Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women.
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.
Semba
Richard D
RD
Johns Hopkins University School of Medicine, 550 N. Broadway, Suite 700, Baltimore, MD 21205, USA. rdsemba@jhmi.edu
Ferrucci
Luigi
L
Sun
Kai
K
Beck
Justine
J
Dalal
Mansi
M
Varadhan
Ravi
R
Walston
Jeremy
J
Guralnik
Jack M
JM
Fried
Linda P
LP
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
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C048496:N(6)-carboxymethyllysine; D008239:Lysine