Study to Assess the Changes in Blood Clotting Factors and Blood Vessel Wall Function in Obstructive Sleep Apnea

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.

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.