title: Carotid atherosclerosis, disease measures, oxidized low-density lipoproteins, and atheroprotective natural antibodies for cardiovascular disease in early rheumatoid arthritis -- an inception cohort study.
abstract: OBJECTIVE
  Although an enhanced risk of cardiovascular disease (CVD) in persons with rheumatoid arthritis (RA) is well established, the mechanisms behind it remain unclear. We studied whether carotid atherosclerosis, RA disease measures, or potential cardiovascular biomarkers influenced the incidence of CVD in an RA inception cohort.
  
  
  METHODS
  RA disease measures and CVD biomarkers were assessed at 0, 3, 12, 24, and 60 months after disease onset, and carotid ultrasonography after 5 years. The study outcome was incident CVD events - acute myocardial infarction, angina pectoris, congestive heart failure, or ischemic cerebrovascular event. Survival analysis and Cox and longitudinal regressions were used for statistical analyses.
  
  
  RESULTS
  A total of 105 patients, without CVD events prior to RA onset, experienced 17 CVD events, an incidence rate of 1.35 events per 100 person-years (95% CI 0.71-2.0). The rate of CVD events did not differ with regard to measures of carotid intima-media thickness, but it was higher for patients with bilateral carotid plaques than for those without (p = 0.012). Improvement in Disease Activity Score for 28 joints, visual analog scale for pain, and Stanford Health Assessment Questionnaire score over the first year, as well as usage of methotrexate (MTX), was associated, independent of age, with reduction of risk of CVD event [hazard ratios 0.68 (95% CI 0.5-0.97), 0.97 (95% CI 0.95-0.99), 0.35 (95% CI 0.15-0.82), and 0.34 (95% CI 0.12-0.91), respectively]. In longitudinal analyses, increasing oxidized low-density lipoprotein (oxLDL) and probability for low antiphosphorylcholine antibodies (anti-PC) were observed in those who experienced a subsequent CVD event.
  
  
  CONCLUSIONS
  Bilateral carotid plaques were associated with poor CVD-free survival. Early reductions of inflammation, pain, and disability as well as MTX usage were associated with better CVD outcome. Elevated oxLDL and low IgM anti-PC levels may link chronic inflammation in RA to enhanced risk of CVD events.
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden. sofia.ajeganova@karolinska.se
authors.forename: Sofia
authors.initials: S
authors.lastname: Ajeganova
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.forename: Tomas
authors.initials: T
authors.lastname: Jogestrand
authors.forename: Johan
authors.initials: J
authors.lastname: Frostegård
authors.forename: Ingiäld
authors.initials: I
authors.lastname: Hafström
mesh_terms: D000906:Antibodies / Q000097:blood; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D015897:Comorbidity; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006304:Health Status; D006801:Humans; D007113:Immunity, Innate; D015994:Incidence; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010767:Phosphorylcholine / Q000276:immunology; D011446:Prospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D013548:Sweden / Q000453:epidemiology; D014463:Ultrasonography
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D010767:Phosphorylcholine; D008727:Methotrexate