Endothelial Damage and Atherosclerosis in Obstructive Sleep Apnea
The investigators hypothesize that obstructive sleep apnea (OSA) may lead to increased formation/accumulation of advanced glycation ends (AGEs), and that the increase in AGEs is contributed in part by increased insulin resistance. The investigators further hypothesize that AGEs contribute to vascular endothelial damage and ultimately atherosclerosis in OSA.
The objectives of this study are:
- To explore the relationship between insulin resistance and AGEs in OSA
- To study the relationship between AGE and vascular endothelial dysfunction in OSA
- To study the relationship between AGE and early atherosclerosis in OSA
Obstructive Sleep Apnea
Device: CPAP machine
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
|Official Title:||Endothelial Damage and Atherosclerosis in Obstructive Sleep Apnea: the Role of Advanced Glycation End-products|
- AGEs levels [ Time Frame: 4 weeks and 12 weeks ] [ Designated as safety issue: No ]
- endothelial function as assessed by reactive hyperemia-induced peripheral arterial tone response [ Time Frame: 4 weeks and 12 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||May 2008|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
No Intervention: no treatment
being observed at 4 weeks and 12 weeks
Active Comparator: CPAP treatment
a machine delivers positive airway pressure into the upper airway via nasal mask
Device: CPAP machine
a machine delivers positive airway pressure into the upper airway via a nasal mask
Other Name: Continuous Positive Airway Pressure
There is growing evidence to suggest that pathophysiology of OSA may lead to atherosclerosis, independent of confounding variables which are often present in these subjects with OSA. Many mechanisms have been reported to contribute to vasculopathy in OSA, but whether increased AGEs formation contribute significantly to the pathogenesis of cardiovascular morbidity in OSA remains to be determined.
Advanced glycation product is formed by non-enzymatic reaction of reducing sugars such as glucose with the amino groups of proteins, and subsequent glycoxidation. AGEs can form on long-lived extracellular proteins as well as short-lived molecules, cytoplasmic proteins and nuclear acids. AGEs cause a number of adverse cellular events and they have been demonstrated in fatty streaks and atherosclerotic plaques. The formation and tissue accumulation of AGE is shown to be enhanced by hyperglycemia and/or increased oxidative stress. There is increasing evidence to support this as an important mechanism of vascular and other end organ damage in diabetes and some other diseases. In OSA, there is evidence to support an increased insulin resistance and excessive oxidative stress, both of which may predispose to AGE formation. We have preliminary data to suggest increased levels of circulating AGE in non-diabetic OSA subjects. Since insulin resistance with elevated blood glucose levels, albeit not up to diabetic thresholds, may partially contribute to increase in AGE.
Many potential mechanisms of atherosclerosis have been reported, but direct evidence for atherosclerosis is still lacking. Subjects with OSA also have comorbidities which may give rise to atherosclerosis. With the advancement of non-invasive techniques for detection of vascular endothelial damage and early atherosclerosis, it is possible to detect early vascular abnormalities in otherwise healthy OSA subjects. This hypothesis underlies our objectives to explore the relationship between AGE and the markers of endothelial dysfunction and early atherosclerosis. Some of these early changes, especially at endothelial level, may be reversible if the insult of OSA is removed. Thus a longitudinal comparison of OSA-treated and OSA-untreated subjects on such changes would further help to clarify the issue.