Predictive Significance of Plasma Levels of Interleukin-6 and High-Sensitivity C-Reactive Protein in Atrial Fibrillation after Coronary Artery Bypass Surgery
Background. Postoperative atrial fibrillation (AF) plays a major role in the determination of hemodynamic deterioration and can be associated with cardiovascular events after coronary artery surgery. Elevated interleukin (IL)-6 and Creactive protein (CRP) levels in patients with AF suggest a role of inflammation in the pathogenesis of AF. We conducted a study to investigate the correlation between postoperative AF and IL-6 and high-sensitivity CRP (hsCRP).
Materials and Methods. Forty-nine patients with a mean age of 60.3 ± 10.7 years were enrolled in this study. Preoperative and postoperative first day blood samples were collected to assess the IL-6 and hsCRP levels. IL-6 levels were measured by enzyme-linked immunosorbent assay, and hsCRP was measured by rate turbidimetry method.
Results. Fourteen patients (28.5%) developed AF postoperatively. Patients who developed AF showed elevated serum concentrations of postoperative first day IL-6 (P < .001), preoperative hsCRP (P < .005), and postoperative first day hsCRP (P < 0.001). Preoperative hsCRP levels (P < .002) and postoperative first day IL-6 (P < .001) and hsCRP (P < 0.001) levels were associated with prolonged endotracheal intubation time. Prolonged intensive care unit stay showed significant correlations with elevated levels of preoperative hsCRP (P < 0.002) and postoperative first day IL-6 (P < 0.001) and hsCRP (P < 0.001). There was also statistical significance between the AF+ and AF- groups regarding intensive care unit stay and endotracheal intubation times (P < .001 and P < .001, respectively). Cut-off points for postoperative first day IL-6, preoperative hsCRP, and postoperative first day hsCRP were 46.4 pg/mL (sensitivity = 92.9% and specificity = 80%), 0.46 mg/L (sensitivity = 71% and specificity = 75%), and 17.9 mg/L (sensitivity = 92.9% and specificity = 78%), respectively.
Conclusions. Elevated IL-6 and hsCRP levels in patients with postoperative AF suggest inflammatory components have a role of in the pathogenesis of AF.
Aviles RJ, Martin DO, Apperson-Hansen C, et al. 2003. Inflammation as a risk factor for atrial fibrillation. Circulation 108: 3006-10.nAlmassi GH, Schowalter T, Nicolosi AC, et al. 1997. Atrial fibrillation after cardiac surgery: a major morbid event? Ann Surg 226:501-11.nAranki SF, Shaw DP, Adams DH, et al. 1996. Predictors of atrial fibrillation after coronary artery surgery: current trends and impact on hospital resources. Circulation 94:390-7.nBruins P, Velthuis H, Yazdanbakhsh AP, et al. 1997. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation 96:3542-8.nChamoro A. 2004. Role of inflammation in stroke and atherothrombosis. Cerebrovasc Dis 2004;17:1-5.nChung MK, Martin DO, Sprecher D, et al. 2001. C-reactive protein elevation in patients with atrial arrhythmias. Inflammatory mechanisms and persistence of atrial fibrillation. Circulation 199:2886-91.nConway DS, Buggins P, Hughe E, Lip GY. 2004. Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation. Am Heart J 148:462-6.nCremer J, Martin M, Redl H, et al. 1996. Systemic inflammatory response after cardiac operations. Ann Thorac Surg 61:1714-20.nCrosby LH, Pifalo WB, Woll KR, Burkholder JA. 1990. Risk factors for atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 66:1520-2.nCzerny M, Baumer H, Kilo J, et al. 2000. Inflammatory response and myocardial injury following coronary artery bypass grafting with or without cardiopulmonary bypass. Eur J Cardiothorac Surg 17:737-42.nDaoud EG, Strickberger SA, Man KC, et al. 1997. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N Engl J Med 337:1785-91.nDavies MJ, Pomerance A. 1972. Pathology of atrial fibrillation in man. Br Heart J 34:520-5.nDernellis J, Panaretou M. 2004. Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation. Eur Heart J 25:1100-7.nDucceschi V, D'Andrea A, Liccardo B, et al. 1999. Perioperative clinical predictors of atrial fibrillation occurrence following coronary artery surgery. Eur J Cardiothorac Surg 16:435-9.nFrustaci A, Cristina C, Fulvio B, Emanuela M, Matteo A, Attilio M. 1997. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 96:1180-4.nGaudino M, Andreotti F, Zamparelli R, et al. 2003. The -174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation. Is atrial fibrillation an inflammatory complication? Circulation 108:195-9.nGaudino M, Nasso G, Andreotti F, et al. 2002. Preoperative C-reactive protein level and outcome following coronary surgery. Eur J Cardiothorac Surg 22:521-6.nGu YJ, Mariani MA, van Oeveren W, Grandjean JG, Boonstra PW. 1998. Reduction of the inflammatory response in patients undergoing minimally invasive coronary artery bypass grafting. Ann Thorac Surg 65:420-4.nHogue CW, Murphy SF, Schechtman KB, Davila-Roman VG. 1999. Risk factors for early or delayed stroke after cardiac surgery. Circulation 100:642-7.nKerr R, Stirling D, Ludlam CA. 2001. Interleukin 6 and haemostasis. Br J Hematol 115:3-12.nLip GY, Lowe GD, Rumley A, Dunn FG. 1995. Increased markers of thrombogenesis in chronic atrial fibrillation: effects of warfarin treatment. Br Heart J 73:527-33.nMendes LA, Connelly GP, McKenney PA, et al. 1995. Right coronary artery stenosis: an independent predictor of atrial fibrillation after coronary artery bypass surgery. J Am Coll Cardiol 25:198-202.nMoulton MJ, Creswell LL, Machery ME, Cox JL, Rosenbloom M. 1996. Reexploration for bleeding is a risk factor for adverse outcome after cardiac operations. J Thorac Cardiovasc Surg 111:1037-46.nPsychari SN, Apostolou TS, Sinos L, Hamodraka E, Liakos G, Kremastinos DT. 2005. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation. Am J Cardiol 95:764-7.nRoldan V, Marin F, Blann AD, et al. 2003. Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation. Eur Heart J 24:1373-80.nRubens FD, Nathan H, Labow R, et al. 2005. Effects of methylprednisolone and a biocompatible copolymer circuit on blood activation during cardiopulmonary bypass. Ann Thorac Surg 79:655-65.nSata N, Hamada N, Horinouchi T, et al. 2004. C-reactive protein and atrial fibrillation: is inflammation a consequence or a cause of atrial fibrillation? Jpn Heart J 45:441-5.nSawa Y, Ichikawa H, Kagisaki K, Ohata T, Matsuda H. 1998. Interleukin-6 derived from hypoxic myocytes promotes neutrophilmediated reperfusion injury in myocardium. J Thorac Cardiovasc Surg 116:511-7.nStamou SC, Dangas G, Hill PC, et al. 2000. Atrial fibrillation after beating heart surgery. Am J Cardiol 86:64-7.nTaylor K. 1996. SIRS: the systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg 61:1607-8.nWan S, DeSmet JM, Barvais L, Goldstein M, Vincent JL, LeClerc JL. 1996. Myocardium is a major source of proinflammatory cytokines in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 112:806-11.n
How to Cite
Author Disclosure & Copyright Transfer Agreement
In order to publish the original work of another person(s), The Heart Surgery Forum® must receive an acknowledgment of the Author Agreement and Copyright Transfer Statement transferring to Forum Multimedia Publishing, L.L.C., a subsidiary of Carden Jennings Publishing Co., Ltd. the exclusive rights to print and distribute the author(s) work in all media forms. Failure to check Copyright Transfer agreement box below will delay publication of the manuscript.
A current form follows:
The author(s) hereby transfer(s), assign(s), or otherwise convey(s) all copyright ownership of the manuscript submitted to Forum Multimedia Publishing, LLC (Publisher). The copyright transfer covers the exclusive rights to reproduce and distribute the article and the material contained therein throughout the world in all languages and in all media of expression now known or later developed, including but not limited to reprints, photographic reproduction, microfilm, electronic data processing (including programming, storage, and transmission to other electronic data record(s), or any other reproductions of similar nature), and translations.
However, Publisher grants back to the author(s) the following:
- The right to make and distribute copies of all or part of this work for use of the author(s) in teaching;
- The right to use, after publication in The Heart Surgery Forum, all or part of the material from this work in a book by the author(s), or in a collection of work by the author(s);
- The royalty-free right to make copies of this work for internal distribution within the institution/company that employs the author(s) subject to the provisions below for a work-made-for-hire;
- The right to use figures and tables from this work, and up to 250 words of text, for any purpose;
- The right to make oral presentations of material from this work.
Publisher reserves the right to grant or refuse permission to third parties to republish all or part of the article or translations thereof. To republish, such third parties must obtain written permission from the Publisher. (This is in accordance with the Copyright Statute, United States Code, Title 17. Exception: If all authors were bona fide officers or employees of the U.S. Government at the time the paper was prepared, the work is a “work of the US Government” (prepared by an officer or employee of the US Government as part of official duties), and therefore is not subject to US copyright; such exception should be indicated on signature lines. If this work was prepared under US Government contract or grant, the US Government may reproduce, royalty-free, all or portions of this work and may authorize others to do so, for official US Government purposes only, if the US Government contract or grant so requires.
I have participated in the conception and design of this work and in the writing of the manuscript and take public responsibility for it. Neither this manuscript nor one with substantially similar content under my authorship has been published, has been submitted for publication elsewhere, or will be submitted for publication elsewhere while under consideration by The Heart Surgery Forum, except as described in an attachment. I have reviewed this manuscript (original version) and approve its submission. If I am listed above as corresponding author, I will provide all authors with information regarding this manuscript and will obtain their approval before submitting any revision. I attest to the validity, accuracy, and legitimacy of the content of the manuscript and understand that Publisher assumes no responsibility for the validity, accuracy, and legitimacy of its content. I warrant that this manuscript is original with me and that I have full power to make this Agreement. I warrant that it contains no matter that is libelous or otherwise unlawful or that invades individual privacy or infringes any copyright or other proprietary right. I agree to indemnify and hold Publisher harmless of and from any claim made against Publisher that relates to or arises out of the publication of the manuscript and agree that this indemnification shall include payment of all costs and expenses relating to the defense of any such claim, including all reasonable attorney’s fees.
I warrant that I have no financial interest in the drugs, devices, or procedures described in the manuscript (except as disclosed in the attached statement).
I state that the institutional Human Subjects Committee and/or the Ethics Committee approved the clinical protocol reported in this manuscript for the use of experimental techniques, drugs, or devices in human subjects and appropriate informed consent documents were utilized.
Furthermore, I state that any and all animals used for experimental purposes received humane care in USDA registered facilities in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 85-23, revised 1985).