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Assessment of role of autonomic nervous system in the association of obstructive sleep apnea and cardiovascular diseases using non-invasive methods

dc.contributor.advisorČekerevac, Ivan
dc.contributor.otherDavidović, Goran
dc.contributor.otherPetrović, Marina
dc.contributor.otherTomašević, Miloje V.
dc.contributor.otherVukčević, Miodrag
dc.creatorVučković-Filipović, Jelena
dc.date.accessioned2019-03-25T12:54:39Z
dc.date.available2019-03-25T12:54:39Z
dc.date.available2020-07-03T15:15:45Z
dc.date.issued2018-12-17
dc.identifier.urihttp://eteze.kg.ac.rs/application/showtheses?thesesId=6538
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/10946
dc.identifier.urihttps://fedorakg.kg.ac.rs/fedora/get/o:1062/bdef:Content/download
dc.description.abstractSleep apnea se opisuje kao prisustvo najmanje pet prekida disanja dužih od 10 sekundi na jedan sat spavanja uz postojanje noćno-dnevnih tegoba. Hipopnea se definiše kao smanjenje protoka vazduha za više od 50% udružen sa smanjenjem SatO2 za najmanje 4%. Pokazano je da hipopnea ima iste kliničke posledice kao apnea u snu. U zavisnosti od mehanizma prekida disanja izvršena je podela sleep apnee na opstruktivnu, centralnu i mešovitu. Postoje brojni mehanizmi kojima se objašnjava povezanost sleep apnee i kardiovaskularnih poremećaja, od kojih je najznačajnija povećana aktivnost simpatičkog nervnog sistema. Cilj ovog istraživanja je da se neinvazivnim metodama ispita uloga simpatičkog nervnog sistema u povezanosti sleep apnee i kardiovaskularnih poremećaja, kao i njihova učestalost. Aktivnost simpatičkog nervnog sistema ispitivana je indirektnom metodom spektralne analize varijabilnosti srčane frekvence. Ispitivana je učestalost sledećih kardiovaskularnih poremećaja kod bolesnika sa sleep apneom: učestalost i tip hipertenzije, varijabilnost i odsustvo noćnog pada krvnog pritiska; poremećaji srčanog ritma, ishemijske promene i metabolički poremećaji (dijabetes melitus, poremećaji lipida). Metodologija: Studija je dizajnirana kao prospektivno, neterapijsko, interventno kliničko istraživanje, usmereno na ispitivanje učestalosti kardiovaskularnih poremećaja kod bolesnika sa sleep apneom. Za istraživanje su regrutovani pacijenti oba pola, starosti od 18 do 80 godina, koji su bili hospitalizovani na Klinici za pulmologiju Kliničkog centra Kragujevac, u periodu od juna do decembra 2014.godine, zbog poligrafskog ispitivanja a zbog sumnje na opstruktivnu sleep apneu (OSA). Na osnovu rezultata poligrafa, pacijenti su podeljeni na tri jednake grupe od po 25 pacijenata, sa verifikovanom OЅA. Kontrolnu grupu činili su odrasli pacijenti bez dijagnostikovane, odnosno sa isključenom OЅA. Podaci su prikupljani prospektivno, a deo podataka je prikupljan i analiziran retrospektivno iz istorija bolesti pacijenata (podaci o prethodno dijagnostikovanim bolestima, komorbiditetima, prethodnoj terapiji...). Svim ispitanicima je najpre urađena procena stepena dnevne pospanosti, na osnovu rezultata Epwort-ove skale. Svi ispitanici su podvrgnuti poligrafskom ispitivanju na Klinici za Pulmologiju, KC Kragujevac, na osnovu koje je postavljena/isključena dijagnoza OЅA, određivan stepen težine OЅA i merena saturacija kiseonikom i desaturacija. Nakon poligrafije su svim ispitanicima urađeni 24-časovni monitoring srčanog ritma (radi neinvazivne procene simpatičke aktivnosti praćenjem varijabilnosti srčane frekvence tokom 24 časa, praćenja prisustva poremećaja ritma i procene minimalne, srednje i maksimalne srčane frekvence); ambulatorni monitoring krvnog pritiska (radi ispitivanja profila krvnog pritiska tokom 24 časa, određivanja tipa hipertenzije, praćenja promena različitih parametara tokom 24 časa i određivanja prisustva/odsustva noćnog pada krvnog pritiska); ehokardiografski pregled i laboratorijska ispitivanja (parametri lipoproteinskog profila, glikemija). Podaci su analizirani korišćenjem statističkog softvera SPSS 19.0 za Windows za deskriptivnu statistiku, analizu varijanse, korelaciju. Rezultati su prezentovani kao vrednosti sa standardnom devijacijom. Za procenu značajnih razlika između grupa korišćeni su Studentova T podela, chi-kvadrat test, Mann Whitney U test i ANOVA. Vrednost r manja od 0.05 smatrana je značajnom. Logističkom regresionom analizom izdvajani su prediktori pojave OЅA različitog stepena težine. Cilj ove analize bio je da se definišu parametri razlika između ispitanika bez OЅA i ispitanika sa OЅA lakog, umerenog i teškog stepena, odnosno da se definišu faktori rizika vezani za pojavu OЅA, kao i posledice koje ona ima na zdravlje ispitanika. Rezultati:  Potvrđena je značajno učestalija pojava OЅA kod muškaraca sa odnosom muškarci:žene = 3:1 što potvrđuje rezultate ranijih istraživanja.  Telesna težina, indeks telesne mase, obim struka i obim vrata značajno su se razlikovali u smislu većih vrednosti kod pacijenata sa OSA.  Stepen dnevne pospanosti, procenjen pomoću Epwort skale pospanosti linearno se povećavao sa povećanjem stepena težine OЅA.  Kod ispitanika sa OЅA postoji značajan stepen hipoksije što se pokazalo linearnim smanjenjem minimalne i srednje saturacije kiseonikom i linearnim povećanjem stepena desturacije sa povećanjem stepena OЅA:  Bez obzira na povišen nivo simpatičke aktivnosti i stepen težine OЅA nije bila povišena srednja srčana frekvenca tokom 24-časovnog praćenja, kao ni značajne promene minimalne i maksimalne srčane frekvence, što se može objasniti primenom beta-blokatora u visokom procentu (> 60%). OЅA nije značajno uticala na povećanje učestalosti poremećaja srčanog ritma i sprovođenja  Najčešći komorbiditeti kod ispitanika sa OЅA bili su dislipidemija i hipertenzija.  Učestalost hipertenzije bila je značajna kod ispitanika sa OЅA. Analiza vrednosti dobijenih ambulatornim monitoringom krvnog pritiska nije izdvojila dijastolnu hipertenziju kao dominantan tip hipertenzije kao što je očekivano. Na osnovu dobijenih rezultata, uzimajući u obzir sve faktore koji mogu da utiču na vrednosti krvnog pritiska, mogli bismo da navedemo kombinovanu sistolnu i dijastolnu dnevnu hipertenziju kao potencijalno dominantan tip kod ispitivane populacije ispitanika sa OЅA. Non-dipping se u posmatranom uzorku nije izdvojio kao statistički značajan ni u jednoj od sprovedenih analiza.sr
dc.description.abstractSleep apnea is described as a presence of at least five consecutive breathing interruptions longer than 10 seconds per hour of sleep with the presence of symptoms durig night and day. Hypopnea is defined as a reduction in airflow by more than 50% associated with a reduction of oxygen saturation by at least 4%. It has been shown that hypopnea has the same clinical consequences as sleep apnea. Depending on the respiratory failure mechanism, the sleep apnea was divided into obstructive, central and mixed. There are numerous mechanisms that explain the connection of sleep apnea and cardiovascular disorders, the most significant of which is the increased activity of the sympathetic nervous system. The aim of this study was to examine the role of the sympathetic nervous system using non-invasive methods in connection with sleep apnea and cardiovascular disorders, as well as their frequency. The activity of the sympathetic nervous system is tested by the indirect method of spectral analysis of heart rate variability. The frequency of the following cardiovascular disorders in patients with sleep apnea was investigated: the frequency and type of hypertension, the variability and absence of a nighttime fall in blood pressure; heart rhythm disorders, ischemic changes and metabolic disorders (diabetes mellitus, lipid disorders). Methodology: Study was designed as prospective, non-therapeutical, interventional clinical research, to examine the prevalence of cardiovascular disturbances/diseases in patients with sleep apnea. For the purpose of research we regruted patients of both genders, aged 18-80 years, hospitalized on Clinic for Pulmology, Clinical Center Kragujevac, from June to December 2014. for polygraphy due to a suspision on obstructive sleep apnea. Based on polygraphic results patients were classified into 3 equal groups of 25 patients, with diagnosed OSA. Control group were patients without diagnosed OSA. Data were collected prospectively and part of the data were collected and analyzed retrospectively from patients records (data on previous diseases, comorbidities and therapy). First step for all subjects was assessment of daily sleepiness using Epwort scale. All patients were submited then to polygraphic assessment on Clinic of Pulmology, Clinical Center Kragujevac, based on which we confirmed or excluded diagnosis of OSA, determined severity of OSA and measured saturation and desaturation index. After polygraphy, on Clinic of Cardiology, patients were examined using: 24h heart rhythm mmonitoring (for non-invasive assessment of sympathic nerve activity using heart rate variability, presence and incidence of rhythm disorders, minimal, mean and maximal heart rate during 24h); ambulatory blood pressure monitoring (assessment of blood pressure profile during 24h, determination of hypertension type, assessment of changes of various parameters during 24h and presence or absence of blood pressure dipping); echocardiography and laboratory (parameters of lipoprotein profile and glycemia). Data were analyzed using statistical software SPSS 19.0 for Windows for descriptive statistics, variance analysis, correlations. Results were presented as values with standard deviation. For the assessment of significant differences between groups we used Student-T-test, chi-square test, Mann Whitney U test and ANOVA. P values less than 0.05 were considered significant. Logistic regresion analysis was used to distinguish predictors of severity of OSA. The aim of this analysis was to define parameters of difference between subjects without OSA and subjects with mild, moderate and severe OSA, and to define risk factors associated with the development of OSA. Results:  Obstructive sleep apnea was more frequent in men, with male-female ratio: women = 3: 1, which confirms the results of previous studies.  Body weight, body mass index, waist circumference, and neck circumference significantly differed in terms of higher values in patients with OSA.  The degree of daily sleepiness, estimated with the Epwort scale, increased linearly with increasing degree of OSA.  There is a significant degree of hypoxia in subjects with OSA, which has been shown by a linear decrease in the minimum and mean oxygen saturation and a linear increase in the desaturation degree with an increase in OSA severity:  Regardless of the elevated level of sympathetic activity and severity of OAS, mean heart rate was not increased during 24-hour follow-up, nor significant change in minimum and maximum heart rate were observed, which can be explained by a high percentage of usage of beta-blockers (>60%). OSA did not significantly affect the incidence of cardiac rhythm disorders.  The most common comorbidities in OSA patients were dyslipidemia and hypertension.  The incidence of hypertension was significant in subjects with OSA. An analysis of the values obtained by ambulatory blood pressure monitoring did not distinguish diastolic hypertension as the dominant type of hypertension as expected. On the basis of the obtained results, taking into account all the factors that can affect the blood pressure values, we could refer to combined systolic and diastolic daily hypertension as a potentially dominant type in the observed population of the OSA respondents. Non-dipping did not distinguish itself in the observed sample as statistically significant in any of the conducted analyzes.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Крагујевцу, Факултет медицинских наукаsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Крагујевцуsr
dc.subjectSleep apneasr
dc.subjectSleep apneaen
dc.subjectkardiovaskularni poremećajisr
dc.subjectautonomni nervni sistem neinvazivna procenasr
dc.subjectcardiovascular disturbances autonomic nervous systemen
dc.subjectnon-invasive assessmenten
dc.titleProcena uloge autonomnog nervnog sistema u povezanosti opstruktivne sleep apnee i kardiovaskularnih poremećaja neinvazivnim metodamasr
dc.title.alternativeAssessment of role of autonomic nervous system in the association of obstructive sleep apnea and cardiovascular diseases using non-invasive methodsen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/48745/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/48746/Jelena_Vuckovic_Filipovic_Medicina.pdf


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