title: Apelin concentrations are associated with altered atherosclerotic plaque stability mediator levels and atherosclerosis in rheumatoid arthritis.
abstract: Apelin-APJ signaling reduces cardiovascular disease (CVD) risk. In rheumatoid arthritis (RA), the atherosclerosis burden and plaque vulnerability to rupture are increased. We explored relationships between apelin concentrations and subclinical CVD in RA.
  
  
  
  Apelin levels were measured in 235 (114 black, 121 white) RA patients. Associations between apelin concentrations and ultrasound determined carotid artery intima-media thickness (cIMT) and plaque, and levels of matrix metalloproteinase (MMP)-2 and -9 that mediate plaque stability and vulnerability respectively, were identified in confounder adjusted multivariate regression analysis.
  
  
  
  In all patients, apelin concentrations were directly associated with those of MMP-2 (β (SE) = 0.324 (0.112), p = 0.004) and inversely with those of MMP-9 (β (SE) = -0.239 (0.060), p = 0.000). Apelin concentration-subclinical CVD relations were influenced by population origin, RA disease activity, erythrocyte sedimentation rate (ESR) and interleukin (IL)-6 concentrations (interaction p = 0.001 to 0.04). Accordingly, the apelin-MMP-2 concentration relationship was reproduced in white (β (SE) = 0.367 (0.146), p = 0.01) but not black RA patients (β (SE) = 0.197 (0.220), p = 0.4), and only in those without (but not with) large erythrocyte sedimentation rates (β (SE) = 0.428 (0.143), p = 0.003) or interleukin-6 levels (β (SE) = 0.485 (0.288), p = 0.04). By contrast, the apelin-MMP-9 concentration relation was reproduced more consistently. Apelin levels were inversely related to cIMT in patients with RA remission or mild (β (SE) = -0.068 (0.033), p = 0.04) but not moderate or high disease activity (β (SE) = 0.015 (0.112), p = 0.7).
  
  
  
  Apelin concentrations are associated with altered plaque stability mediator levels and atherosclerosis in patients with RA. These relations are partially dependent on population origin and systemic inflammatory status.
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Sule
authors.initials: S
authors.lastname: Gunter
authors.affiliation: Department of Rheumatology, Charlotte Maxeke Johannesburg Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Solomon
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Linda
authors.initials: L
authors.lastname: Tsang
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Woodiwiss
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Chanel
authors.initials: C
authors.lastname: Robinson
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Aletta M E
authors.initials: AM
authors.lastname: Millen
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Norton
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Rheumatology Division, Universitair Ziekenhuis and Vrije Universiteit Brussel, Belgium. Electronic address: patrick.dessein22@gmail.com.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Dessein
mesh_terms: D000368:Aged; D000073861:Apelin; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D044383:Black People; D001799:Blood Sedimentation; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000208:ethnology / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D058226:Plaque, Atherosclerotic; D012307:Risk Factors; D012422:Rupture, Spontaneous; D013019:South Africa / Q000453:epidemiology; D044465:White People
chemical_list: C115436:APLN protein, human; D000073861:Apelin; D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Apelin; Atherosclerosis; Plaque stability; Rheumatoid arthritis