Background. Early identification of children at risk of atherosclerosis (AS) is paramount for implementing primary preventive measures addressing vascular health. This dissertation presents the background of the pathophysiology of AS development in children, with the cohorts of children carrying risk factors for early vascular aging. Known methods of vascular health evaluation focusing on ultrasound technology, which evaluates changes in the vascular wall of the peripheral vascular tree, are briefly introduced. Among these methods, a noninvasive biomarker of AS progression, carotid intima–media thickness (cIMT), was chosen to evaluate vascular wall properties in the study population. A new semi-automatic technology, $^{RF}$QIMT, is claimed to be useful for non-radiology and non-cardiology specialists in clinical practice, and it was tested. However, this method has no known reference values for the European healthy pediatric population.
Objectives. To evaluate the normative values of cIMT, the radiofrequency-based software-guided technique RF-Quality Intima–Media Thickness ($^{RF}$QIMT) was used in a healthy cohort of Caucasian children 6 to 18 years old. In addition, the correlation of sex, age, height, pubertal status, obesity, blood pressure, and low physical fitness with cIMT value was analyzed.
Methods and Subjects. Healthy volunteers 6 to 18 years old were enrolled in the study with parental consent. Individuals with chronic illness were excluded. Age, chronic illness, medication use, and pubertal status were acquired with a questionnaire. Anthropometric and blood pressure measurements were obtained using standardized methods. Descriptive statistics for age, sex, pubertal developmental stage, anthropometrics, obesity measures, blood pressure, and physical fitness and their standard deviation scores were calculated. Sex-, age-, and height-specific normative values of cIMT for the $^{RF}$QIMT method were calculated using the LMS method for the non-obese and non-hypertensive sub-cohort (cohort A) of children. A systematic literature review of published normal cIMT values in children was carried out using the PRISMA methodology, and the normative values identified were compared to those in this study.
The association of covariates was assessed with a one-way ANOVA test on a total healthy cohort (cohort B). In a sub-cohort with available physical fitness data and obesity scores from the SLOfit database (cohort C), the influence of physical fitness and obesity on cIMT progression was studied. A multiple linear regression model was used to analyze the effects of independent variables on cIMT.
Statistical analysis was performed using R-project 3.6.0 software (
https://cran.r-project.org) in all statistical calculations and analysis.
Hypotheses. cIMT measured using the $^{RF}$QIMT method increases with age, linear growth, and pubertal maturation in children and adolescents 6 to 18 years old. Sex influences the cIMT value measured by the $^{RF}$QIMT method. The normative values of cIMT using the $^{RF}$QIMT method in children and adolescents 6 to 18 years old are comparable to the normative values of cIMT published in the literature that were established using other validated manual and semi-automatic methods of cIMT measurement. cIMT measured using the $^{RF}$QIMT method is already higher in children and adolescents in the presence of risk factors: obesity, higher blood pressure, and low physical fitness.
Results. A total of 1,241 children were enrolled in the study. Of these, 1,202 healthy Caucasian children and adolescents 6 to 18 years old were included in the evaluation. From these, sub-cohort A of 1,137 non-obese normotensive children (males: n = 512; mean age 12.04 ± 3.52 years, females: n = 625, mean age 12.98 ± 3.83 years) were included in the calculation of sex, age, and height-specific normative cIMT using the LMS method. Normative values of cIMT measured using the $^{RF}$QIMT method are presented in the form of percentile charts, percentile tables, and LMS tables, separately for sex, age, and height for further clinical use. cIMT increased with age, height, hip circumference, and BMI, and it was was higher in males. Obesity, blood pressure, and poor physical fitness were associated with higher cIMT values for cohort C, for which the data from the SLOfit dataset were available.
Conclusions. The $^{RF}$QIMT technique provided reliable measurements of cIMT for sex-, age-, and height-specific normative cIMT values in children 6 to 18 years old. In addition, the correlation of obesity, high blood pressure, and poor physical fitness with higher cIMT values can already be seen in the pediatric population.
| Jezik: | Slovenski jezik |
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| Naslov: | Pomen polavtomatske ultrazvočne opredelitve debeline intime-medije karotidne arterije za oceno žilnega zdravja pri otrocih in mladostnikih |
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Uvod. Zgodnja opredelitev otrok, ki imajo povišano tveganje za zgodnji razvoj ateroskleroze je neobhodno potrebno za načrtovanje ukrepov primarne preventive za ohranjanje žilnega zdravja. V tem doktorskem delu je orisana patofiziologija razvoja ateroskleroze pri otrocih, s poudarkom na kohortah otrok s kroničnimi boleznimi, ki prispevajo k zgodnjim zapletom ateroskleroze. Predstavljene so dostopne metode ocene žilnega zdravja, s poudarkom na ultrazvočni oceni perifernega ožilja. Izmed teh smo za oceno žilnega zdravja v izbrani populaciji izbrali neinvazivni biomarker napredovanja ateroskleroze, debelino intime-medie karotidne arterije. Testirali smo novo, polavtomatsko radiofrekvenčno ultrazvočno metodo meritve cIMT, $^{RF}$QIMT, ki je predstavljena kot primerna za uporabo pri kliničnem delu tudi za specialiste ne-radioloških in ne-kardioloških ved. Metoda za zdravo evropsko otroško populacijo ni imela znanih referenčnih vrednosti debeline intime medie karotidne arterije.
Cilji. Oceniti debelino intime medie karotidne arterije z radiofrekvenčno ultrazvočno metodo, ki nudi programsko vodeno meritev (RF-Quality Intima-Media Thickness $^{RF}$QIMT, Esaote®, Genova, Italija). Meritev smo opravili na zdravi kohorti kavkazijskih otrok starih od 6 do 18 let. Dodaten cilj je bil opredeliti vpliv spola, starosti, telesne višine, pubertetnega statusa, debelosti, krvnega tlaka in nizke telesne zmogljivosti na debelino intime medie karotidne arterije.
Metode in Preiskovanci. Z vprašalnikom smo pridobili podatke o starosti, morebitnih kroničnih boleznih in uporabi zdravil ter pubertetnem statusu. Antropometrične meritve ter meritve krvnega tlaka so bile izvedene po ustaljenih postopkih. Sledil je izračun opisne statistike za starost, spol, pubertetni status antropometrične mere, oceno debelosti, krvnega tlaka, fizične zmogljivosti in njihovih SDS vrednosti. Normativne vrednosti cIMT za $^{RF}$QIMT metodo je bil izračunan z metodo LMS. Vpliv spremenljivk na cIMT je bil ocenjen z ANOVA testom. Vpliv neodvisnih spremenljivk na vrednost cIMT smo ocenili z modelom multiple linearne regresije. Narejen je bil sistematski pregled objavljenih normativnih vrednosti cIMT v literature, vrednosti so bile primerjane z izdelanimi normative te študije. Statistična analiza je bila narejena z uporabo programa R-project 3.6.0 software ( https://cran.r-project.org).
Hipoteze. cIMT izmerjena z uporabo $^{RF}$QIMT metode narašča s starostjo, linearno rastjo in pubertetnim razvojem pri otrocih in mladostnikih starosti 6 do 18 let. Spol pomembno vpliva na debelino cIMT izmerjene z $^{RF}$QIMT metodo. Normativne vrednosti cIMT izmerjene z $^{RF}$QIMT metodo so primerljive z normativnimi vrednostmi objavljenimi v literaturi, ki so bile izmerjene z uporabo drugih validiranih ultrazvočnih metod. cIMT izmerjena z $^{RF}$QIMT metodo je višja že pri otrocih in mladostnikih ob prisotnih dejavnikih tveganja: debelosti, višjem krvnem tlaku ter nizki fizični zmogljivosti.
Rezultati. 1137 otrok z normalno telesno težo ter vrednostmi krvnega tlaka (dečki: N = 512; povprečna starost 12.04 ± 3.52 let, deklice: N = 625, povprečna starost 12.98 ± 3.83 let) je bilo vključenih v izračun normativnih vrednosti cIMT za spol, starost ter telesno višino z uporabo LMS metode. Normativne vrednosti so predstavljene v percentilnih krivuljah, tabelah ter LMS tabeli ločeno po spolu, starosti in telesni višini in so pripravljene za nadaljnjo klinično uporabo. cIMT narašča s starostjo, višino, obsegom bokov ter ITM in je višji pri dečkih. Debelost, krvni tlak in fizična zmogljivost lahko vplivajo na višje vrednosti cIMT že v opisani kohorti otrok in mladostnikov.
Zaključki. $^{RF}$QIMT metoda omogoča meritev cIMT že od 6. leta dalje. Vrednost cIMT zavisi od spola, starosti in telesne višine. Vpliv debelosti, višjega krvnega tlaka in slabe fizične zmogljivosti na hitrejši potek zgodnjih stopenj ateroskleroze se kaže že v otroški dobi.
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| Ključne besede: | žilno zdravje, debelina intime-medije karotidne arterije, cIMT, srčno-žilno tveganje, ateroskleroza, ultrazvok |
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