Sleep Apnea and Cardiovascular Disease. An American Heart Association/American College of Cardiology Foundation Scientific Statement From the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing In Collaboration With the National Heart, Lung

Journal of the American College of Cardiology (Impact Factor: 16.5). 09/2008; 52(8):686-717. DOI: 10.1016/j.jacc.2008.05.002
Source: PubMed


In the context of the current epidemics of obesity, hypertension, atrial fibrillation, and heart failure, the prevalence and consequences of both OSA and CSA are likely to increase. Numerous hurdles face the cardiovascular community in the development of consensus regarding best practice. One objective of this document is to help develop the platform from which, in collaboration with specialists in sleep medicine and related disciplines, such consensus may emerge. Challenges to be met include 1) the general absence of any structured sleep medicine education in cardiovascular training programs; 2) the logistic and economic obstacles to diagnosing and treating sleep apnea; 3) widespread comorbidities, including obesity, that obscure clearer understanding of any independent cardiovascular consequence of sleep apnea per se; 4) treatment options that are varied, predominantly device based, and not easily tolerated, particularly in patients with CSA; and 5) the absence of robust longitudinal interventional studies addressing whether treating sleep apnea confers any tangible benefit in terms of cardiovascular events. We also remain uncertain about what in the apneic patient facilitates cardiovascular disease and its progression. There is no clear evidence as to the best measurement for quantifying the severity of sleep apnea. Is it the frequency of apneas, the severity of desaturation, the overall burden of nocturnal hypoxemia, the arousals, sleep deprivation, or a combination of these and perhaps other characteristics that are key in promoting heart and blood vessel damage? In addition, we do not know the threshold of severity of apnea that we should treat and whether the thresholds for therapy are different in people with cardiovascular disease compared with those who are otherwise healthy. Recognition that a multidisciplinary strategy is critical to appropriate evaluation of sleep-related disease (416) and heightened interaction between specialists in cardiovascular and sleep medicine hold promise for future improved and integrated patient care. In the meantime, the relative lack of definitive outcomes data to guide clinical practice necessitates a highly individualized approach to evaluation and management of those patients with comorbid cardiovascular disease and sleep apnea. There will likely be continued rapid evolution in interpretation, dissemination, and implementation of mechanistic, prognostic, and therapeutic data. Evidence of activation of cardiovascular disease mechanisms by sleep apnea and evidence of sleep apnea as an independent etiologic factor in cardiovascular disease should serve as catalysts for definitive intervention studies. Important next steps in understanding and treating SDB as a means of preventing and mitigating cardiac and vascular disease should include further characterizing fundamental disease mechanisms, identifying economical and better-tolerated therapeutic options, confirming whether therapy attenuates cardiovascular morbidity and mortality, and defining appropriate therapeutic targets and cost-effective benefits of such therapy. © 2008 American Heart Association, Inc, and the American College of Cardiology Foundation.

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    • "ng systemic hypertension related to OSA . There is a dose – response relationship between the severity of OSA and the odds ratio for development of sys - temic hypertension ( Young et al . , 2002 ) . The exposure to clinically significant OSA is thought to be responsible for many of the long - term cardiovascular and cerebrovascular consequences ( Somers et al . , 2008 ) , including systemic hypertension ( Morrell et al . , 2000 ; Nieto et al . , 2000 ; Pep - pard et al . , 2000 ; Lavie , 2005 ) . Hypertension is character - ized by endothelial dysfunction , arterial stiffness , and increased oxidative stress among untreated OSA patients ( Montezano and Touyz , 2012 ) . Adult rats that were sub - ject"
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    ABSTRACT: The incidence of dementia and obstructive sleep apnea (OSA) increases with age. Late-onset Alzheimer's disease (AD) is an irreversible neurodegenerative disease of the elderly characterized by amyloid β (Aβ) plaques and neurofibrillary tangles. The disease involves widespread synaptic loss in the neocortex and the hippocampus. Rodent and clinical studies suggest that OSA impairs the structural integrity of several brain regions, including the medial temporal lobe. Indeed, hypoxia, hypertension, hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress noted in OSA patients also occur in AD patients. This Review highlights pathological commonality, showing that OSA upregulates Aβ, tau hyperphosphorylation, and synaptic dysfunction. Indeed, OSA and hypertension trigger hypoperfusion and hypometabolism of brain regions, including cortex and hippocampus. Several studies show that hypertension-driven brain damage and pathogenic mechanisms lead to an Aβ increase. The pathophysiological mechanism by which OSA enhances hypertension may be linked to sympathoexcitation, oxidative stress, and endothelial dysfunction. Strong pathophysiological similarities that exist between OSA and AD are underscored here. For example, the hippocampus is negatively impacted in both OSA and AD. OSA promotes hippocampal atrophy, which is associated with memory impairment. Cognitive impairment, even in the absence of manifest dementia, is an important independent predictor of mortality. However, several pathophysiological mechanisms in OSA are reversible with appropriate therapy. OSA, therefore, is a modifiable risk factor of cognitive dysfunction, and treating OSA prior to mild cognitive impairment may be an effective prevention strategy to reduce risk for cognitive decline and AD in middle-aged persons and the elderly. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Aug 2015 · Journal of Neuroscience Research
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    • "Reactive oxygen species and reactive nitrogen species have been proposed as mediators of cardiovascular and cognitive alterations in OSA patients (Somers et al. 2008; Garvey at al. 2009; Dempsey et al. 2010) and animal models of OSA (Del Rio et al. 2010; Peng & Prabhakar, 2003). Studies in rats showed that CIH for 10–21 days produces systemic and local CB oxidative stress (Peng & Prabhakar, 2003; Iturriaga et al. 2009; Del Rio et al. 2010, 2011). "
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    ABSTRACT: New findings: What is the topic of this review? This article describes the contribution of oxidative stress and pro-inflammatory cytokines to the enhanced carotid body chemosensory responsiveness to the hypoxia and systemic hypertension induced by chronic intermittent hypoxia. What advances does it highlight? Chronic intermittent hypoxia enhances the carotid body chemosensory discharge during normoxia and hypoxia, leading to sympathetic overactivity and hypertension. New evidence suggests that chronic intermittent hypoxia increases pro-inflammatory cytokines. Here, we discuss the role of inflammation in the alterations of the carotid chemoreceptor function as well as the cardiorespiratory alterations following chronic intermittent hypoxia. Chronic intermittent hypoxia (CIH), the main characteristic of obstructive sleep apnoea, enhances carotid body (CB) chemosensory discharges during normoxia and hypoxia and elicits hypertension. These alterations are attributed to oxidative stress, because antioxidants prevent the enhanced CB chemosensory discharges and the hypertension. In this report, we discuss new evidence supporting the suggestion that oxidative stress-induced upregulation of pro-inflammatory cytokines (i.e. tumour necrosis factor-α and interleukin-1β) in the CB is involved in the chemosensory potentiation and the hypertension following CIH. Anti-inflammatory treatment with ibuprofen prevents the increased tumour necrosis factor-α and interleukin-1β levels in the CB and the hypertension, but does not reduce the enhanced chemosensory hypoxic response and the local oxidative stress in the CB. In contrast, antioxidant treatment with ascorbic acid prevents the increase in cytokine concentrations and CB oxidative stress, the chemosensory potentiation and the hypertension. Thus, the enhanced CB chemosensory responses to hypoxia depend critically on the oxidative stress, but not on the increased tumour necrosis factor-α and interleukin-1β in the CB. We discuss a possible role for pro-inflammatory cytokines in development of the hypertension produced by CIH, acting on cardiorespiratory centres located in the CNS.
    Full-text · Article · Dec 2014 · Experimental physiology
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    • "This hallmark is the main factor involved in the increased cardiovascular morbidity and mortality in OSA patients. Thus, OSA is now recognized as an independent cardiovascular risk factor [1]. In particular, OSA patients present early signs of atherosclerosis [2] that are independent of other cardiovascular and metabolic risk factors and correlate to hypoxia severity. "
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    ABSTRACT: The n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), displays anti-inflammatory properties that may prevent atherosclerosis progression. Exposure of Apolipoprotein-E deficient (ApoE−/−) mice to chronic intermittent hypoxia (CIH) accelerates atherosclerosis progression. Our aim was to assess DHA-supplementation influence on fatty acid incorporation in different tissues/organs and on atherosclerosis progression in ApoE−/− mice exposed to CIH. ApoE−/− mice were exposed to CIH or normoxia (N) and randomized to four groups (N control, CIH control, N+DHA, CIH+DHA). DHA-supplementation enhanced DHA and reduced arachidonic acid (AA) contents in tissues/organs. CIH control mice exhibited increased atherosclerosis lesion sizes compared to N control mice. DHA prevented CIHinduced atherosclerosis but did not improve atherosclerosis burden in N mice. Aortic matrix metalloproteinase-2 (MMP-2) expression was decreased in CIH+DHA mice (p=0.007). DHA-supplementation prevented CIH–induced atherosclerosis acceleration. This was associated with a decrease of AA incorporation and of aortic MMP-2 gene expression.
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