title: Circulating intermediate CD14++CD16+monocytes are increased in patients with atrial fibrillation and reflect the functional remodelling of the left atrium.
abstract: OBJECTIVE
  A recent large clinical study demonstrated the association between intermediate CD14++CD16+monocytes and cardiovascular events. However, whether that monocyte subset contributes to the pathogenesis of atrial fibrillation (AF) has not been clarified. We compared the circulating monocyte subsets in AF patients and healthy people, and investigated the possible role of intermediate CD14++CD16+monocytes in the pathophysiology of AF.
  
  
  RESULTS
  This case-control study included 44 consecutive AF patients without systemic diseases referred for catheter ablation at our hospital, and 40 healthy controls. Patients with systemic diseases, including structural heart disease, hepatic or renal dysfunction, collagen disease, malignancy, and inflammation were excluded. Monocyte subset analyses were performed (three distinct human monocyte subsets: classical CD14++CD16-, intermediate CD14++CD16+, and non-classical CD14+CD16++monocytes). We compared the monocyte subsets and evaluated the correlation with other clinical findings. A total of 60 participants (30 AF patients and 30 controls as an age-matched group) were included after excluding 14 AF patients due to inflammation. Atrial fibrillation patients had a higher proportion of circulating intermediate CD14++CD16+monocytes than the controls (17.0 ± 9.6 vs. 7.5 ± 4.1%, P < 0.001). A multivariable logistic regression analysis demonstrated that only the proportion of intermediate CD14++CD16+monocytes (odds ratio: 1.316; 95% confidence interval: 1.095-1.582, P = 0.003) was independently associated with the presence of AF. Intermediate CD14++CD16+monocytes were negatively correlated with the left atrial appendage flow during sinus rhythm (r= -0.679, P = 0.003) and positively with the brain natriuretic peptide (r = 0.439, P = 0.015).
  
  
  CONCLUSIONS
  Intermediate CD14++CD16+monocytes might be closely related to the pathogenesis of AF and reflect functional remodelling of the left atrium.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan kfuku@med.kobe-u.ac.jp.|Section of Arrhythmia, Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuzawa
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Emoto
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Asumi
authors.initials: A
authors.lastname: Takei
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ryudo
authors.initials: R
authors.lastname: Fujiwara
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Ichibori
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.|Section of Arrhythmia, Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Hirata
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology; D016279:Atrial Function, Left; D064752:Atrial Remodeling; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D007564:Japan; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification / Q000276:immunology*; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood; D016017:Odds Ratio; D011237:Predictive Value of Tests; D017452:Receptors, IgG / Q000097:blood*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D020097:Natriuretic Peptide, Brain
keywords: Atrial fibrillation; CD14++CD16+monocytes; Inflammation; Monocyte subsets; Pathophysiology of atrial fibrillation