Skip to main content
SpringerLink
Log in

High C-Reactive Protein Is Associated with Poor Sleep Quality Independent of Nocturnal Symptoms in Patients with Inflammatory Bowel Disease

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Sleep disruption is common in inflammatory bowel diseases (IBD). However, studies demonstrating a similar prevalence in irritable bowel syndrome suggest that nighttime disruption due to diarrhea and abdominal pain may be key drivers of poor sleep quality. Whether inflammation is associated with poor sleep independently has not been examined previously.

Methods

This single-center study included subjects with IBD recruited to an ongoing prospective registry who completed a questionnaire assessing sleep quality and mood. Inflammatory marker levels [C-reactive protein (CRP), erythrocyte sedimentation rate] and clinical disease activity including nighttime disruption on the day of enrollment were obtained from the medical record. Logistic regression models were used to identify predictors of sleep quality.

Results

The study included 131 subjects (72 women) with a median age of IBD diagnosis of 25 years. Twenty-three subjects (19 %) had a high C-reactive protein level (≥8 mg/dL). Poor sleep was more common in those with high CRP levels than with normal values (70 vs. 39 %, p = 0.009). This association remained significant on multivariate analysis [Odds ratio (OR) 4.12, 95 % confidence interval (CI) 1.38–12.29]. Adjusting for the presence of nighttime disruption did not significant alter this association (OR 3.16, 95 % CI 1.01–9.90). High CRP correlated with poor sleep even in patients not experiencing nocturnal symptoms (n = 101, OR 4.89, 95 % CI 1.24–19.36).

Conclusion

High CRP is associated with poor sleep quality in IBD independent of the presence of nighttime disruptions, suggesting that a relationship exists between circulating inflammatory markers and sleep.

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

Similar content being viewed by others

References

  1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361:2066–2078.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Bernstein CN, Loftus EV Jr, Ng SC, et al. Hospitalisations and surgery in Crohn’s disease. Gut. 2012;61:622–629.

    Article  PubMed  Google Scholar 

  3. Ghosh S, Mitchell R. Impact of inflammatory bowel disease on quality of life: results of the European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA) patient survey. J Crohns Colitis. 2007;1:10–20.

    Article  PubMed  Google Scholar 

  4. Ananthakrishnan AN, Weber LR, Knox JF, et al. Permanent work disability in Crohn’s disease. Am J Gastroenterol. 2008;103:154–161.

    Article  PubMed  Google Scholar 

  5. Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491:119–124.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Cosnes J, Gower-Rousseau C, Seksik P, et al. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140:1785–1794.

    Article  PubMed  Google Scholar 

  7. Danese S, Fiocchi C. Etiopathogenesis of inflammatory bowel diseases. World J Gastroenterol. 2006;12:4807–4812.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Ananthakrishnan AN. Environmental risk factors for inflammatory bowel diseases: a review. Dig Dis Sci. 2015;60:290–298.

  9. Ananthakrishnan AN, Khalili H, Pan A, et al. Association between depressive symptoms and incidence of Crohn’s disease and ulcerative colitis: results from the Nurses’ Health Study. Clin Gastroenterol Hepatol. 2013;11:57–62.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Ananthakrishnan AN, Long MD, Martin CF, et al. Sleep disturbance and risk of active disease in patients with Crohn’s disease and ulcerative colitis. Clin Gastroenterol Hepatol. 2013;11:965–971.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Bernstein CN, Singh S, Graff LA, et al. A prospective population-based study of triggers of symptomatic flares in IBD. Am J Gastroenterol. 2010;105:1994–2002.

    Article  PubMed  Google Scholar 

  12. Bitton A, Dobkin PL, Edwardes MD, et al. Predicting relapse in Crohn’s disease: a biopsychosocial model. Gut. 2008;57:1386–1392.

    Article  CAS  PubMed  Google Scholar 

  13. Graff LA, Vincent N, Walker JR, et al. A population-based study of fatigue and sleep difficulties in inflammatory bowel disease. Inflamm Bowel Dis. 2011;17:1882–1889.

    Article  PubMed  Google Scholar 

  14. Singh S, Graff LA, Bernstein CN. Do NSAIDs, antibiotics, infections, or stress trigger flares in IBD? Am J Gastroenterol. 2009;104:1298–1313. (quiz 1314).

    Article  CAS  PubMed  Google Scholar 

  15. Abad VC, Sarinas PS, Guilleminault C. Sleep and rheumatologic disorders. Sleep Med Rev. 2008;12:211–228.

    Article  PubMed  Google Scholar 

  16. Ayas NT, White DP, Manson JE, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003;163:205–209.

    Article  PubMed  Google Scholar 

  17. Brass SD, Duquette P, Proulx-Therrien J, et al. Sleep disorders in patients with multiple sclerosis. Sleep Med Rev. 2010;14:121–129.

    Article  PubMed  Google Scholar 

  18. Cappuccio FP, Cooper D, D’Elia L, et al. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. Eur Heart J. 2011;32:1484–1492.

    Article  PubMed  Google Scholar 

  19. Cappuccio FP, D’Elia L, Strazzullo P, et al. Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Sleep. 2010;33:585–592.

    PubMed Central  PubMed  Google Scholar 

  20. Chandrasekhara PK, Jayachandran NV, Rajasekhar L, et al. The prevalence and associations of sleep disturbances in patients with systemic lupus erythematosus. Mod Rheumatol. 2009;19:407–415.

    Article  PubMed  Google Scholar 

  21. Keefer L, Stepanski EJ, Ranjbaran Z, et al. An initial report of sleep disturbance in inactive inflammatory bowel disease. J Clin Sleep Med. 2006;2:409–416.

    PubMed  Google Scholar 

  22. Ranjbaran Z, Keefer L, Farhadi A, et al. Impact of sleep disturbances in inflammatory bowel disease. J Gastroenterol Hepatol. 2007;22:1748–1753.

    Article  PubMed  Google Scholar 

  23. Ranjbaran Z, Keefer L, Stepanski E, et al. The relevance of sleep abnormalities to chronic inflammatory conditions. Inflamm Res. 2007;56:51–57.

    Article  CAS  PubMed  Google Scholar 

  24. Abedelmalek S, Souissi N, Chtourou H, et al. Effects of partial sleep deprivation on proinflammatory cytokines, growth hormone, and steroid hormone concentrations during repeated brief sprint interval exercise. Chronobiol Int. 2013;30:502–509.

    Article  CAS  PubMed  Google Scholar 

  25. Ali T, Madhoun MF, Orr WC, et al. Assessment of the relationship between quality of sleep and disease activity in inflammatory bowel disease patients. Inflamm Bowel Dis. 2013;19:2440–2443.

    Article  PubMed  Google Scholar 

  26. Axelsson J, Rehman JU, Akerstedt T, et al. Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/T helper 2 balance in humans. PLoS One. 2013;8:e82291.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Banks S, Dinges DF. Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med. 2007;3:519–528.

    PubMed Central  PubMed  Google Scholar 

  28. Fragiadaki K, Tektonidou MG, Konsta M, et al. Sleep disturbances and interleukin 6 receptor inhibition in rheumatoid arthritis. J Rheumatol. 2012;39:60–62.

    Article  CAS  PubMed  Google Scholar 

  29. Rohleder N, Aringer M, Boentert M. Role of interleukin-6 in stress, sleep, and fatigue. Ann N Y Acad Sci. 2012;1261:88–96.

    Article  CAS  PubMed  Google Scholar 

  30. Buysse DJ, Yu L, Moul DE, et al. Development and validation of patient-reported outcome measures for sleep disturbance and sleep-related impairments. Sleep. 2010;33:781–792.

    PubMed Central  PubMed  Google Scholar 

  31. Yu L, Buysse DJ, Germain A, et al. Development of short forms from the PROMIS sleep disturbance and Sleep-Related Impairment item banks. Behav Sleep Med. 2012;10:6–24.

    Article  Google Scholar 

  32. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19:5–36.

    Google Scholar 

  33. Patel SR, Zhu X, Storfer-Isser A, et al. Sleep duration and biomarkers of inflammation. Sleep. 2009;32:200–204.

    PubMed Central  PubMed  Google Scholar 

  34. Shoham S, Davenne D, Cady AB, et al. Recombinant tumor necrosis factor and interleukin 1 enhance slow-wave sleep. Am J Physiol. 1987;253:R142–R149.

    CAS  PubMed  Google Scholar 

  35. Ananthakrishnan AN, Khalili H, Konijeti GG, et al. Sleep duration affects risk for ulcerative colitis: a prospective cohort study. Clin Gastroenterol Hepatol. 2014;12:1879–1886.

    Article  PubMed  Google Scholar 

  36. Parekh PJ, Oldfield Iv EC, Challapallisri V, et al. Sleep disorders and inflammatory disease activity: chicken or the egg? Am J Gastroenterol. 2014. doi:10.1038/ajg.2014.247.

  37. Simpson N, Dinges DF. Sleep and inflammation. Nutr Rev. 2007;65:S244–S252.

    Article  PubMed  Google Scholar 

  38. Swanson GR, Burgess HJ, Keshavarzian A. Sleep disturbances and inflammatory bowel disease: a potential trigger for disease flare? Expert Rev Clin Immunol. 2011;7:29–36.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Tang Y, Preuss F, Turek FW, et al. Sleep deprivation worsens inflammation and delays recovery in a mouse model of colitis. Sleep Med. 2009;10:597–603.

    Article  PubMed Central  PubMed  Google Scholar 

  40. Swanson G, Forsyth CB, Tang Y, et al. Role of intestinal circadian genes in alcohol-induced gut leakiness. Alcohol Clin Exp Res. 2012;35:1305–1314.

    Article  Google Scholar 

  41. Ruperto N, Lovell DJ, Li T, et al. Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2010;62:1542–1551.

    Article  Google Scholar 

  42. Ali T, Choe J, Awab A, et al. Sleep, immunity and inflammation in gastrointestinal disorders. World J Gastroenterol. 2013;19:9231–9239.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Tobaldini E, Cogliati C, Fiorelli EM, et al. One night on-call: sleep deprivation affects cardiac autonomic control and inflammation in physicians. Eur J Intern Med. 2013;24:664–670.

    Article  PubMed  Google Scholar 

  44. Trammell RA, Verhulst S, Toth LA. Effects of sleep fragmentation on sleep and markers of inflammation in mice. Comp Med. 2014;64:13–24.

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Baglioni C, Battagliese G, Feige B, et al. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J Affect Disord. 2011;135:10–19.

    Article  PubMed  Google Scholar 

  46. Graff LA, Walker JR, Bernstein CN. Depression and anxiety in inflammatory bowel disease: a review of comorbidity and management. Inflamm Bowel Dis. 2009;15:1105–1118.

    Article  PubMed  Google Scholar 

  47. Sutton EL. Psychiatric disorders and sleep issues. Med Clin North Am. 2014;98:1123–1143.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the valuable contributions of the participants and the research staff of our registry. This work was presented as a poster at the American College of Gastroenterology Annual Meeting 2014, Philadelphia, PA. This work is supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA

    Robin G. Wilson, Betsy W. Stevens, Abra Y. Guo, Caitlin N. Russell, Anna Thornton, Melissa A. Cohen, Holly C. Sturgeon, Cosmas Giallourakis, Hamed Khalili, Deanna D. Nguyen, Vijay Yajnik, Jenny Sauk & Ashwin N. Ananthakrishnan

  2. Harvard Medical School, Boston, MA, USA

    Cosmas Giallourakis, Hamed Khalili, Deanna D. Nguyen, Vijay Yajnik, Jenny Sauk & Ashwin N. Ananthakrishnan

  3. Massachusetts General Hospital Crohn’s and Colitis Centre, 165 Cambridge Street, 9th Floor, Boston, MA, 02114, USA

    Ashwin N. Ananthakrishnan

Authors
  1. Robin G. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Betsy W. Stevens
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abra Y. Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Caitlin N. Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anna Thornton
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Melissa A. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Holly C. Sturgeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cosmas Giallourakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hamed Khalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Deanna D. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Vijay Yajnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jenny Sauk
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ashwin N. Ananthakrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashwin N. Ananthakrishnan.

Appendix: Assessment of Sleep and Mood Using the NIH PROMIS Questions

Appendix: Assessment of Sleep and Mood Using the NIH PROMIS Questions

Sleep Habits

figure a

Mood

figure b
figure c

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wilson, R.G., Stevens, B.W., Guo, A.Y. et al. High C-Reactive Protein Is Associated with Poor Sleep Quality Independent of Nocturnal Symptoms in Patients with Inflammatory Bowel Disease. Dig Dis Sci 60, 2136–2143 (2015). https://doi.org/10.1007/s10620-015-3580-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-015-3580-5

Keywords

Search

Navigation