title: Studies on ageing and the severity of radiographic joint damage in rheumatoid arthritis.
abstract: BACKGROUND
  The western population is ageing. It is unknown whether age at diagnosis affects the severity of Rheumatoid Arthritis (RA), we therefore performed the present study.
  
  
  METHODS
  1,875 RA-patients (7,219 radiographs) included in five European and North-American cohorts (Leiden-EAC, Wichita, Umeå, Groningen and Lund) were studied on associations between age at diagnosis and joint damage severity. In 698 Leiden RA-patients with 7-years follow-up it was explored if symptom duration, anti-citrullinated-peptide-antibodies (ACPA), swollen joint count (SJC) and C-reactive-protein (CRP) mediated the association of age with joint damage. Fifty-six other RA-patients of the EAC-cohort underwent baseline MRIs of wrist, MCP and MTP-joints; MRI-inflammation (RAMRIS-synovitis plus bone marrow edema) was also evaluated in mediation analyses. Linear regression and multivariate normal regression models were used.
  
  
  RESULTS
  Analysis on the five cohorts and the Leiden-EAC separately revealed 1.026-fold and 1.034-fold increase of radiographic joint damage per year increase in age (β=1.026, 1.034, both p<0.001); this effect was present at baseline and persisted over time. Age correlated stronger with baseline erosion-scores compared to joint space narrowing (JSN)-scores (r=0.38 versus 0.29). Symptom duration, ACPA, SJC and CRP did not mediate the association of age with joint damage severity. Age was significantly associated with the MRI-inflammation-score after adjusting for CRP and SJC (β=1.018, p=0.027). The association of age with joint damage (β=1.032, p=0.004) decreased after also including the MRI-inflammation-score (β=1.025, p=0.021), suggesting partial mediation.
  
  
  CONCLUSIONS
  RA-patients presenting at higher age have more severe joint damage; this might be partially explained by more severe MRI-detected inflammation at higher age.
authors: Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. L.Mangnus@lumc.nl.
authors: Lukas
authors: L
authors: Mangnus
authors: Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. H.W.van_Steenbergen@lumc.nl.
authors: Hanna W
authors: HW
authors: van Steenbergen
authors: Department of Rheumatology, Lund University and Skåne University hospital Lund, Lund, Sweden. Elisabet.Lindqvist@skane.se.
authors: Elisabet
authors: E
authors: Lindqvist
authors: Department of Rheumatology, University Medical Center Groningen, Groningen, Netherlands. e.brouwer@umcg.nl.
authors: Elisabeth
authors: E
authors: Brouwer
authors: Department of Radiology, Leiden University Medical Center, Leiden, Netherlands. M.Reijnierse@lumc.nl.
authors: Monique
authors: M
authors: Reijnierse
authors: Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. T.W.J.Huizinga@lumc.nl.
authors: Tom W J
authors: TW
authors: Huizinga
authors: Feinstein Institute for Medical Research and North Shore-LIJ Health System, Manhasset, New York, USA. PGregers@NSHS.edu.
authors: Peter K
authors: PK
authors: Gregersen
authors: Department of Public Health and Clinical Medicine/Rheumatology, University Hospital, Umea, Sweden. ewa.berglin@vll.se.
authors: Ewa
authors: E
authors: Berglin
authors: Department of Public Health and Clinical Medicine/Rheumatology, University Hospital, Umea, Sweden. solbritt.rantapaa.dahlqvist@medicin.umu.se.
authors: Solbritt
authors: S
authors: Rantapää-Dahlqvist
authors: Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. mail@dvanderheijde.nl.
authors: Désirée
authors: D
authors: van der Heijde
authors: Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. A.H.M.van_der_Helm@lumc.nl.
authors: Annette H M
authors: AH
authors: van der Helm-van Mil
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology*; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D002097:C-Reactive Protein / Q000032:analysis; D002956:Citrulline / Q000276:immunology; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000473:pathology; D007596:Joints / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009656:North America; D010456:Peptides, Cyclic / Q000276:immunology; D011859:Radiography; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; D002956:Citrulline; D002097:C-Reactive Protein