Uloga markera endotelne disfunkcije

doctoral thesis

• Title: Uloga markera endotelne disfunkcije : asimetričnoga dimetil arginina i dušičnoga oksida u procjeni kardiovaskularnoga rizika nakon transplantacije jetre
• Title (english): The role of markers of endothelial dysfunction : asymmetric dimethylarfinine and nitric oxide in the assessment of cardiovascular risk after liver transplation
• Author: Maro Dragičević
• Mentor: Anna Mrzljak (mentor)
• Mentor: Marijana Vučić Lovrenčić (komentor)
• Committee member: Anton Šmalcelj (predsjednik povjerenstva)
• Committee member: Jadranka Sertić (član povjerenstva)
• Committee member: Tajana Filipec Kanižaj (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2021-04-09, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Uvod i ciljevi rada: Nakon transplantacije jetre (TJ) su učestale kardiometaboličke
komplikacije. ADMA i NO su se u općoj populaciji pokazali kao markeri endotelne
disfunkcije i odraz kardiovaskularnih bolesti. Njihova uloga nakon transplantacije jetre u
procjeni kardiovaskularnog rizika je slabo istražena što je cilj ovoga istraživanja.
Ispitanici i metode: U ovo istraživanje je uključeno 177 bolesnika koji su bili kandidati za
transplantaciju jetre. Bolesnicima su prije transplantacije jetre određeni klinički i
laboratorijski parametri kao i u periodu 6 i 12 mjeseci nakon transplantacije jetre. Određene
su incidencije i prevalencije kardiovaskularnih bolesti, njihovih rizičnih čimbenika te
kardiovaskularni rizik (KV) prema SCORE indeksu kao i njihova povezanost s ADMA i NO.
Rezultati: U bolesnika s terminalnom bolesti jetre, koncentracije ADMA i NO koreliraju s
kategorijom višega kardijalnog rizika (p=0.046, te p=0.044). Nadalje je utvrđeno povećanje
vrijednosti ADMA (p=0.042), NO (p=0.049), glukoze u plazmi (p=0.017), te HDLkolesterola
(p=0.047) kao značajni prediktor KV rizika dok je hepatocelularni karcinom
identificiran kao pridruženi biološki čimbenik (p=0.044). Nakon TJ se prati uspostava
povezanosti vrijednosti ADMA i NO, već nakon 6 mjeseci od TJ (p= 0.011), koja perzistira i
12 mjeseci nakon TJ (p=0.007). Nije dokazana povezanost vrijednosti ADMA i NO s višim
kategorijama KV rizika nakon TJ dok su se vrijednosti HDL-kolesterola (p=0.047), glikemije
(p=0.006) uz cirozu jetre prije transplantacije (p=0.002), izdvojili kao značajni pridruženi
čimbenici KV rizika.
Zaključak: Iako je ovim istraživanjem utvrđena povezanost ADMA i NO s višim kardijalnim
rizikom u bolesnika s terminalnom bolesti jetre, njihova povezanost s istim, nakon TJ nije
dokazana. Klasični čimbenici KV rizika pridonose povećanju KV rizika nakon TJ. Potrebna se u daljnja istraživanja da se utvrdi moguća uloga markera endotelne disfunkcije na
kardiovaskularni pobol i rizik u kasnijem razdoblju nakon transplantacije jetre.

Abstract (english)

Introduction and aims: Cardiometabolic complications often occur after liver transplantation
(LT). ADMA and NO have been identified as markers of endothelial dysfunction and the
manifestation of cardiovascular diseases in the general population. Their role in
cardiovascular risk assessment after liver transplantation has been poorly evaluated, which is
the aim of this study.
Patients and methods: This study included 177 patients who were liver transplant
candidates. The patients had their clinical and laboratory parameters assessed before and after
6 and 12 months after LT. The incidence and prevalence of cardiovascular diseases along with
cardiovascular risk according to SCORE were determined and associated with ADMA and
NO.
Results: In patients with end-stage liver disease, ADMA and NO concentrations correlate
with higher cardiac risk category (p=0.046, p=0.044 respectively). Furthermore, an increase in
ADMA (p=0.042), NO (p=0.049), fasting plasma glucose (p=0.017), and HDL- cholesterol
(p=0.047) concentrations were identified as predictors of cardiovascular risk, whereas
hepatocellular carcinoma was determined as a cofounding biological factor (p=0.044). After
LT, a physiological connection of the ADMA/NO pathway was established, identified 6
months after LT (p= 0.011), and persisted further 12 months after LT (p=0.007). No
connection of ADMA or NO concentrations with higher cardiovascular risk categories after LT was proven, but HDL- cholesterol concentrations (p=0.047), level of glycemia (p=0.006),
and liver cirrhosis before LT (p=0.002) were identified as cofounding cardiovascular risk
factors.
Conclusion: Although this study determined a connection of ADMA and NO with higher
cardiovascular risk in patients with end-stage liver disease, their connection with
cardiovascular risk after LT was not proven. Classical cardiovascular risk factors increase the
total cardiovascular risk after LT. Further research is needed to establish the possible impact
of markers of endothelial dysfunction on cardiovascular diseases and risk increase in later
periods after LT.

• Keywords: transplantacija jetre; markeri endotelne disfunkcije; kardiovaskularni rizik
• Keywords (english): liver transplantation; markers of endothelial dysfunction; cardiovascular risk
• Language: croatian
• URN:NBN: urn:nbn:hr:105:682772
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 82 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-06-24 10:47:31