Inflammation in Atrial Fibrillation
Yutao Guo, MDR,*† Gregory Y. H. Lip, MD,* Stavros Apostolakis, MD, PHD*
Birmingham, United Kingdom; and Beijing, China
Atrial fibrillation (AF) is associated with increased risk for stroke and systemic embolism. There is plausible evi-
dence linking inflammation to the initiation and perpetuation of AF and AF-related thrombosis. Various inflam-
matory markers (C-reactive protein, tumor necrosis factor-?, interleukin-2, interleukin-6, and interleukin-8) have
been associated with AF. Proposed mechanisms linking inflammation and the prothrombotic AF state include
endothelial activation/damage, production of tissue factor from monocytes, increased platelet activation, and
increased expression of fibrinogen. The present review aims to provide an update on the association of inflam-
mation and AF, including the impact of inflammatory markers on clinical presentation and outcome of AF
patients.(J Am Coll Cardiol 2012;60:2263–70) © 2012 by the American College of Cardiology Foundation
The pathophysiology of atrial fibrillation (AF) is complex
and incompletely understood. Several studies have described
an association between AF and abnormal prothrombotic
plasma markers, including fibrinogen, von Willebrand fac-
tor (vWF), and soluble P-selectin, suggesting that the
arrhythmia itself contributes to the development of a pro-
thrombotic state (1). Furthermore, various inflammatory
markers and mediators such as C-reactive protein (CRP),
tumor necrosis factor (TNF)-?, interleukin (IL)-2, IL-6,
IL-8, and monocyte chemoattractant protein (MCP)-1
have been linked with the presence or the outcome of AF
(2). Finally, recent studies indicate that activated inflamma-
tory cells and inflammatory mediators may confer a pro-
thrombotic state by promoting endothelial damage/
dysfunction and platelet activation in patients with AF, thus
linking inflammation and thrombosis.
In the present review article, we summarize the available
data on the potential mechanisms linking inflammation to
AF and to AF-related thrombosis. Current research in this
field mainly focuses on the impact of inflammatory markers
on clinical presentation and outcome of AF and it further
aims to address four important questions. 1) Is inflamma-
tion a consequence or a cause of AF? 2) Is inflammation
related to AF a systemic or local phenomenon? 3) Could
inflammation reflect underlying disease not associated with
AF per se? 4) What role does inflammation play in
thromboembolism in the setting of AF?
We searched PubMed database between January 1990 and
December 2011 with the following terms individually or in
combination: “atrial fibrillation,” “inflammation,” “interleu-
kin,” “chemokine,” “IL-2,” “IL-6,” “IL-8,” “CRP,” “TNF-
?,” “MCP-1,” and “prothrombotic state.” References from
the relevant articles were reviewed, and related articles were
Inflammatory Markers and Atrial Fibrillation
Leukocyte activation is considered an important inflamma-
tory pathway underlying AF (3). Cytokines and chemo-
kines orchestrate leukocyte trafficking and activation and
have been assessed as potential mediators in the estab-
lishment and perpetuation of AF and AF-related throm-
bosis (Online Refs. 1–5). The source, biological effect,
and prognostic role of the main inflammatory markers
associated with AF are summarized in Table 1.
C-reactive protein. C-reactive protein is the prototype
marker of inflammation and is predominantly synthesized in
hepatocytes as an acute-phase reactant (4). In human
monocytes, CRP not only promotes MCP-1–mediated
chemotaxis by upregulating CC-chemokine receptor 2 ex-
pression, but also induces tissue factor (TF) secretion and
promotes procoagulant activity. Indeed, Chung et al.
(Online Ref. 6) showed an association between serum CRP
and AF, but this was a cross-sectional study and, therefore, did
not address whether inflammatory marker elevation was the
From the *Haemostasis, Thrombosis and Vascular Biology Unit, University of
Birmingham Centre for Cardiovascular Science, City Hospital, Birmingham, United
Kingdom; and the †Department of Geriatric Cardiology, Chinese PLA General
Hospital, Beijing, China. Drs. Apostolakis and Lip have received research funding
and honoraria from various pharmaceutical companies in relation to atrial fibrillation
for meetings and educational symposia. Dr. Lip has served as a consultant for Bayer,
Astellas, Merck, AstraZeneca, Sanofi, BMS/Pfizer, Daiichi-Sankyo, Biotronik, Por-
tola, and Boehringer Ingelheim; has been on the speaker’s bureau for Bayer,
BMS/Pfizer, Boehringer Ingelheim, and Sanofi Aventis; is a member of advisory
boards and trial steering committees; he was clinical advisor to the UK National
NICE Guidelines on Atrial Fibrillation Management; and was on the writing group
for the European Society of Cardiology Guidelines on Atrial Fibrillation Manage-
ment; he is also a panelist on the revised (9th edition) American College of Chest
Physicians Guidelines on Antithrombotic Therapy. Dr. Guo has reported that he has
no relationships relevant to the contents of this paper to disclose.
Manuscript received January 30, 2012; revised manuscript received March 7, 2012,
accepted April 1, 2012.
Journal of the American College of Cardiology
© 2012 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 60, No. 22, 2012
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Key Words: atrial fibrillation y inflammation y prothrombotic state.
For supplementary references, please see the online version of this article.
2270 Guo et al.
Inflammation in Atrial Fibrillation
JACC Vol. 60, No. 22, 2012
December 4, 2012:2263–70