Obstructive Sleep Apnea
Conditions
Keywords
OSA
Brief summary
Obstructive sleep apnea is a condition in which people have decreased breathing during their sleep. Untreated sleep apnea has been linked to increased risk for cardiovascular diseases. This research study is looking at blood clotting factors and blood vessel function in health volunteers and patients with newly diagnosed or untreated obstructive sleep apnea to better understand the underlying mechanisms for increased cardiovascular risk.
Detailed description
Cardiovascular disease (CVD), which includes strokes, has been the number one killer in the United States.Each year about 700,000 people experience a new or recurrent stroke, which translates into about one stroke every 45 seconds. Apart from traditional risk factors for stroke such as hypertension, smoking and atrial fibrillation, obstructive sleep apnea is now being increasingly recognized as another important treatable risk factor. The majority of strokes and myocardial infarctions are due to atherothrombotic events. Impaired fibrinolytic activity increases the propensity for thromboembolic events. Many different candidate molecules have been studied as the cause of a hypercoagulable state. Plasminogen Activator Inhibitor-1 (PAI-1) is the major physiologic inhibitor of the body's fibrinolytic system including the principal serine protease tissue-type plasminogen activator (t-PA). It is therefore poised to be a pivotal regulator of the fibrinolytic system.Recent studies have shown that PAI-1 levels are elevated in patients with obstructive sleep apnea (OSA) and that PAI-1 levels correlate with severity of OSA. The purpose of this pilot study is twofold: * To characterize changes in the blood levels of plasminogen activator inhibitor-1 (PAI-1) and tissue type plasminogen activator ( t-PA) across the 24 hour cycle in patients with obstructive sleep apnea, as compared to normal controls, and to further identify the pattern of changes with varying severity of obstructive sleep apnea, and * To study endothelial function in patients with obstructive sleep apnea, as compared to normal controls. Data gathered from this pilot study will be used to initiate a more comprehensive prospective study exploring the link between OSA, endothelial function, the fibrinolytic system and cardiovascular events. This area can be further explored by prospectively following patients to assess for a reduction in such events with treatment of OSA.
Interventions
None listed
Sponsors
Vanderbilt University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age 18 years or older. * Subjects are able and willing to provide informed consent. * Subjects are willing to cooperate with polysomnography and have serial blood draws over a 24-hour period. * Evidence for OSA (AHI\>5 events/hour) without treatment or suspected OSA based on symptoms in the patient group. * Body mass index of 25-45
Exclusion criteria
* History of myocardial infarction, stroke or transient ischemic attack (TIA) or peripheral vascular disease. * History of chronic diseases such as diabetes mellitus, uncontrolled hypertension (SBP \>160, DBP \> 120), renal failure on dialysis, cancer, autoimmune or liver disease. * A significant history of medical or psychiatric disease that may impair participation in the trial. * Evidence of medical instability (cardiac arrhythmias, congestive heart failure, pulmonary disease) that require an expedited evaluation and treatment of the OSA. * History of alcohol, or drug abuse during the one-year-period prior to trial participation. * Current use of tobacco products. * Current treatment with angiotensin converting enzyme-inhibitors and or chronic use of non-steroidal anti-inflammatory agents. * Another primary sleep disorder that requires intervention with medications or cause disrupted sleep. * Patients with unusual sleep or wake habits, including shift work. * Transmeridian travel in the previous 3 months. * Patients with OSA who have already received treatment with CPAP, surgery or oral appliance. * Pregnancy; as hormonal changes affect sleep disordered breathing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of Levels of Mean PAI-1 Activity in Patients With Obstructive Sleep Apnea and Controls. | at the initial visit |
Secondary
| Measure | Time frame |
|---|---|
| Comparison of Endothelial (Blood Vessel) Wall Diameter in Patients With Obstructive Sleep Apnea Versus Controls. | at initial visit |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Vanderbilt sleep disorders clinics and from the community using emails and flyers from study start date in 2008- 2012
Pre-assignment details
Once patients were enrolled in the trial and assigned to the groups, we were able to complete the protocols without having to exclude any participants.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Controls 18 years or older with body mass index between 25-45 | 17 |
| Obstructive Sleep Apnea Group Age 18 years or older with body mass index between 25 and 45 | 17 |
| Total | 34 |
Baseline characteristics
| Characteristic | Obstructive Sleep Apnea Group | Healthy Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 17 Participants | 34 Participants |
| Age Continuous | 49 years STANDARD_DEVIATION 11 | 37 years STANDARD_DEVIATION 11 | 43 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 17 participants | 17 participants | 34 participants |
| Sex: Female, Male Female | 11 Participants | 15 Participants | 26 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Comparison of Levels of Mean PAI-1 Activity in Patients With Obstructive Sleep Apnea and Controls.
Time frame: at the initial visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Comparison of Levels of Mean PAI-1 Activity in Patients With Obstructive Sleep Apnea and Controls. | 17.2 IU/ml | Standard Error 5.3 |
| Obstructive Sleep Apnea Group | Comparison of Levels of Mean PAI-1 Activity in Patients With Obstructive Sleep Apnea and Controls. | 23.9 IU/ml | Standard Error 5.1 |
Secondary
Comparison of Endothelial (Blood Vessel) Wall Diameter in Patients With Obstructive Sleep Apnea Versus Controls.
Time frame: at initial visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Comparison of Endothelial (Blood Vessel) Wall Diameter in Patients With Obstructive Sleep Apnea Versus Controls. | 0.43 mm | Standard Deviation 0.08 |
| Obstructive Sleep Apnea Group | Comparison of Endothelial (Blood Vessel) Wall Diameter in Patients With Obstructive Sleep Apnea Versus Controls. | 0.43 mm | Standard Deviation 0.06 |