title: Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women.
abstract: OBJECTIVE
  To characterize the relationship between advanced glycation end products (AGEs) and circulating receptors for AGEs (RAGE) with cardiovascular disease mortality.
  
  
  METHODS
  The relationships between serum AGEs, total RAGE (sRAGE), and endogenous secretory RAGE (esRAGE), and mortality were characterized in 559 community-dwelling women, double dagger 65 years, in Baltimore, Maryland.
  
  
  RESULTS
  During 4.5 years of follow-up, 123 (22%) women died, of whom 54 died with cardiovascular disease. The measure of serum AGEs was carboxymethyl-lysine (CML), a dominant AGE. Serum CML predicted cardiovascular disease mortality (Hazards Ratio [HR] for highest vs lower three quartiles, 1.94, 95% Confidence Interval [CI] 1.08-3.48, p=0.026), after adjusting for age, race, body mass index, and renal insufficiency. Serum sRAGE (ng/mL) and esRAGE (ng/mL) predicted cardiovascular disease mortality (HR per 1 Standard Deviation [SD] 1.27, 95% CI 0.98-1.65, p=0.07; HR 1.28, 95% CI 1.02-1.63, p=0.03), after adjusting for the same covariates. Among non-diabetic women, serum CML, sRAGE, and esRAGE, respectively, predicted cardiovascular disease mortality (HR for highest vs lower three quartiles, 2.29, 95% CI 1.21-4.34, p=0.01; HR per 1 SD, 1.24, 95% CI 0.92-1.65, p=0.16; HR per 1 SD 1.45, 95% CI 1.08-1.93, p=0.01), after adjusting for the same covariates.
  
  
  CONCLUSIONS
  High circulating AGEs and RAGE predict cardiovascular disease mortality among older community-dwelling women. AGEs are a potential target for interventions, as serum AGEs can be lowered by change in dietary pattern and pharmacological treatment.
authors.affiliation: Johns Hopkins University School of Medicine, 550 N. Broadway, Suite 700, Baltimore, MD 21205, USA. rdsemba@jhmi.edu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Justine
authors.initials: J
authors.lastname: Beck
authors.forename: Mansi
authors.initials: M
authors.lastname: Dalal
authors.forename: Ravi
authors.initials: R
authors.lastname: Varadhan
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walston
authors.forename: Jack M
authors.initials: JM
authors.lastname: Guralnik
authors.forename: Linda P
authors.initials: LP
authors.lastname: Fried
mesh_terms: D000368:Aged; D000375:Aging; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality*; D003920:Diabetes Mellitus / Q000097:blood / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D011237:Predictive Value of Tests; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D051437:Renal Insufficiency / Q000097:blood / Q000401:mortality; D012111:Residence Characteristics; D012307:Risk Factors
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C048496:N(6)-carboxymethyllysine; D008239:Lysine