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. pmc Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study
    Selma F Mohammed
    Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
    Circ Heart Fail 5:710-9. 2012
  2. pmc Major cardiovascular risk factors in Latin America: a comparison with the United States. The Latin American Consortium of Studies in Obesity (LASO)
    J Jaime Miranda
    CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru
    PLoS ONE 8:e54056. 2013
  3. pmc CPAP, weight loss, or both for obstructive sleep apnea
    Julio A Chirinos
    From the Philadelphia Veterans Affairs Medical Center J A C, I G, Perelman School of Medicine, University of Pennsylvania Hospital of the University of Pennsylvania J A C, I G, D J R, T A W, R T, G M, H S, P B, A I P, Monell Chemical Senses Center K T, Temple University School of Medicine G D F, and University of Pennsylvania School of Nursing J C, A L H all in Philadelphia
    N Engl J Med 370:2265-75. 2014
  4. pmc Optimal definitions for abdominal obesity and the metabolic syndrome in Andean Hispanics: the PREVENCION study
    Josefina Medina-Lezama
    Santa Maria Catholic University School of Medicine and the Santa Maria Research Institute, Arequipa, Peru
    Diabetes Care 33:1385-8. 2010
  5. doi Surrogate markers of cardiovascular disease in CKD: what's under the hood?
    Mario F Rubin
    Massachussetts General Hospital, Boston, MA, USA
    Am J Kidney Dis 57:488-97. 2011
  6. 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
  7. 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
  8. 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

Scientific Experts

  • Frederick Samaha
  • Julio A Chirinos
  • Mario F Rubin
  • Josefina Medina-Lezama
  • J Jaime Miranda
  • Selma F Mohammed
  • Luis Rosero
  • Cynthia M Pérez
  • Myriam Oróstegui
  • Juan P Casas
  • Pablo Perel
  • Victor M Herrera
  • Noberto Schapochnik
  • Daniel Ferrante
  • Eglé Silva
  • Angel Gonzalez
  • Jose R Sanchez
  • Ximena Aguilera
  • Ana P Ortiz
  • Erick Suarez
  • Zulma Ortiz
  • Leonelo E Bautista
  • Rafael Pichardo
  • Catterina Ferreccio
  • Luis F Gomez
  • Barry A Borlaug
  • Veronique L Roger
  • Richard J Rodeheffer
  • Margaret M Redfield
  • Sultan A Mirzoyev
  • Fernando Corrales-Medina
  • Diana Andrea Chirinos
  • Humberto Zea-Diaz
  • Julio Chirinos-Pacheco
  • Oscar Leopoldo Morey-Vargas
  • Edgar Munoz-Atahualpa
  • Antonio Bernabe-Ortiz
  • Catherine A Pastorius

Detail Information

Publications9

  1. pmc Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study
    Selma F Mohammed
    Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
    Circ Heart Fail 5:710-9. 2012
    ..We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities...
  2. pmc Major cardiovascular risk factors in Latin America: a comparison with the United States. The Latin American Consortium of Studies in Obesity (LASO)
    J Jaime Miranda
    CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru
    PLoS ONE 8:e54056. 2013
    ..Limited knowledge on the prevalence and distribution of risk factors impairs the planning and implementation of cardiovascular prevention programs in the Latin American and Caribbean (LAC) region...
  3. pmc CPAP, weight loss, or both for obstructive sleep apnea
    Julio A Chirinos
    From the Philadelphia Veterans Affairs Medical Center J A C, I G, Perelman School of Medicine, University of Pennsylvania Hospital of the University of Pennsylvania J A C, I G, D J R, T A W, R T, G M, H S, P B, A I P, Monell Chemical Senses Center K T, Temple University School of Medicine G D F, and University of Pennsylvania School of Nursing J C, A L H all in Philadelphia
    N Engl J Med 370:2265-75. 2014
    ..Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear...
  4. pmc Optimal definitions for abdominal obesity and the metabolic syndrome in Andean Hispanics: the PREVENCION study
    Josefina Medina-Lezama
    Santa Maria Catholic University School of Medicine and the Santa Maria Research Institute, Arequipa, Peru
    Diabetes Care 33:1385-8. 2010
    ..We aimed to establish optimal definitions for abdominal obesity and metabolic syndrome (MetS) among Andean adults...
  5. doi Surrogate markers of cardiovascular disease in CKD: what's under the hood?
    Mario F Rubin
    Massachussetts General Hospital, Boston, MA, USA
    Am J Kidney Dis 57:488-97. 2011
    ..In this narrative review, we discuss the role of each of these measures, with a particular emphasis on patients with chronic kidney disease...
  6. 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...
  7. 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...
  8. 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...