Mechanism of Endothelial Dysfunction in Obstructive Sleep Apnea (OSA)

Mechanism of Endothelial Dysfunction in Obstructive Sleep Apnea

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.

Study Overview

• Status: Terminated
• Conditions: Obstructive Sleep Apnea

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 Type: Observational
• Enrollment (Actual): 90

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Davis Heart and Lung Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants: will be 36 patients with newly diagnosed OSA and 36 age and BMI matched controls.

Patients with OSA will be enrolled from the sleep disorders center at OSU among patients who underwent a recent (past 4 weeks) polysomnography that is positive for OSA, and never were treated with CPAP.

Inclusion criteria will be AHI > 15 events per hours.

Description

Inclusion criteria:

1. Apnea-Hypopnea Index (AHI) > 15 events per hours.

Exclusion criteria:

1. Hypertension defined by existing treatment with antihypertensives or any measurement of systolic pressure above 130 mmHg, or diastolic pressure above 85 mmHg;
2. Dyslipidemia defined by fasting cholesterol above 200; or fasting LDL over 150 mg/dl;
3. Diabetes defined as existing diagnosis, hemoglobin A1C >7 or fasting glucose >110 on two separate measurements (standard fasting glucose or HbA1C criteria);
4. CAD defined by history of angina, coronary event or abnormal stress test;
5. Peripheral Vascular Disease (PVD) defined by history of stroke, claudication or abnormal Ankle brachial index;
6. Concurrent smoking;
7. Pregnancy;
8. 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
OSA; patients diagnosed with obstructive sleep apnea who do not have existing cardiovascular disease
control; patients without obstructive sleep apnea who are matched in weight and age to the OSA patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eNOS Expression	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.	Measured at basline and 3-months post-treatment (CPAP) initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peroxynitrite Formation	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.	Measured at basline and 3-months post-treatment (CPAP) initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Superoxide Production	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.	Measured at basline and 3-months post-treatment (CPAP) initiation
Plasma BH2 and BH4 Levels	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).	Measured at basline and 3-months post-treatment (CPAP) initiation
Plasma ADMA Levels	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).	Measured at basline and 3-months post-treatment (CPAP) initiation

Collaborators and Investigators

• Sponsor: Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2009
• Primary Completion (Actual): February 4, 2022
• Study Completion (Actual): February 4, 2022

Study Registration Dates

• First Submitted: December 4, 2009
• First Submitted That Met QC Criteria: December 4, 2009
• First Posted (Estimate): December 7, 2009

Study Record Updates

• Last Update Posted (Actual): June 28, 2022
• Last Update Submitted That Met QC Criteria: June 22, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: 2009H0212