RSS-Feed abonnieren
PDF herunterladen
DOI: 10.1055/a-2308-2290
The Association between Obstructive Sleep Apnea and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study
Funding This study was supported by the High-level Talents Scientific Research Start-up Funds of the Affiliated Hospital of Guangdong Medical University (GCC2022028), the Health Development Promotion Project-Anesthesia and Critical Care Research Project (KM-20231120-01), Guangdong Medical Research Fund Project (A2024728, A2024723), Zhanjiang Science and Technology Research Project in 2022 (No: 2022A01197), and the Science and Technology Development Special Fund Competitive Allocation Project of Zhanjiang City (No: 2021A05086).
Abstract
Background Despite previous observational studies linking obstructive sleep apnea (OSA) to venous thromboembolism (VTE), these findings remain controversial. This study aimed to explore the association between OSA and VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), at a genetic level using a bidirectional two-sample Mendelian randomization (MR) analysis.
Methods Utilizing summary-level data from large-scale genome-wide association studies in European individuals, we designed a bidirectional two-sample MR analysis to comprehensively assess the genetic association between OSA and VTE. The inverse variance weighted was used as the primary method for MR analysis. In addition, MR–Egger, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for complementary analyses. Furthermore, a series of sensitivity analyses were performed to ensure the validity and robustness of the results.
Results The initial and validation MR analyses indicated that genetically predicted OSA had no effects on the risk of VTE (including PE and DVT). Likewise, the reverse MR analysis did not find substantial support for a significant association between VTE (including PE and DVT) and OSA. Supplementary MR methods and sensitivity analyses provided additional confirmation of the reliability of the MR results.
Conclusion Our bidirectional two-sample MR analysis did not find genetic evidence supporting a significant association between OSA and VTE in either direction.
Data Availability Statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Authors' Contribution
All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.
* These authors contributed equally to this study.
Publikationsverlauf
Eingereicht: 27. November 2023
Angenommen: 11. April 2024
Accepted Manuscript online:
17. April 2024
Artikel online veröffentlicht:
23. Mai 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Wang SH, Chen WS, Tang SE. et al. Benzodiazepines associated with acute respiratory failure in patients with obstructive sleep apnea. Front Pharmacol 2019; 9: 1513
- 2 Innes CR, Kelly PT, Hlavac M, Melzer TR, Jones RD. Decreased regional cerebral perfusion in moderate-severe obstructive sleep apnoea during wakefulness. Sleep 2015; 38 (05) 699-706
- 3 Senaratna CV, Perret JL, Lodge CJ. et al. Prevalence of obstructive sleep apnea in the general population: a systematic review. Sleep Med Rev 2017; 34: 70-81
- 4 Bai J, Wen H, Tai J. et al. Altered spontaneous brain activity related to neurologic and sleep dysfunction in children with obstructive sleep apnea syndrome. Front Neurosci 2021; 15: 595412
- 5 Marin JM, Agusti A, Villar I. et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA 2012; 307 (20) 2169-2176
- 6
Redline S,
Yenokyan G,
Gottlieb DJ.
et al.
Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study.
Am J Respir Crit Care Med 2010; 182 (02) 269-277
MissingFormLabel
- 7 Mesarwi O, Malhotra A. Obstructive sleep apnea and pulmonary hypertension: a bidirectional relationship. J Clin Sleep Med 2020; 16: 1223-1224
- 8 Piccirillo F, Crispino SP, Buzzelli L, Segreti A, Incalzi RA, Grigioni F. A state-of-the-art review on sleep apnea syndrome and heart failure. Am J Cardiol 2023; 195: 57-69
- 9 Glise Sandblad K, Rosengren A, Sörbo J, Jern S, Hansson PO. Pulmonary embolism and deep vein thrombosis-comorbidities and temporary provoking factors in a register-based study of 1.48 million people. Res Pract Thromb Haemost 2022; 6 (04) e12714
- 10 Raj R, Paturi A, Ahmed MA, Thomas SE, Gorantla VR. Obstructive sleep apnea as a risk factor for venous thromboembolism: a systematic review. Cureus 2022; 14 (02) e22729
- 11 Lin CC, Keller JJ, Kang JH, Hsu TC, Lin HC. Obstructive sleep apnea is associated with an increased risk of venous thromboembolism. J Vasc Surg Venous Lymphat Disord 2013; 1 (02) 139-145
- 12 Peng YH, Liao WC, Chung WS. et al. Association between obstructive sleep apnea and deep vein thrombosis / pulmonary embolism: a population-based retrospective cohort study. Thromb Res 2014; 134 (02) 340-345
- 13 Nepveu O, Orione C, Tromeur C. et al. Association between obstructive sleep apnea and venous thromboembolism recurrence: results from a French cohort. Thromb J 2022; 20 (01) 1
- 14 Dabbagh O, Sabharwal M, Hassan O. et al. Obstructive sleep apnea is an independent risk factor for venous thromboembolism among females not males. Chest 2010; 138: 937A-937A
- 15 Bosanquet JP, Bade BC, Zia MF. et al. Patients with venous thromboembolism appear to have higher prevalence of obstructive sleep apnea than the general population. Clin Appl Thromb Hemost 2011; 17 (06) E119-E124
- 16 Xue A, Jiang L, Zhu Z. et al. Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes. Nat Commun 2021; 12 (01) 20211
- 17 Pu B, Gu P, Zheng C, Ma L, Zheng X, Zeng Z. Self-reported and genetically predicted effects of coffee intake on rheumatoid arthritis: epidemiological studies and Mendelian randomization analysis. Front Nutr 2022; 9: 926190
- 18 Jiang L, Zheng Z, Fang H, Yang J. A generalized linear mixed model association tool for biobank-scale data. Nat Genet 2021; 53 (11) 1616-1621
- 19 Campos AI, Ingold N, Huang Y. et al; 23andMe Research Team. Discovery of genomic loci associated with sleep apnea risk through multi-trait GWAS analysis with snoring. Sleep 2023; 46 (03) 46
- 20 Feng R, Lu M, Xu J. et al. Pulmonary embolism and 529 human blood metabolites: genetic correlation and two-sample Mendelian randomization study. BMC Genom Data 2022; 23 (01) 69
- 21 Molenberg R, Thio CHL, Aalbers MW. et al; ISGC Intracranial Aneurysm Working Group*. Sex hormones and risk of aneurysmal subarachnoid hemorrhage: a Mendelian randomization study. Stroke 2022; 53 (09) 2870-2875
- 22 Wang SH, Keenan BT, Wiemken A. et al. Effect of weight loss on upper airway anatomy and the apnea-hypopnea index. the importance of tongue fat. Am J Respir Crit Care Med 2020; 201 (06) 718-727
- 23 Hotoleanu C. Association between obesity and venous thromboembolism. Med Pharm Rep 2020; 93 (02) 162-168
- 24 Zhao H, Jin X. Causal associations between dietary antioxidant vitamin intake and lung cancer: a Mendelian randomization study. Front Nutr 2022; 9: 965911
- 25 Tang B, Wang Y, Jiang X. et al. Genetic variation in targets of antidiabetic drugs and Alzheimer disease risk: a Mendelian randomization study. Neurology 2022; 99 (07) e650-e659
- 26 Dong SS, Zhang K, Guo Y. et al. Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study. Genome Med 2021; 13 (01) 48
- 27 Huang W, Xiao J, Ji J, Chen L. Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study. eLife 2021; 10: 10
- 28 Chen X, Kong J, Pan J. et al. Kidney damage causally affects the brain cortical structure: a Mendelian randomization study. EBioMedicine 2021; 72: 103592
- 29 Arnulf I, Merino-Andreu M, Perrier A, Birolleau S, Similowski T, Derenne JP. Obstructive sleep apnea and venous thromboembolism. JAMA 2002; 287 (20) 2655-2656
- 30 Chou KT, Huang CC, Chen YM. et al. Sleep apnea and risk of deep vein thrombosis: a non-randomized, pair-matched cohort study. Am J Med 2012; 125 (04) 374-380
- 31 Alonso-Fernández A, de la Peña M, Romero D. et al. Association between obstructive sleep apnea and pulmonary embolism. Mayo Clin Proc 2013; 88 (06) 579-587
- 32 Ambrosetti M, Lucioni A, Ageno W, Conti S, Neri M. Is venous thromboembolism more frequent in patients with obstructive sleep apnea syndrome?. J Thromb Haemost 2004; 2 (10) 1858-1860
- 33 Reutrakul S, Mokhlesi B. Obstructive sleep apnea and diabetes: a state of the art review. Chest 2017; 152 (05) 1070-1086
- 34 Lindström S, Germain M, Crous-Bou M. et al; INVENT Consortium. Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Hum Genet 2017; 136 (07) 897-902
- 35 Genuardi MV, Rathore A, Ogilvie RP. et al. Incidence of VTE in patients with OSA: a cohort study. Chest 2022; 161 (04) 1073-1082
- 36 Aman R, Michael VG, Rachel PO. et al Obstructive sleep apnea does not increase risk of venous thromboembolism. American Thoracic Society 2019; A4459-A4459
- 37 Esmon CT. Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev 2009; 23 (05) 225-229
- 38 García-Ortega A, Mañas E, López-Reyes R. et al. Obstructive sleep apnoea and venous thromboembolism: pathophysiological links and clinical implications. Eur Respir J 2019; 53 (02) 53
- 39 Xiong H, Lao M, Wang L. et al. The incidence of cancer is increased in hospitalized adult patients with obstructive sleep apnea in China: a retrospective cohort study. Front Oncol 2022; 12: 856121
- 40 Holt A, Bjerre J, Zareini B. et al. Sleep apnea, the risk of developing heart failure, and potential benefits of continuous positive airway pressure (CPAP) therapy. J Am Heart Assoc 2018; 7 (13) e008684
- 41 Alonso-Fernández A, Toledo-Pons N, García-Río F. Obstructive sleep apnea and venous thromboembolism: overview of an emerging relationship. Sleep Med Rev 2020; 50: 101233
- 42 Hong SN, Yun HC, Yoo JH, Lee SH. Association between hypercoagulability and severe obstructive sleep apnea. JAMA Otolaryngol Head Neck Surg 2017; 143 (10) 996-1002
- 43 Robinson GV, Pepperell JC, Segal HC, Davies RJ, Stradling JR. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 2004; 59 (09) 777-782
- 44 von Känel R, Loredo JS, Powell FL, Adler KA, Dimsdale JE. Short-term isocapnic hypoxia and coagulation activation in patients with sleep apnea. Clin Hemorheol Microcirc 2005; 33 (04) 369-377
- 45 Zolotoff C, Bertoletti L, Gozal D. et al. Obstructive sleep apnea, hypercoagulability, and the blood-brain barrier. J Clin Med 2021; 10 (14) 3099