Admira Bilalić
Ime i prezime: dr. sc. ADMIRA BILALIĆ, dr. med.
Naslov disertacije: „RAZINA INAKTIVNOG MATRIKS GLA PROTEINA U BOLESNIKA S AKUTNIM INFARKTOM MIOKARDA“
Mentorica: prof. dr. sc. Tina Tičinović Kurir
Datum obrane: 8. prosinca 2023.
Poveznica:
https://dr.nsk.hr/islandora/object/mefst%3A2204
Kvalifikacijski znanstveni rad za doktorsku disertaciju:
Bilalic A, Kurir TT, Borovac JA, Kumric M, Supe-Domic D, Vilovic M, Martinovic D, Bozic J. Association of Dephosphorylated-Uncarboxylated Matrix Gla Protein and Risk of Major Bleeding in Patients Presenting with Acute Myocardial Infarction. Life (Basel). 2021;11(8):733.
https://doi.org/10.3390/life11080733
JCR (2020) IF 3,817
Bilalic A, Ticinovic Kurir T, Kumric M, Borovac JA, Matetic A, Supe-Domic D, Bozic J. Circulating Levels of Dephosphorylated-Uncarboxylated Matrix Gla Protein in Patients with Acute Coronary Syndrome. Molecules. 2021;26(4):1108.
https://doi.org/10.3390/molecules26041108
JCR (2020) IF 4,412
Sažetak:
Uvod: U patofiziologiji infarkta miokarda značajnu ulogu ima vaskularna kalcifikacija. Dosadašnje studije ukazuju da je Matriks Gla protein (MGP) jedan od važnijih čimbenika u prevenciji vaskularne kalcifikacije, a povišene razine inaktivnog MGP-a povezane su s povećanim rizikom nastanka aterosklerotskih plakova. Do sada nije istražena razina inaktivnog MGP-a u bolesnika s akutnim infarktom miokarda sa ST elevacijom (STEMI) i infarktom miokarda bez ST elevacije (NSTEMI) te povezanost s rizikom smrtnosti i velikih krvarenja u bolesnika s infarktom miokarda.
Cilj: Cilj je ove studije bio usporediti razinu inaktivnog MGP-a u bolesnika s NSTEMI-jem u odnosu na bolesnike sa STEMI-jem te ispitati povezanost razine dp-ucMGP-a s rizikom smrtnosti i rizikom velikih krvarenja tijekom hospitalizacije.
Metode: Ukupno 90 ispitanika s dijagnozom akutnog infarkta miokada podijeljeno je u dvije skupine - 46 ispitanika s dijagnozom STEMI-ja i 44 ispitanika s dijagnozom NSTEMI-ja. Ispitanicima su određivane plazmatske vrijednosti dp-ucMGP-a i procijenjen rizik smrtnosti pomoću GRACE bodovne ljestvice. Za određivanje rizika velikih krvarenja uključeno je 80 bolesnika s infarktom miokarda od čega 40 bolesnika sa STEMI-jem i 40 bolesnika s NSTEMIjem. Ispitivala se povezanost plazmatske razine inaktivnog MGP-a s rizikom krvarenja procijenjenog CRUSADE bodovnom ljestvicom.
Rezultati: Plazmatska koncentracija dp-ucMGP-a bila je statistički značajno viša u skupini ispitanika s NSTEMI-jem u usporedbi sa skupinom ispitanika sa STEMI-jem (1063,39 ± 518,58 vs. 742,74 ± 166,59 pmol/L, P < 0,001). U skupini ispitanika s NSTEMI-jem pronađene su statistički značajno veće plazmatske vrijednosti dp-ucMGP-a u ispitanika s visokim rizikom smrtnosti u odnosu na ispitanike s niskim rizikom smrtnosti procijenjene GRACE bodovnom ljestvicom (1417,75 ± 956,78 vs. 984,64 ± 335,01 pmol/L, P = 0,03). Pronađena je statistički značajna pozitivna korelacija plazmatske vrijednosti dp-ucMGP-a s dobi ispitanika (r = 0,259, P = 0,014), vrijednostima kreatinina (r = 0,428, P < 0,001) te rizikom smrtnosti tijekom hospitalizacije procijenjene GRACE bodovnom ljestvicom (r = 0,247, P = 0,019) u svih ispitanika s infarktom miokarda. Utvrđeno je da su najznačajniji prediktori najviših plazmatskih vrijednosti dp-ucMGP-a NSTEMI (6,19, 95 % CI 1,56-14,57) i pozitivna obiteljska anamneza na kardiovaskularne bolesti (6,23, 95 % CI 1,80 - 15,64). U skupini ispitanika s NSTEMI-jem utvrđen je značajno veći rizik velikog krvarenja procijenjen CRUSADE bodovnom ljestvicom u odnosu na skupinu bolesnika sa STEMI-jem (P = 0,011). Pronađena je značajna pozitivna bodovnom ljestvicom i vrijednosti plazmatskog dp-ucMGP-a (r = 0,442, P < 0,001). Statistički značajno veće plazmatske koncentracije dp-ucMGP-a bile su u ispitanika s infarktom miokarda s visokim i vrlo visokim rizikom velikih krvarenja procijenjenog CRUSADE bodovnom ljestvicom u odnosu na ispitanike s niskim, vrlo niskim i umjerenim rizikom velikih krvarenja (1277 vs. 794 pmol/L; P < 0,001, odnosno 1277 vs. 941 pmol/L, P = 0,047). Značajna pozitivna korelacija bila je između rizika velikog intrahospitalnog krvarenja procijenjenog CRUSADE bodovnom ljestvicom i rizika intrahospitalne smrtnosti procijenjene GRACE bodovnom ljestvicom (r = 0,520, P < 0,001).
Zaključak: Ovo je istraživanje pokazalo da su plazmatske razine inaktivnog MGP-a bile značajno više u bolesnika s NSTEMI-jem u odnosu na bolesnike sa STEMI-jem. Razine inaktivnog MGP-a pokazale su pozitivnu korelaciju s rizikom smrtnosti i s rizikom velikih krvarenja u bolesnika s infarktom miokarda. Istraživanje je potvrdilo dokaze o značajnoj ulozi vaskularne kalcifikacije procijenjene mjerenjem plazmatske razine inaktivnog MGP-a u patofiziologiji i riziku smrtnosti i velikih krvarenja u bolesnika s akutnim infarktom miokarda.
SUMMARY:
Background: Vascular calcification has an important role in myocardial infarction pathophysiology. Current studies indicate that Matrix Gla protein is one of the most important factors in vascular calcification inhibition, and that higher levels of inactive MGP are related to a higher risk of atherosclerotic plaques formation. Until now, there have been no studies that investigated the differences in the inactive MGP plasma level in Non ST Elevation Myocardial Infarction (NSTEMI) and ST Elevation Myocardial Infarction (STEMI) patients and the relation of inactive MGP plasma levels with the mortality risk and the risk of major bleeding in patients with myocardial infarction.
Aim: The aim of this study was to compare plasma inactive MGP levels between patients with NSTEMI and STEMI. The additional goal was to investigate the relationship of plasma dp-uc MGP with the mortality risk and the risk of major bleeding during hospitalization.
Methods: This cross-sectional evaluation study of serum inactive MGP levels was conducted on 90 patients with myocardial infarction - 46 patients with the STEMI diagnosis and 44 with the NSTEMI diagnosis. Plasma dp-ucMGP levels were analyzed and in-hospital mortality risk was assessed by the GRACE score. Furthermore, the evaluation study of the major bleeding risk included 80 patients with myocardial infarction - 40 patients with the STEMI diagnosis and 40 with the NSTEMI diagnosis. The plasma dp-ucMGP levels with the major bleeding risk assessed by CRUSADE score were examined.
Results: The dp-ucMGP plasma levels were significantly higher in the NSTEMI patients in comparison to the STEMI patients (1063.39 ± 518.58 vs. 742.74 ± 166.59 pmol/L, P < 0.001). Among the patients with NSTEMI, higher plasma levels of dp-ucMGP were associated with a greater risk of in-hospital mortality assessed by the GRACE score (1417.75 ± 956.78 vs. 984.64 ± 335.01 pmol/L, P = 0.03). Furthermore, there was a significant positive correlation between the plasma dp-ucMGP levels with age (r = 0.259, P = 0.014), creatinine serum levels (r = 0.428, P < 0,001), and in-hospital mortality risk assessed by the GRACE score (r = 0.247, P = 0.019) in the total study population. The significant predictor of the highest tertile of the plasma dpucMGP levels were NSTEMI (OR 6.23, 95%, CI 1.80-15.64) and positive family history of cardiovascular diseases (OR 6.19, 95%, CI 1.56-14.57). The NSTEMI patients had a
significantly higher major bleeding risk in comparison to the STEMI patients (P = 0.011). A significant positive correlation was recorded between the major in-hospital bleeding risk assessed by the CRUSADE score and plasma dp-ucMGP levels (r = 0.442, P < 0.001). The patients at high/very high risk of major bleeding assessed by the CRUSADE score had significantly higher dp-ucMGP levels compared to the patients at very low/low and moderate risk of major bleeding (1277 vs. 794 pmol/L; P < 0.001, respectively 1277 vs. 941 pmol/L, P = 0.047). A significant positive correlation was recorded between the major in-hospital bleeding risk assessed by the CRUSADE score and in-hospital mortality risk assessed by the GRACE score (r = 0.520, P < 0.001).
Conclusion: This study demonstrated that dp-ucMGP levels are significantly higher in the NSTEMI patients in comparison to the patients with STEMI. Plasma dp-ucMGP levels positively correlated with the mortality risk and the major bleeding risk in the patients with myocardial infarction. This study suggests that vascular calcification assessed by the plasma dp-ucMGP levels has an important role in pathophysiology, mortality risk and risk of major bleeding in patients with myocardial infarction.
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