title: Association of inflammatory, lipid and mineral markers with cardiac calcification in older adults.
abstract: OBJECTIVE
  Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults.
  
  
  METHODS
  We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein (Lp) (a), Lp-associated phospholipase A2(LpPLA2) mass and activity), inflammatory (interleukin-6, soluble (s) CD14) and mineral metabolism (fetuin-A, fibroblast growth factor (FGF)-23) pathways that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcification (AVC), aortic annular calcification (AAC) and mitral annular calcification (MAC) were assessed with relative risk (RR) regression.
  
  
  RESULTS
  Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA2mass and activity and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were as follows: Lp(a), 1.051 (1.022 to 1.081); LpPLA2mass, 1.036 (1.006 to 1.066) and LpPLA2activity, 1.037 (1.004 to 1.071); sCD14, 1.039 (1.005 to 1.073). FGF-23 was positively associated with MAC, 1.040 (1.004 to 1.078) and fetuin-A was negatively associated, 0.949 (0.911 to 0.989). No biomarkers were significantly associated with AAC.
  
  
  CONCLUSIONS
  This study shows novel associations of circulating FGF-23 and fetuin-A with MAC, and LpPLA2and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of Lp and inflammatory pathways may provide added insight into the aetiology of AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC.
authors.affiliation: Cardiology Division, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Bortnick
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington, USA.
authors.forename: Traci M
authors.initials: TM
authors.lastname: Bartz
authors.affiliation: Department of Medicine, and the Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California, and Nephrology Section, Veteran Affairs San Diego Health Care System, San Diego, California, USA.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, Aurora, Colorado, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Reiner
authors.affiliation: Departments of Pathology and Biochemistry, University of Vermont, Burlington, Vermont, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington, USA.
authors.forename: David
authors.initials: D
authors.lastname: Owens
authors.affiliation: Department of Research and Education, St. Francis Hospital, The Heart Center, Roslyn, New York, USA.
authors.forename: Eddy
authors.initials: E
authors.lastname: Barasch
authors.affiliation: New York Academy of Medicine, New York, New York, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Division of Cardiovascular Medicine, Department of Cardiology, University of Maryland, Baltimore, Maryland, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Gottdiener
authors.affiliation: Cardiology Division, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA.|Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Kizer