Abstract 11110: Advanced Glycation Endproduct Carboxymethyl-Lysine and Risk of Cardiovascular Disease in Older Adults

Abstract

Background: Advanced glycation endproducts (AGEs) accumulate in the setting of hyperglycemia or increased oxidative stress, such as occur in diabetes, chronic kidney disease and aging. AGE deposition in the arterial wall increases vascular stiffness, and fosters inflammatory and atherogenic processes, but the prospective association between AGEs and risk of cardiovascular disease (CVD) in older adults remains understudied.

Methods: We investigated the association of plasma carboxymethyl-lysine (CML), the predominant AGE in tissue proteins, and first-ever CVD (coronary heart disease and stroke) in a large prospective cohort of U.S. adults ages ≥65 (Cardiovascular Health Study). CML was measured by ELISA in participants free of prevalent CVD at the 1996-97 exam with available plasma.

Results: There were 2,111 eligible participants: age 77±4.5; 64% women; 15% diabetes; 22% estimated glomerular filtration rate (eGFR)<60 ml/m/1.73 m2; 11% and 2% micro- and macroalbuminuria. CML was positively correlated with age (r=0.11), systolic blood pressure (r=0.04), and urine albumin-creatinine ratio (UACR=0.08), but negatively correlated with body mass index (BMI) (r=-0.15) and estimated glomerular filtration rate (r=-0.22) (all p0.43), but significant effect modification by UACR (p<0.001) was detected. The increased risk of CML was amplified among participants with macroalbuminuria (fully adjusted HR=1.71 per 1-SD [1.37-2.13]), as compared to those without macroalbuminuria (fully adjusted HR=1.06 per 1-SD [0.98-1.15]), in whom it was modest and of marginal significance. These findings were not meaningfully altered with exclusion of diabetic participants.

Conclusions: In this large older cohort, CML was independently associated with increased risk of CVD particularly in participants with macroalbuminuria, with no evidence of effect modification by diabetes status or eGFR. These findings suggest that the adverse effects of CML accrual in the vasculature are most pronounced once glomerular microvascular damage has supervened, and that studies of dietary and pharmacological interventions to reduce AGE accumulation should target older adults with macroalbuminuria to prevent CVD.