title: Does reduction of disease activity improve early markers of cardiovascular disease in newly diagnosed rheumatoid arthritis patients?
abstract: OBJECTIVE
  The incidence of cardiovascular disease (CVD) is increased in RA. This study was designed to evaluate whether a reduction in disease activity influences early markers of CVD.
  
  
  METHODS
  In a prospective longitudinal study, 58 newly diagnosed RA patients and 58 age- and sex-matched healthy controls (HCs) were included. Endothelial dysfunction was measured by small artery elasticity (SAE) and endothelial cell activation was assessed by measuring soluble vascular cellular activation molecule 1(sVCAM-1) and von Willebrand factor (vWF). Advanced glycation end products (AGEs) were quantified by skin autofluorescence. After 1 year, measurements were repeated in all RA patients.
  
  
  RESULTS
  At entry, SAE was decreased in RA vs HCs [median 3.4 ml/mmHg100 (range 1.2-9.0) vs 6.1 (range 5.0-15.3), P < 0.0001] and sVCAM-1 and vWF were increased: 391 ng/ml (range 256-680) vs 341 (range 223-691) (P = 0.0015) and 120 ng/ml (range 26.5-342) vs 99 (range 22-298) (P = 0.02), respectively. SAE was inversely correlated with the 28-joint DAS (DAS28; r = -0.31, P = 0.016). AGEs were increased by 2.55 arbitrary units (range 1.29-4.65) vs 2.12 (range 1.32-3.82) in HCs (P = 0.003). In multivariate analysis, the presence of RA, age and systolic blood pressure were independently and inversely related to SAE. After 1 year, SAE had significantly improved in RA, from 3.4 (range 1.2-9.0) to 3.8 (range 1.5-10.3) (P = 0.03).
  
  
  CONCLUSIONS
  Endothelial dysfunction is present in newly diagnosed RA patients, independently of traditional risk factors and is inversely correlated with disease activity. By reducing disease activity, endothelial dysfunction improves, although not to normal values. Also, a reduction in disease activity targeting traditional risk factors remains important in preventing CVD in RA.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Vascular Disease, University Medical Centre, University of Groningen and Department of Internal Medicine and Rheumatology, Martini Hospital, Groningen, The Netherlands lodewijk.de.groot@umcg.nl.
authors.forename: Lodewijk
authors.initials: L
authors.lastname: de Groot
authors.affiliation: Department of Rheumatology and Clinical Immunology, Vascular Disease, University Medical Centre, University of Groningen and Department of Internal Medicine and Rheumatology, Martini Hospital, Groningen, The Netherlands.
authors.forename: Nynke A
authors.initials: NA
authors.lastname: Jager
authors.affiliation: Department of Rheumatology and Clinical Immunology, Vascular Disease, University Medical Centre, University of Groningen and Department of Internal Medicine and Rheumatology, Martini Hospital, Groningen, The Netherlands.
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
authors.affiliation: Department of Rheumatology and Clinical Immunology, Vascular Disease, University Medical Centre, University of Groningen and Department of Internal Medicine and Rheumatology, Martini Hospital, Groningen, The Netherlands.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Smit
authors.affiliation: Department of Rheumatology and Clinical Immunology, Vascular Disease, University Medical Centre, University of Groningen and Department of Internal Medicine and Rheumatology, Martini Hospital, Groningen, The Netherlands.
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.affiliation: Department of Rheumatology and Clinical Immunology, Vascular Disease, University Medical Centre, University of Groningen and Department of Internal Medicine and Rheumatology, Martini Hospital, Groningen, The Netherlands.
authors.forename: Marcel D
authors.initials: MD
authors.lastname: Posthumus
authors.affiliation: Department of Rheumatology and Clinical Immunology, Vascular Disease, University Medical Centre, University of Groningen and Department of Internal Medicine and Rheumatology, Martini Hospital, Groningen, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Bijl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D016022:Case-Control Studies; D004548:Elasticity / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D017127:Glycation End Products, Advanced; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor
keywords: advanced glycation end products; atherosclerosis; endothelial cell activation; endothelial dysfunction; intima-media thickness; rheumatoid arthritis; small artery elasticity