title: Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis is associated with increased cardiovascular mortality and morbidity.
  
  
  OBJECTIVE
  To assess the effect of severe extra-articular rheumatoid arthritis (ExRA) manifestations on the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis.
  
  
  METHODS
  Patients with ExRA (n = 81) according to predefined criteria and controls (n = 184) without evidence of extra-articular disease were identified from a large research database of patients with rheumatoid arthritis. In a structured review of the medical records, the occurrence and the date of onset of clinically diagnosed CVD events were noted. Cox proportional hazards models were used to estimate the effect of ExRA on the risk of first ever CVD events after the diagnosis of rheumatoid arthritis. ExRA manifestations were modelled as time-dependent covariates, with adjustment for age, sex and smoking at the diagnosis of rheumatoid arthritis. Onset of erosive disease and rheumatoid factor seropositivity were entered as time-dependent variables. Patients were followed until onset of CVD, death or loss to follow-up.
  
  
  RESULTS
  ExRA was associated with a significantly increased risk of first ever CVD events (p<0.001), and also with an increased risk of new-onset coronary artery disease, adjusted for age, sex and smoking (hazard ratio (HR): 3.16; 95% confidence interval (95% CI: 1.58 to 6.33). The association between ExRA and any first ever CVD event remained significant when controlling for age, sex, smoking, rheumatoid factor and erosive disease (HR: 3.25; 95% CI: 1.59 to 6.64).
  
  
  CONCLUSIONS
  Severe ExRA manifestations are associated with an increased risk of CVD events in patients with rheumatoid arthritis. This association is not due to differences in age, sex, smoking, rheumatoid factor or erosive joint damage. It is suggested that systemic extra-articular disease is a major determinant of cardiovascular morbidity in rheumatoid arthritis.
authors.affiliation: Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. turesson.carl@mayo.edu
authors.forename: C
authors.initials: C
authors.lastname: Turesson
authors.forename: R L
authors.initials: RL
authors.lastname: McClelland
authors.forename: T J H
authors.initials: TJ
authors.lastname: Christianson
authors.forename: E L
authors.initials: EL
authors.lastname: Matteson
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000150:complications*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012217:Rheumatoid Factor / Q000032:analysis; D012306:Risk; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D015415:Biomarkers; D012217:Rheumatoid Factor