Obstructive sleep apnoea and venous thromboembolism: pathophysiological links and clinical implications

García-Ortega, Alberto; Baena, Eva Mañas; López‐Reyes, Raquel; Selma, María José; García‐Sánchez, Aldara; Oscullo, Grace; Jiménez, David; Martínez‐García, Miguel Ángel

doi:10.1183/13993003.00893-2018

Cited by 34 publications

(25 citation statements)

References 124 publications

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“…OSA has been identified as an independent risk factor for a large number of diseases. Among these, acute coronary syndrome (ACS) [ 111 ], atrial fibrillation (AF) [ 112 , 113 ], stroke [ 114 ], and venous thromboembolism (VTE) [ 115 , 116 ] are prominently represented.…”

Section: Potential Therapiesmentioning

confidence: 99%

Obstructive Sleep Apnea, Hypercoagulability, and the Blood–Brain Barrier

Zolotoff

Bertoletti

Gozal

et al. 2021

JCM

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Obstructive sleep apnea (OSA) is characterized by repeated episodes of intermittent hypoxia (IH) and is recognized as an independent risk factor for vascular diseases that are mediated by a multitude of mechanistic pathophysiological cascades including procoagulant factors. The pro-coagulant state contributes to the development of blood clots and to the increase in the permeability of the blood–brain barrier (BBB). Such alteration of BBB may alter brain function and increase the risk of neurodegenerative diseases. We aim to provide a narrative review of the relationship between the hypercoagulable state, observed in OSA and characterized by increased coagulation factor activity, as well as platelet activation, and the underlying neural dysfunction, as related to disruption of the BBB. We aim to provide a critical overview of the existing evidence about the effect of OSA on the coagulation balance (characterized by increased coagulation factor activity and platelet activation) as on the BBB. Then, we will present the emerging data on the effect of BBB disruption on the risk of underlying neural dysfunction. Finally, we will discuss the potential of OSA therapy on the coagulation balance and the improvement of BBB.

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Section: Potential Therapiesmentioning

confidence: 99%

Obstructive Sleep Apnea, Hypercoagulability, and the Blood–Brain Barrier

Zolotoff

Bertoletti

Gozal

et al. 2021

JCM

View full text Add to dashboard Cite

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“…Chronic intermittent hypoxia and increased sympathetic tone induce production of pro-inflammatory molecules, such as interleukin (IL)-6, IL-1β, tumour necrosis factor-α [1] or complement elements [2] and suppresses the release of anti-inflammatory [3,4] molecules. Linked to inflammation and sympathetic activity, OSA is characterised by a hypercoagulation state [5][6][7][8][9]. Accelerated systemic inflammation and increased coagulation may contribute to the development of cardiovascular disease and acute cardiovascular events [10].…”

Section: Introductionmentioning

confidence: 99%

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea

et al. 2020

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Background and Objectives: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. Materials and Methods: A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. Results: There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, p = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, p = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, p < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, p = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, p < 0.01). Conclusions: Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.Medicina 2020, 56, 77 2 of 10 Soluble urokinase-type plasminogen activator receptor (suPAR) is a molecule which plays a role in both inflammation and coagulation. It is produced upon cleavage of the membrane-bound urokinase-type plasminogen activator receptor (uPAR). The cleavage is facilitated by urokinase-type plasminogen activator (uPA), plasmin, matrix metalloproteases, neutrophil elastase and cathepsin G [11]. The urokinase receptor (also known as uPAR) is expressed by endothelial cells, macrophages, monocytes, neutrophils, lymphocytes, smooth muscle cells and fibroblasts [12,13]. It is upregulated under infections and as an effect of pro-inflammatory cytokines [11,[13][14][15], while suPAR contributes to plasminogen activation, cell adhesion, chemotaxis and immune cell activation [16]. However, uPAR also acts as a scavenger receptor for uPA, inhibiting its actions [17]. In large studies, plasma suPAR was elevated in coronary artery disease and cerebrovascular disease and correlated with their severity and cardiovascular mortality [18][19][20]. Higher suPAR levels were also observed in obesity [21], which is the main etiological factor for OSA in the Western population [22].Only one study has investigated suPAR in probable OSA so far [23]. Patients were categorised to high and low-risk OSA based on the Berlin questionnaire and neck circumferences; however, no objective sleep tests were performed. In this study, there was a tendency for higher suPAR levels in the high-risk group, but...

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“…Recent research indicates that sleep-disordered breathing might be an independent risk factor for venous thromboembolism 15. However, it is still unknown if sleep-disordered breathing has any impact on the clinical course of PE or if nocturnal CPAP therapy can potentially prevent PE recurrence.…”

Section: Methods and Analysismentioning

confidence: 99%

Long-term outcomes in patients with acute pulmonary embolism after in-hospital treatment: study protocol of the prospective Lungenembolie Augsburg Studie (LEA study)

et al. 2019

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IntroductionAcute pulmonary embolism (PE) is a frequent life-threatening event and an important cause of hospitalisation, morbidity and mortality worldwide. Limited information on the long-term course of PE patients is available so far. The Lungenembolie Augsburg study will provide a view on the predisposing and PE-provoking factors, diagnostic procedures and short as well as long-term treatment options. Especially, the data on the long-term course of the disease—in combination with omics data obtained in biospecimens—will generate new knowledge regarding triggers, disease progression, treatment, long-term sequelae, prognosis and prevention of disease recurrence.Methods and analysisIn this prospective study, we will include about 1000 patients admitted to the university hospital of Augsburg, aged 18 years and older with a confirmed diagnosis of acute PE. At baseline, demographic information, symptoms on presentation, delay in diagnosis, predisposing and PE-provoking factors, comorbidity, quality of life, symptoms of anxiety and depression, information on invasive and non-invasive treatment procedures, complications and laboratory parameters will be collected. During the hospital stay, 30 mL blood will be collected from the patients, processed, aliquoted and frozen at −80°C. In a subgroup of patients, an eight-channel polygraphy will be carried out to assess sleep-disordered breathing. All study participants will be followed up for 60 months via postal questionnaires or telephone interviews after hospital discharge. Long-term survival, bleeding complications and PE recurrence during the follow-up are the primary study outcomes. To identify risk factors and determinants associated with these outcomes, confounder-adjusted Cox-regressions will be used for modelling and to estimate relative risks. Effect modification by age and sex will be examined.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Ludwig-Maximilians-Universität München (Date of approval: 1 August 2017, Reference number: 17-378). Study results will be presented at national and international conferences and published in peer-reviewed scientific journals.

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Obstructive sleep apnoea and venous thromboembolism: pathophysiological links and clinical implications

Cited by 34 publications

References 124 publications

Obstructive Sleep Apnea, Hypercoagulability, and the Blood–Brain Barrier

Obstructive Sleep Apnea, Hypercoagulability, and the Blood–Brain Barrier

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea

Long-term outcomes in patients with acute pulmonary embolism after in-hospital treatment: study protocol of the prospective Lungenembolie Augsburg Studie (LEA study)

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