Povezanost eozinofilnoga kationskoga proteina s uznapredovalošću ateroskleroze karotidne arterije i sveukupnim preživljenjem bolesnika na programu kronične hemodijalize [Correlation of eosinophil cationic protein with severity of carotid atherosclerosis and all-cause mortality in patients on hemodialysis]

Sičaja, Mario (2013) Povezanost eozinofilnoga kationskoga proteina s uznapredovalošću ateroskleroze karotidne arterije i sveukupnim preživljenjem bolesnika na programu kronične hemodijalize [Correlation of eosinophil cationic protein with severity of carotid atherosclerosis and all-cause mortality in patients on hemodialysis]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

The prevalence of cardiovascular diseases in patients with renal insufficiency treated with chronic dialysis is high. It is considered that increased prevalence of cardiovascular diseases in this population is a result of accelerated atherosclerosis which is associated with “new” risk factors such as highly sensitive protein C (hs CRP), proband brain natriuretic peptide (NT-pro-BNP), homocysteine, lipoproteine (a), inflammation and oxidative stress. Eosinophile cationic protein (ECP) is zinc cationic protein which is stored in human organism in the eosinophiles’ granolas. According to the recent studies serum concentration of ECP in proportional to severity of coronary atherosclerosis, and it is considered as biomarker of coronary atherosclerosis. The aim of this study is to investigate the correlation between ECP and surrogates of atherosclerosis and to investigate whether there is prognostic significance of biomarkers such as ECP, hsCRP, red cell distribution width (RDW) in regard to overall survival of patients on chronic hemodialysis. Results of our research show that patients on chronic dialysis have advanced atherosclerotic changes on carotid arteries (intima media thickness – IMT 0,68±0,19; overall severity of plaque burden – PS 14,75±14,85) and significantly higher serum concentrations of ECP (ECP 17,01±14,12) in regard to general population (IMT 0,50±0,12, PS 6,57±3,75, ECP 10,78±9,38) (P<0,0001; p<0,0001; P=0,0012, respectively). According to our results there is no statistically significant correlation between ECP and IMT (rho 0,168, P=0,0938). Between ECP and overall severity of plaque burden of carotid arteries there is statistically significant, but marginal correlation (r=0,234, P=0,0193). We have validated prognostic significance of previously known important biomarkers such as hsCRP. In univariate Cox proportional analysis ECP is identified as statistically significant prognostic marker (HR 1,0322, P=0,049), but after correction for known risk factors for atherosclerosis, it became insignificant. We have identified RDW as strong independent and additive prognostic biomarker of overall survival of patients on chronic dialysis (HR 1,5346; P=0,0028) which remained significant even after correction for known atherosclerotic risk factors. In the population of patients treated with chronic dialysis ECP does not represents significant biomarker of carotid atherosclerosis, and as such it does not have clinical applicable value. RDW seems as an independent and additive prognostic biomarker for overall survival of patients on chronic dialysis.

Abstract in Croatian

Prevalencija srčano-žilnih bolesti u bolesnika s bubrežnom insuficijencijom na programu kronične hemodijalize je visoka. Smatra se da je povećana prevalencija srčano-žilnih bolesti u tih bolesnika uzrokovana ubrzanom aterosklerozom koja se povezuje s tzv. „novim“ čimbenicima rizika kao što su visoko osjetljivi C-reaktivni protein (hsCRP), proband moždanog natrijuretskog peptida (NT-pro-BNP), homocistein, lipoprotein (a), upala i oksidacijski stres. Eozinofilni kationski protein (ECP) je cink-kationski upalni protein koji se u ljudskom organizmu nalazi uskladišten u granulama eozinofila. Prema rezultatima nedavnih studija serumska koncentracija ECP-a proporcionalna je proširenosti aterosklerotske bolesti na koronarnim arterijama te se smatra biomarkerom koronarne ateroskleroze. Cilj ovoga rada je istražiti povezanost eozinofilnog kationskog proteina sa surogatima proširenosti ateroskleroze, ispitati ECP-a kao biomarker karotidne ateroskleroze te istražiti postoji li prognostička značajnost biomarkera kao što su ECP, hsCRP, volumen distribucije eritrocita (RDW)-a u odnosu na sveukupno preživljenje bolesnika na programu kronične hemodijalize. Rezultati našega istraživanja pokazuju da bolesnici na dijalizi imaju uznapredovale aterosklerotske promjene karotidne arterije (debljina intima-medie - IMT 0,68±0,19; ukupna težina aterosklerotskog plaka - PS 14,75±14,85) i značajno više koncentracije serumskog ECP-a (ECP 17,01±14,12) u odnosu na opću populaciju (IMT 0,50±0,12, PS 6,57±3,75, ECP 10,78±9,38) (P<0,0001; p<0,0001; P=0,0012). Temeljem našega istraživanja ne nalaze se statistički značajne povezanosti između ECP-a i debljine intima-medie karotidne arterije (rho 0,168, P=0,0938). Između ECP-a i ukupne težine aterosklerotskog plaka karotidne arterije nalazi se statistički značajna, no marginalna povezanost (r=0,234, P=0,0193). Potvrđena je prognostička značajnost ranije validiranih biomarkera kao što su hsCRP, NT-pro-BNP. U univarijatnoj analizi ECP je identificiran kao prognostički značajan parametar (HR 1,0322, P=0,049), no nakon korekcije za ranije poznate čimbenike rizika za aterosklerotsku bolest, isti je postao statistički nesignifikantan. Identificiran je RDW kao snažan nezavisni i dodatni prognostički biomarker ukupnog preživljenja bolesnika na programu kronične dijalize (HR 1,5346; P=0,0028) koji je ostao statistički značajan i nakon korekcije za ranije poznate čimbenike rizika. U populaciji bolesnika koji se liječe metodom kronične hemodijalize ECP ne predstavlja značajan biomarker karotidne ateroskleroze, te kao takav nema klinički primjenjivu prognostičku značajnost u navedenoj populaciji bolesnika. Identificiran je volumen distribucije eritrocita (RDW) kao snažan dodatni i nezavisni prediktor sveukupnog mortaliteta u skupini bolesnika koji se liječe metodom kronične hemodijalize.

Item Type: Thesis (PhD)
Mentors:
Mentor
Božikov, Velimir
Departments: Izvan medicinskog fakulteta
Depositing User: dr.med. Helena Markulin
University: Sveučilište u Zagrebu
Institution: Medicinski fakultet
Number of Pages: 100
Status: Unpublished
Creators:
CreatorsEmail
Sičaja, MarioUNSPECIFIED
Date: 21 March 2013
Date Deposited: 28 May 2014 11:40
Last Modified: 28 May 2014 11:40
Subjects: WG Cardiovascular System > WG 200-460 Heart. Heart Diseases
Related URLs:
    URI: http://medlib.mef.hr/id/eprint/2125

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