Association between Neutrophil to Lymphocyte Ratio and Atrial Fibrillation Zhao Li, Lijun Cui, Junwei Ma, Xianghong Ma, Guangping Li PII: DOI: Reference:
S0167-5273(15)00353-8 doi: 10.1016/j.ijcard.2015.03.114 IJCA 19878
To appear in:
International Journal of Cardiology
Received date: Accepted date:
29 January 2015 7 March 2015
Please cite this article as: Li Zhao, Cui Lijun, Ma Junwei, Ma Xianghong, Li Guangping, Association between Neutrophil to Lymphocyte Ratio and Atrial Fibrillation, International Journal of Cardiology (2015), doi: 10.1016/j.ijcard.2015.03.114
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
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T
Letter to the editor
SC R
Association between Neutrophil to Lymphocyte Ratio and Atrial Fibrillation
NU
Zhao Li1, Lijun Cui, Junwei Ma, Xianghong Ma*, Guangping Li
MA
Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin
CE P
TE
D
Medical University, Tianjin 300211, the People's Republic of China
Key words： neutrophil to lymphocyte ratio，atrial fibrillation，Coronary Artery
AC
Bypass Grafting，ablation，stroke
Word count (excluding references): 468 words
Conflicts of interest: None Financial disclosures: None
*Address for correspondence: Xianghong Ma, M.D, PH.D. (E-mail:[email protected]). Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People’s Republic of China. Tel.: +86-22-88328119; Fax: +86-22-88328225.??
ACCEPTED MANUSCRIPT 1 First two authors are equal to this article. Neutrophil to Lymphocyte Ratio(NLR) is a ratio of subtypes of leukocyte and has been attracting attention as a significant biomarker of systemic inflammation [1].
IP
T
Inflammation has a significant role in atherosclerosis [2]. NLR has been shown to be related to adverse outcomes in patients with coronary heart disease (CHD) [3-9] and
SC R
can independently predict mortality of CHD in an asymptomatic population [9]. Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and increases the risk of stroke and death. Inflammation, which is related to the initiation and maintenance
NU
of AF, plays a key role in AF [10-12]. However, little is known about the association
MA
between NLR levels and AF.
The complex nature of the inflammatory response after cardiac surgery and its
D
relation to postoperative AF are still to be detected. The postoperative level of N/L
TE
ratio is more closely related to new-onset AF after Coronary Artery Bypass Grafting (CABG), compared with other biomarkers of inflammatory, such as CRP,
CE P
interleukin-6. Moreover, both the pre- and postoperative N/L ratios are associated with an increased risk of developing AF after CABG.[13] Thus, it is considered that in association with other factors, NLR might contribute to identifying patients at high
AC
risk of postoperative AF after CABG.
A number of patients experience recurrence after AF ablation. Investigations of the mechanism of early recurrence are scarce. An increase in post-ablation NLR to ≥ 5.6 may identify patients at high risk of early recurrence after AF radiofrequency catheter ablation.[14] The pre-ablation NLR was one of the powerful and independent predictors of AF recurrence after cryoablation.[15] The measurement of NLR may assist in identifying high-risk patients who need more aggressive intervention to prevent recurrence of AF after ablation. NLR values in persistent AF patients were lower than in postoperative patients after CABG. The lower NLR values may be associated with inflammation of lower grade. NLR is insufficient to predict recurrence after electrical cardioversion in persistent AF patients.[16]
ACCEPTED MANUSCRIPT
NLR is also associated with the presence of thrombus within left atrial in patients with nonvalvular AF[17]. Thrombus precedes a stroke or thromboembolic event.
IP
T
CHADS2 scores were significantly higher in the high NLR group relatively. NLR is demonstrated to be an independent predictor of thromboembolic stroke in patients
SC R
with non-valvular AF.[18]
A high level of neutrophil count might reflect subclinical inflammation. The
NU
lymphocyte count might serve as an index for general health, influenced by acute physiologic stress. Thus, the N/L ratio includes information on both the inflammatory
MA
milieu and the stress response. In addition, as a simple hematological marker, the NLR is widely available and repeatable. We hope more prospective studies in large
Acknowledgment
TE
D
populations about the relationship between NLR and AF should be made.
CE P
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
AC
References
[1] de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care. 14(5). England,2010. R192. [2] Ross R. Atherosclerosis — An Inflammatory Disease. New England Journal of MedicineNew England Journal of MedicineN Engl J Med. 1999;340:115. [3] Nunez J, Nunez E, Bodi V, Sanchis J, Minana G, Mainar L, et al. Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction. Am J Cardiol. 101(6). United States,2008. 747-52.
ACCEPTED MANUSCRIPT [4] Azab B, Zaher M, Weiserbs KF, Torbey E, Lacossiere K, Gaddam S, et al. Usefulness of neutrophil to lymphocyte ratio in predicting short- and long-term mortality after non-ST-elevation myocardial infarction. Am J Cardiol. 106(4). United
IP
T
States,2010. 470-6.
[5] Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS.
SC R
Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 102(6). United States,2008. 653-7.
NU
[6] Papa A, Emdin M, Passino C, Michelassi C, Battaglia D, Cocci F. Predictive value of elevated neutrophil-lymphocyte ratio on cardiac mortality in patients with stable
MA
coronary artery disease. Clin Chim Acta. 395(1-2). Netherlands,2008. 27-31. [7] Kaya MG, Akpek M, Lam YY, Yarlioglues M, Celik T, Gunebakmaz O, et al.
D
Prognostic value of neutrophil/lymphocyte ratio in patients with ST-elevated
TE
myocardial infarction undergoing primary coronary intervention: a prospective, multicenter study. Int J Cardiol. 168(2). Netherlands,2013. 1154-9.
CE P
[8] Balta S, Demirkol S, Aparci M, Celik T, Ozturk C. The neutrophil lymphocyte ratio in coronary heart disease. Int J Cardiol. 176(1). Netherlands,2014. 267. [9] Shah N, Parikh V, Patel N, Patel N, Badheka A, Deshmukh A, et al. Neutrophil
AC
lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality: insights from the National Health and Nutrition Examination Survey-III. Int J Cardiol. 2014;171:390-7. [10] Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA, et al. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003;108:3006-10. [11] Aronson D, Boulos M, Suleiman A, Bidoosi S, Agmon Y, Kapeliovich M, et al. Relation of C-reactive protein and new-onset atrial fibrillation in patients with acute myocardial infarction. Am J Cardiol. 100(5). United States,2007. 753-7. [12] Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A, Carnes CA, et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation. 104(24). United
ACCEPTED MANUSCRIPT States,2001. 2886-91. [13] Gibson PH, Cuthbertson BH, Croal BL, Rae D, El-Shafei H, Gibson G, et al. Usefulness of neutrophil/lymphocyte ratio as predictor of new-onset atrial
IP
T
fibrillation after coronary artery bypass grafting. Am J Cardiol. 105(2). United States,2010. 186-91.
SC R
[14] Im SI, Shin SY, Na JO, Kim YH, Choi CU, Kim SH, et al. Usefulness of neutrophil/lymphocyte ratio in predicting early recurrence after radiofrequency catheter ablation in patients with atrial fibrillation. Int J Cardiol. 168(4).
NU
Netherlands,2013. 4398-400.
[15] Canpolat U, Aytemir K, Yorgun H, Sahiner L, Kaya EB, Kabakci G, et al. Role of
MA
preablation neutrophil/lymphocyte ratio on outcomes of cryoballoon-based atrial fibrillation ablation. Am J Cardiol. 2013;112:513-9.
D
[16] Aribas A, Akilli H, Gul EE, Kayrak M, Demir K, Duman C, et al. Can
TE
neutrophil/lymphocyte ratio predict recurrence of non-valvular atrial fibrillation after cardioversion. Anadolu Kardiyol Derg. 2013;13:123-30.
CE P
[17] Yalcin M, Aparci M, Uz O, Isilak Z, Balta S, Dogan M, et al. Neutrophil-Lymphocyte Ratio May Predict Left Atrial Thrombus in Patients With Nonvalvular Atrial Fibrillation. Clin Appl Thromb Hemost. ,2013.
AC
[18] Ertas G, Sonmez O, Turfan M, Kul S, Erdogan E, Tasal A, et al. Neutrophil/lymphocyte ratio is associated with thromboembolic stroke in patients with non-valvular atrial fibrillation. J Neurol Sci. 324(1-2). Netherlands,2013. 49-52.
S0167-5273(15)00353-8 doi: 10.1016/j.ijcard.2015.03.114 IJCA 19878
To appear in:
International Journal of Cardiology
Received date: Accepted date:
29 January 2015 7 March 2015
Please cite this article as: Li Zhao, Cui Lijun, Ma Junwei, Ma Xianghong, Li Guangping, Association between Neutrophil to Lymphocyte Ratio and Atrial Fibrillation, International Journal of Cardiology (2015), doi: 10.1016/j.ijcard.2015.03.114
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
IP
T
Letter to the editor
SC R
Association between Neutrophil to Lymphocyte Ratio and Atrial Fibrillation
NU
Zhao Li1, Lijun Cui, Junwei Ma, Xianghong Ma*, Guangping Li
MA
Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin
CE P
TE
D
Medical University, Tianjin 300211, the People's Republic of China
Key words： neutrophil to lymphocyte ratio，atrial fibrillation，Coronary Artery
AC
Bypass Grafting，ablation，stroke
Word count (excluding references): 468 words
Conflicts of interest: None Financial disclosures: None
*Address for correspondence: Xianghong Ma, M.D, PH.D. (E-mail:[email protected]). Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People’s Republic of China. Tel.: +86-22-88328119; Fax: +86-22-88328225.??
ACCEPTED MANUSCRIPT 1 First two authors are equal to this article. Neutrophil to Lymphocyte Ratio(NLR) is a ratio of subtypes of leukocyte and has been attracting attention as a significant biomarker of systemic inflammation [1].
IP
T
Inflammation has a significant role in atherosclerosis [2]. NLR has been shown to be related to adverse outcomes in patients with coronary heart disease (CHD) [3-9] and
SC R
can independently predict mortality of CHD in an asymptomatic population [9]. Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and increases the risk of stroke and death. Inflammation, which is related to the initiation and maintenance
NU
of AF, plays a key role in AF [10-12]. However, little is known about the association
MA
between NLR levels and AF.
The complex nature of the inflammatory response after cardiac surgery and its
D
relation to postoperative AF are still to be detected. The postoperative level of N/L
TE
ratio is more closely related to new-onset AF after Coronary Artery Bypass Grafting (CABG), compared with other biomarkers of inflammatory, such as CRP,
CE P
interleukin-6. Moreover, both the pre- and postoperative N/L ratios are associated with an increased risk of developing AF after CABG.[13] Thus, it is considered that in association with other factors, NLR might contribute to identifying patients at high
AC
risk of postoperative AF after CABG.
A number of patients experience recurrence after AF ablation. Investigations of the mechanism of early recurrence are scarce. An increase in post-ablation NLR to ≥ 5.6 may identify patients at high risk of early recurrence after AF radiofrequency catheter ablation.[14] The pre-ablation NLR was one of the powerful and independent predictors of AF recurrence after cryoablation.[15] The measurement of NLR may assist in identifying high-risk patients who need more aggressive intervention to prevent recurrence of AF after ablation. NLR values in persistent AF patients were lower than in postoperative patients after CABG. The lower NLR values may be associated with inflammation of lower grade. NLR is insufficient to predict recurrence after electrical cardioversion in persistent AF patients.[16]
ACCEPTED MANUSCRIPT
NLR is also associated with the presence of thrombus within left atrial in patients with nonvalvular AF[17]. Thrombus precedes a stroke or thromboembolic event.
IP
T
CHADS2 scores were significantly higher in the high NLR group relatively. NLR is demonstrated to be an independent predictor of thromboembolic stroke in patients
SC R
with non-valvular AF.[18]
A high level of neutrophil count might reflect subclinical inflammation. The
NU
lymphocyte count might serve as an index for general health, influenced by acute physiologic stress. Thus, the N/L ratio includes information on both the inflammatory
MA
milieu and the stress response. In addition, as a simple hematological marker, the NLR is widely available and repeatable. We hope more prospective studies in large
Acknowledgment
TE
D
populations about the relationship between NLR and AF should be made.
CE P
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
AC
References
[1] de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care. 14(5). England,2010. R192. [2] Ross R. Atherosclerosis — An Inflammatory Disease. New England Journal of MedicineNew England Journal of MedicineN Engl J Med. 1999;340:115. [3] Nunez J, Nunez E, Bodi V, Sanchis J, Minana G, Mainar L, et al. Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction. Am J Cardiol. 101(6). United States,2008. 747-52.
ACCEPTED MANUSCRIPT [4] Azab B, Zaher M, Weiserbs KF, Torbey E, Lacossiere K, Gaddam S, et al. Usefulness of neutrophil to lymphocyte ratio in predicting short- and long-term mortality after non-ST-elevation myocardial infarction. Am J Cardiol. 106(4). United
IP
T
States,2010. 470-6.
[5] Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS.
SC R
Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 102(6). United States,2008. 653-7.
NU
[6] Papa A, Emdin M, Passino C, Michelassi C, Battaglia D, Cocci F. Predictive value of elevated neutrophil-lymphocyte ratio on cardiac mortality in patients with stable
MA
coronary artery disease. Clin Chim Acta. 395(1-2). Netherlands,2008. 27-31. [7] Kaya MG, Akpek M, Lam YY, Yarlioglues M, Celik T, Gunebakmaz O, et al.
D
Prognostic value of neutrophil/lymphocyte ratio in patients with ST-elevated
TE
myocardial infarction undergoing primary coronary intervention: a prospective, multicenter study. Int J Cardiol. 168(2). Netherlands,2013. 1154-9.
CE P
[8] Balta S, Demirkol S, Aparci M, Celik T, Ozturk C. The neutrophil lymphocyte ratio in coronary heart disease. Int J Cardiol. 176(1). Netherlands,2014. 267. [9] Shah N, Parikh V, Patel N, Patel N, Badheka A, Deshmukh A, et al. Neutrophil
AC
lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality: insights from the National Health and Nutrition Examination Survey-III. Int J Cardiol. 2014;171:390-7. [10] Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA, et al. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003;108:3006-10. [11] Aronson D, Boulos M, Suleiman A, Bidoosi S, Agmon Y, Kapeliovich M, et al. Relation of C-reactive protein and new-onset atrial fibrillation in patients with acute myocardial infarction. Am J Cardiol. 100(5). United States,2007. 753-7. [12] Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A, Carnes CA, et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation. 104(24). United
ACCEPTED MANUSCRIPT States,2001. 2886-91. [13] Gibson PH, Cuthbertson BH, Croal BL, Rae D, El-Shafei H, Gibson G, et al. Usefulness of neutrophil/lymphocyte ratio as predictor of new-onset atrial
IP
T
fibrillation after coronary artery bypass grafting. Am J Cardiol. 105(2). United States,2010. 186-91.
SC R
[14] Im SI, Shin SY, Na JO, Kim YH, Choi CU, Kim SH, et al. Usefulness of neutrophil/lymphocyte ratio in predicting early recurrence after radiofrequency catheter ablation in patients with atrial fibrillation. Int J Cardiol. 168(4).
NU
Netherlands,2013. 4398-400.
[15] Canpolat U, Aytemir K, Yorgun H, Sahiner L, Kaya EB, Kabakci G, et al. Role of
MA
preablation neutrophil/lymphocyte ratio on outcomes of cryoballoon-based atrial fibrillation ablation. Am J Cardiol. 2013;112:513-9.
D
[16] Aribas A, Akilli H, Gul EE, Kayrak M, Demir K, Duman C, et al. Can
TE
neutrophil/lymphocyte ratio predict recurrence of non-valvular atrial fibrillation after cardioversion. Anadolu Kardiyol Derg. 2013;13:123-30.
CE P
[17] Yalcin M, Aparci M, Uz O, Isilak Z, Balta S, Dogan M, et al. Neutrophil-Lymphocyte Ratio May Predict Left Atrial Thrombus in Patients With Nonvalvular Atrial Fibrillation. Clin Appl Thromb Hemost. ,2013.
AC
[18] Ertas G, Sonmez O, Turfan M, Kul S, Erdogan E, Tasal A, et al. Neutrophil/lymphocyte ratio is associated with thromboembolic stroke in patients with non-valvular atrial fibrillation. J Neurol Sci. 324(1-2). Netherlands,2013. 49-52.
