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. 2009 Apr;21(2):182-90.
doi: 10.1007/BF03325227.

Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women

Richard D Semba  1 , Luigi Ferrucci, Kai Sun, Justine Beck, Mansi Dalal, Ravi Varadhan, Jeremy Walston, Jack M Guralnik, Linda P Fried
Affiliations

Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women

Richard D Semba et al. Aging Clin Exp Res. 2009 Apr.

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, 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.

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Figures

Figure 1
Figure 1
Survival curves for all-cause mortality among women, ≥65 years, in the Women’s Health and Aging Study I in Baltimore, Maryland, by quartile of serum CML. Women in the highest quartile (quartile 4) of serum CML had lower survival compared to women in the lower three tertiles together (P = 0.013, log-rank test).
Figure 2
Figure 2
Survival curves for cardiovascular disease mortality among women, ≥65 years, in the Women’s Health and Aging Study I in Baltimore, Maryland, by quartile of serum CML. Women in the highest quartile (quartile 4) of serum CML had lower survival compared to women in the lower three tertiles together (P = 0.0009, log-rank test).
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