Obstructive sleep apnoea syndrome:
a new paradigm by chronic nocturnal intermittent
hypoxia and sleep disruption

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SUMMARY

Obstructive sleep apnoea syndrome (OSAS) is associated with severe cerebro-cardiovascular morbidity and mortality. It is an independent risk factor for atherosclerosis, arterial thrombosis and metabolic syndrome, and recently has been associated with an increased incidence of cancer and death. A causal link between OSAS and atherosclerosis has been partially established. Recent research on atherosclerosis in OSAS has focused on thrombotic tendency and blood viscosity, providing new insight into disease mechanisms. Hypoxia is a critical pathophysiological element in OSAS that leads to intensive sympathetic activity, in association with inflammation, oxidative stress and procoagulant activity. Hypoxia and the induction of oxidative stress can simultaneously represent an underlying mechanism in the pathogenesis of cancer development and progression. This mini-review will discuss the latest findings on the association and potential relationship between OSA and pathological vascular sequelae.

RIASSUNTO

La sindrome delle apnee ostruttive durante il sonno è associata ad un aumento della morbilità e mortalità cerebro-cardiovascolare. Si tratta di un fattore di rischio indipendente per aterosclerosi precoce, trombosi vascolare e sindrome metabolica e di recente è stata anche associata ad un aumento dell'incidenza di cancro. Un nesso di causalità tra OSAS ed aterosclerosi è parzialmente fondata ma non completamente chiarita. Una recente ricerca su aterosclerosi precoce in OSAS ha messo in correlazione la tendenza alla trombosi e la viscosità del sangue, fornendo una nuova visione dei meccanismi della malattia. L'ipossia intermittente notturna cronica tipica dell'OSAS insieme alle alterazioni macro e micro strutturali del sonno e la conseguente induzione ematica di stress ossidativo infiammatorio cronico cellulare con alterazioni genetiche possono contemporaneamente allo sviluppo di aterosclerosi precoce, rappresentare anche un meccanismo sottostante a lungo termine che induce atipie cellulari e patogenesi e progressione del cancro

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Most cited references 48

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Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort.

Terry Young, Laurel Ann Finn, Paul Peppard … (2008)

Sleep-disordered breathing (SDB) is a treatable but markedly under-diagnosed condition of frequent breathing pauses during sleep. SDB is linked to incident cardiovascular disease, stroke, and other morbidity. However, the risk of mortality with untreated SDB, determined by polysomnography screening, in the general population has not been established. An 18-year mortality follow-up was conducted on the population-based Wisconsin Sleep Cohort sample (n = 1522), assessed at baseline for SDB with polysomnography, the clinical diagnostic standard. SDB was described by the number of apnea and hypopnea episodes/hour of sleep; cutpoints at 5, 15 and 30 identified mild, moderate, and severe SDB, respectively. Cox proportional hazards regression was used to estimate all-cause and cardiovascular mortality risks, adjusted for potential confounding factors, associated with SDB severity levels. All-cause mortality risk, adjusted for age, sex, BMI, and other factors was significantly increased with SDB severity. The adjusted hazard ratio (HR, 95% CI) for all-cause mortality with severe versus no SDB was 3.0 (1.4,6.3). After excluding persons who had used CPAP treatment (n = 126), the adjusted HR (95% CI) for all-cause mortality with severe versus no SDB was 3.8 (1.6,9.0); the adjusted HR (95% CI) for cardiovascular mortality was 5.2 (1.4,19.2). Results were unchanged after accounting for daytime sleepiness. Our findings of a significant, high mortality risk with untreated SDB, independent of age, sex, and BMI underscore the need for heightened clinical recognition and treatment of SDB, indicated by frequent episodes of apnea and hypopnea, irrespective of symptoms of sleepiness.

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Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities.

W McNicholas, M R Bonsigore, M Bonsignore (2007)

Considerable evidence is available in support of an independent association between obstructive sleep apnoea syndrome (OSAS) and cardiovascular disease, which is particularly strong for systemic arterial hypertension and growing for ischaemic heart disease, stroke, heart failure, atrial fibrillation and cardiac sudden death. The pathogenesis of cardiovascular disease in OSAS is not completely understood but likely to be multifactorial, involving a diverse range of mechanisms including sympathetic nervous system overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. The present report, which arose out of a European Union Cooperation in the field of Scientific and Technical Research (COST) action on OSAS (COST B26), reviews the current evidence for an independent association and proposes research priorities to identify the underlying mechanisms involved, with a view to identifying novel therapeutic strategies. Large-scale collaborative studies of carefully defined patient populations with obstructive sleep apnoea syndrome, adequately controlled for potential confounders, are needed. Such studies carry the prospect of evaluating potential interactions between different basic mechanisms operating in obstructive sleep apnoea syndrome and cardiovascular disease, and interactions with other related disorders, such as obesity, diabetes and dyslipidaemia. Furthermore, translational studies involving cell culture and animal models linked to studies of obstructive sleep apnoea syndrome patients are necessary to integrate basic mechanisms with the clinical disorder.

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Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study.

P. Liu, Carlos K. H. Wong, M Knuiman … (2008)

Previously published cohort studies in clinical populations have suggested that obstructive sleep apnea (OSA) is a risk factor for mortality associated with cardiovascular disease. However, it is unknown whether sleep apnea is an independent risk factor for all-cause mortality in a community-based sample free from clinical referral bias. Residents of the Western Australian town of Busselton underwent investigation with a home sleep apnea monitoring device (MESAM IV). OSA was quantified via the respiratory disturbance index (RDI). Mortality status was determined in 397/400 participants (99.3%) after up to 14 years (mean follow-up 13.4 years) by data matching with the Australian National Death Index and the Western Australian Death Register. Univariate analyses and multivariate Cox proportional hazards modelling were used to ascertain the association between sleep apnea and mortality after adjustment for age, gender, body mass index, mean arterial pressure, total cholesterol, high-density lipoprotein cholesterol, diabetes, and medically diagnosed angina in those free from heart attack or stroke at baseline (n = 380). Among the 380 participants, 18 had moderate-severe OSA (RDI > or = 15/hr, 6 deaths) and 77 had mild OSA(RDI 5 to < 15/hr, 5 deaths). Moderate-to-severe OSA was independently associated with greater risk of all-cause mortality (fully adjusted hazard ratio [HR] = 6.24, 95% CL 2.01, 19.39) than non-OSA (n = 285, 22 deaths). Mild OSA (RDI 5 to < 15/hr) was not an independent risk factor for higher mortality (HR = 0.47, 95% CL 0.17, 1.29). Moderate-to-severe sleep apnea is independently associated with a large increased risk of all-cause mortality in this community-based sample.

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Author and article information

Journal

Journal ID (nlm-ta): Acta Otorhinolaryngol Ital

Journal ID (iso-abbrev): Acta Otorhinolaryngol Ital

Journal ID (publisher-id): Pacini

Title: Acta Otorhinolaryngologica Italica

Publisher: Pacini Editore SpA

ISSN (Print): 0392-100X

ISSN (Electronic): 1827-675X

Publication date (Print): April 2015

Volume: 35

Issue: 2

Pages: 69-74

Affiliations

[1 ] "V. Fazzi" Hospital Rehabilitation Dept, Respiratory Care Unit, ASL Lecce, Italy;

[2 ] Laboratory of Human Anatomy and Neuroscience, Dept. of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy;

[3 ] "V. Fazzi" Hospital, ENT Unit, ASL Lecce, Italy;

[4 ] Institute of Clinical Physiology, National Research Council (CNR), Lecce, Italy

Author notes

Address for correspondence: Domenico M. Toraldo, via A.C. Casetti 2, 73100 Lecce, Italy. E-mail: d.torald@ 123456tin.it

Article

Publisher ID: Pacini

PMC ID: 4443563

PubMed ID: 26019388

SO-VID: 8043a246-8140-4810-806f-a6d39fa0297c

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License, which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way. For details, please refer to http://creativecommons.org/licenses/by-nc-nd/3.0/

Obstructive sleep apnoea syndrome: a new paradigm by chronic nocturnal intermittent hypoxia and sleep disruption Translated title: Ipossia cronica intermittente notturna e alterazioni dell'architettura del sonno: nuovo paradigma causale dell'aterosclerosi e cancro

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RIASSUNTO

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Most cited references 48

Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort.

Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities.

Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study.

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