Endothelial Damage and Atherosclerosis in Obstructive Sleep Apnea

Endothelial Damage and Atherosclerosis in Obstructive Sleep Apnea: the Role of Advanced Glycation End-products

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:

1. To explore the relationship between insulin resistance and AGEs in OSA
2. To study the relationship between AGE and vascular endothelial dysfunction in OSA
3. To study the relationship between AGE and early atherosclerosis in OSA

Study Overview

• Status: Terminated
• Conditions: Insulin Resistance; Obstructive Sleep Apnea; Oxidative Stress; Endothelial Function
• Intervention / Treatment: Device: CPAP machine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Pokfulam, Hong Kong
    • Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18-65 years old
• AHI >= 15
• BMI < 35

Exclusion Criteria:

• Known cardiovascular disease, including hypertension
• Diabetes
• Acute or unstable chronic disease
• Renal failure
• Major organ system failure, including liver, renal, cardiac and respiratory failure
• Taking long-term medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Continuous Positive Airway Pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AGEs levels	4 weeks and 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
endothelial function as assessed by reactive hyperemia-induced peripheral arterial tone response	4 weeks and 12 weeks

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Mary SM Ip, MD, Queen Mary Hospital, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: July 20, 2009
• First Submitted That Met QC Criteria: July 20, 2009
• First Posted (Estimate): July 21, 2009

Study Record Updates

• Last Update Posted (Estimate): July 4, 2012
• Last Update Submitted That Met QC Criteria: July 3, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Respiratory Tract Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Hyperinsulinism; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Insulin Resistance; Atherosclerosis
• Other Study ID Numbers: HKCTR-772