Učinki kombinacije nizkih odmerkov fluvastatina in valsartana na arterijsko steno pri moških srednjih let po srčnem infarktu ali z zmernim srčno-žilnim tveganjem

Turk Veselič, Martina (author), Šabovič, Mišo (mentor)

Uvod: Pri bolnikih po srčnem infarktu in posameznikih z zmernim srčno-žilnim tveganjem izboljšanje lastnosti arterijske stene napoveduje boljšo srčno-žilno prognozo. Namen raziskave je bil ugotoviti, ali lahko v teh skupinah dosežemo preventivni fenotip arterijske stene s kombinacijo nizkih odmerkov fluvastatina in valsartana (flu/val). Metode: Izvedli smo randomizirano dvojno-slepo raziskavo. Vključili smo 36 moških srednjih let po srčnem infarktu, ki smo jih razdelili v intervencijsko (n=20) in kontrolno skupino (n=16). Nadalje smo vključili 20 moških srednjih let z zmernim srčno-žilnim tveganjem (po SCORE točkovniku), ki smo jih prav tako razdelili v intervencijsko (n=10) in kontrolno skupino (n=10). Preiskovanci v intervencijski skupini so 30 dni prejemali kombinacijo nizkih odmerkov fluvastatina (10 mg) in valsartana (20 mg), preiskovanci v kontrolni skupini pa placebo. Ob vključitvi, po 30 dneh terapije in 10 tednov po zaključeni terapiji smo spremljali naslednje parametre: od pretoka odvisno razširitveno sposobnost brahialne arterije (FMD), &#946;-koeficient togosti, karotidno in karotidno-femoralno hitrost pulznega vala (c-PWV in cf-PWV), indeks reaktivne hiperemije, debelino intima-medije, visoko občutljivostni C-reaktivni protein (hs-CRP), interlevkin 6, žilno celično adhezijsko molekulo 1 (VCAM-1), skupni antioksidativni status ter izražanje več zaščitnih genov (SIRT1, MTOR, NFKB1, NFE2L2, PRKAA1). Rezultati: Po terapiji s flu/val so se pri bolnikih po srčnem infarktu izboljšali FMD (iz 3,1 % na 4,8%, p<0,001), cf-PWV (iz 7,8 na 6,7 m/s, p<0,01), VCAM-1 (iz 772,0 na 745,4 ng/ml, p<0,05) in stopnja izražanja SIRT1 (za 1,69, p<0,05); pri preiskovancih z zmernim srčno-žilnim tveganjem pa FMD (iz 3,0 % na 4,2%, p<0,01), c-PWV (iz 6,7 na 6,2 m/s, p<0,01), hs-CRP (iz 5,39 na 3,35 mg/l, p<0,05) in stopnja izražanja SIRT1 (za 3,34, p<0,05). Ob tem pomembnih sprememb v vrednostih krvnega tlaka in lipidov nismo beležili. Preostali proučevani parametri (arterijske stene, vnetja, oksidativnega stresa in izražanje genov) se niso pomembno spremenili. V kontrolni skupini pomembnih sprememb nismo ugotovili. Pomembno izboljšanje FMD je vztrajalo tudi 10 tednov po zaključeni terapiji. Zaključki: Kratkotrajna intervencija s flu/val pomembno vpliva na premik fenotipa arterijske stene v preventivno smer na treh različnih, čeprav povezanih nivojih: žilnem, vnetnem in genetskem. Ugotovljeno izboljšanje delovanja endotelija, togosti arterijske stene, kazalcev vnetja in izražanja SIRT1 bi lahko preko zmanjšanja srčno-žilnega tveganja vodilo v tehtne klinične koristi, kar pa zahteva nadaljnje raziskave.

• Language: Slovenian
• Keywords: /
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2019
• PID: 20.500.12556/RUL-107104
• COBISS.SI-ID: 299639808
• Publication date in RUL: 28.03.2019

Secondary language

• Language: English
• Title: The effects of low-dose fluvastatin and valsartan combination on arterial wall in middle-aged men after myocardial infarction or at moderate cardiovascular risk

Abstract

Background: The improvement of arterial wall characteristics in groups of patients after myocardial infarction (MI) and subjects at moderate cardiovascular risk leads to better cardiovascular prognosis. We explored whether in these groups the preventive arterial wall phenotype could be attained with low-dose combination of fluvastatin and valsartan (low-flu/val). Methods: The randomized double-blind study was conducted. 36 post-MI middle-aged males were enrolled in the intervention group (n=20) or control group (n=16). Further on, 20 middle-aged males at moderate cardiovascular risk (as classified by SCORE) were also enrolled in the intervention group (n=10) or control group (n=10). The intervention group was receiving low-dose combination of fluvastatin (10 mg) and valsartan (20 mg), and the control group was receiving placebo for 30 days. At inclusion, after 30 days of treatment, and 10 weeks after treatment completion brachial flow-mediated dilatation (FMD), &#946;-stiffness coefficient, carotid and carotid-femoral pulse wave velocity (c-PWV and cf-PWV), reactive hyperaemia index, intima media thickness, high-sensitivity C-reactive protein (hs-CRP), interleukin 6, vascular cell adhesion molecule 1 (VCAM-1), total antioxidant status and expression of protective genes (SIRT1, MTOR, NFKB1, NFE2L2, PRKAA1) were followed. Results: In post-MI patients the low-flu/val treatment improved FMD (from 3.1 % to 4.8%, p<0.001), cf-PWV (from 7.8 to 6.7 m/s, p<0.01), VCAM-1 (from 772.0 to 745.4 ng/ml, p<0.05) and SIRT1 expression (1.69-fold difference, p<0.05). In subjects at moderate cardiovascular risk the flu/val treatment resulted in improved FMD (from 3.0% to 4.2%, p<0.01), c-PWV (from 6.7 to 6.2 m/s, p<0.01), hs-CRP (from 5.39 to 3.35 mg/l, p<0.05) and SIRT1 expression (3.34-fold difference, p<0.05). The obtained improvements were not followed by changes of blood pressure or lipid levels. No other vascular, inflammation, oxidative and genetic parameters changed. No changes were obtained in the control group. The improved FMD persisted even 10 weeks after treatment cessation. Conclusions: The study confirmed that the short-term intervention with low-flu/val importantly shifts the arterial wall phenotype in a preventive direction, improving three different, although interrelated preventive levels of arterial wall characteristics: vascular, inflammatory and genetic. These improvements of endothelial function, arterial stiffness, markers of inflammation and expression of SIRT1 could be interpolated into clinical benefits enabled by cardiovascular risk reduction what warrants further research.

• Keywords: /