Paediatrics (RCH) - Theses

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End date: 2022 × Type: PhD thesis × Subject: carotid × Subject: intima-media thickness ×

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    Early-life predictors of vascular phenotypes : in the Child Health CheckPoint and Longitudinal Study of Australian Children
    Liu, Richard ( 2018)
    Background: Cardiovascular disease (CVD) is a leading cause of global mortality and morbidity in the 21st century. The main pathological mechanism in CVD, atherosclerosis, begins early in life. Effective CVD prevention strategies require better understanding of the early-life patterns of CVD risk. Aims: In a cohort of Australian 11- to 12-year-old children and their parents, I sought to describe, in the early-life period, patterns in CVD risk factors and vascular phenotypes indicative of atherosclerosis. Specifically, I sought: I. To investigate, through systematic review, whether early-life SEP influences adult inflammation II. To examine whether early-life SEP is associated with child vascular phenotypes III. To examine whether traditional risk factors (BP, body mass index (BMI), glucose, cholesterol, smoking, diet and physical exercise) in the Ideal Cardiovascular Health (ICVH) score, are associated with child vascular phenotypes IV. To determine whether inflammation, measured by glycoprotein acetyls (GlycA), is associated with child risk factors, and to what extent inflammation also predicts child vascular phenotypes Methods: To address the first aim, I conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies examining child SEP and adult inflammation, in particular C-reactive protein (CRP). The next three aims utilised data from the Child Health CheckPoint (n=1874 child-parent dyads, 49% girls, 88% mothers), a biophysical markers cross-sectional study nested within the Longitudinal Study of Australian Children. It was conducted in 2015 sequentially across 15 cities and towns around Australia. Associations were evaluated with multivariable linear regression, supplemented with survey weights and methods and multiple imputation. Adult associations were examined in parallel when equivalent data were available. Results: In addressing the first aim, meta-analysis showed individuals with parents in the lowest SEP bracket had 25% higher CRP levels than those in the highest SEP bracket in age- and sex-adjusted analyses. The inclusion of adult BMI into models attenuated this association. In the following CheckPoint analyses, both family and neighbourhood socioeconomic disadvantage were associated with structural and functional vascular phenotypes at age 11-12 years, in age- and sex-adjusted linear regression analyses. Structural vascular phenotype associations were independent of traditional CVD risk factors, while functional vascular phenotype associations largely attenuated when adjusted for BMI. The absence of adequate grandparental SEP data precluded parallel adult analyses. Further, each additional CVD risk factor at age 11-12 years was cross-sectionally associated with adverse functional, but not structural, vascular phenotypes. Adult associations were larger in magnitude and associations existed for both structural and functional vascular phenotypes. Associations with BP and BMI were largest in magnitude and independent of other CVD risk factors. Finally, in addressing the last aim, I observed GlycA at age 11-12 years was associated with structural and functional vascular phenotypes in age- and sex-adjusted models. Associations attenuated with inclusion of traditional CVD risk factors, specifically BMI and BP. Adult associations were similar, however GlycA remained associated with PWV independent of CVD risk factors. Conclusion: Socioeconomic gradients in childhood were associated with vascular phenotypes and CVD risk factors. These risk factors were themselves associated with functional vascular phenotypes in children. In adults, CVD risk factors were associated with both vascular structure and function. These findings broadly support CVD prevention strategies starting earlier in life. Further investigation of socioeconomic influences on both novel and traditional CVD risk factors may afford opportunities to improve population cardiovascular health.