P. Impaired immune phenotype of circulating endothelial-derived microparticles in patients with metabolic syndrome and diabetes mellitus. J Endocrinol Invest 2015;38:865–74.10.1007/s40618-015-0273-zSearch in Google Scholar
20. Mastronardi ML, Mostefai HA, Meziani F, Martínez MC, Asfar P, Andriantsitohaina R. Circulating microparticles from septic shock patients exert differential tissue expression of enzymes related to inflammation and oxidative stress. Crit Care Med 2011;39:1739–48.10.1097/CCM.0b013e3182190b4bSearch in Google Scholar
23. MacKman N, Davis GE. Blood coagulation and blood vessel development: is tissue factor the missing link? Arterioscler Thromb Vasc Biol 2011;31:2364–6.10.1161/ATVBAHA.111.236703Search in Google Scholar
24. Meziani F, Tesse A, Andriantsitohaina R. Microparticles are vectors of paradoxical information in vascular cells including the endothelium: role in health and diseases. Pharmacol Rep 2008;60:75–84.Search in Google Scholar
26. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, et al. ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14:803–69.10.1093/eurjhf/hfs105Search in Google Scholar
27. Bluemke DA, Achenbach S, Budoff M, Gerber TC, Gersh B, Hillis LD, et al. Noninvasive coronary artery imaging: magnetic resonance angiography and multidetector computed tomography angiography: a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention of the Council on Cardiovascular Radiology and Intervention, and the Councils on Clinical Cardiology and Cardiovascular Disease in the Young. Circulation 2008;118:586–606.10.1161/CIRCULATIONAHA.108.189695Search in Google Scholar
28. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358–67.10.1016/S0894-7317(89)80014-8Search in Google Scholar
29. Pellerin D, Sharma R, Elliott P, Veyrat C. Tissue Doppler, strain, and strain rate echocardiography for the assessment of left and right systolic ventricular function. Heart 2003;89 (90003):iii9–17.10.1136/heart.89.suppl_3.iii9Search in Google Scholar PubMed PubMed Central
30. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.10.1007/BF00280883Search in Google Scholar PubMed
31. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2012;39:1–266.Search in Google Scholar
34. Giuseppina N, Marinella P, Claudia V, Pietro S, Marianna F, Riccardo DM, et al. Early subclinical ventricular dysfunction in patients with insulin resistance. J Cardiovasc Med (Hagerstown) 2014;15:110–4.10.2459/JCM.0b013e3283638164Search in Google Scholar PubMed
35. Vardeny O, Gupta DK, Claggett B, Burke S, Shah A, Loehr L, et al. Insulin Resistance and Incident Heart Failure: The ARIC Study (Atherosclerosis Risk in Communities). JACC Heart Fail 2013;1:531–6.10.1016/j.jchf.2013.07.006Search in Google Scholar
36. Morel O, Toti F, Bakouboula B, Grunebaum L, Freyssinet JM. Procoagulant microparticles: ‘criminal partners’ in atherothrombosis and deleterious cellular exchanges. Pathophysiol Haemost Thromb 2006;35:15–22.10.1159/000093538Search in Google Scholar
39. Chang HR, Hsieh JC, Hsu BG, Wang LY, Chen MY, Wang JH. Inverse association of N-terminal pro-B-type natriuretic peptide with metabolic syndrome in patients with congestive heart failure. PLoS One 2013;8:e79096.10.1371/journal.pone.0079096Search in Google Scholar PubMed PubMed Central
40. Alsaadon H, Kruzliak P, Smardencas A, Hayes A, Bader M, Angus P, et al. Increased aortic intimal proliferation due to MasR deletion in vitro. Int J Exp Pathol 2015;96:183–7.10.1111/iep.12118Search in Google Scholar PubMed PubMed Central
41. Peterson DB, Sander T, Kaul S, Wakim BT, Halligan B, Twigger S, et al. Comparative proteomic analysis of PAI-1 and TNF-alpha-derived endothelial microparticles. Proteomics 2008;8:2430–46.10.1002/pmic.200701029Search in Google Scholar PubMed PubMed Central
42. Toda N, Okamura T. Obesity impairs vasodilatation and blood flow increase mediated by endothelial nitric oxide: an overview. J Clin Pharmacol 2013;53:1228–39.10.1002/jcph.179Search in Google Scholar PubMed
43. Singh N, Van Craeyveld E, Tjwa M, Ciarka A, Emmerechts J, Droogne W, et al. Circulating apoptotic endothelial cells and apoptotic endothelial microparticles independently predict the presence of cardiac allograft vasculopathy. J Am Coll Cardiol 2012;60:324–31.10.1016/j.jacc.2012.02.065Search in Google Scholar PubMed
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