Skip to main content
SpringerLink
Log in

Association of Homocysteine and Risks of Long-Term Cardiovascular Events and All-Cause Death among Older Patients with Obstructive Sleep Apnea: A Prospective Study

  • Original Research
  • Published:
The journal of nutrition, health & aging

Abstract

Objectives

This study aimed to assess whether raised baseline plasma tHcy concentrations increased the risks of major adverse cardiovascular events (MACE) and all-cause death outcomes in older patients with obstructive sleep apnea (OSA).

Design

A multicenter, prospective, observational study.

Setting

Beijing, Shandong Province, Gansu Province of China.

Participants

A total of 1, 290 OSA patients aged 60 to 96 years from sleep centers of six hospitals in China consecutively recruited between January 2015 and October 2017.

Measurements

Cox proportional models assessed the association between tHcy and the risk of new-onset all events among Chinese older OSA patients.

Results

The final analysis (60.1% male; median age, 66 years) used data from 1, 100 subjects during a median follow-up of 42 months, a total of 105 (9.5%) patients developed MACE and 42 (3.8%) patients died. Multivariable Cox regression analysis showed higher adjusted hazard ratios (aHRs) of MACE, myocardial infarction (MI), hospitalization for unstable angina, and composite of all events with tHcy levels in the 4th quartile (HR=5.93, 95% CI: 2.79–12.59; HR=4.72, 95% CI:1.36–4.61; HR=4.26, 95% CI:1.62–5.71; HR=4.17, 95% CI:2.23–7.81) and the 3rd quartile (HR=3.79, 95% CI:1.76–8.20; HR=3.65, 95% CI:1.04–2.98; HR=2.75, 95% CI:1.08–3.76; HR=2.51, 95% CI:1.31–4.83) compared to reference tHcy levels in quartile 1, respectively, while the aHRs (95% CIs) of all-cause death showed significantly higher only in the highest tHcy level quartile than in the lowest quartile (HR=3.20, 95% CI=1.16–8.84, P=0.025) with no significant differences in risks of cardiovascular death and hospitalisation for heart failure among groups (P>0.05).

Conclusions

tHcy, a marker of prognosis for older OSA patients, was significantly associated with the increased risk of MACE and all-cause death in this population independent of BMI, smoking status, and other potential risk factors, but not all clinical components events of MACE. New therapeutic approaches for older patients with OSA should mitigate tHcy-associated risks of MACE, and even all-cause death.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

Availability of data and materials: Our data may not be shared directly, because it is our teamwork; informed consent should be attained from all the team members. Our data or material may be available after contacting the corresponding author or first author.

References

  1. Joosten SA, Landry SA, Wong AM, et al. Assessing the physiologic endotypes responsible for REM- and NREM-based OSA. Chest. 2021;159(5):1998–2007. https://doi.org/10.1016/j.chest.2020.10.080.

    Article  PubMed  Google Scholar 

  2. Koo CY, de la Torre AS, Loo G, et al. Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnoea in Patients with Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study. Heart Lung Circ. 2017;26(5):486–494. https://doi.org/10.1016/j.hlc.2016.09.010.

    Article  PubMed  Google Scholar 

  3. Khalyfa A, Marin JM, Qiao Z, Rubio DS, Kheirandish-Gozal L, Gozal D. Plasma exosomes in OSA patients promote endothelial senescence: effect of long-term adherent continuous positive airway pressure. Sleep. 2020;43(2):zsz217. https://doi.org/10.1093/sleep/zsz217.

    Article  PubMed  Google Scholar 

  4. Carneiro G, Zanella MT. Obesity metabolic and hormonal disorders associated with obstructive sleep apnea and their impact on the risk of cardiovascular events. Metabolism. 2018;84:76–84. https://doi.org/10.1016/j.metabol.2018.03.008.

    Article  PubMed  CAS  Google Scholar 

  5. Ayers L, Stoewhas AC, Ferry B, Stradling J, Kohler M. Elevated levels of endothelial cell-derived microparticles following short-term withdrawal of continuous positive airway pressure in patients with obstructive sleep apnea: data from a randomized controlled trial. Respiration. 2013;85(6):478–485. https://doi.org/10.1159/000342877.

    Article  PubMed  Google Scholar 

  6. Lehotský J, Tothová B, Kovalská M, et al. Role of homocysteine in the ischemic stroke and development of ischemic tolerance. Frontiers neurosci. 2016;10:538. https://doi.org/10.3389/fnins.2016.00538.

    Article  Google Scholar 

  7. Tawfik A, Elsherbiny NM, Zaidi Y, Rajpurohit P. Homocysteine and age-related central nervous system diseases: role of inflammation. Int J Mol Sci. 2021;22(12). https://doi.org/10.3390/ijms22126259.

  8. Yang J, Fang P, Yu D, et al. Chronic kidney disease induces inflammatory CD40+ monocyte differentiation via homocysteine elevation and DNA hypomethylation. Circ Res. 2016;119(11):1226–1241. https://doi.org/10.1161/CIRCRESAHA.116.308750.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Zhou Z, Liang Y, Qu H, et al. Plasma homocysteine concentrations and risk of intracerebral hemorrhage: a systematic review and meta-analysis. Sci Rep. 2018;8(1):2568. https://doi.org/10.1038/s41598-018-21019-3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Ahmad A, Corban MT, Toya T, et al. Coronary microvascular endothelial dysfunction in patients with angina and nonobstructive coronary artery disease is Associated with elevated Serum homocysteine levels. J Am Heart Assoc. 2020;9(19):e017746. https://doi.org/10.1161/JAHA.120.017746.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cacciapuoti F. Hyper-homocysteinemia: a novel risk factor or a powerful marker for cardiovascular diseases? Pathogenetic and therapeutical uncertainties. J Thromb Thrombolysis. 2011;32(1):82–88. https://doi.org/10.1007/s11239-011-0550-4.

    Article  PubMed  CAS  Google Scholar 

  12. Hoogeveen EK, Kostense PJ, Jakobs C, et al. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation. 2000;101(13):1506–1511. https://doi.org/10.1161/01.cir.101.13.1506.

    Article  PubMed  CAS  Google Scholar 

  13. Smith AD, Refsum H. Homocysteine-from disease biomarker to disease prevention. J Intern Med. 2021;290(4):826–854. https://doi.org/10.1111/joim.13279.

    Article  PubMed  CAS  Google Scholar 

  14. Zhang D, Sun X, Liu J, Xie X, Cui W, Zhu Y. Homocysteine accelerates senescence of endothelial cells via DNA hypomethylation of human telomerase reverse transcriptase. Arterioscler Thromb Vasc Biol. 2015;35(1):71–78. https://doi.org/10.1161/ATVBAHA.114.303899.

    Article  PubMed  CAS  Google Scholar 

  15. Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353(10):999–1007. https://doi.org/10.1056/NEJMoa043814.

    Article  PubMed  CAS  Google Scholar 

  16. Xu R, Huang F, Wang Y, Liu Q, Lv Y, Zhang Q. Gender- and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China. Sci Rep. 2020;10(1):17401. https://doi.org/10.1038/s41598-020-74596-7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Keller AC, Klawitter J, Hildreth KL, et al. Elevated plasma homocysteine and cysteine are associated with endothelial dysfunction across menopausal stages in healthy women. J Appl Physiol (1985). 2019;126(6):1533–1540. https://doi.org/10.1152/japplphysiol.00819.2018.

    Article  CAS  Google Scholar 

  18. Liang C, Wang QS, Yang X, et al. Homocysteine causes endothelial dysfunction via inflammatory factor-mediated activation of epithelial sodium channel (ENaC). Front Cell Dev Biol. 2021;9:672335. https://doi.org/10.3389/fcell.2021.672335.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hoyos CM, Melehan KL, Liu PY, Grunstein RR, Phillips CL. Does obstructive sleep apnea cause endothelial dysfunction? A critical review of the literature. Sleep Med Rev. 2015;20:15–26. https://doi.org/10.1016/j.smrv.2014.06.003.

    Article  PubMed  Google Scholar 

  20. Kokturk O, Ciftci TU, Mollarecep E, Ciftci B. Serum homocysteine levels and cardiovascular morbidity in obstructive sleep apnea syndrome. Respir Med. 2006;100(3):536–541. https://doi.org/10.1016/j.rmed.2005.05.025.

    Article  PubMed  Google Scholar 

  21. Ozkan Y, Firat H, Simşek B, Torun M, Yardim-Akaydin S. Circulating nitric oxide(NO), asymmetric dimethylarginine(ADMA), homocysteine, and oxidative status in obstructive sleep apnea-hypopnea syndrome(OSAHS). Sleep Breath. 2008;12(2):149–154. https://doi.org/10.1007/s11325-007-0148-4.

    Article  PubMed  Google Scholar 

  22. Winnicki M, Palatini P. Obstructive sleep apnoea and plasma homocysteine: an overview. Eur Heart J. 2004;25(15):1281–1283. https://doi.org/10.1016/j.ehj.2004.06.012.

    Article  PubMed  CAS  Google Scholar 

  23. Liu L, Wu Q, Yan H, Zheng X, Zhou Q. Plasma homocysteine and autonomic nervous dysfunction: association and clinical Relevance in OSAS. Dis Markers. 2020;2020:4378505. https://doi.org/10.1155/2020/4378505.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Kim J, Lee SK, Yoon DW, Shin C. Concurrent presence of obstructive sleep apnea and elevated homocysteine levels exacerbate the development of hypertension: a KoGES six-year follow-up study. Sci Rep. 2018;8(1):2665. https://doi.org/10.1038/s41598-018-21033-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Nurk E, Tell GS, Vollset SE, Nygård O, Refsum H, Ueland PM. Plasma total homocysteine and hospitalizations for cardiovascular disease: the Hordaland Homocysteine Study. Arch Intern Med. 2002;162(12):1374–1381. https://doi.org/10.1001/archinte.162.12.1374.

    Article  PubMed  Google Scholar 

  26. Su X, Li JH, Gao Y, et al. Impact of obstructive sleep apnea complicated with type 2 diabetes on long-term cardiovascular risks and all-cause mortality in elderly patients. BMC geriatr. 2021;21(1):508. https://doi.org/10.1186/s12877-021-02461-x.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kapur VK, Auckley DH, Chowdhuri S, et al. Clinical ractice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(3):479–504. https://doi.org/10.5664/jcsm.6506.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Priou P, Le Vaillant M, Meslier N, et al. Independent association between obstructive sleep apnea severity and glycated hemoglobin in adults without diabetes. Diabetes care. 2012;35(9):1902–1906. https://doi.org/10.2337/dc11-2538.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Putcha N, Crainiceanu C, Norato G, et al. Influence of lung function and sleep-disordered breathing on all-cause mortality. a community-based study. Am J Respir Crit Care Med. 2016;194(8):1007–1014. https://doi.org/10.1164/rccm.201511-2178OC.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138(17):e484–e594. https://doi.org/10.1016/j.jacc.2017.11.006.

    PubMed  Google Scholar 

  31. Adderley NJ, Subramanian A, Toulis K, et al. Obstructive sleep apnea, a risk factor for cardiovascular and microvascular disease in patients with type 2 diabetes: findings from a population-based cohort study. Diabetes care. 2020;43(8):1868–1877. https://doi.org/10.2337/dc19-2116.

    Article  PubMed  Google Scholar 

  32. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–2962. https://doi.org/10.1093/eurheartj/ehw210.

    Article  PubMed  Google Scholar 

  33. Kasami R, Kaneto H, Katakami N, et al. Relationship between carotid intima-media thickness and the presence and extent of coronary stenosis in type 2 diabetic patients with carotid atherosclerosis but without history of coronary artery disease. Diabetes care. 2011;34(2):468–470. https://doi.org/10.2337/dc10-1222.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. https://doi.org/10.1016/0021-9681(87)90171-8.

    Article  PubMed  CAS  Google Scholar 

  35. Park S, Lee S, Kim Y, et al. Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study. Nutrients. 2021;13(3):906. https://doi.org/10.3390/nu13030906.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Fu Z, Yang X, Shen M, et al. Prognostic ability of cystatin C and homocysteine plasma levels for long-term outcomes in very old acute myocardial infarction patients. Clin Interv Aging. 2018;13:1201–1209. https://doi.org/10.2147/CIA.S151211.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Daugherty A, Tabas I, Rader DJ. Accelerating the pace of atherosclerosis research. Arterioscler Thromb Vasc Biol. 2015;35(1):11–12. https://doi.org/10.1161/ATVBAHA.114.304833.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. McCully KS. Homocysteine and the pathogenesis of atherosclerosis. Expert Rev Clin Pharmacol. 2015;8(2):211–219. https://doi.org/10.1586/17512433.2015.1010516.

    Article  PubMed  CAS  Google Scholar 

  39. Ponce-Ruiz N, Murillo-González FE, Rojas-García AE, et al. PON1 status and homocysteine levels as potential biomarkers for cardiovascular disease. Exp Gerontol. 2020;140:111062. https://doi.org/10.1016/j.exger.2020.111062.

    Article  PubMed  CAS  Google Scholar 

  40. Ma CH, Chiua YC, Wu CH, et al. Homocysteine causes dysfunction of chondrocytes and oxidative stress through repression of SIRT1/AMPK pathway: A possible link between hyperhomocysteinemia and osteoarthritis. Redox biology. 2018;15:504–512. https://doi.org/10.1016/j.redox.2018.01.010.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6. https://doi.org/10.1186/1475-2891-14-6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Chernyavskiy I, Veeranki S, Sen U, Tyagi SC. Atherogenesis: hyperhomocysteinemia interactions with LDL, macrophage function, paraoxonase 1, and exercise. Ann N Y Acad Sci. 2016;1363(1):138–154. https://doi.org/10.1111/nyas.13009.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Refsum H, Nurk E, Smith AD, et al. The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. Nutr J. 2006;136 (6 Suppl):1731s–1740s. https://doi.org/10.1093/jn/136.6.1731S.

    Article  Google Scholar 

  44. Liu W, Wang T, Sun P, Zhou Y. Expression of Hcy and blood lipid levels in serum of CHD patients and analysis of risk factors for CHD. Exp Ther Med. 2019;17(3):1756–1760. https://doi.org/10.3892/etm.2018.7111.

    PubMed  CAS  Google Scholar 

  45. Guan J, Wu L, Xiao Q, Pan L. Levels and clinical significance of serum homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), vaspin, and visfatin in elderly patients with different types of coronary heart disease. Ann Palliat Med. 2021;10(5):5679–5686. https://doi.org/10.21037/apm-21-1001.

    Article  PubMed  Google Scholar 

  46. Han K, Lu Q, Zhu WJ, Wang TZ, Du Y, Bai L. Correlations of degree of coronary artery stenosis with blood lipid, CRP, Hcy, GGT, SCD36 and fibrinogen levels in elderly patients with coronary heart disease. Eur Rev Med Pharmacol Sci. 2019;23(21):9582–9589. https://doi.org/10.26355/eurrev_201911_19453.

    PubMed  CAS  Google Scholar 

  47. Mohammad G, Kowluru RA. Homocysteine Disrupts Balance between MMP-9 and Its Tissue Inhibitor in Diabetic Retinopathy: The Role of DNA Methylation. Int J Mol Sci. 2020;21(5). https://doi.org/10.3390/ijms21051771.

  48. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408(6809):239–247. https://doi.org/10.1038/35041687.

    Article  PubMed  CAS  Google Scholar 

  49. Moat SJ, Lang D, McDowell IF, et al. Folate, homocysteine, endothelial function and cardiovascular disease. J Nutr Biochem. 2004;15(2):64–79. https://doi.org/10.1016/j.jnutbio.2003.08.010.

    Article  PubMed  CAS  Google Scholar 

  50. Tamura T, Kuriyama N, Koyama T, et al. Association between plasma levels of homocysteine, folate, and vitamin B(12), and dietary folate intake and hypertension in a cross-sectional study. Sci Rep. 2020;10(1):18499. https://doi.org/10.1038/s41598-020-75267-3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Souza HP, Frediani D, Cobra AL, et al. Angiotensin II modulates CD40 expression in vascular smooth muscle cells. Clin Sci (Lond). 2009;116(5):423–431. https://doi.org/10.1042/CS20080155.

    Article  CAS  Google Scholar 

  52. Lutgens E, Daemen MJ. CD40-CD40L interactions in atherosclerosis. TrendsCardiovasc Med. 2002;12(1):27–32. https://doi.org/10.1016/s1050-1738(01)00142-6.

    CAS  Google Scholar 

  53. Fan R, Zhang A, Zhong F. Association between homocysteine levels and all-cause mortality: a dose-response meta-analysis of prospective studies. Sci Rep. 2017;7(1):4769. https://doi.org/10.1038/s41598-017-05205-3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem. 2004;50(1):3–32. https://doi.org/10.1373/clinchem.2003.021634.

    Article  PubMed  CAS  Google Scholar 

  55. Patel SR, Zhu X, Storfer-Isser A, et al. Sleep duration and biomarkers of inflammation. Sleep. 2009;32(2):200–204. https://doi.org/10.1093/sleep/32.2.200.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Shim YJ, Lee HJ, Park KJ, Kim HT, Hong IH, Kim ST. Botulinum toxin therapy for managing sleep bruxism: a randomized and placebo-controlled trial. Toxins. 2020;12(3). https://doi.org/10.3390/toxins12030168.

  57. Haba-Rubio J, Marques-Vidal P, Andries D, et al. Objective sleep structure and cardiovascular risk factors in the general population: the HypnoLaus Study. Sleep. 2015;38(3):391–400. https://doi.org/10.5665/sleep.4496.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Author information

Author notes

  1. Authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China

    L. Liu, X. Su, H. Wang & Xiangqun Fang

  2. Medical College, Yan’an University, Yan’an, Shannxi Province, China

    X. Su, L. Yang, Y. Yang & Jiming Han

  3. Graduate School of Medical School of Chinese PLA General Hospital, Beijing, China

    L. Zhao

  4. Cardiology Department of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China

    L. Zhao, J. Li, W. Xu & Li Fan

  5. PKU-UPenn Sleep Center, Peking University International Hospital, Beijing, China

    Y. Gao

  6. Sleep center, the affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou City, Gansu Province, China

    K. Chen

  7. Department of General Practice, 960th Hospital of PLA, Jinan, Shandong Province, China

    Y. Gao

  8. Sleep Medicine Center, Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, China

    J. J. Guo

  9. Department of Pulmonary and Critical Care Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China

    J. Lin

Authors
  1. L. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X. Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W. Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y. Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Y. Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J. J. Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. H. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J. Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jiming Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Li Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Xiangqun Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Authors’ contributions: LL, XS, LZ, JL, WX, YHG, YG, KC, JG, LY, YY, and WH collected the data. LL, XS, and LZ analyzed the data and wrote the manuscript draft. XF, LF, and JH designed this study. All authors have read and approved the manuscript.

Corresponding authors

Correspondence to Jiming Han, Li Fan or Xiangqun Fang.

Ethics declarations

Ethics approval and consent to participate: The Ethics Committee of Chinese PLA General Hospital (S2019-352-01) approved the study. Written informed consent was obtained from all participants.

Competing interests: The authors declare no conflict of interest, financial or otherwise.

Additional information

Consent for publication: Not applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, L., Su, X., Zhao, L. et al. Association of Homocysteine and Risks of Long-Term Cardiovascular Events and All-Cause Death among Older Patients with Obstructive Sleep Apnea: A Prospective Study. J Nutr Health Aging 26, 879–888 (2022). https://doi.org/10.1007/s12603-022-1840-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12603-022-1840-6

Key words

Search

Navigation