High prevalence of peripheral arterial disease in patients with obstructive sleep apnoea

Schaefer, Christian; Adam, Luise; Weisser-Thomas, Jutta; Pingel, Simon; Vogel, G; Klarmann‐Schulz, Ute; Nickenig, Georg; Pizarro, Carmen; Skowasch, Dirk

doi:10.1007/s00392-015-0834-3

Cited by 39 publications

(34 citation statements)

References 41 publications

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“…Indeed, ankle-brachial PWV assesses arterial stiffness over the aortic segment and also in the lower limbs. The brachial-ankle PWV or the Cardio-Ankle Vascular Index (CAVI), another non-standard measure of arterial stiffness, should not be used in patients with peripheral arterial disease (PAD), a very highly prevalent condition in patients with OSA 32. Alberto et al carefully excluded patients with PAD in their study and only observed a non-significant trend between CAVI and nocturnal intermittent hypoxia 33…”

Section: Discussionmentioning

confidence: 99%

Contribution of obstructive sleep apnoea to arterial stiffness: a meta-analysis using individual patient data

Joyeux‐Faure

Tamisier

Borel

et al. 2018

Thorax

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Section: Discussionmentioning

confidence: 99%

Contribution of obstructive sleep apnoea to arterial stiffness: a meta-analysis using individual patient data

Joyeux‐Faure

Tamisier

Borel

et al. 2018

Thorax

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“…The presence of altered concentrations, cell sources, and intrinsic properties of circulating microvesicles have been previously noted by several investigators in the context of OSA, whereby the ability of these microvesicles to induce coagulation, angiogenesis, and cell adhesion was noted, and globally believed to reflect a proatherogenic state. 9,[42][43][44][45] The enhanced pro-atherogenic state of OSA is further exemplified by not only the high cardiovascular morbidity burden of this condition, 46 but also by the elevated prevalence of peripheral vascular disease in OSA patients, 47 and multiple investigators have explored the vascular consequences of OSA in different settings. [48][49][50] Our study relied on healthy young adults subjected to a relatively brief IH exposure, such that we can only infer that more chronic exposures to IH in the context of OSA may further exacerbate the pathological changes induced by the disease, and hypothesize that the exosome-related activity on the endothelium will contribute to such processes, as illustrated by the current in vitro experiments.…”

Section: Discussionmentioning

confidence: 99%

Effect on Intermittent Hypoxia on Plasma Exosomal Micro RNA Signature and Endothelial Function in Healthy Adults

Khalyfa

Zhang

Khalyfa

et al. 2016

Sleep

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Study Objective: Intermittent hypoxia (IH) is associated with increased risk of cardiovascular disease. Exosomes are secreted by most cell types and released in biological fluids, including plasma, and play a role in modifying the functional phenotype of target cells. Using an experimental human model of IH, we investigated potential exosome-derived biomarkers of IH-induced vascular dysfunction. Methods: Ten male volunteers were exposed to room air (D0), IH (6 h/day) for 4 days (D4) and allowed to recover for 4 days (D8). Circulating plasma exosomes were isolated and incubated with human endothelial monolayer cultures for impedance measurements and RNA extracted and processed with messenger RNA (mRNA) arrays to identify gene targets. In addition, immunofluorescent assessments of endothelial nitric oxide synthase (eNOS) mRNA expression, ICAM-1 cellular distribution were conducted. Results: Plasma exosomal micro RNAs (miRNAs) were profiled. D4 exosomes, primarily from endothelial sources, disrupted impedance levels compared to D0 and D8. ICAM-1 expression was markedly upregulated in endothelial cells exposed to D4 exosomes along with significant reductions in eNOS expression. Microarray approaches identified a restricted and further validated signature of exosomal miRNAs in D4 exosomes, and mRNA arrays revealed putative endothelial gene target pathways. Conclusions:In humans, intermittent hypoxia alters exosome cargo in the circulation which promotes increased permeability and dysfunction of endothelial cells in vitro. A select number of circulating exosomal miRNAs may play important roles in the cardiovascular dysfunction associated with OSA by targeting specific effector pathways.

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“…Similarly, in a Taiwanese nationwide case-control study using population-based claims data, cases with sleep apnea diagnosed by clinical symptoms and/or AHI≥5 events/hr were 30% more likely to have been diagnosed with PAD than controls [20]. Additionally, in small clinical samples (N≤100), prevalent PAD among patients with suspected sleep apnea was high [21], as was prevalent sleep apnea among PAD patients needing surgical revascularization[22]. Sleep apnea defined by AHI≥20 was also associated with long-term morbidity and mortality after surgical revascularization in 84 PAD patients[23].…”

Section: Discussionmentioning

confidence: 99%

Association of sleep apnea and sleep duration with peripheral artery disease: The Multi-Ethnic Study of Atherosclerosis (MESA)

et al. 2016

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Background and aims Numerous biological pathways linking sleep disturbances to atherosclerosis have been identified, such as insulin resistance, inflammation, hypertension, and endothelial dysfunction. Yet, the association of sleep apnea and sleep duration with peripheral artery disease (PAD) is not well characterized. Methods We evaluated the cross-sectional association between objectively measured sleep and prevalent PAD in 1,844 participants (mean age 68 years) who in 2010–2013 had in-home polysomnography, 7-day wrist actigraphy and ankle-brachial index (ABI) measurements. We also evaluated the relation between self-reported diagnosed sleep apnea and PAD incidence in 5,365 participants followed from 2000 to 2012. PAD was defined as ABI<0.90. Results In cross-sectional analyses, severe sleep apnea [apnea-hypopnea index (AHI) ≥30 vs. AHI <5] was associated with greater prevalent PAD only among black participants [multivariate adjusted prevalence ratio (95% CI): 2.29 (1.07–4.89); p-interaction = 0.05]. Short and long sleep duration was also associated with a 2-fold higher prevalence of PAD as compared with those who slept 7h/night, in the full sample. In longitudinal analyses, participants with self-reported diagnosed sleep apnea were at higher risk of incident PAD [multivariable adjusted hazard ratio (95% CI): 1.93 (1.05–3.53)], with no evidence of interaction by race/ethnicity. Conclusions These findings support a significant association between sleep apnea and prevalent and incident PAD, with evidence for stronger associations with objectively measured sleep apnea and cross sectional PAD in blacks. In addition, short and long sleep duration was associated with PAD. These results identify sleep disturbances as a potential risk factor for PAD.

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High prevalence of peripheral arterial disease in patients with obstructive sleep apnoea

Abstract: OSA is associated with a high prevalence of PAD. This implies substantial diseasés under-recognition and a presumable atherogenic role of OSA in the pathogenesis of PAD. However, vasoprotective impact of OSA treatment remains to be determined.

Cited by 39 publications

References 41 publications

Contribution of obstructive sleep apnoea to arterial stiffness: a meta-analysis using individual patient data

Contribution of obstructive sleep apnoea to arterial stiffness: a meta-analysis using individual patient data

Effect on Intermittent Hypoxia on Plasma Exosomal Micro RNA Signature and Endothelial Function in Healthy Adults

Association of sleep apnea and sleep duration with peripheral artery disease: The Multi-Ethnic Study of Atherosclerosis (MESA)

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