Koncentracija cirkulirajućeg oksidiranog LDL-a (oxLDL) i protutijela na oxLDL u koronarnih bolesnika prije i nakon revaskularizacije

Starčević, Boris (2007) Koncentracija cirkulirajućeg oksidiranog LDL-a (oxLDL) i protutijela na oxLDL u koronarnih bolesnika prije i nakon revaskularizacije. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: Endotel injury response theory and inflammation completely interconnect pathophysiological mechanisms of atherosclerosis with oxidative stress and hyperlipoproteinemias, especially with oxidative forms of lipoproteins (oxLDL), indicating them as key molecules in a lipid accumulation inside atherosclerotic plaque. Furthermore, immunological responses to atherosclerotic inflammation process and production of antibodies against oxLDL have an important role in atherogenesis, but one can not disregard their potentially protective effect. Both molecules have been found in elevated concentrations in plasma at patients with atherosclerosis, but it has not been tested whether their concentration dynamics depend on type of revascularization procedure (PTCA or CABG). ----- Patients and methods: In this study we included 62 coronary artery disease positive patients with stable and unstable angina, which were assessed with coronarography, and then distributed to surgical (CABAG) or PTCA revascularization. Distribution of atherosclerosis was assessed with ultrasound examination of great vessels. Preoperative and postoperative, within 7 days, in regular time intervals, and on the 30th day, we determined concentrations of standard lipoproteins, oxLDL and antibodies against oxLDL, and MDA as a measurement of oxidative stress. Early success of vascularization procedure was assessed with clinical appearance, serial EKG, heart ultrasound, and standard biochemical markers. ----- Results: In our patients we have found preoperative elevated concentrations of antibodies against oxLDL in hypertension positive patients, but not in diabetics and smokers. None of the risk factors listed had any influence on oxLDL concentrations. Patients who were distributed to CABG had statistically higher oxLDL concentrations, compared to patients who were on PTCA; while preoperative we found no difference in antibodies against oxLDL between these two groups. In clinically unstable patients we did not found elevated oxLDL or antibodies against LDL. After revascularization we had a decrease in concentrations of oxLDL and related antiobodies in both groups (PTCA vs.CABG), but there were no statistically significant difference in dynamics between these two groups. Early postoperative outcome did not have a statistically important influence on oxLDL concentrations, only 48h after revascularization at patients with worse clinical outcome we had a statistically significant decrease, which correlated with CRP concentrations. Outcome of procedure did not have any influence on plasma antibodies against oxLDL concentrations. ----- Conclusion: Preoperative serum concentrations of oxLDL and antibodies against oxLDL does not affect on success of revascularization procedure, and elevated concentrations of oxLDL have been found in surgically revascularized patients in comparison to patients who have undergone PTCA. Hypertension has a significant influence on elevation of concentrations of antibodies against oxLDL. Even though both revascularizations procedures have a negative effect on concentrations of oxLDL and antibodies, there is no difference among them, according to the type of procedure.

Abstract in Croatian

Uvod: Teorija odgovora endotela na ozljedu i upala u potpunosti povezuju patofiziološke mehanizme ateroskleroze sa oksidativnim stresom i hiperlipoproteinemijama, a naročito sa oksidiranim formama lipoproteina (oxLDL), kao ključnih molekula u akumulaciji lipida unutar plakova. Također imunološki odgovor na aterosklerotski upalni proces i pojava protutijela na oxLDL imaju važnu ulogu u aterogenezi, međutim ne može se zanemariti ni njihov potencijalni protektivni faktor. Obje molekule su u povišenim koncentracijama nađene u plazmi bolesnika, koji boluju od ateroskleroze, ali nije pobliže ispitivano kretanje njihovih koncentracija nakon koronarne revaskularizacije (PTCA ili ACBP), a što je cilj ovog rada. ----- Ispitanici i metode: U ovu studiju uključeno je 62 koronarnih bolesnika sa stabilnom i nestabilnom kliničkom slikom, koronarografiranih, čime se odredila raširenost koronarne bolesti, te uputilo na revaskularizaciju, kardiokiruršku (31 bol.)ili PTCA (31 bol.). Raširenost ateroskleroze se ispitala UZV velikih krvnih žila. Preoperativno, te postoperativno unutar 7 dana, u pravilnim vremenskim razmacima, te 30.-ti dan je određena koncentracija lipoproteina, oxLDL i protutijela na oxLDL, te MDA kao mjera oksidativnog stresa. Bolesnicima je rani uspjeh operativnog zahvata procijenjen kliničkom slikom, serijskim snimanjem EKG-a, UZV srca i standardnim biokemijskim parametrima. ----- Rezultati: U koronarnih bolesnika preoperativno su nađene povišene vrijednosti protutijela na oxLDL u hipertoničnih bolesnika, ali ne u dijabetičara i pušača. Nijedan od ova tri faktora rizika za koronarnu bolest nije utjecao na koncentracije samog oxLDL-a. Bolesnici predviđeni za ACBP imali su statistički značajnije više koncentracije oxLDL-a, od bolesnika predviđenih za PTCA, dok se preoperativno koncentracije protutijela nisu razlikovale. U klinički nestabilnih pacijenata nisu nađene povišene vrijednosti oxLDL-a, niti protutijela. Postoperativno i u dilatiranih i u operiranih dolazi do značajnog pada koncentracija protutijela i oxLDL-a, a između ove dvije grupe nema razlike. Rani postoperativni ishod nije značajnije utjecao na serumske koncentracije oxLDL-a, jedino je 48 sati nakon zahvata u bolesnika s lošijim ranim ishodom zabilježen statistički značajniji pad koncentracija, koji korelira s koncentracijama CRP-a. Ishod zahvata ne utječe na kretanje koncentracija protutijela. ----- Zaključak: Preoperativne serumske koncentracije oxLDL-a i protutijela ne utječu na uspjeh operativnog zahvata, a povišene koncentracije oxLDL-a su nađene u kardiokirurških u odnosu na dilatirane bolesnike. Hipertenzivna bolest značajno utječe na povišenje koncentracija serumskih protutijela na oxLDL-a u populaciji koronarnih bolesnika. Postoperativno dolazi do značajnog pada koncentracija oxLDL-a i protutijela na oxLDL, ali serumske koncentracije ne ovise značajnije o vrsti revaskularizacije ili ranom postoperativnom ishodu.

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