Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults

Background: Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress - such as diabetes, chronic kidney disease and aging - where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined. Methods: To test the hypothesis that circulating levels of N-epsilon-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older. Results: During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase 1.11, 95% confidence interval [CI] 1.03-1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke. Conclusions: In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML's value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population. (C) 2014 Elsevier Ireland Ltd. All rights reserved.