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dc.contributor.advisorSteigen, Terje Kristian
dc.contributor.authorSubbotina, Anna
dc.date.accessioned2024-11-09T15:36:18Z
dc.date.available2024-11-09T15:36:18Z
dc.date.embargoEndDate2026-12-02
dc.date.issued2024-12-05
dc.description.abstractHypertension, which affects about one-third of adults worldwide, is a leading cause of heart disease, stroke, and kidney failure. Despite the known benefits of lowering blood pressure, control remains inadequate worldwide. Only half of those with hypertension are aware of their condition, and even fewer receive adequate treatment. Among those treated, many do not achieve target blood pressure levels. True resistant hypertension (TRH) affects 10-20% of hypertensive patients. Renal sympathetic denervation (RDN) is a minimally invasive procedure that disrupts afferent and efferent nerves in the adventitia of the renal arteries, reducing sympathetic nervous system activity and decreasing blood pressure. In the Re-Shape cardiovascular risk study at the University Hospital of North Norway, 23 patients with TRH underwent RDN. Significant reductions in ambulatory blood pressure were observed at six months and sustained at 24 months post-procedure. Quality of life assessments showed modest improvements post-RDN, particularly at six months, alongside a decrease in antihypertensive medications. Echocardiographic evaluations revealed no significant change in left ventricular mass index (LVMI), but higher baseline LVMI was associated with greater reduction. Patients who did not achieve normal blood pressure showed progression towards concentric hypertrophy, indicating that blood pressure reduction alone does not reverse cardiac remodeling. The study also examined microRNA (miRNA) expression changes post-RDN. Twenty-two miRNAs showed significant changes in expression, with miR-485-5p and miR-625-3p proposed as potential biomarkers for identifying patients likely to benefit from RDN due to their differential expression in responders and involvement in pathways related to sympathetic activity downregulation.en_US
dc.description.abstractHypertensjon, som rammer omtrent en tredjedel av voksne på verdensbasis, er en ledende årsak til hjertesykdom, hjerneslag og nyresvikt. Til tross for de kjente fordelene ved å senke blodtrykket, forblir kontrollen utilstrekkelig. Bare halvparten av de med hypertensjon er klar over sin tilstand, og enda færre får tilstrekkelig behandling. Blant de som behandles, er det mange som ikke oppnår målblodtrykket. Ekte behandlingsresistent hypertensjon rammer 10-20 % av hypertensive pasienter. Renal sympatisk denervering (RDN) er en minimalt invasiv prosedyre som ødelegger afferente og efferente nerver i adventitia av nyrearteriene og med det reduserer aktiviteten i det sympatiske nervesystemet og senker blodtrykket. I Re-Shape-studien av kardiovaskulær risiko ved Universitetssykehuset Nord-Norge gjennomgikk 23 pasienter med behandlingsresistent hypertensjon RDN. Betydelig reduksjon i ambulatorisk blodtrykk ble observert ved seks måneder og opprettholdt 24 måneder etter prosedyren. Vurderinger av livskvalitet viste beskjedne forbedringer etter RDN, spesielt ved seks måneder, sammen med en nedgang i antall antihypertensive medikamenter. Ekkokardiografiske evalueringer avslørte ingen signifikant endring i venstre ventrikkel masseindeks (LVMI), men høyere baseline LVMI var forbundet med større reduksjon. Pasienter som ikke oppnådde normalt blodtrykk, viste progresjon mot konsentrisk hypertrofi, noe som indikerer at blodtrykksreduksjon alene ikke reverserer hjerteremodellering. Studien undersøkte også endringer i mikroRNA (miRNA)-uttrykk etter RDN. Tjueto miRNA-er viste signifikante endringer i uttrykk, med miR-485-5p og miR-625-3p foreslått som potensielle biomarkører for å identifisere pasienter som sannsynligvis vil ha nytte av RDN da de har forskjellig uttrykk hos respondere og er involvert i signalveier relatert til nedregulering av sympatisk aktivitet.en_US
dc.description.doctoraltypeph.d.en_US
dc.description.popularabstractHigh blood pressure gives little symptoms; about half of sufferers don't know they have it. Over time, however, it affects multiple organs and can lead to renal and heart injury, stroke, and dementia. One in ten patients struggle to reach healthy blood pressure levels despite taking all the prescribed medications. Renal denervation is a new treatment opportunity for patients with resistant hypertension. It decreases the overactivity of our sympathetic ("fight-or-flight") nervous system by destroying small nerves around the kidney arteries. We followed a group of patients treated with renal denervation for two years. We show that renal denervation lowers blood pressure, especially in patients with very high levels, and slows heart damage in those most affected. It had a slight positive effect on the patient's quality of life. We also showed that specific small molecules, microRNAs, can be detected in blood tests to help predict who benefits most from renal denervation.en_US
dc.identifier.urihttps://hdl.handle.net/10037/35600
dc.language.isoengen_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.relation.haspart<p>Paper I: Hanssen, T.A., Subbotina, A., Miroslawska, A., Solbu, M.D. & Steigen, T.K. (2022). Quality of life following renal sympathetic denervation in treatment-resistant hypertensive patients: a two-year follow-up study. <i>Scandinavian Cardiovascular Journal, 56</i>(1), 174-179. Also available in Munin at <a href=https://hdl.handle.net/10037/27642>https://hdl.handle.net/10037/27642</a>. <p>Paper II: Subbotina, A., Skjølsvik, E., Solbu, M.D., Miroslawska, A. & Steigen, T. (2024). Echocardiographic findings following renal sympathetic denervation for treatment resistant hypertension, the ReShape CV-risk study. <i>Blood Pressure, 33</i>(1), 2326298. Also available in Munin at <a href=https://hdl.handle.net/10037/34714>https://hdl.handle.net/10037/34714</a>. <p>Paper III: Subbotina, A., Nielsen, S.R., Sajib, S.D., Berge, A.K.M., Chen, M., Calin, G.A., Solbu, M., Steigen, T. & Knutsen, E. MicroRNA profiling of plasma identifies miR-485-5p and miR-625-3p as potential markers of the effect of renal sympathetic denervation. (Manuscript).en_US
dc.rights.accessRightsembargoedAccessen_US
dc.rights.holderCopyright 2024 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)en_US
dc.subjectRenal denervationen_US
dc.subjectRDNen_US
dc.subjectTrue resistant hypertensionen_US
dc.subjectLeft ventricle hypertrophyen_US
dc.subjectQuality of lifeen_US
dc.subjectCirculating miRNAen_US
dc.titleRenal Sympathetic Denervation. Quality of Life, Hypertensive Heart Disease and Biomarker Discoveryen_US
dc.typeDoctoral thesisen_US
dc.typeDoktorgradsavhandlingen_US


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