title: The associations of leptin, adiponectin and resistin with incident atrial fibrillation in women.
abstract: Higher body mass index (BMI) is an important risk factor for atrial fibrillation (AF). The adipokines leptin, adiponectin and resistin are correlates of BMI, but their association with incident AF is not well known. We explored this relationship in a large cohort of postmenopausal women.
  
  
  
  We studied an ethnically diverse cohort of community-dwelling postmenopausal women aged 50-79 who were nationally recruited at 40 clinical centres as part of the Women's Health Initiative investigation. Participants underwent measurements of baseline serum leptin, adiponectin and resistin levels and were followed for incident AF. Adipokine levels were log transformed and normalised using inverse probability weighting. Cox proportional hazard regression models were used to estimate associations with adjustment for known AF risk factors.
  
  
  
  Of the 4937 participants included, 892 developed AF over a follow-up of 11.1 years. Those with AF had higher mean leptin (14.9 pg/mL vs 13.9 pg/mL), adiponectin (26.3 ug/mL vs 24.5 ug/mL) and resistin (12.9 ng/mL vs 12.1 ng/mL) levels. After multivariable adjustment, neither log leptin nor log adiponectin levels were significantly associated with incident AF. However, log resistin levels remained significantly associated with incident AF (HR=1.57 per 1 log (ng/mL) increase, p=0.006). Additional adjustment for inflammatory cytokines only partially attenuated the association between resistin and incident AF (HR=1.43, p=0.06 adjusting for C-reactive protein (CRP); HR=1.39, p=0.08 adjusting for IL-6). Adjusting for resistin partially attenuated the association between BMI and incident AF (HR=1.14 per 5 kg/m(2), p=0.006 without resistin; HR=1.12, p=0.02 with resistin).
  
  
  
  In women, elevated levels of serum resistin are significantly associated with higher rates of incident AF and partially mediate the association between BMI and AF. In the same population, leptin and adiponectin levels are not significantly associated with AF.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford, University School of Medicine, Stanford, California, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Ermakov
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford, University School of Medicine, Stanford, California, USA.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Azarbal
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford, University School of Medicine, Stanford, California, USA.
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.affiliation: Department of Social and Prevention Medicine, School of Public Health and Health Professions, University of Buffalo, Buffalo, New York, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: LaMonte
authors.affiliation: Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Tharp
authors.affiliation: GW Medical Faculty Associates Cardiology Division, School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia, USA.
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, California, USA.
authors.forename: Rami
authors.initials: R
authors.lastname: Nassir
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Salmoirago-Blotcher
authors.affiliation: Department of Medicine, Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Albert
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford, University School of Medicine, Stanford, California, USA.
authors.forename: Themistocles L
authors.initials: TL
authors.lastname: Assimes
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford, University School of Medicine, Stanford, California, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hlatky
authors.affiliation: Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Larson
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford, University School of Medicine, Stanford, California, USA.
authors.forename: Marco V
authors.initials: MV
authors.lastname: Perez
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology* / Q000208:ethnology; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016009:Chi-Square Distribution; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D015994:Incidence; D018836:Inflammation Mediators / Q000097:blood; D020738:Leptin / Q000097:blood*; D016014:Linear Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000453:epidemiology; D017698:Postmenopause / Q000097:blood; D016016:Proportional Hazards Models; D011446:Prospective Studies; D052243:Resistin / Q000097:blood*; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D020738:Leptin; C499624:RETN protein, human; D052243:Resistin