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postgraduate thesis: Relationship of obstructive sleep apnea, alteration in vascular biomarkers and cardio-metabolic diseases
Title | Relationship of obstructive sleep apnea, alteration in vascular biomarkers and cardio-metabolic diseases |
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Authors | |
Issue Date | 2020 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Lui, M. [雷美詩]. (2020). Relationship of obstructive sleep apnea, alteration in vascular biomarkers and cardio-metabolic diseases. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Obstructive sleep apnea (OSA) is an important public health problem, with
rising prevalence in nations affected by obesity epidemic and aging population
structure. It is characterized by intermittent hypoxia and sleep fragmentation as a result
of repetitive partial or complete upper airway collapse during sleep. OSA is causally
associated with hypertension, disorders of glucose metabolism, atherosclerosis and the
related complications, as suggested by many prospective clinical studies including the
Caucasians and other ethnicities. In this thesis, the association of OSA and cardiometabolic
diseases or alterations in relevant biomarkers will be investigated based on
Chinese cohorts in Hong Kong recruited from the sleep disorder center or the specialist
clinics of Queen Mary Hospital.
The intermittent hypoxia and sleep fragmentation in OSA leads to a sequence
of pathological events, including heightening of systemic inflammation, oxidative
stress, endothelial dysfunction and impaired endothelial repair capacity. Serum C
reactive protein is a sensitive biomarker of inflammation, and it is widely used for
prognostication of atherosclerotic diseases. In a cross-sectional study of otherwise
healthy subjects presenting for suspected sleep apnea, high sensitivity C reactive
protein level was associated with severity of OSA, independent of traditional risk factors including visceral adiposity. This shed light on a pathogenetic role of OSA in
vascular diseases. In a randomized controlled trial of the effect of OSA treatment with
continuous positive airway pressure (CPAP) on cardio-metabolic biomarkers, a
significant reduction in adipocyte fatty acid binding protein was identified.
Endothelial dysfunction predates the development of atherosclerosis. In a study
cohort free of chronic medical diseases, endothelial function, as measured by digital
peripheral arterial tonometry, was impaired with increasing sleep apnea severity, while
the dysfunction was accentuated by increasing pack-years of smoking exposure. In
another study investigating impaired vascular repair capacity as an intermediary
mechanism of vascular pathogenesis in OSA, primitive endothelial progenitor cells,
which were mobilized from bone marrow to repair vascular injury, were depleted with
increasing severity of sleep apnea and accumulation of advanced glycation endproducts.
Taken together, the data showed that endothelial function and repair mechanisms are
impaired in OSA, and concomitant atherogenic risk factors add to the detriment in those
suffering from OSA.
OSA often remains unrecognized in subjects known to have hypertension or
diabetes mellitus, and this may contribute silently to adverse cardio-metabolic
outcomes. In two separate prevalence studies, ninety percent of subjects in the
hypertension clinic cohort and fifty four percent of subjects in the diabetic clinic cohort
had undiagnosed OSA, and most of the subjects were not sleepy. Severity of sleep
apnea was correlated with worse blood pressure control in both studies, and predicted
the presence of myocardial injury as indicated by troponin I in the hypertensive subjects.
CPAP for eight weeks could effectively improve blood pressure and alleviate
myocardial injury (troponin I) and ventricular strain (brain natriuretic peptides).
In conclusion, the association between obstructive sleep apnea and cardiometabolic
diseases is multi-faceted, and the study of biomarkers facilitates further understanding of the pathogenesis and potential benefit of treatment in OSA towards
improving cardio-metabolic outcomes.
|
Degree | Doctor of Medicine |
Subject | Sleep apnea syndromes Cardiovascular system - Diseases Metabolism - Disorders |
Dept/Program | Medicine |
Persistent Identifier | http://hdl.handle.net/10722/294348 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lui, Mei-sze | - |
dc.contributor.author | 雷美詩 | - |
dc.date.accessioned | 2020-11-26T09:49:06Z | - |
dc.date.available | 2020-11-26T09:49:06Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Lui, M. [雷美詩]. (2020). Relationship of obstructive sleep apnea, alteration in vascular biomarkers and cardio-metabolic diseases. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/294348 | - |
dc.description.abstract | Obstructive sleep apnea (OSA) is an important public health problem, with rising prevalence in nations affected by obesity epidemic and aging population structure. It is characterized by intermittent hypoxia and sleep fragmentation as a result of repetitive partial or complete upper airway collapse during sleep. OSA is causally associated with hypertension, disorders of glucose metabolism, atherosclerosis and the related complications, as suggested by many prospective clinical studies including the Caucasians and other ethnicities. In this thesis, the association of OSA and cardiometabolic diseases or alterations in relevant biomarkers will be investigated based on Chinese cohorts in Hong Kong recruited from the sleep disorder center or the specialist clinics of Queen Mary Hospital. The intermittent hypoxia and sleep fragmentation in OSA leads to a sequence of pathological events, including heightening of systemic inflammation, oxidative stress, endothelial dysfunction and impaired endothelial repair capacity. Serum C reactive protein is a sensitive biomarker of inflammation, and it is widely used for prognostication of atherosclerotic diseases. In a cross-sectional study of otherwise healthy subjects presenting for suspected sleep apnea, high sensitivity C reactive protein level was associated with severity of OSA, independent of traditional risk factors including visceral adiposity. This shed light on a pathogenetic role of OSA in vascular diseases. In a randomized controlled trial of the effect of OSA treatment with continuous positive airway pressure (CPAP) on cardio-metabolic biomarkers, a significant reduction in adipocyte fatty acid binding protein was identified. Endothelial dysfunction predates the development of atherosclerosis. In a study cohort free of chronic medical diseases, endothelial function, as measured by digital peripheral arterial tonometry, was impaired with increasing sleep apnea severity, while the dysfunction was accentuated by increasing pack-years of smoking exposure. In another study investigating impaired vascular repair capacity as an intermediary mechanism of vascular pathogenesis in OSA, primitive endothelial progenitor cells, which were mobilized from bone marrow to repair vascular injury, were depleted with increasing severity of sleep apnea and accumulation of advanced glycation endproducts. Taken together, the data showed that endothelial function and repair mechanisms are impaired in OSA, and concomitant atherogenic risk factors add to the detriment in those suffering from OSA. OSA often remains unrecognized in subjects known to have hypertension or diabetes mellitus, and this may contribute silently to adverse cardio-metabolic outcomes. In two separate prevalence studies, ninety percent of subjects in the hypertension clinic cohort and fifty four percent of subjects in the diabetic clinic cohort had undiagnosed OSA, and most of the subjects were not sleepy. Severity of sleep apnea was correlated with worse blood pressure control in both studies, and predicted the presence of myocardial injury as indicated by troponin I in the hypertensive subjects. CPAP for eight weeks could effectively improve blood pressure and alleviate myocardial injury (troponin I) and ventricular strain (brain natriuretic peptides). In conclusion, the association between obstructive sleep apnea and cardiometabolic diseases is multi-faceted, and the study of biomarkers facilitates further understanding of the pathogenesis and potential benefit of treatment in OSA towards improving cardio-metabolic outcomes. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject.lcsh | Sleep apnea syndromes | - |
dc.subject.lcsh | Cardiovascular system - Diseases | - |
dc.subject.lcsh | Metabolism - Disorders | - |
dc.title | Relationship of obstructive sleep apnea, alteration in vascular biomarkers and cardio-metabolic diseases | - |
dc.type | PG_Thesis | - |
dc.description.thesisname | Doctor of Medicine | - |
dc.description.thesislevel | Master | - |
dc.description.thesisdiscipline | Medicine | - |
dc.description.nature | published_or_final_version | - |
dc.date.hkucongregation | 2020 | - |
dc.identifier.mmsid | 991044296097103414 | - |