Mechanism of Endothelial Dysfunction in Obstructive Sleep Apnea (OSA)
Study Details
Study Description
Brief Summary
The investigators hypothesized that patients with Obstructive Sleep Apnea (OSA) who are free of any cardiovascular disease will have early microcirculatory changes that are unique to OSA, and therefore would resolve with treatment of OSA.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Impaired vascular regulation of the microcirculation is a consequence of Obstructive Sleep Apnea (OSA). Nitric Oxide (NO) related endothelial dysfunction occurs in OSA as the earliest vascular abnormality prior to the manifestation of vascular disease and it results in impaired vasodilatory response to hypoxia. These abnormalities have already been described in OSA patients. The role of oxidative stress in endothelial dysfunction is present in vascular disorders. The presence of oxidative stress in OSA patients is also well established. The effect of increased superoxide on endothelial function has also been described in the literature. The mechanism of this effect is unknown and is the focus of this research.
We hypothesized that patients with Obstructive Sleep Apnea (OSA) who are free of any cardiovascular disease will have early microcirculatory changes that are unique to OSA, and therefore would resolve with treatment of OSA.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| OSA patients diagnosed with obstructive sleep apnea who do not have existing cardiovascular disease |
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| control patients without obstructive sleep apnea who are matched in weight and age to the OSA patients |
Outcome Measures
Primary Outcome Measures
- eNOS Expression [Measured at basline and 3-months post-treatment (CPAP) initiation]
All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline.
Secondary Outcome Measures
- Peroxynitrite Formation [Measured at basline and 3-months post-treatment (CPAP) initiation]
All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline.
Other Outcome Measures
- Superoxide Production [Measured at basline and 3-months post-treatment (CPAP) initiation]
All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline.
- Plasma BH2 and BH4 Levels [Measured at basline and 3-months post-treatment (CPAP) initiation]
All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline. The BH2/BH4 ratio will be measured using high pressure liquid chromatography (HPLC).
- Plasma ADMA Levels [Measured at basline and 3-months post-treatment (CPAP) initiation]
All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline. Plasma ADMA levels will be measured using high pressure liquid chromatography (HPLC).
Eligibility Criteria
Criteria
Inclusion criteria:
- Apnea-Hypopnea Index (AHI) > 15 events per hours.
Exclusion criteria:
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Hypertension defined by existing treatment with antihypertensives or any measurement of systolic pressure above 130 mmHg, or diastolic pressure above 85 mmHg;
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Dyslipidemia defined by fasting cholesterol above 200; or fasting LDL over 150 mg/dl;
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Diabetes defined as existing diagnosis, hemoglobin A1C >7 or fasting glucose >110 on two separate measurements (standard fasting glucose or HbA1C criteria);
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CAD defined by history of angina, coronary event or abnormal stress test;
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Peripheral Vascular Disease (PVD) defined by history of stroke, claudication or abnormal Ankle brachial index;
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Concurrent smoking;
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Pregnancy;
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Use of erectile dysfunction drugs, or any medications for chronic conditions; 9)Chronic liver or renal disease. Fasting blood test for glucose, cholesterol, on all participants who have not had these tests in the 6 month prior to enrollment, will be obtained at the time of screening. The remaining criteria will be evaluated by reviewing the medical records and history taking on the day of first visit.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Davis Heart and Lung Research Institute | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- Ohio State University
Investigators
- Principal Investigator: Rami Khayat, MD, Ohio State University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2009H0212