1 / 66

OSAS & INFLAMMATION IS THERE ANY LINK ?

OSAS & INFLAMMATION IS THERE ANY LINK ?. AHMED ELMASRY MD AIN SHAMS UNIVERSITY PHD UPPSALA UNIVERSITY. AHMED ELMASRY MODEL 2000. OSAS - INFLAMMATION.

geordi
Download Presentation

OSAS & INFLAMMATION IS THERE ANY LINK ?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. OSAS & INFLAMMATIONIS THERE ANY LINK ? AHMED ELMASRY MD AIN SHAMS UNIVERSITY PHD UPPSALA UNIVERSITY

  2. AHMED ELMASRY MODEL 2000

  3. OSAS - INFLAMMATION • Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnoea has been treated as a "localabnormality" of the respiratory track rather than as a "systemicillness". • In 1997, it was the first report that the pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were elevated in patients with disorders of EDS and proposed that these cytokines were mediators of daytime sleepiness. • Arch PhysiolBiochem. 2008 Oct;114(4):211-23.

  4. OSAS - INFLAMMATION • In subsequent studies, it was shown that IL-6, TNF-alpha, and insulin levels were elevated in sleep apnoea independently of obesity and that visceral fat was the primary parameter linked with sleep apnoea. • Further studies showed that women with the polycystic ovary syndrome (PCOS) were much more likely than controls to have SDB and EDS, suggesting a pathogenetic role of insulin resistance in OSA. • Arch PhysiolBiochem. 2008 Oct;114(4):211-23.

  5. OSAS - INFLAMMATION • Additional accumulated evidence that supports the role of obesity and the associated metabolicaberrations in the pathogenesis of sleep apnoea and related symptoms include: • obesity without sleep apnoea is associated with daytime sleepiness; • the protective role of gonadal hormones as suggested by the increased prevalence of sleep apnoea in post-menopausal women, • the significantly reduced risk for OSA in women on hormonal therapy, • partial effects of CPAP in obese patients with apnoea on hypercytokinemia, insulin resistance indices, and visceral fat. • Arch PhysiolBiochem. 2008 Oct;114(4):211-23.

  6. OSAS - INFLAMMATION • Furthermore, the beneficial effect of a cytokine antagonist on EDS and apnoea in obese, male apnoeics and that of exercise and weight loss on SDB and EDS in general random or clinical samples, supports the hypothesis that cytokines and insulin resistance are mediators of EDS and sleep apnoea in humans. • In conclusion, accumulating evidence provides support to hypothesis that obesity via inflammation, insulin resistance, visceral adiposity, and central neural mechanisms, e.g. hypofunctioning hypothalamus, play a major role in the pathogenesis of sleep apnoea, sleepiness, and the associated cardiovascular co-morbidities. • Arch PhysiolBiochem. 2008 Oct;114(4):211-23.

  7. OSAS - INFLAMMATION • Intermittent hypoxemia, one of the physiological markers of OSAS, is characterized by transient periods of oxygen desaturation followed by reoxygenation. • The cycles of hypoxia-reoxygenation are associated with oxidative stress that, in turn, triggers the activation of pathways that lead to cardiovascular damage. • Rev Invest Clin. 2008 Nov-Dec;60(6):502-16.

  8. OSAS - INFLAMMATION • These pathways include an increased chemoreflex sensitivity that induces the over-activation of the sympathetic nervous system, decreased baroreflex sensitivity, the activation of systemic inflammation pathways mediated primarily by the nuclear transcriptional factor kappaB that favors the development of atherosclerosis through the synthesis of cytokines and the expression of adhesionmolecules, endothelialdysfunction with a decreased availability of nitricoxide, dyslipidemia, insulinresistance and stimulation of the renin-angiotensin system. • Rev Invest Clin. 2008 Nov-Dec;60(6):502-16.

  9. OSAS - INFLAMMATION • Other mechanisms proposed include arousals that increase sympathetic activity and exaggerated intrathoracic pressure changes that generate high transmural pressure. • Most of these mechanisms respond favorably to treatment with CPAP. • A better understanding of the mechanisms of cardiovascular damage opens the possibility of instituting new treatments that will contribute to limiting the cardiovascular consequences associated with OSAS. • Rev Invest Clin. 2008 Nov-Dec;60(6):502-16.

  10. OSAS - INFLAMMATION • OSA is a highly prevalent sleep disorder leading to cardiovascular and metabolic complications. • OSA is also a multicomponent disorder, with intermittent hypoxia (IH) as the main trigger for the associated cardiovascular and metabolic alterations. • Indeed, recurrent pharyngeal collapses during sleep lead to repetitive sequences of hypoxia–reoxygenation. • This IH induces several consequences such as hemodynamic, hormonometabolic, oxidative, and immuno-inflammatory alterations that may interact and aggravate each other, resulting in artery changes, from adaptive to degenerative atherosclerotic remodeling. • Seminars in Immunopathology. June 2009, Volume 31, Issue 1, pp 113-125

  11. OSAS - INFLAMMATION • Atherosclerosis has been found in OSA patients free of other cardiovascular risk factors and is related to the severity of nocturnal hypoxia. • Early stages of artery alteration, including functional and structural changes, have been evidenced in both OSA patients and rodents experimentally exposed to IH. • Impaired vasoreactivity with endothelialdysfunction and/or increased vasoconstrictive responses due to sympathetic, endothelin, and renin–angiotensin systems have been reported and also contribute to vascular remodeling and inflammation. • Seminars in Immunopathology. June 2009, Volume 31, Issue 1, pp 113-125

  12. OSAS - INFLAMMATION • Oxidativestress, inflammation, and vascular remodeling can be directly triggered by IH, further aggravated by the OSA-associated hormonometabolic alterations, such as insulin resistance, dyslipidemia, and adipokineimbalance. • As shown in OSA patients and in the animal model, genetic susceptibility, comorbidities (obesity), and life habits (high fat diet) may aggravate atherosclerosis development or progression. • Seminars in Immunopathology. June 2009, Volume 31, Issue 1, pp 113-125

  13. OSAS - INFLAMMATION • The intimate molecular mechanisms are still largely unknown, and their understanding may contribute to delineate new targets for prevention strategies and/or development of new treatment of OSA-related atherosclerosis, especially in patients at risk for cardiovascular disease. • Seminars in Immunopathology. June 2009, Volume 31, Issue 1, pp 113-125

  14. OSAS - INFLAMMATION • The pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS) is not fully understood but is likely multifactorial in origin. • Inflammatory processes play an important role in the pathogenesis of atherosclerosis. • Circulating levels of several markers of inflammation have been associated with future cardiovascular risk. • Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):392-9.

  15. OSAS - INFLAMMATION • These include : • Cell adhesion molecules such as intercellularadhesionmolecule-1 (ICAM-1) and selectins • Cytokines such as tumour necrosis factor alpha (TNF-alpha)and interleukin 6 (IL-6) • Chemokines such as interleukin8 (IL-8) • C-reactive protein (CRP) • Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):392-9.

More Related