title: Rheumatoid Arthritis, Anti-Cyclic Citrullinated Peptide Positivity, and Cardiovascular Disease Risk in the Women's Health Initiative.
abstract: OBJECTIVE
  To evaluate the incidence of cardiovascular disease (CVD) morbidity and mortality over the course of 10 years among the more than 160,000 postmenopausal women in the Women's Health Initiative (WHI) in relation to self-reported rheumatoid arthritis (RA), taking disease-modifying antirheumatic drugs (DMARDs), anti-cyclic citrullinated peptide (anti-CCP) positivity, rheumatoid factor (RF) positivity, CVD risk factors, joint pain, and inflammation (white blood cell count and interleukin-6 levels).
  
  
  METHODS
  Anti-CCP and RF were measured in a sample of WHI participants with self-reported RA (n = 9,988). RA was classified as self-reported RA plus anti-CCP positivity and/or taking DMARDs. Anti-CCP-negative women with self-reported RA and not taking DMARDs were classified as having "unverified RA."
  
  
  RESULTS
  Age-adjusted rates of coronary heart disease (CHD), stroke, CVD, fatal CVD, and total mortality were higher in women with RA than in women with no reported RA, with multivariable-adjusted hazard ratios of 1.46 (95% confidence interval [95% CI] 1.17-1.83) for CHD and 2.55 (95% CI 1.86-3.51) for fatal CVD. Among women with RA, anti-CCP positivity and RF positivity were not significantly associated with higher risk of any outcomes, despite slightly higher risk of death for those who were anti-CCP positive than for those who were anti-CCP negative. Joint pain severity and CVD risk factors were strongly associated with CVD risk, even in women with no reported RA. CVD incidence was increased in women with RA versus women with no reported RA at almost all risk factor levels, except for low levels of joint pain or inflammation. Among women with RA, inflammation was more strongly associated with fatal CVD and total mortality than with CHD or CVD.
  
  
  CONCLUSIONS
  Among postmenopausal women, RA was associated with 1.5-2.5-fold higher CVD risk. CVD risk was strongly associated with CVD risk factors, joint pain severity, and inflammation, but not with anti-CCP positivity or RF positivity.
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Mackey
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.affiliation: University of Colorado, Denver.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Deane
authors.affiliation: Washington Hospital Center, Washington, DC.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Walitt
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Yue-Fang
authors.initials: YF
authors.lastname: Chang
authors.affiliation: University of Colorado, Denver.
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.affiliation: Stanford University, Stanford, California, and VA Palo Alto Health Care System, Palo Alto, California.
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.affiliation: University of Vermont, Burlington.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Stanford University, Stanford, California.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hlatky
authors.affiliation: Brown University, Providence, Rhode Island.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Eaton
authors.affiliation: Brown University, Providence, Rhode Island.
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
authors.affiliation: Vanderbilt University and Nashville VA Medical Center, Nashville, Tennessee.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Freiberg
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mehret Birru
authors.initials: MB
authors.lastname: Talabi
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Schelbert
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Moreland
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000276:immunology; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology* / Q000276:immunology; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D015994:Incidence; D015850:Interleukin-6 / Q000276:immunology; D007958:Leukocyte Count; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D017698:Postmenopause; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000276:immunology; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology* / Q000276:immunology; D014481:United States / Q000453:epidemiology
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; C508600:IL6 protein, human; D015850:Interleukin-6; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor