The Effects of Treating Obese and Lean Patients With Sleep Apnea

Obesity and obstructive sleep apnea (OSA) are independent risk factors for insulin
resistance, systemic hypertension and cardiovascular disease. Both obesity and OSA are
associated with increased sympathetic activity, inflammatory activity, and oxidative stress,
the presumed mediators of their shared clinical consequences. Due to the conflicting
results of previous intervention studies treating OSA patients with CPAP, the investigators
still do not know if treatment of obese OSA patients has a substantial benefit on these risk
factors. In Aim 1, to determine the effects of obesity on the response to CPAP treatment in
OSA patients, the investigators will compare responses in daytime sleepiness, insulin
resistance, and arterial blood pressure following CPAP treatment in obese and lean OSA
patients, stratified by the amount of abdominal visceral adipose tissue, a fat depot
associated with increased sympathetic activity, inflammation, and oxidative stress, and a
more powerful predictor than BMI of adverse cardiovascular and metabolic outcomes. Aim 2
will determine the effect of CPAP treatment in these two patients groups on sympathetic
activity, and inflammatory and oxidative stress biomarkers. The overall hypothesis is that,
adjusting for OSA severity and obtaining normative data from non-OSA subjects with
comparable amounts of visceral adiposity (Aim 3), the two OSA groups will have comparable
improvements in daytime sleepiness, but that the cardiovascular and metabolic improvements
following CPAP therapy will be decreased in OSA patients with increased visceral adipose
tissue. The investigators anticipate that, although there will be a greater absolute change
in markers of sympathetic activity, inflammation and oxidative stress in obese compared to
lean OSA patients following CPAP treatment, the levels will still be abnormally high in the
obese patients resulting in the decreased improvements in insulin resistance, arterial blood
pressure, and vascular health in obese versus lean OSA patients. Relevance: Obese patients
are at increased risk of developing sleep apnea. Both obesity and sleep apnea are felt to
increase the risk of diabetes, hypertension, and cardiovascular disease. The proposed
research will begin to determine if treating obese patients with sleep apnea helps to reduce
these risks. If the beneficial effects of CPAP treatment are reduced in obese compared to
lean patients with sleep apnea, then treatment of sleep apnea in obese patients needs to be
combined with effective management of their obesity.

Inclusion Criteria:

- Age 40-65 years; Will only recruit post-menopausal women not on hormone replacement
therapy to avoid the potential confounding effects of female hormones on OSA
prevalence and severity, fat distribution as well as the end-points (50-60)

- Lean subjects need to have a waist circumference score <= 107 cm in men and <= 96 cm
in women.

- Obese subjects need to have a waist circumference score > 107 cm in men and > 96 cm
in women

- For OSA volunteers, 15 ≤ AHI ≤ 75 (see Preliminary Results for justification of upper
limit) on full-night in-laboratory polysomnogram within the last 6 months.

- Stable medical history and no change in medications, including anti-hypertensive and
lipid-lowering medications, in the previous 2 months

- No regular daytime use (> 3 times/week) of sedative or hypnotic medications in the
last 2 months

- Arm circumference ≤ 50 cm (manufacturer limit for performing ambulatory BP recording)

Exclusion Criteria:

- Unable or unwilling to provide informed consent.

- Not satisfied with reimbursement

- Time constraints

- No telephone access or inability to return for follow up testing.

- BMI > 40 kg/m2.

- Diagnosis of another sleep disorder in addition to OSA based on PSG (e.g., periodic
limb movement disorder [≥ 15 limb movements/hour of sleep with arousal], central
sleep apnea [≥ 50% of apneas on diagnostic PSG are central apneas], insomnia,
restless legs syndrome obesity hypoventilation syndrome, or narcolepsy).

- Previous treatment with positive airway pressure, home oxygen therapy, tracheotomy,
uvulopalatopharyngoplasty, or other surgery for OSA

- Requiring oxygen or bi-level positive airway pressure for treatment of OSA.

- A clinically unstable medical condition as defined by a new diagnosis or change in
medical management in the previous 2 months (e.g., myocardial infarction, congestive
heart failure, Cheyne-Stokes breathing, unstable angina, thyroid disease, depression
or psychosis, ventricular arrhythmias, cirrhosis, surgery, or recently diagnosed
cancer)

- Positive urine toxicology screen

- Rotating Night shift workers in situations or occupations where they regularly
experience jet lag, or have irregular work schedules by history over the last 6
months.

- Routine consumption of more than 2 alcoholic beverages per day as determined by the
CAGE questionnaire (63-65).

- Unable to perform tests due to inability to communicate verbally, inability to write
and read in English; less than a 5th grade reading level; visual, hearing or
cognitive impairment (e.g. previous head injury); or upper extremity motor deficit
(e.g., previous stroke that prevents patient from using CPAP treatment).

- Current illicit drug use

- Excessive caffeine use (More than 10 caffeinated beverages per day)

- Recent or recurring history of recreational drug use leading to tolerance or
dependance.

- Subjects with known moderate to severe renal disease will not undergo the enhanced or
dynamic portion of the study.

- Women with a positive pregnancy test will be excluded from the study.

- Subjects who are found to have mild sleep apnea will be ineligible to participate
further in the study and will paid up until that time.

- Active infection, malignancy or chronic inflammatory disorders such as autoimmune
diseases since these conditions can alter inflammatory biomarker levels.

- No metal parts in the body as participants would not be allowed to enter the magnet
during their MRI