title: TNF-related apoptosis-inducing ligand and cardiovascular disease in rheumatoid arthritis.
abstract: OBJECTIVE
  We examined the association of TNF-related apoptosis-inducing ligand (TRAIL) concentrations with cardiovascular disease (CVD) in rheumatoid arthritis (RA) and, since osteoprotegerin (OPG) can act as a decoy receptor for TRAIL, whether TRAIL concentrations impact on the OPG level-atherosclerotic CVD relation that was recently documented in the present cohort.
  
  
  METHODS
  TRAIL concentrations were assessed by ELISA in 151 RA patients of which 75 (49.7%) had CVD comprising ischaemic heart disease (n=27), cerebrovascular accident (n=26), peripheral artery disease (n=9) or/and heart failure (HF) (n=27), and 62 controls.
  
  
  RESULTS
  Mean RA duration was 12 years. In RA patients, C-reactive protein (CRP) levels and cholesterol-HDL cholesterol ratio related to TRAIL concentrations [partial R=-0.222 (p=0.006) and 0.174 (p=0.04), respectively]. TRAIL concentrations were smaller in RA patients compared to controls (median (interquartile range) = 80.2 (60.9-120.4) versus 130.4 (89.4-167.7) pg/ml, p<0.0001)). TRAIL levels were larger in RA patients with compared to those without HF (105.5 (66.5-143.4) versus 79.9 (57.8-110.6), p=0.02); this difference was independent of demographic characteristics and traditional cardiovascular risk factors (p=0.04) but not CRP concentrations (p=0.1). TRAIL levels were consistently unrelated to atherosclerotic CVD. Our previously reported OPG-atherosclerotic CVD relation in RA survived adjustment for TRAIL concentrations in a mixed regression model (p=0.04).
  
  
  CONCLUSIONS
  TRAIL concentrations are markedly reduced and associated with HF in established RA, this relationship being explained by CRP levels. OPG may directly enhance CVD risk in RA.
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Dessein
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Lopez-Mejias
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Begona
authors.initials: B
authors.lastname: Ubilla
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Genre
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Corrales
authors.affiliation: Department of Internal Medicine, Hospital Universitario Marques de Valdecilla, University of Cantabria, RETICEF, IDIVAL, Santander, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Hernandez
authors.affiliation: Rheumatology Division, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ferraz-Amaro
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: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Trinitario
authors.initials: T
authors.lastname: Pina
authors.affiliation: Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVAL, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Cardiology Division, Hospital Lucus Augusti, Lugo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez-Juanatey
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, University of the Witwatersrand, Johannesburg, South Africa; and Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology, IDIVAL, Santander, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gonzalez-Gay
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism; D002097:C-Reactive Protein / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000453:epidemiology / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000378:metabolism; D053244:Osteoprotegerin / Q000097:blood*; D058729:Peripheral Arterial Disease / Q000453:epidemiology / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors; D013030:Spain; D020521:Stroke / Q000453:epidemiology / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*
chemical_list: D008076:Cholesterol, HDL; D053244:Osteoprotegerin; D053221:TNF-Related Apoptosis-Inducing Ligand; D002097:C-Reactive Protein