Causal association between obstructive sleep apnea and venous thromboembolism: a Mendelian randomization study_West China Medical Journal

Authors：

FANG Zixuan ¹ , GUO Weijian ¹ , CHEN Jiasong ¹ , CHEN Lihong ¹ ,  WU Hui ²

1. The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510000, P. R. China;
2. Department of Cardiology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510000, P. R. China;

Corresponding author：

WU Hui, Email: wuhui026@126.com

Keywords：

Obstructive sleep apnea; venous thromboembolism; deep vein thrombosis; pulmonary embolism; Mendelian randomization

DOI：

10.7507/1002-0179.202410137

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To explore the causal association between obstructive sleep apnea (OSA) and venous thromboembolism (VTE). Methods Using the summary statistical data from the FinnGen biological sample library and IEU OpenGWAS database, the relationship between OSA and VTE, including deep vein thrombosis (DVT) and pulmonary embolism, was explored through Mendelian randomization (MR) method, with inverse variance weighted (IVW) as the main analysis method. Results The results of univariate MR analysis using IVW method showed that OSA was associated with VTE and pulmonary embolism (P<0.05), with odds ratios and 95% confidence intervals of 1.204 (1.067, 1.351) and 1.352 (1.179, 1.544), respectively. There was no correlation with DVT (P>0.05). Multivariate MR analysis showed that after adjustment for confounding factors (smoking, diabetes, obesity and cancer), OSA was associated with VTE, DVT and pulmonary embolism (P<0.05), with odds ratios and 95% confidence intervals of 1.168 (1.053, 1.322), 1.247 (1.064, 1.491) and 1.158 (1.021, 1.326), respectively. Conclusion OSA increases the risk of VTE, DVT, and pulmonary embolism.

Citation： FANG Zixuan, GUO Weijian, CHEN Jiasong, CHEN Lihong, WU Hui. Causal association between obstructive sleep apnea and venous thromboembolism: a Mendelian randomization study. West China Medical Journal, 2025, 40(8): 1283-1287. doi: 10.7507/1002-0179.202410137 Copy

1.	黄佳, 黄浩贤, 陆立基, 等. 阻塞性睡眠呼吸暂停综合征患者困难气道评估的研究. 实用医学杂志, 2024, 40(10): 1460-1466.
2.	Benjafield AV, Ayas NT, Eastwood PR, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med, 2019, 7(8): 687-698.
3.	Kapur VK, Baldwin CM, Resnick HE, et al. Sleepiness in patients with moderate to severe sleep-disordered breathing. Sleep, 2005, 28(4): 472-477.
4.	Canessa N, Castronovo V, Cappa SF, et al. Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment. Am J Respir Crit Care Med, 2011, 183(10): 1419-1426.
5.	Lévy P, Bonsignore MR, Eckel J. Sleep, sleep-disordered breathing and metabolic consequences. Eur Respir J, 2009, 34(1): 243-260.
6.	McNicholas WT, Bonsigore MR, Management Committee of EU COST ACTION B26. Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J, 2007, 29(1): 156-178.
7.	McColl MD, Ellison J, Greer IA, et al. Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism. Br J Haematol, 2000, 108(2): 272-274.
8.	Hawkins D. The role of oral direct thrombin inhibitors in the prophylaxis of venous thromboembolism. Pharmacotherapy, 2004, 24(10): 179S-183S.
9.	Arzt M, Luigart R, Schum C, et al. Sleep-disordered breathing in deep vein thrombosis and acute pulmonary embolism. Eur Respir J, 2012, 40(4): 919-924.
10.	D’Apuzzo MR, Browne JA. Obstructive sleep apnea as a risk factor for postoperative complications after revision joint arthroplasty. J Arthroplasty, 2012, 27(Suppl 8): 95-98.
11.	Mraovic B, Hipszer BR, Epstein RH, et al. Preadmission hyperglycemia is an independent risk factor for in-hospital symptomatic pulmonary embolism after major orthopedic surgery. J Arthroplasty, 2010, 25(1): 64-70.
12.	Memtsoudis S, Liu SS, Ma Y, et al. Perioperative pulmonary outcomes in patients with sleep apnea after noncardiac surgery. Anesth Analg, 2011, 112(1): 113-121.
13.	Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520, 000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet, 2018, 50(4): 524-537.
14.	Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ, 2018, 362: k601.
15.	Hemani G, Zheng J, Elsworth B, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
16.	Yavorska OO, Burgess S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol, 2017, 46(6): 1734-1739.
17.	Osman AM, Carter SG, Carberry JC, et al. Obstructive sleep apnea: current perspectives. Nat Sci Sleep, 2018, 10: 21-34.
18.	Lippi G, Mattiuzzi C, Franchini M. Sleep apnea and venous thromboembolism. A systematic review. Thromb Haemost, 2015, 114(5): 958-963.
19.	Lin CC, Keller JJ, Kang JH, et al. Obstructive sleep apnea is associated with an increased risk of venous thromboembolism. J Vasc Surg Venous Lymphat Disord, 2013, 1(2): 139-145.
20.	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(2): 340-345.
21.	Esmon CT. Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev, 2009, 23(5): 225-229.
22.	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(2): 1800893.
23.	Ageno W, Becattini C, Brighton T, et al. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation, 2008, 117(1): 93-102.
24.	Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: a review. Open J Prev Med, 2012, 2(4): 499-509.
25.	Wang J, Yu W, Gao M, et al. Impact of obstructive sleep apnea syndrome on endothelial function, arterial stiffening, and serum inflammatory markers: an updated meta-analysis and metaregression of 18 studies. J Am Heart Assoc, 2015, 4(11): e002454.
26.	Thomas SR, Chen K, Keaney JF Jr. Hydrogen peroxide activates endothelial nitric-oxide synthase through coordinated phosphorylation and dephosphorylation via a phosphoinositide 3-kinase-dependent signaling pathway. J Biol Chem, 2002, 277(8): 6017-6024.
27.	Tanaka T, Nakamura H, Yodoi J, et al. Redox regulation of the signaling pathways leading to eNOS phosphorylation. Free Radic Biol Med, 2005, 38(9): 1231-1242.
28.	Kokturk O, Ciftci TU, Mollarecep E, et al. Elevated C-reactive protein levels and increased cardiovascular risk in patients with obstructive sleep apnea syndrome. Int Heart J, 2005, 46(5): 801-809.
29.	von Känel R, Loredo JS, Ancoli-Israel S, et al. Association between sleep apnea severity and blood coagulability: treatment effects of nasal continuous positive airway pressure. Sleep Breath, 2006, 10(3): 139-146.
30.	Huang Z, Zheng Z, Pang L, et al. The association between obstructive sleep apnea and venous thromboembolism: a bidirectional two-sample mendelian randomization study. Thromb Haemost, 2024, 124(11): 1061-1074.

1. 黄佳, 黄浩贤, 陆立基, 等. 阻塞性睡眠呼吸暂停综合征患者困难气道评估的研究. 实用医学杂志, 2024, 40(10): 1460-1466.
2. Benjafield AV, Ayas NT, Eastwood PR, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med, 2019, 7(8): 687-698.
3. Kapur VK, Baldwin CM, Resnick HE, et al. Sleepiness in patients with moderate to severe sleep-disordered breathing. Sleep, 2005, 28(4): 472-477.
4. Canessa N, Castronovo V, Cappa SF, et al. Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment. Am J Respir Crit Care Med, 2011, 183(10): 1419-1426.
5. Lévy P, Bonsignore MR, Eckel J. Sleep, sleep-disordered breathing and metabolic consequences. Eur Respir J, 2009, 34(1): 243-260.
6. McNicholas WT, Bonsigore MR, Management Committee of EU COST ACTION B26. Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J, 2007, 29(1): 156-178.
7. McColl MD, Ellison J, Greer IA, et al. Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism. Br J Haematol, 2000, 108(2): 272-274.
8. Hawkins D. The role of oral direct thrombin inhibitors in the prophylaxis of venous thromboembolism. Pharmacotherapy, 2004, 24(10): 179S-183S.
9. Arzt M, Luigart R, Schum C, et al. Sleep-disordered breathing in deep vein thrombosis and acute pulmonary embolism. Eur Respir J, 2012, 40(4): 919-924.
10. D’Apuzzo MR, Browne JA. Obstructive sleep apnea as a risk factor for postoperative complications after revision joint arthroplasty. J Arthroplasty, 2012, 27(Suppl 8): 95-98.
11. Mraovic B, Hipszer BR, Epstein RH, et al. Preadmission hyperglycemia is an independent risk factor for in-hospital symptomatic pulmonary embolism after major orthopedic surgery. J Arthroplasty, 2010, 25(1): 64-70.
12. Memtsoudis S, Liu SS, Ma Y, et al. Perioperative pulmonary outcomes in patients with sleep apnea after noncardiac surgery. Anesth Analg, 2011, 112(1): 113-121.
13. Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520, 000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet, 2018, 50(4): 524-537.
14. Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ, 2018, 362: k601.
15. Hemani G, Zheng J, Elsworth B, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
16. Yavorska OO, Burgess S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol, 2017, 46(6): 1734-1739.
17. Osman AM, Carter SG, Carberry JC, et al. Obstructive sleep apnea: current perspectives. Nat Sci Sleep, 2018, 10: 21-34.
18. Lippi G, Mattiuzzi C, Franchini M. Sleep apnea and venous thromboembolism. A systematic review. Thromb Haemost, 2015, 114(5): 958-963.
19. Lin CC, Keller JJ, Kang JH, et al. Obstructive sleep apnea is associated with an increased risk of venous thromboembolism. J Vasc Surg Venous Lymphat Disord, 2013, 1(2): 139-145.
20. 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(2): 340-345.
21. Esmon CT. Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev, 2009, 23(5): 225-229.
22. 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(2): 1800893.
23. Ageno W, Becattini C, Brighton T, et al. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation, 2008, 117(1): 93-102.
24. Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: a review. Open J Prev Med, 2012, 2(4): 499-509.
25. Wang J, Yu W, Gao M, et al. Impact of obstructive sleep apnea syndrome on endothelial function, arterial stiffening, and serum inflammatory markers: an updated meta-analysis and metaregression of 18 studies. J Am Heart Assoc, 2015, 4(11): e002454.
26. Thomas SR, Chen K, Keaney JF Jr. Hydrogen peroxide activates endothelial nitric-oxide synthase through coordinated phosphorylation and dephosphorylation via a phosphoinositide 3-kinase-dependent signaling pathway. J Biol Chem, 2002, 277(8): 6017-6024.
27. Tanaka T, Nakamura H, Yodoi J, et al. Redox regulation of the signaling pathways leading to eNOS phosphorylation. Free Radic Biol Med, 2005, 38(9): 1231-1242.
28. Kokturk O, Ciftci TU, Mollarecep E, et al. Elevated C-reactive protein levels and increased cardiovascular risk in patients with obstructive sleep apnea syndrome. Int Heart J, 2005, 46(5): 801-809.
29. von Känel R, Loredo JS, Ancoli-Israel S, et al. Association between sleep apnea severity and blood coagulability: treatment effects of nasal continuous positive airway pressure. Sleep Breath, 2006, 10(3): 139-146.
30. Huang Z, Zheng Z, Pang L, et al. The association between obstructive sleep apnea and venous thromboembolism: a bidirectional two-sample mendelian randomization study. Thromb Haemost, 2024, 124(11): 1061-1074.

Previous Article
Causal relationship between gut microbiome and psoriasis: a two-sample two way Mendelian randomization study
Next Article
Scoping review of sarcopenia risk prediction models in China

West China Medical Journal

Causal association between obstructive sleep apnea and venous thromboembolism: a Mendelian randomization study

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content