Abstract 13849: Advanced Glycation Endproduct Carboxymethyl-Lysine (CML) and Risk of Atrial Fibrillation in Older Adults
Background: Advanced glycation endproducts (AGEs) form through chemical modification of proteins from hyperglycemia or increased oxidative stress, as occurs in diabetes, chronic kidney disease (CKD), and aging. Deposition of AGEs in the myocardium and arterial wall causes structural and biochemical changes, promoting increased cardiac and vascular stiffness and activation of inflammatory, fibrotic and atherogenic pathways. These processes are integral to the pathogenesis of atrial fibrillation (AF), but the prospective association between AGEs and AF in populations at risk has not been previously examined.
Methods: We evaluated the association of plasma CML, a major AGE, and incident AF in the Cardiovascular Health Study, a large cohort of older U.S. adults. CML was measured by ELISA in subjects free of prevalent AF at the 1996-97 exam.
Results: Of 2,882 eligible subjects (age 78±5; 62% women; 17% black; 29% prevalent cardiovascular disease [CVD]); 25% CKD; 42% high NT-proBNP), 742 developed AF during median follow-up of 9 years. After adjustment for potential confounders, including age, sex, race, clinic, weight, height, systolic BP, anti-HTN Rx, diabetes, smoking, and alcohol, CML was significantly positively associated with incident AF (HR per SD [225 ng/ml] increase = 1.12 [1.05-1.20]). Further adjustment for potential mediators, namely, PR interval, ECG LVH, and major ECG abnormalities; or prevalent CHD, CHF or PAD; or CRP; or eGFR and albuminuria did not substantially modify the association between CML and AF. Adjustment for NT-proBNP, however, rendered the association non-significant (HR = 1.05 [0.97-1.12]). There was no evidence of interaction by age, sex, race, diabetes, eGFR, or albuminuria. However, the increased risk for CML was greater in subjects without elevated NT-proBNP (confounder-adjusted HR = 1.21 [1.07-1.37] or no prevalent CVD (HR = 1.19 [1.09-1.30]).
Conclusions: In this older cohort, plasma CML was associated with increased risk of AF independent of multiple potential confounders, and this association was more marked in participants without cardiac strain or overt CVD. These findings point up the need to test whether interventions to reduce AGE levels in older adults could lower the burden of AF in this high-risk population.
- © 2013 by American Heart Association, Inc.