title: sRAGE, inflammation, and risk of atrial fibrillation: results from the Atherosclerosis Risk in Communities (ARIC) Study.
abstract: OBJECTIVE
  Advanced glycation end products (AGEs) may cause inflammation by binding to their cellular receptors (RAGE). Soluble RAGE (sRAGE) acts as a decoy receptor for AGEs and may prevent inflammation. Chronic low-grade inflammation is a risk factor for cardiovascular disease, including atrial fibrillation (AF).
  
  
  METHODS
  We studied 1,068 participants in a subsample of the Atherosclerosis Risk in Communities (ARIC) Study who had baseline measurements of sRAGE (mean age 56, 60% female, 21% Black). Inflammation was assessed using measurements of high sensitivity C-reactive protein (hsCRP), fibrinogen, gamma-glutamyl transferase (GGT) and white blood cell (WBC) count. AF events were identified using ECG data, hospitalization discharge codes, and linkage to the National Death Index.
  
  
  RESULTS
  Compared to the highest quartile (>1272.4 pg/mL), the lowest quartile of sRAGE (<714 pg/mL) was associated with higher baseline levels of inflammation (hsCRP ≥3 mg/L: OR=2.21 [95% CI 1.41-3.49], fibrinogen ≥400 mg/dL: OR=4.31 [95% CI 1.50-12.41], GGT ≥36 U/L in women and ≥61 U/L in men: OR=5.22 [95% CI 2.66-10.22], WBC >6.2×10⁹/L: OR=2.38 [95% CI 1.52-3.72]). sRAGE was not prospectively associated with 6-year change in inflammatory markers (hsCRP or GGT). There was no significant association of sRAGE and risk of AF (HR 1.49 [95% CI: 0.80-2.78] for the 1st vs. 4th quartile of sRAGE).
  
  
  CONCLUSIONS
  sRAGE was strongly inversely associated with markers of inflammation at baseline, but not prospectively. sRAGE was not significantly associated with incident AF. This supports a role for sRAGE in attenuating current inflammation, but it remains unclear whether sRAGE plays a role in the development of AF.
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health and the Welch Center for Prevention, Epidemiology and Clinical Research.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al Rifai
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health and the Welch Center for Prevention, Epidemiology and Clinical Research; Department of Medicine, Johns Hopkins University School of Medicine.
authors.forename: Andrea L C
authors.initials: AL
authors.lastname: Schneider
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health and the Welch Center for Prevention, Epidemiology and Clinical Research; Department of Medicine, Johns Hopkins University School of Medicine.
authors.forename: Nisa
authors.initials: N
authors.lastname: Maruthur
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health and the Welch Center for Prevention, Epidemiology and Clinical Research.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Parrinello
authors.affiliation: Departments of Medicine and Population Health Sciences, University of Wisconsin School of Medicine and Public Health.
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.affiliation: Department of Medicine, Section of Cardiovascular Research, Baylor College of Medicine and Houston Methodist DeBakey Heart and Vascular Center.
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.affiliation: Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, and Department of Internal Medicine-Cardiology, Wake Forest School of Medicine.
authors.forename: Elsayed Z
authors.initials: EZ
authors.lastname: Soliman
authors.affiliation: Cardiovascular Division, Department of Medicine, University of Minnesota Medical School.
authors.forename: Lin Y
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Department of Medicine, Section of Cardiovascular Research, Baylor College of Medicine and Houston Methodist DeBakey Heart and Vascular Center.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine.
authors.forename: Marc K
authors.initials: MK
authors.lastname: Halushka
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health and the Welch Center for Prevention, Epidemiology and Clinical Research; Department of Medicine, Johns Hopkins University School of Medicine. Electronic address: eselvin@jhu.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
mesh_terms: D050197:Atherosclerosis / Q000097:blood / Q000453:epidemiology / Q000276:immunology; D001281:Atrial Fibrillation / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000276:immunology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D015994:Incidence; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000737:chemistry; D012307:Risk Factors; D012995:Solubility; D014481:United States / Q000453:epidemiology; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D005340:Fibrinogen; D002097:C-Reactive Protein; D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human
keywords: Advanced glycation end products; Atrial fibrillation; C-reactive protein; Epidemiology; Inflammation