Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women
Richard D. Semba1, Luigi Ferrucci2, Kai Sun1, Justine Beck1, Mansi Dalal1, Ravi Varadhan1, Jeremy Walston1, Jack M. Guralnik3 and Linda P. Fried1
1Johns Hopkins University School of Medicine, Baltimore, 2Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, 3Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, USA

Abstract

Aims: 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, ‡ 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. (Aging Clin Exp Res 2009; 21: 182-190) ©2009, Editrice Kurtis

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