The Impact of Obstructive Sleep Apnoea on the Mechanisms in the Vessel Wall that Promote Atherosclerosis
Date
2021
Authors
Andrews, Jordan Anne
Editors
Advisors
Nicholls, Stephen
Brown, Alex
McEvoy, Doug
Brown, Alex
McEvoy, Doug
Journal Title
Journal ISSN
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Thesis
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Abstract
Despite use of established therapies, atherosclerotic cardiovascular disease (CVD)
morbidity and mortality rates remain unacceptably high, prompting the need to identify
additional factors driving residual CVD risk. Obstructive sleep apnoea (OSA) has emerged as
a major CVD risk factor, with the majority of deaths in OSA patients being cardiovascular.
The studies presented in this thesis investigated relationship between the presence and severity
of OSA and the development of atherosclerotic burden in different vascular territories.
A review of the literature was performed, focusing on the prevalence of OSA, its
clinical and mechanistic links to atherosclerosis, and results cardiovascular outcome trials of
treatment for OSA. This provided a theoretical basis for the studies presented.
A systematic review of high-quality studies catalogued in the Cochrane Library,
PubMed, and Embase Library was performed to evaluate the current literature on the impact
of the OSA treatment of continuous positive airways pressure (CPAP) therapy on the markers
of subclinical atherosclerosis carotid intimal thickening (CIMT) as measured by ultrasound,
arterial stiffness, measured by pulse wave velocity (PWV), and endothelial function as
measured by flow-mediated dilation (FMD). Treatment with CPAP in patients with OSA has
a favourable effect on measures of subclinical atherosclerosis.
The relationship between symptoms suggestive of OSA and global and focal coronary
artery disease (CAD) severity was investigated. In the cath lab setting, increased risk of OSA,
as measured by a sleep questionnaire validated for use in primary care, did not associate with
CAD severity.
Angiogenic function and gene expression of vascular inflammatory and angiogenic
markers were measured to investigate the relationship between symptoms suggestive of OSA
and coronary artery stenosis severity, angiogenic function, and vascular inflammation in vitro.
Serum was added to tumour necrosis factor (TNF)-stimulated human umbilical vein endothelial cells (HUVECs) in culture. Angiogenesis capacity of treated HUVECs was
assessed using the Matrigel tubulogenesis assay. Patients at high OSA risk demonstrated
differences in angiogenic potential, but not in atherosclerotic disease burden or vascular
inflammation.
The relationship between epicardial adipose tissue (EAT), a metabolically active fat
depot, and OSA severity with EAT volume, EAT density and body mass index (BMI) were
investigated. Participants underwent clinically indicated cardiac computed tomography (CT)
and overnight polysomnography (PSG). EAT volume and coronary plaque volume were
quantified on coronary computed tomography angiography (CTCA). EAT volume was
observed to be associated with OSA severity, independent of BMI.
The impact of OSA on changes in coronary atherosclerotic plaque was examined in
short-term and longer-term treatment investigations for CAD as measured by intravascular
ultrasound (IVUS). OSA was found to be associated with a greater increase in atheroma
volume compared to those without OSA after short-term treatment for an acute coronary
syndrome (ACS) event, while patients with OSA had a greater decrease in atheroma volume
compared to those without OSA after optimal treatment for CAD.
The studies presented in this thesis demonstrate that the vessel wall is impacted by
exposure to OSA. These findings provide a rationale for screening and treating patients for
OSA to beneficially impact the progression of atherosclerosis.
School/Discipline
School of Medicine
Dissertation Note
Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2021
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