Journal Mobile Options
Table of Contents
Vol. 24, No. 5, 2007
Issue release date: October 2007
Cerebrovasc Dis 2007;24:412–417
(DOI:10.1159/000108430)

C-Reactive Protein and Fibrinogen in Acute Stroke Patients with and without Sleep Apnea

Dziewas R. · Ritter M. · Krüger L. · Berger S. · Langer C. · Kraus J. · Dittrich R. · Schäbitz W.R. · Ringelstein E.B. · Young P.
aDepartment of Neurology, University Hospital of Münster, and bInstitute of Clinical Chemistry and Laboratory Medicine, Münster, Germany; cDepartment of Neurology, University Hospital Salzburg, Salzburg, Austria

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Background and Purpose: Although sleep apnea (SA) is a risk factor for ischemic stroke and an important prognosticator in affected patients, the exact pathophysiological link between SA and stroke remains to be established. We investigated whether levels of C-reactive protein (CRP) and fibrinogen are increased in patients with acute stroke and SA compared with stroke patients without SA. Patients and Methods: 117 consecutive patients with ischemic stroke admitted to our stroke unit within 12 h after stroke onset were included in this study. On admission, CRP and fibrinogen levels were determined. All patients received cardiorespiratory polygraphy during the first 72 h of their hospital stay. In all patients, demographic data, National Institutes of Health Stroke Scale score and cerebrovascular risk factors were assessed. Results: SA defined by an apnea-hypopnea index (AHI) of ≧10/h was found in 64 (55%) patients. Elevated CRP and fibrinogen levels were seen twice as often in patients with SA than in patients without (CRP: 52 vs. 26%; fibrinogen: 72 vs. 37%). After multivariate logistic regression analysis, an AHI of ≧10/h was independently correlated with raised levels of both of these parameters. Conclusion: SA is independently associated with raised levels of CRP and fibrinogen in patients with acute ischemic stroke. We assume that both proteins are part of the pathophysiological pathway linking SA to stroke.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Iranzo A, Santamaria J, Berenguer J, Sanchez M, Chamorro A: Prevalence and clinical importance of sleep apnea in the first night after cerebral infarction. Neurology 2002;58:911–916.
  2. Turkington PM, Bamford J, Wanklyn P, Elliott MW: Prevalence and predictors of upper airway obstruction in the first 24 h after acute stroke. Stroke 2002;33:2037–2042.
  3. Harbison J, Ford GA, James OFW, Gibson GJ: Sleep-disordered breathing following acute stroke. Q J Med 2002;95:741–747.
  4. Bassetti C, Aldrich MS: Sleep apnea in acute cerebrovascular diseases: final report on 128 patients. Sleep 1999;22:217–223.
  5. Bassetti C, Aldrich MS, Chervin RD, Quint D: Sleep apnea in patients with transient ischemic attacks and stroke. A prospective study of 59 patients. Neurology 1996;47:1167–1173.
  6. Bassetti C, Aldrich MS, Quint D: Sleep-disordered breathing in patients with acute supra- and infratentorial strokes. A prospective study of 39 patients. Stroke 1997;28:1765–1772.
  7. Parra O, Arboix A, Bechich S, Garcia-Eroles L, Montserrat JM, Lopez JA, Ballester E, Guerra JM, Sopena JJ: Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack. Am J Respir Crit Care Med 2000;16:375–380.
  8. Mohensin V, Valor R: Sleep apnea in patients with hemispheric stroke. Arch Phys Med Rehabil 1995;76:71–76.
  9. Good DC, Henkle JQ, Gelber D, Welsh J, Verhulst S: Sleep-disordered breathing and poor functional outcome after stroke. Stroke 1996;27:252–259.
  10. Dyken ME, Somers VK, Yamada T, Ren Z, Zimmermann B: Investigating the relationship between stroke and obstructive sleep apnea. Stroke 1996;27:401–407.
  11. Dziewas R, Humpert M, Hopmann B, Kloska SP, Ritter M, Dittrich R, Young P, Ringelstein EB, Nabavi DG: Increased prevalence of sleep apnea in patients with recurring ischemic stroke compared with first stroke victims. J Neurol 2005;252:1394–1398.
  12. Dziewas R, Hopmann B, Humpert M, Böntert M, Dittrich R, Lüdemann P, Young P, Ringelstein EB, Nabavi DG: Capnography screening for sleep apnea in patients with acute stroke. Neurol Res 2005;27:83–87.
  13. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S: The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230–1235.
  14. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohensin V: Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005;353:2034–2041.
  15. Martin JM, Carrizo SJ, Vicente E, Agusti AG: Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005;365:1046–1053.

    External Resources

  16. Turkington PM, Allgar V, Bamford J, Wanklyn P, Elliot MW: Effect of upper airway obstruction in acute stroke on functional outcome at 6 months. Thorax 2004;59:367–371.
  17. Guilleminault C, Connolly SJ, Winckle RA: Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome. Am J Cardiol 1983;52:490–494.
  18. Netzer N, Werner P, Jochums I, Lehmann M, Strohl KP: Blood flow of the middle cerebral artery with sleep-disordered breathing. Correlation with obstructive hypopneas. Stroke 1998;29:87–93.
  19. von Kaenel R, Dinsdale JE: Hemostatic alterations in patients with obstructive sleep apnea and the implications for cardiovascular disease. Chest 2003;124:1956–1967.
  20. Christensen H, Boysen G: C-reactive protein and white blood cell count increases in the first 24 hours after acute stroke. Cerebrovasc Dis 2004;18:214–219.
  21. Di Napoli M, Papa F, Bocola V: Prognostic influence of increased C-reactive protein and fibrinogen levels in ischemic stroke. Stroke 2001;32:133–138.
  22. Di Napoli M, Papa F, Bocola V: C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke 2001;32:917–924.
  23. Rothwell PM, Howard SC, Power DA, Gutnikov SA, Algra A, van Gijn J, Clark TG, Murphy MFG, Warlow CP: Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5,113 patients with transient ischemic attack and minor ischemic stroke. Stroke 2004;35:2300–2305.
  24. Woodward M, Lowe GDO, Campbell DJ, Coman S, Rumley A, Chalmers J, Neal BC, Patel A, Jenkins AJ, Kemp BE, MacMahon SW: Association of inflammatory and hemostatic variables with the risk of recurrent stroke. Stroke 2005;36:2143–2147.
  25. Ford ES, Giles WH: Serum C-reactive protein and self-reported stroke: findings from the Third National Health and Nutrition Examination Survey. Arterioscler Thromb Vasc Biol 2000;20:1052–1056.
  26. Rost NS, Wolf PA, Kase CS, Kelly-Hayes M, Silbershatz H, Massaro JM, D’Agostino RB, Franzblau C, Wilson PW: Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke 2001;32:2575–2579.
  27. Curb JD, Abbott RD, Rodriguez BL, Sakkinen P, Popper JS, Yano K, Tracy RP: C-reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation 2003;107:2016–2020.
  28. Smith A, Patterson C, Yarnell J, Rumley A, Ben-Shlomo Y, Lowe G: Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? Circulation 2005;112:3080–3087.
  29. Fibrinogen Studies Collaboration, Danesh J, Lewington S, Thompson SG, et al: Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 2005;294:1799–1809.

    External Resources

  30. Anuk T, Assayag EG, Rotstein R, Fusman R, Zeltser D, Berliner S, Avitzour D, Shapira I, Arber N, Bornstein NM: Prognostic implications of admission inflammatory profile in acute ischemic neurological events. Acta Neurol Scand 2002;106:196–199.
  31. Shamsuzzaman AS, Winnicke M, Lanfranchi P, Wolk R, Kara T, Accuso V, Somers VK: Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 2002;105:2462–2464.
  32. Steiner S, Jax T, Evers S, Hennersdorf M, Schwalen A, Strauer BE: Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk. Cardiology 2005;104:92–96.
  33. Brott T, Adams HP, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V: Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989;20:864–870.
  34. Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35–41.
  35. Khera A, McGuire DK, Murphy SA, Stanek HG, Das SB, Vongpatanasin W, Wians FB, Grundy SM, de Lemos JA: Race and gender differences in C-reactive protein levels. J Am Coll Cardiol 2005;46:464–469.
  36. Di Napoli M, Schwaninger M, Cappelli R, Ceccarelli E, Di Gianfilippo G, Donati C, Emsley HCA, Forconi S, Hopkins SJ, Masotti L, Muir KW, Paciucci A, Papa F, Roncacci S, Sander D, Sander K, Smith CJ, Stefanini A, Weber D: Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke. Stroke 2005;36:1316–1329.
  37. Tamam Y, Iltumur K, Apak I: Assessment of acute phase proteins in acute ischemic stroke. Tohoku J Exp Med 2005;206:91–98.
  38. Thompson S, Kienast J, Pyke S, Haverkate F, van de Loo J: Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995;332:635–641.
  39. Wessendorf TE, Thilmann AF, Wang YM, Schreiber A, Konietzko N, Teschler H: Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med 2000;162:2039–2042.
  40. Chin K, Ohi M, Kita H, Noguchi T, Otsuka N, Tsuboi T, Mishima M, Kuno K: Effects of NCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 1996;153:1972–1976.
  41. Nobili L, Schiavi G, Bozano E, De Carle F, Ferrillo F, Nobili F: Morning increase of whole blood viscosity in obstructive sleep apnea syndrome. Clin Hemorheol Microcirc 2000;22:21–27.
  42. Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G, Hirano T, Adachi M: Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous airway pressure. Circulation 2003;107:1129–1134.
  43. Larkin EK, Rosen CL, Kirchner HL, Storfer-Isser A, Emancipator JL, Johnson NL, Zambito AMV, Tracy RP, Jenny NS, Redline S: Variation of C-reactive protein levels in adolescents. Association with sleep-disordered breathing and sleep duration. Circulation 2005;111:1978–1984.
  44. Shamsuzzaman AS, Gersh BJ, Somers VK: Obstructive sleep apnea. Implications for cardiac and vascular disease. JAMA 2003;290:1906–1914.
  45. Paul A, Ko K, Li L, Yechoor V, McCrory MA, Szalai AJ, Chan L: C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2004;109:647–655.
  46. Verma S, Yeh ET: C-reactive protein and atherothrombosis – Beyond a biomarker: an actual partaker of lesion formation. Am J Physiol Regul Integr Comp Physiol 2003;285:1253–1256.
  47. Winbeck K, Kukla C, Poppert H, Klingelhöfer J, Conrad B, Sander D: Elevated C-reactive protein is associated with an increased intima to media thickness of the common carotid artery. Cerebrovasc Dis 2002;13:57–63.
  48. Pepys MB, Hirschfield GM: C-reactive protein and atherothrombosis. Ital Heart J 2001;2:196–199.
  49. Nijmeijer R, Lagrand WK, Lubbers YT, Visser CA, Meijer CJ, Niesen HW, Hack CE: C-reactive protein activates complement in infarcted human myocardium. Am J Pathol 2003;163:269–275.
  50. Eber B, Schumacher M: Fibrinogen: its role in the hemostatic regulation in atherosclerosis. Semin Thromb Hemost 1993;19:104–107.
  51. Martinez-Vila E, Paramo JA, Beloqui O, Orbe J, Irimia P, Colina I, Monreal I, Benito A, Barba J, Zubieta JL, Diez J: Independent association of fibrinogen with carotid intima-media thickness in asymptomatic subjects. Cerebrovasc Dis 2003;16:356–362.
  52. Lowe GDO, Rumley A, Whincup PH, Danesh J: Hemostatic and rheological variables and risk of cardiovascular disease. Semin Vasc Med 2002;2:429–440.

    External Resources



Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50