title: Vascular calcifications on hand radiographs in rheumatoid arthritis and associations with autoantibodies, cardiovascular risk factors and mortality.
abstract: OBJECTIVE
  To examine whether vascular calcifications on hand films in RA might aid in determining mortality risk.
  
  
  METHODS
  Hand radiographs from 906 RA patients were scored as positive or negative for vascular calcifications. Patient characteristics associated with vascular calcifications were assessed using multivariable logistic regression, and associations with mortality were examined using Cox proportional hazards regression. Cytokines and multiplex ACPA were measured in both groups.
  
  
  RESULTS
  A total of 99 patients (11%) demonstrated radiographic vascular calcifications. Factors independently associated with vascular calcifications included diabetes [odds ratio (OR) 2.85; 95% CI 1.43, 5.66], cardiovascular disease at enrolment (OR 2.48; 95% CI 1.01, 6.09), prednisone use (OR 1.90; 95% CI 1.25, 2.91), current smoking (OR 0.06; 95% CI 0.01, 0.23) and former smoking (OR 0.36; 95% CI 0.27, 0.48) vs never smoking. In cytokine and ACPA subtype analysis, IL-4 and anti-citrullinated apolipoprotein E were significantly increased in patients with vascular calcifications in fully adjusted multivariable models. After multivariable adjustment, vascular calcifications were associated with an increase in all-cause mortality (hazard ratio 1.41; 95% CI 1.12, 1.78; P = 0.004).
  
  
  CONCLUSIONS
  Vascular calcifications on hand radiographs were independently associated with increased all-cause mortality in RA. Mechanisms underpinning the associations of IL-4 and select ACPA with vascular calcifications and their utility as biomarkers predictive of cardiovascular disease risk in RA merit further study.
authors: Division of Rheumatic Diseases, UT Southwestern, Dallas, TX.
authors: E Blair
authors: EB
authors: Solow
authors: Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha.
authors: Fang
authors: F
authors: Yu
authors: Division of Rheumatology and Immunology, Omaha Veterans Affairs Medical Center, Omaha, NE.
authors: Geoffrey M
authors: GM
authors: Thiele
authors: Division of Rheumatology, VA Palo Alto Health Care System, Palo Alto, CA.
authors: Jeremy
authors: J
authors: Sokolove
authors: Division of Rheumatology, VA Palo Alto Health Care System, Palo Alto, CA.
authors: William H
authors: WH
authors: Robinson
authors: Division of Rheumatology and Immunology, Omaha Veterans Affairs Medical Center, Omaha, NE.
authors: Zachary M
authors: ZM
authors: Pruhs
authors: Division of Rheumatology and Immunology, Omaha Veterans Affairs Medical Center, Omaha, NE, National Data Bank for Rheumatic Diseases, Wichita, KS.
authors: Kaleb D
authors: KD
authors: Michaud
authors: Division of Rheumatology and Immunology, Omaha Veterans Affairs Medical Center, Omaha, NE.
authors: Alan R
authors: AR
authors: Erickson
authors: Division of Rheumatology and Immunology, Omaha Veterans Affairs Medical Center, Omaha, NE.
authors: Harlan
authors: H
authors: Sayles
authors: Department of Medicine, Veterans Affairs Medical Center, Washington, DC.
authors: Gail S
authors: GS
authors: Kerr
authors: Department of Medicine, Birmingham Veterans Affairs Medical Center, Birmingham, AL.
authors: Angelo L
authors: AL
authors: Gaffo
authors: Division of Rheumatology, Denver Veterans Affairs Medical Center, Denver, CO.
authors: Liron
authors: L
authors: Caplan
authors: Division of Rheumatology, Denver Veterans Affairs Medical Center, Denver, CO.
authors: Lisa A
authors: LA
authors: Davis
authors: Division of Rheumatology, George Wahlen Veterans Affairs Medical Center, Salt Lake City, UT.
authors: Grant W
authors: GW
authors: Cannon
authors: Division of Rheumatic Diseases, UT Southwestern, Dallas, TX, Division of Rheumatology, Dallas Veterans Affairs Medical Center, Dallas, TX.
authors: Andreas M
authors: AM
authors: Reimold
authors: Division of Rheumatology, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA.
authors: Joshua
authors: J
authors: Baker
authors: Division of Rheumatology, Portland Veterans Affairs Medical Center, Portland, OR and.
authors: Pascale
authors: P
authors: Schwab
authors: Division of Cardiology, University of Nebraska Medical Center, Omaha, NE.
authors: Daniel R
authors: DR
authors: Anderson
authors: Division of Rheumatology and Immunology, Omaha Veterans Affairs Medical Center, Omaha, NE, tmikuls@unmc.edu.
authors: Ted R
authors: TR
authors: Mikuls
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality*; D005260:Female; D006225:Hand / Q000098:blood supply / Q000000981:diagnostic imaging*; D006801:Humans; D015847:Interleukin-4 / Q000097:blood; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011859:Radiography; D012307:Risk Factors; D015996:Survival Rate; D061205:Vascular Calcification / Q000150:complications* / Q000000981:diagnostic imaging*
chemical_list: D001057:Apolipoproteins E; D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D015847:Interleukin-4
keywords: anti-citrullinated protein autoantibodies; hand radiographs; mortality; rheumatoid arthritis; vascular calcifications