Inflammatory response to sleep apnea in obese subjects

Summary

Principal Investigator: Julio A Chirinos
Affiliation: University of Pennsylvania
Country: USA
Abstract: Obstructive sleep apnea (OSA) is associated with an increased risk for cardiovascular events. Whether the mechanism for this association is directly attributable to pro-atherosclerotic effects of OSA or primarily related to obesity is not known. Obesity is common in patients with OSA, and is itself associated with an inflammatory state and insulin resistance. In individuals with both obesity and OSA, the repetitive hypoxia associated with OSA may promote inflammation and insulin resistance. Our primary aim is to test the hypothesis that OSA plays a primary role in the inflammatory state of patients with obesity and moderate- severe OSA, and that therefore the elimination of apnea by continuous positive airway pressure (CPAP) therapy in these patients will more greatly reduce inflammation (measured by C-reactive protein or CRP) than weight loss alone, and that combining these two therapies will have additive effects on reducing inflammation.; Our second aim is to test the hypothesize that OSA and obesity independently contribute to the insulin resistant state in these patients, and thus combined weight loss and CPAP therapy will have greater effects on lowering insulin resistance than either therapy alone. Our third aim is to test the hypothesis that OSA and obesity contribute independently to vascular endothelial dysfunction, through their effects''on inflammation and insulin resistance, and that therefore combining weight loss and CPAP therapy will improve endothelial function more than either therapy alone. To address these aims, we plan to randomize 201 subjects with obesity and moderate-severe OSA, and baseline CRP>1.0 mg/L to 1) weight loss theYapy alone; 2) CPAP therapy alone; or 3) weight loss plus CPAP therapy for 6 months. We will measure CRP, insulin resistance (area under the curve of a glucose tolerance test), and endothelial function (by brachial artery flow studies) at baseline, and weeks 6, 12, and 24. We propose that this study design will provide the best way to separate the independent effects of obesity and OSA on cardiovascular risk.
Funding Period: 2009-07-01 - 2011-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Low-carbohydrate diets, obesity, and metabolic risk factors for cardiovascular disease
    Frederick F Samaha
    University of Pennsylvania Medical Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, 8th Floor Cardiology MC 111C, Philadelphia, PA 19104, USA
    Curr Atheroscler Rep 9:441-7. 2007
  2. doi Endogenous nitric oxide synthase inhibitors, arterial hemodynamics, and subclinical vascular disease: the PREVENCION Study
    Julio A Chirinos
    University of Pennsylvania, Philadelphia, USA
    Hypertension 52:1051-9. 2008
  3. pmc Arterial load and ventricular-arterial coupling: physiologic relations with body size and effect of obesity
    Julio A Chirinos
    IBITECH, Ghent University, De Pintelaan 185, Ghent, Belgium
    Hypertension 54:558-66. 2009

Detail Information

Publications3

  1. ncbi Low-carbohydrate diets, obesity, and metabolic risk factors for cardiovascular disease
    Frederick F Samaha
    University of Pennsylvania Medical Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, 8th Floor Cardiology MC 111C, Philadelphia, PA 19104, USA
    Curr Atheroscler Rep 9:441-7. 2007
    ..These studies should take into consideration that patients with insulin resistance syndromes would be the most likely group to benefit from carbohydrate restriction...
  2. doi Endogenous nitric oxide synthase inhibitors, arterial hemodynamics, and subclinical vascular disease: the PREVENCION Study
    Julio A Chirinos
    University of Pennsylvania, Philadelphia, USA
    Hypertension 52:1051-9. 2008
    ..L-arginine is independently associated with abnormal pulsatile (but not resistive) arterial hemodynamic indices, which may reflect abnormal L-arginine transport, leading to decreased intracellular bioavailability for NO synthesis...
  3. pmc Arterial load and ventricular-arterial coupling: physiologic relations with body size and effect of obesity
    Julio A Chirinos
    IBITECH, Ghent University, De Pintelaan 185, Ghent, Belgium
    Hypertension 54:558-66. 2009
    ..Obesity exerts adverse effects on arterial load and ventricular stiffening that go beyond the normal relationship with body size. Allometric normalization should allow more accurate quantification of arterial load in future studies...