While the association between obesity and cardiovascular disease is well established, the mechanisms leading to cardiovascular abnormalities in obesity remain unclear. However, there is an increasing appreciation for the possible importance of the obstructive sleep apnea syndrome (OSA). Recent data have convincingly shown that sleep apnea is causally associated with systemic hypertension. There is also some data to support a role for OSA in the development of insulin resistance, sympathetic excitation, and endothelial dysfunction. While the importance of sytemic inflammation, fibrinolytic abnormalities and dyslipidemia are well known in relationship to cardiovascular disease, the role of sleep-disordered breathing in causing abnormalities in these areas remains unexplored. Furthermore, the clear overlap between obesity and OSA make it difficult to distinguish the independent effects of one versus the other. We propose to make a thorough assessment of the independent and perhaps synergistic roles of sleep apnea and obesity in leading to abnormalities in autonomic activation, endothelial function, insulin sensitivity, serum lipids, inflammation and fibrinolysis. In doing so, our protocols will provide useful insights into the mechanisms of obesity associated cardiovascular disease, and the specific role played by sleep-disordered breathing. This data may have important implications for the diagnosis and treatment of these abnormalities.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL073146-04
Application #
7369683
Study Section
Special Emphasis Panel (ZHL1-CSR-S (F1))
Program Officer
Twery, Michael
Project Start
2003-09-01
Project End
2010-02-28
Budget Start
2008-03-01
Budget End
2010-02-28
Support Year
4
Fiscal Year
2008
Total Cost
$410,088
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Kezirian, Eric J; Goding Jr, George S; Malhotra, Atul et al. (2014) Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes. J Sleep Res 23:77-83
Gederi, Elnaz; Nemati, Shamim; Edwards, Bradley A et al. (2014) Model-based estimation of loop gain using spontaneous breathing: a validation study. Respir Physiol Neurobiol 201:84-92
Bakker, J P; Balachandran, J S; Tecilazich, F et al. (2013) Pilot study of the effects of bariatric surgery and continuous positive airway pressure treatment on vascular function in obese subjects with obstructive sleep apnoea. Intern Med J 43:993-8
Malhotra, Atul; Drazen, Jeffrey M (2013) High-frequency oscillatory ventilation on shaky ground. N Engl J Med 368:863-5
Montesi, Sydney B; Edwards, Bradley A; Malhotra, Atul et al. (2012) The effect of continuous positive airway pressure treatment on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Clin Sleep Med 8:587-96
Lee, Joon; Nemati, Shamim; Silva, Ikaro et al. (2012) Transfer entropy estimation and directional coupling change detection in biomedical time series. Biomed Eng Online 11:19
Patel, Sanjay R; Malhotra, Atul; Gao, Xiang et al. (2012) A prospective study of sleep duration and pneumonia risk in women. Sleep 35:97-101
Strohl, Kingman P; Butler, James P; Malhotra, Atul (2012) Mechanical properties of the upper airway. Compr Physiol 2:1853-72
Yim-Yeh, Susie; Rahangdale, Shilpa; Nguyen, Anh Tu Duy et al. (2011) Vascular dysfunction in obstructive sleep apnea and type 2 diabetes mellitus. Obesity (Silver Spring) 19:17-22
Sharma, Bhavneesh; McSharry, David; Malhotra, Atul (2011) Sleep disordered breathing in patients with heart failure: pathophysiology and management. Curr Treat Options Cardiovasc Med 13:506-16

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