title: Serum carboxymethyl-lysine, disability, and frailty in older persons: the Cardiovascular Health Study.
abstract: BACKGROUND
  Advanced glycation endproducts are biologically active compounds that accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML), a ubiquitous human advanced glycation endproduct, has been associated with age-related conditions and mortality. Our objective was to ascertain the relationship between CML and geriatric outcomes (disability and frailty) in a large cohort of older men and women.
  
  
  METHODS
  In 1996-1997, serum CML was measured in 3,373 Cardiovascular Health Study participants (mean age 78.1 ± 4.8 years). Disability, defined as difficulty in any of six activities of daily living, was assessed every 6-12 months for 14 years. Frailty was defined according to five standard criteria at the 1996-1997 visit. Cox proportional hazard models estimated the relationship between CML and incident disability (N = 2,643). Logistic regression models estimated the relationship between CML and prevalent frailty.
  
  
  RESULTS
  Adjusting for multiple potential confounders, higher CML was associated with incident disability (hazard ratio per standard deviation [225 ng/mL] increase: 1.05, 95% CI 1.01-1.11). In men, odds of frailty increased with higher CML values (odds ratio = 1.30 per standard deviation, 95% CI 1.14-1.48), but the relationship was attenuated by adjustment for cognitive status, kidney function, and arthritis. CML was not associated with frailty in women.
  
  
  CONCLUSIONS
  Higher serum CML levels in late life are associated with incident disability and prevalent frailty. Further work is needed to understand CML's value as a risk stratifier, biomarker, or target for interventions that promote healthy aging.
authors.affiliation: Department of Medicine, Duke University, Durham, North Carolina. Durham VA Medical Center, GRECC, Durham, North Carolina. heather.whitson@duke.edu.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Whitson
authors.affiliation: Department of Biostatistics, University of Washington, Seattle.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Arnold
authors.affiliation: Department of Biostatistics, University of Washington, Seattle.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yee
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.affiliation: Department of Medicine, and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Kizer
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors.forename: Luc
authors.initials: L
authors.lastname: Djousse
authors.affiliation: Departments of Medicine & Prevention and Family Medicine, University of California, San Diego. Nephrology Section, Veterans Affairs San Diego Healthcare System, California.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Department of Medicine, University of Washington, Seattle.
authors.forename: David
authors.initials: D
authors.lastname: Siscovick
authors.affiliation: Department of Pathology, University of Vermont, Colchester.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Puget Sound VA Medical Center, Seattle, Wahington. Department of Psychiatry, University of Washington, Seattle.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Thielke
authors.affiliation: Department of Medicine, University of California Davis.
authors.forename: Calvin
authors.initials: C
authors.lastname: Hirsch
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pennsylvania.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.affiliation: National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
authors.forename: Susan
authors.initials: S
authors.lastname: Zieman
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D000072038:Cardiac Rehabilitation; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D006233:Persons with Disabilities; D005260:Female; D005500:Follow-Up Studies; D016330:Frail Elderly; D006304:Health Status; D006801:Humans; D015994:Incidence; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C048496:N(6)-carboxymethyllysine; D008239:Lysine
keywords: Biomarkers; Disablement process; Epidemiology; Frailty; Metabolism.