Obesity and obstructive sleep apnea (OSA) are independent risk factors for insulin resistance, systemic hypertension and cardiovascular disease. Both disorders are associated with increased sympathetic and inflammatory activity, and increased oxidative stress, presumed mediators of their shared clinical consequences. Due to conflicting results of previous intervention studies treating OSA patients with CPAP, we 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, we 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 groups on sympathetic activity, and inflammatory and oxidative stress biomarkers. Our 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. We 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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL094307-04
Application #
8377422
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$286,872
Indirect Cost
$92,345
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Eysteinsdottir, Bjorg; Gislason, Thorarinn; Pack, Allan I et al. (2017) Insomnia complaints in lean patients with obstructive sleep apnea negatively affect positive airway pressure treatment adherence. J Sleep Res 26:159-165
Jain, Snigdha; Gurubhagavatula, Indira; Townsend, Raymond et al. (2017) Effect of CPAP, Weight Loss, or CPAP Plus Weight Loss on Central Hemodynamics and Arterial Stiffness. Hypertension 70:1283-1290
Kim, Jinyoung; Pack, Allan I; Riegel, Barbara J et al. (2017) Objective snoring time and carotid intima-media thickness in non-apneic female snorers. J Sleep Res 26:147-150
Schwab, Richard J; Leinwand, Sarah E; Bearn, Cary B et al. (2017) Digital Morphometrics: A New Upper Airway Phenotyping Paradigm in OSA. Chest 152:330-342
Horner, Richard L; Grace, Kevin P; Wellman, Andrew (2017) A resource of potential drug targets and strategic decision-making for obstructive sleep apnoea pharmacotherapy. Respirology 22:861-873
Lyons, M Melanie; Keenan, Brendan T; Li, Junxin et al. (2017) Symptomless Multi-Variable Apnea Prediction Index Assesses Obstructive Sleep Apnea Risk and Adverse Outcomes in Elective Surgery. Sleep 40:
Magalang, Ulysses J; Arnardottir, Erna S; Chen, Ning-Hung et al. (2016) Agreement in the Scoring of Respiratory Events Among International Sleep Centers for Home Sleep Testing. J Clin Sleep Med 12:71-7
Soans, Rajath E; Lim, Diane C; Keenan, Brendan T et al. (2016) Automated Protein Localization of Blood Brain Barrier Vasculature in Brightfield IHC Images. PLoS One 11:e0148411
Li, Qing Yun; Berry, Richard B; Goetting, Mark G et al. (2015) Detection of upper airway status and respiratory events by a current generation positive airway pressure device. Sleep 38:597-605
Lim, Diane C; Brady, Daniel C; Po, Pengse et al. (2015) Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia. J Appl Physiol (1985) 118:544-57

Showing the most recent 10 out of 40 publications