Sleep Disordered Breathing and Cardiopulmonary Disease in Peruvian Highlanders

Overall objective: To understand the feasibility of performing a randomized trial using a simple, minimally-invasive postural therapy approach to improve sleep disordered breathing (SDB).

Specific Aims: To examine the relative efficacy of postural therapy (a 15-degree wedge mattress) on measures of chronic cardiometabolic stress in high altitude residents. To determine the tolerability of postural therapy. Primary outcomes, at 4 and 8 weeks: Mean nocturnal oxyhemoglobin saturation (SPO2) Apnea-hypopnea index (AHI). Secondary outcomes Markers of hypoxemia exposure: the investigators will evaluate for differences in average hemoglobin and erythropoietin concentrations between intervention groups using t-tests or Wilcoxon rank sum tests, as considered appropriate. If transformations are necessary, the investigators will use Box-Cox power transform to identify the best transformation for the investigators' data. Markers of metabolic dysfunction: the investigators will evaluate for differences in average Glycated hemoglobin test (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL), High-density lipoprotein cholesterol (HDL), triglycerides, SVEGF-R1 , and soluble Vascular Endothelial Growth Factor (SVEGF-1) concentrations between intervention groups using t-tests or Wilcoxon rank sum tests, as appropriate. If transformations are necessary, the investigators will use Box-Cox power transform to identify the best transformation for the investigators' data. Markers of cardiometabolic stress: the investigators will evaluate for differences in average systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse, and % change in endothelial function (reactive hyperemia index) as assessed by brachial artery reactivity testing (BART) between intervention groups using t-tests or Wilcoxon rank sum tests, as considered appropriate. Adherence (the average number of nights during the 8-week period that participants slept on the wedge mattress),

Subjects will undergo sleep study in subjects' randomized sleep posture. Randomization will be recorded separately from sleep study recordings. These recordings will be reviewed by trained sleep study technicians who will be blinded to randomization. Blood samples will also be assayed for markers of glucose control.

Study participants randomized to the interventional arm will be instructed to sleep on inclined wedge mattress.

The investigators will measure a change in Respiratory Disturbance Index (RDI) defined as an oxygen desaturation of at least 4 percent associated with autonomic signs of arousal. Specifically, autonomic arousals are defined as concurrent rises in heart rate and attenuation of arterial tonometry. Normal < 5 percent 5 percent < Mild < 15 percent 15 percent < Moderate < 30 percent Severe > 30 percent

The investigators will measure mean oxyhemoglobin saturation (%SaO2) during sleep as assessed by WatchPAT home sleep study at baseline and week 8.

Adherence monitor will measure sleep over the set time points and tolerability is defined as a recorded time on the wedge for a minimum of 5 hours.

The concentration of EPO in the sample is expressed in International Units per litre (U/L) and is determined by calibration against a reference standard.

Assessed by endothelial function using high-frequency ultrasound visualized brachial artery reactivity testing. Endothelial function is characterized by flow-mediated vasodilation of the brachial artery, which is measured by comparing the brachial artery diameter at rest to the diameter after increased forearm blood flow (reactive hyperemia). Unit of measurement is mass units.

Inclusion criteria Age 40-80 years Daytime oxyhemoglobin saturation ≥80%, seated. Body mass index ≥25 kg/m2 Hemoglobin >13 g/dL in women and >15 g/dL in men Ability to provide informed consent Sleeps at home in same bed every night Expected stable residence for at least 6 months Sleeps with two pillows or fewer Demonstrate acute improvement in SDB severity with postural therapy Able to sleep ≥5 hours at an incline for all three nights during the run-in period Exclusion criteria Works the night-shift or a rotating shift Has an indication or preference for sleeping upright, semi-recumbent or at an incline Chronic insomnia or a non-respiratory sleep disorder Physician-established diagnosis of diabetes, lung, cardiovascular, liver, or chronic kidney disease Using home oxygen therapy or other respiratory assistive device [e.g., continuous positive airway pressure (CPAP), nebulizer] Self-reported severe gastrointestinal reflux Self-report of occult blood or history of gastrointestinal bleeding in the past 3 months Pregnancy Unable to sleep ≥5 hours at an incline for all three nights during the run-in period The following exclusion criteria apply only for those undergoing spirometry for safety reasons. Participants with any one of these criteria, will be excluded from spirometry but can still participate in the rest of the screening phase: Surgery of the heart, chest, lungs in the past 3 months (participants will be revisited at a later period) Heart attack in the past 3 months (participants will be revisited at a later period) History of eye surgery History of abdominal surgery in the past 3 months.