title: Smoking and overweight determine the likelihood of developing rheumatoid arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is a prototypic chronic inflammatory disease with a debilitating course if untreated. A genetic predisposition for RA is known, and its occurrence is associated with the presence of autoantibodies in the serum and with environmental factors. It is unknown if smoking and overweight are contributory factors for developing RA in individuals with RA-specific autoantibodies in the serum.
  
  
  METHODS
  Fifty-five individuals at risk for developing RA, based on the presence of RA-specific autoantibodies in the serum, who never had any evidence of arthritis upon physical examination, were followed over time. Smoking was assessed as being never or ever smoker and body mass index as <25 (normal) or ≥25 kg/m² (overweight). Clinical endpoint was the occurrence of arthritis. Proportional hazard regression analysis was performed to investigate the potential of (combinations of) variables in predicting the onset of arthritis over time.
  
  
  RESULTS
  After a median follow up time of 13 (IQR 6-27) months, 15 individuals (27%) developed arthritis. Smoking was associated with the development of arthritis (HR (95% CI): 9.6 (1.3 to 73.0); p=0.029). Overweight was, independently of smoking, associated with arthritis (HR (95% CI): 5.6 (1.3 to 25.0); p=0.023). The overall arthritis risk of 28% after a median of 27 months follow up increased to 60% in individuals with a smoking history combined with overweight.
  
  
  CONCLUSIONS
  This is the first prospective study showing that smoking and overweight increase the risk of development of arthritis in a cohort of autoantibody-positive individuals at risk for developing RA. These results show the importance of life style factors in development of RA and should be critically evaluated in future clinical research aimed at disease prevention.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Maria J H
authors.initials: MJ
authors.lastname: de Hair
authors.forename: Robert B M
authors.initials: RB
authors.lastname: Landewé
authors.forename: Marleen G H
authors.initials: MG
authors.lastname: van de Sande
authors.forename: Dirkjan
authors.initials: D
authors.lastname: van Schaardenburg
authors.forename: Lisa G M
authors.initials: LG
authors.lastname: van Baarsen
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Gerlag
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015992:Body Mass Index; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D001323:Autoantibodies
keywords: Autoimmunity; Rheumatoid Arthritis; Smoking