Skip to main content
SpringerLink
Log in

A meta-analysis of the association between gout, serum uric acid level, and obstructive sleep apnea

  • Sleep Breathing Physiology and Disorders • Review
  • Published:
Sleep and Breathing Aims and scope Submit manuscript

Abstract

Previous epidemiological investigations have evaluated the association between gout, serum uric acid levels, and obstructive sleep apnea syndrome (OSAS), but with inconsistent results. We conducted this meta-analysis aiming at providing clear evidence about whether OSAS patients have higher serum uric acid levels and more susceptible to gout. Relevant studies were identified via electronic databases from inception to December 17, 2018. Study selection was conducted according to predesigned eligibility criteria, and two authors independently extracted data from included studies. The hazard ratio (HR) and weighted mean difference (WMD) and their corresponding 95% confidence interval (CI) were derived using random-effects models. We conducted meta-, heterogeneity, publication bias, sensitivity, and subgroup analyses. Eighteen studies, involving a total of 157,607 individuals (32,395 with OSAS, 125,212 without OSAS) and 12,262 gout cases, were included. Results show that serum uric acid levels are elevated in patients with OSAS (WMD = 52.25, 95% CI 36.16–64.33); OSAS did not reach statistical significance as a predictor of gout (but there was a trend, HR = 1.25, 95% CI 0.91–1.70) and that the association between OSAS and serum uric acid was quite robust. OSAS may be a potential risk factor for hyperuricemia and the development of gout and thus, effective OSAS therapy may present as a valuable preventive measure against gout. Still, it is vital to undertake clinical studies with better designing to corroborate these associations and shed new light on it.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Annemans L, Spaepen E, Gaskin M, Bonnemaire M, Malier V, Gilbert T, Nuki G (2008) Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000-2005. Ann Rheum Dis 67(7):960–966. https://doi.org/10.1136/ard.2007.076232

    Article  CAS  PubMed  Google Scholar 

  2. Mikuls TR, Farrar JT, Bilker WB, Fernandes S, Schumacher HR Jr, Saag KG (2005) Gout epidemiology: results from the UK general practice research database, 1990-1999. Ann Rheum Dis 64(2):267–272. https://doi.org/10.1136/ard.2004.024091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zhu Y, Pandya BJ, Choi HK (2011) Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum 63(10):3136–3141. https://doi.org/10.1002/art.30520

    Article  PubMed  Google Scholar 

  4. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M (2015) Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis 74(4):661–667. https://doi.org/10.1136/annrheumdis-2013-204463

    Article  PubMed  Google Scholar 

  5. Klemp P, Stansfield SA, Castle B, Robertson MC (1997) Gout is on the increase in New Zealand. Ann Rheum Dis 56(1):22–26. https://doi.org/10.1136/ard.56.1.22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cassim B, Mody GM, Deenadayalu VK, Hammond MG (1994) Gout in black South Africans: a clinical and genetic study. Ann Rheum Ddis 53(11):759–762. https://doi.org/10.1136/ard.53.11.759

    Article  CAS  Google Scholar 

  7. Zeng Q, Wang Q, Chen R, Xiao Z, Huang S, Xu J (2003) Primary gout in Shantou: a clinical and epidemiological study. Chinese Medical J 116(6):66–69

    Google Scholar 

  8. Roddy E, Choi HK (2014) Epidemiology of gout. Rheum Dis Clin N Am 40(2):155–175. https://doi.org/10.1016/j.rdc.2014.01.001

    Article  Google Scholar 

  9. McAdams-DeMarco MA, Maynard JW, Baer AN, Coresh J (2012) Hypertension and the risk of incident gout in a population-based study: the atherosclerosis risk in communities cohort. J Clin Hypertens 14(10):675–679. https://doi.org/10.1111/j.1751-7176.2012.00674.x

    Article  Google Scholar 

  10. Maynard JW, McAdams-DeMarco MA, Baer AN, Köttgen A, Folsom AR, Coresh J, Gelber AC (2012) Incident gout in women and association with obesity in the Atherosclerosis Risk in Communities (ARIC) Study. Am J Med 125(7):717.e9717. https://doi.org/10.1016/j.amjmed.2011.11.018

    Article  Google Scholar 

  11. Choi HK, Ford ES, Li C, Curhan G (2007) Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 57(1):109–115. https://doi.org/10.1002/art.22466

    Article  PubMed  Google Scholar 

  12. Zhu Y, Pandya BJ, Choi HK (2012) Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am J Med 125(7):679–687.e1. https://doi.org/10.1016/j.amjmed.2011.09.033

    Article  PubMed  Google Scholar 

  13. Richette P, Clerson P, Bouee S et al (2015) Identification of patients with gout: elaboration of a questionnaire for epidemiological studies. Ann Rheum Dis 74(9):1684–1690. https://doi.org/10.1136/annrheumdis-2013-204976

    Article  CAS  PubMed  Google Scholar 

  14. Krishnan E, Svendsen K, Neaton JD, Grandits G, Kuller LH, Research MRFIT (2008) Group: long-term cardiovascular mortality among middle-aged men with gout. Arch Intern Med 168(10):1104–1110. https://doi.org/10.1001/archinte.168.10.1104

    Article  PubMed  Google Scholar 

  15. Kuo CF, See LC, Luo SF, Ko YS, Lin YS, Hwang JS, Lin CM, Chen HW, Yu KH (2010) Gout: an independent risk factor for all-cause and cardiovascular mortality. Rheumatology 49(1):141–146. https://doi.org/10.1093/rheumatology/kep364

    Article  PubMed  Google Scholar 

  16. Listed NA (1999) Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 22(5):662–689

    Article  Google Scholar 

  17. Lindberg E, Gislason T (2000) Epidemiology of sleep-related obstructive breathing. Sleep Med Rev 4(5):411–433. https://doi.org/10.1053/smrv.2000.0118

    Article  CAS  PubMed  Google Scholar 

  18. Sasanabe R, Banno K, Otake K et al (2006) Metabolic syndrome in Japanese patients with obstructive sleep apnea syndrome. Hypertens Res 29(5):315–322. https://doi.org/10.1291/hypres.29.315

    Article  PubMed  Google Scholar 

  19. Parish JM, Adam T, Facchiano L (2007) Relationship of metabolic syndrome and obstructive sleep apnea. J Clin Sleep Med 3(5):467–472

    PubMed  PubMed Central  Google Scholar 

  20. Kono M, Tatsumi K, Saibara T, Nakamura A, Tanabe N, Takiguchi Y, Kuriyama T (2007) Obstructive sleep apnea syndrome is associated with some components of metabolic syndrome. Chest 131:1387–1392. https://doi.org/10.1378/chest.06-1807

    Article  CAS  PubMed  Google Scholar 

  21. Chou YT, Chuang LP, Li HY et al (2010) Hyperlipidaemia in patients with sleep-related breathing disorders: prevalence & risk factors. Indian J Med Res 131(5):121–125. https://doi.org/10.1378/chest.06-1807

    Article  CAS  PubMed  Google Scholar 

  22. West SD, Nicoll DJ, Stradling JR (2006) Prevalence of obstructive sleep apnoea in men with type 2 diabetes. Thorax 61(11):945–950. https://doi.org/10.1136/thx.2005.057745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shahar E, Whitney CW, Redline S et al (2001) Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 163(1):19–25. https://doi.org/10.1164/ajrccm.163.1.2001008

    Article  CAS  PubMed  Google Scholar 

  24. Choi HK, Atkinson K, Karlson EW, Curhan G (2005) Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med 165(7):742–748. https://doi.org/10.1001/archinte.165.7.742

    Article  PubMed  Google Scholar 

  25. Ruiz Garcia A, Sanchez Armengol A et al (2006) Blood uric acid levels in patients with sleep-disordered breathing. Arch Bronconeumol 42(10):492–500. https://doi.org/10.1016/S1579-2129(06)60575-2

    Article  PubMed  Google Scholar 

  26. Plywaczewski R, Bednarek M, Jonczak L, Gorecka D, Sliwiniski P (2005) Hyperuricaemia in males with obstructive sleep apnoea (OSA). Pneumonol Alergol Pol 73(3):254–259

    PubMed  Google Scholar 

  27. Plywaczewski R, Bednarek M, Jonczak L, Gorecka D, Sliwinski P (2006) Hyperuricaemia in females with obstructive sleep apnoea. Pneumonol Alergol Pol 74(4):159–165

    PubMed  Google Scholar 

  28. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA (2010) Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res 62(2):170–180. https://doi.org/10.1002/acr.20065

    Article  Google Scholar 

  29. Krishnan E, Pandya BJ, Chung L, Dabbous O (2011) Hyperuricemia and the risk for subclinical coronary atherosclerosis--data from a prospective observational cohort study. Arthritis Res Ther 13(2):R66. https://doi.org/10.1186/ar3322

    Article  PubMed  PubMed Central  Google Scholar 

  30. Choi HK, Niu J, Neogi T, Chen CA, Chaisson C, Hunter D, Zhang Y (2015) Nocturnal risk of gout attacks. Arthritis Rheumatol 67(2):555–562. https://doi.org/10.1002/art.38917

    Article  PubMed  PubMed Central  Google Scholar 

  31. Mirrakhimov AE, Mirrakhimov EM (2013) Obstructive sleep apnoea, gout and cardiovascular risk: a worth studying association. Med Hypotheses 81(4):749. https://doi.org/10.1016/j.mehy.2013.07.042

    Article  PubMed  Google Scholar 

  32. Abrams B (2012) High prevalence of gout with sleep apnea. Med Hypotheses 78(2):349. https://doi.org/10.1016/j.mehy.2011.10.029

    Article  PubMed  Google Scholar 

  33. Abrams B (2009) Sleep apnea as a cause of gout flares. Medscape J Med 11:3

    PubMed  PubMed Central  Google Scholar 

  34. Simkin PA (2009) The pathogenesis of podagra. Medscape J Med 11(1):3

    Google Scholar 

  35. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62(10):1006–1012. https://doi.org/10.1016/j.jclinepi.2009.06.005

    Article  PubMed  Google Scholar 

  36. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748. https://doi.org/10.1093/jnci/22.4.719

    Article  CAS  PubMed  Google Scholar 

  37. He W, Li Q, Yang M, Jiao J, Ma X, Zhou Y, Song A, Heymsfield SB, Zhang S, Zhu S (2015) Lower BMI cutoffs to define overweight and obesity in China. Obesity 23(3):684–691. https://doi.org/10.1002/oby.20995

    Article  PubMed  Google Scholar 

  38. Li P, Yan L, Su L, Li Q (2009) Changes of uric acid and blood lipids in patients with obstructive sleep apnea hypopnea syndrome complicated with coronary heart disease. Shandong Medical Journal 49(29):33–34. https://doi.org/10.3969/j.issn.1002-266X.2009.29.014

    Article  Google Scholar 

  39. Xu H, Cao F, Wei GR et al (2010) Association between the condition and plasma uric acid levels and carotid atherosclerosis in patients with obstructive sleep apnea hypopnea syndrome. Journal of Clinical Neurology 23(06):411–413

    CAS  Google Scholar 

  40. Liu MQ, Bi JY, Wan JM (2013) Changes of blood uric acid before and after operation in children with obstructive sleep apnea hypopnea syndrome. Medical Journal of Wuhan University 34(05):733–736. https://doi.org/10.14188/j.1671-8852.2013.05.041

    Article  CAS  Google Scholar 

  41. Deng QF (2011) Changes of blood uric acid and lipids in children with obstructive sleep apnea hyperpnoea. Chinese General Practice 14(34):3943–3945. https://doi.org/10.3969/j.issn.1007-9572.2011.34.019

    Article  CAS  Google Scholar 

  42. Deng KP, Zhang LJ, Yang C (2007) Changes of indirect bilirubin and uric acid levels in patients with obstructive sleep apnea hypopnea syndrome. Chinese Journal of Microcirculation 17(02):35–36. https://doi.org/10.3969/j.issn.1005-1740.2007.02.014

    Article  Google Scholar 

  43. Ding SF, Wang L, Liu Y, Liu HY, Xie F (2009) The relationship between obstructive sleep apnea-hypopnea syndrome and blood uric acid levels. Journal of Cardiovascular and Pulmonary Diseases 28(06):400–403. https://doi.org/10.3969/j.issn.1007-5062.2009.06.008

    Article  CAS  Google Scholar 

  44. Wu J, Liu YH (2008) Clinical study on serum uric acid and bilirubin levels in patients with obstructive sleep apnea hypopnea syndrome. Acta Universitatis Medicinalis Anhui 43(06):706–708. https://doi.org/10.3969/j.issn.1000-1492.2008.06.030

    Article  CAS  Google Scholar 

  45. Zhang XY, Ye XW, Feng RX, Rao SS (2008) The study between serum uric acid and early morning blood pressure of obstructive sleep apnea syndrome patients. Chinese Journal of Practical Internal Medicine 28(S1):94–95

    CAS  Google Scholar 

  46. Yi XB (2010) Obstructive sleep apnea-syndrome in patients with serum uric acid and lipid levels of correlation. China Modern Medicine 17(04):11–13. https://doi.org/10.3969/j.issn.1674-4721.2010.04.007

    Article  Google Scholar 

  47. Huang ZY, Liu DB, Wan GP, Zhong JW, Tan ZY, Wei W, Xu JJ, Shao JB, Qiu SY (2011) Correlation between serum uric acid levels and obstructive sleep apnea/hypopnea syndrome in children. Chinese Journal of Pediatrics 49(3):218–220. https://doi.org/10.3760/cma.j.issn.0578-1310.2011.03.014

    Article  PubMed  Google Scholar 

  48. Zhang LF (2015) Association between obstructive sleep apnea hypopnea syndrome and uric acid in male [D]. Fujian University of Medicine CNKI:CDMD:2.1015.991504

  49. Sunnetcioglu A, Gunbatar H, Yıldız H (2018) Red cell distribution width and uric acid in patients with obstructive sleep apnea. Clin Respir J 12(3):1046–1052. https://doi.org/10.1111/crj.12626

    Article  CAS  PubMed  Google Scholar 

  50. Hira HS, Shukla A, Kaur A, Kapoor S (2012) Serum uric acid and lactate levels among patients with obstructive sleep apnea syndrome: which is a better marker of hypoxemia? Ann Saudi Med 32(1):37–42. https://doi.org/10.5144/0256-4947.2012.37

    Article  PubMed  PubMed Central  Google Scholar 

  51. Blagojevic-Bucknall M, Mallen C, Muller S, Hayward R, West S, Choi H, Roddy E (2018) The risk of gout among patients with sleep apnea: a matched cohort study. Arthritis Rheumatol 71(1):154–160. https://doi.org/10.1002/art.40662

    Article  PubMed  Google Scholar 

  52. Zhang Y, Peloquin CE, Dubreuil M, Roddy E, Lu N, Neogi T, Choi HK (2015) Sleep apnea and the risk of incident gout: a population-based, body mass index-matched cohort study. Arthritis Rheumatol 67(12):3298–3302. https://doi.org/10.1002/art.39330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yi-Fong Su Y, Hong JY, Perng DW (2014) Obstructive sleep apnea and risk of gout-a nationwide population-based study. Thorac Med 29(5):272–279

    Google Scholar 

  54. Roddy E, Muller S, Hayward R, Mallen CD (2013) The association of gout with sleep disorders: a cross-sectional study in primary care. BMC Musculoskeletal Dis 14(119). https://doi.org/10.1186/1471-2474-14-119

  55. Gersch C, Palii SP, Kim KM, Angerhofer A, Johnson RJ, Henderson GN (2008) Inactivation of nitric oxide by uric acid. Nucleosides Nucleotides Nucleic Acids 27(8):967–978. https://doi.org/10.1080/15257770802257952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ho WJ, Tsai WP, Yu KH, Tsay PK, Wang CL, Hsu TS, Kuo CT (2010) Association between endothelial dysfunction and hyperuricaemia. Rheumatology 49(10):1929–1934. https://doi.org/10.1093/rheumatology/keq184

    Article  PubMed  Google Scholar 

  57. Yamauchi M, Kimura H (2008) Oxidative stress in obstructive sleep apnea: putative pathways to the cardiovascular complications. Antioxid Redox Signal 10(4):755–768. https://doi.org/10.1089/ars.2007.1946

    Article  CAS  PubMed  Google Scholar 

  58. Jelic S, Padeletti M, Kawut SM, Higgins C, Canfield SM, Onat D, Colombo PC, Basner RC, Factor P, LeJemtel TH (2008) Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation 117(17):2270–2278. https://doi.org/10.1161/CIRCULATIONAHA.107.741512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Prabhakar NR, Kumar GK (2010) Mechanisms of sympathetic activation and blood pressure elevation by intermittent hypoxia. Respir Physiol Neurobiol 174(1–2):156–161. https://doi.org/10.1016/j.resp.2010.08.021

    Article  PubMed  PubMed Central  Google Scholar 

  60. Pant S, Deshmukh A, Gurumurthy GS, Pothineni NV, Watts TE, Romeo F, Mehta JL (2014) Inflammation and atherosclerosis--revisited. J Cardiovasc Pharmacol Ther 19(2):170–178. https://doi.org/10.1177/1074248413504994

    Article  CAS  PubMed  Google Scholar 

  61. Sahebjani H (1998) Changes in urinary uric acid excretion in obstructive sleep apnea before and after therapy with nasal continuous positive airway pressure. Chest 113(6):1604–1608. https://doi.org/10.1378/chest.113.6.1604

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China

    Tingting Shi, Min Min, Yun Zhang, Mingming Liang & Yehuan Sun

  2. The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China

    Chenyu Sun

  3. Arizona College of Osteopathic Medicine, Midwestern University, 19555 N 59th Ave, Glendale, AZ, 85308, USA

    Ce Cheng

  4. Avalon University School of Medicine, Santa Rosaweg 122-124, Willemstad, Curaçao

    Feras Kamel Rizeq

  5. Center for Evidence-Based Practice, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China

    Yehuan Sun

Authors
  1. Tingting Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min Min
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chenyu Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ce Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mingming Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Feras Kamel Rizeq
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yehuan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yehuan Sun.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human and animals participants performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, T., Min, M., Sun, C. et al. A meta-analysis of the association between gout, serum uric acid level, and obstructive sleep apnea. Sleep Breath 23, 1047–1057 (2019). https://doi.org/10.1007/s11325-019-01827-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11325-019-01827-1

Keywords

Search

Navigation