title: Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 diabetes: an analysis from the CARDS trial.
abstract: OBJECTIVE
  Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprise both a secreted isoform (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD), but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS).
  
  
  METHODS
  We used a nested case-control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates.
  
  
  RESULTS
  sRAGE and esRAGE were strongly correlated (ρ = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower estimated glomerular filtration rate (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25-2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11-1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38-1.14). Atorvastatin, 10 mg daily, did not alter sRAGE.
  
  
  CONCLUSIONS
  Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes.
authors.affiliation: Medical Research Institute, University of Dundee, Dundee, U.K. h.colhoun@cpse.dundee.ac.uk
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
authors.forename: D John
authors.initials: DJ
authors.lastname: Betteridge
authors.forename: Paul
authors.initials: P
authors.lastname: Durrington
authors.forename: Graham
authors.initials: G
authors.lastname: Hitman
authors.forename: Andrew
authors.initials: A
authors.lastname: Neil
authors.forename: Shona
authors.initials: S
authors.lastname: Livingstone
authors.forename: Valentine
authors.initials: V
authors.lastname: Charlton-Menys
authors.forename: Weihang
authors.initials: W
authors.lastname: Bao
authors.forename: David A
authors.initials: DA
authors.lastname: Demicco
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Preston
authors.forename: Harshal
authors.initials: H
authors.lastname: Deshmukh
authors.forename: Kathryn
authors.initials: K
authors.lastname: Tan
authors.forename: John H
authors.initials: JH
authors.lastname: Fuller
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D020521:Stroke / Q000097:blood / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic