title: Association Between Vascular Cell Adhesion Molecule 1 and Atrial Fibrillation.
abstract: Accumulating evidence links inflammation and atrial fibrillation (AF).
  
  
  
  To assess whether markers of systemic and atrial inflammation are associated with incident AF in the general population.
  
  
  
  The Bruneck Study is a prospective, population-based cohort study with a 20-year follow-up (n = 909). The population included a random sample of the general community aged 40 to 79 years. Levels of 13 inflammation markers were measured at baseline in 1990. Findings were replicated in a case-control sample nested within the prospective Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study (n = 1770). Data analysis was performed from February to May 2016.
  
  
  
  Levels of 13 inflammation markers.
  
  
  
  Incident AF over a 20-year follow-up period in the Bruneck Study.
  
  
  
  Of the 909 participants included in the Bruneck Study, mean [SD] age was 58.8 (11.4) years and 448 (49.3%) were women. Among the 880 participants free of prevalent AF (n = 29) at baseline, 117 developed AF during the 20-year follow-up period (incidence rate, 8.2; 95% CI, 6.8-9.6 per 1000 person-years). The levels of soluble vascular cell adhesion molecule 1 (VCAM-1) and osteoprotegerin were significantly associated with incident AF (hazard ratio [HR], 1.49; 95% CI, 1.26-1.78; and 1.46; 95% CI, 1.25-1.69, respectively; P < .001 with Bonferroni correction for both), but osteoprotegerin lost significance after age and sex adjustment (HR, 1.05; 95% CI, 0.87-1.27; P > .99 with Bonferroni correction). Matrix metalloproteinase 9, metalloproteinase inhibitor 1, monocyte chemoattractant protein-1, P-selectin, fibrinogen, receptor activator of nuclear factor-κB ligand, high-sensitivity C-reactive protein, adiponectin, leptin, soluble intercellular adhesion molecule 1, and E-selectin all fell short of significance (after Bonferroni correction in unadjusted and age- and sex-adjusted analyses). The HR for a 1-SD higher soluble VCAM-1 level was 1.34 (95% CI, 1.11-1.62; Bonferroni-corrected P = .03) in a multivariable model. The association was of a dose-response type, at least as strong as that obtained for N-terminal pro-B-type natriuretic peptide (multivariable HR for a 1-SD higher N-terminal pro-B-type natriuretic peptide level, 1.15; 95% CI, 1.04-1.26), internally consistent in various subgroups, and successfully replicated in the SAPHIR Study (age- and sex-adjusted, and multivariable odds ratios for a 1-SD higher soluble VCAM-1 level, 1.91; 95% CI, 1.24-2.96, P = .003; and 2.59; 95% CI, 1.45-4.60; P = .001).
  
  
  
  Levels of soluble VCAM-1, but not other inflammation markers, are significantly associated with new-onset AF in the general community. Future studies should address whether soluble VCAM-1 is capable of improving AF risk classification beyond the information provided by standard risk scores.
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Willeit
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Raimund
authors.initials: R
authors.lastname: Pechlaner
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria2Department of Public Health and Primary Care, University of Cambridge, Cambridge, England3Cardiovascular Division, King's British Heart Foundation Centre, King's College London, London, England.
authors.forename: Peter
authors.initials: P
authors.lastname: Willeit
authors.affiliation: Cardiovascular Division, King's British Heart Foundation Centre, King's College London, London, England.
authors.forename: Philipp
authors.initials: P
authors.lastname: Skroblin
authors.affiliation: First Department of Internal Medicine, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
authors.affiliation: Department of Cardiology, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria.
authors.forename: Christiana
authors.initials: C
authors.lastname: Schernthaner
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Toell
authors.affiliation: Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy.
authors.forename: Georg
authors.initials: G
authors.lastname: Egger
authors.affiliation: Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weger
authors.affiliation: Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy.
authors.forename: Martin
authors.initials: M
authors.lastname: Oberhollenzer
authors.affiliation: First Department of Internal Medicine, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria.
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Kedenko
authors.affiliation: Department of Geriatric Medicine, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Iglseder
authors.affiliation: Division of Endocrinology, Diabetes and Metabolic Diseases, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: Cardiovascular Division, King's British Heart Foundation Centre, King's College London, London, England.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D001317:Austria / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood; D007558:Italy / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015203:Reproducibility of Results; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019010:Vascular Cell Adhesion Molecule-1