Abstract P017: Serum N-Carboxymethyl-Lysine and Risk of Mortality in Older Adults
Advanced glycation end products (AGEs) are compounds formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids, and are thought to play a role in the pathogenesis of diseases across multiple organ systems. Carboxymethyl-lysine (CML) is a dominant AGE found in tissue proteins and in the circulation, and a commonly used AGE biomarker. Only a few epidemiological studies have evaluated the association between circulating CML and mortality risk, and none have evaluated the association between CML and cause-specific non-CVD mortality.
We measured CML by ELISA on serum specimens collected from 3,373 Cardiovascular Health Study participants in 1996. Participants were followed for death through 2010, and cause of death was classified using death certificates, medical records, and proxy interview. We used Cox regression to estimate the relative risk of total and cause-specific mortality associated with circulating CML, adjusting for confounders (Models 1 & 2) and estimated glomerular filtration rate (eGFR) as a potential mediator (Model 3). We tested whether sex or diabetes modified the association between CML and mortality.
The mean age among participants was 78 years and 60% were women. The mean CML level among participants was 629 ng/mL. Over median follow-up of 10 years, 2,322 deaths occurred (73.4 per 1,000 person-years). After adjustment for confounders (Models 1 & 2), CML was associated with an increased risk of death from CVD, dementia, infection, fracture/trauma, and renal failure (Table). Aside from renal failure, adjustment for eGFR attenuated the HR estimates modestly. There was no evidence for effect modification of the association of CML and all-cause mortality risk by sex or diabetes.
In a cohort of community-dwelling older individuals, elevated circulating CML was associated with increased risk of mortality from cardiovascular causes, dementia, infection, fracture/trauma, and renal failure. A portion of the increased risk may be mediated through decreased renal function.
Author Disclosures: M. Biggs: B. Research Grant; Significant; Collaborator on research grant. D. Benkeser: None. J. Ix: None. J. Kizer: None. L. Djousse: None. D. Siscovick: None. A. Fitzpatrick: None. R. Tracy: None. K. Mukamal: None.
- © 2014 by American Heart Association, Inc.