Background:
Advanced glycation end-products (AGEs) have been linked to cardiovascular disease (CVD) in populations with and without diabetes. There are limited data, however, regarding the longitudinal associations of the array of circulating AGE adducts with risk of CVD in the general population. We tested the hypothesis that major plasma AGEs, measured by gold-standard liquid chromatography/tandem mass spectrometry (LC/MS) are associated with incident CVD in subsets of two population-based cohort studies with different demographic and risk factor profiles.
Methods:
Analyses were performed in a case-cohort study of 2000 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and in a random cohort of 466 participants in the Cardiovascular Health Study (CHS). Five AGEs were measured by LC/MS: CML, 3DG-H, CEL, G-H1 and MG-H1. Incident CVD was defined as first occurrence of fatal or non-fatal stroke, myocardial infarction, or coronary heart disease death. Cox regression was used to examine associations between AGEs and CVD.
Results:
Participants in CHS were older than in MESA (median age=74 vs 65), had lower eGFR (67 vs 82 ml/min/1.73m
2
) but higher CRP (median 2.53 vs 2.06 mg/L), and had substantially higher levels of all AGEs
(Table)
. During a median follow-up of 11 years in both cohorts, 439 (22%) participants in MESA and 200 (42%) in CHS developed incident CVD. In unadjusted models, all AGEs were strongly and significantly associated with incident CVD in MESA and CHS
(Table).
In multivariable adjusted models, CML, 3DG-H and a summary variable that accounted for all measured AGEs (PC1) were significantly associated with incident CVD in CHS but not in MESA.
Conclusion:
We found AGEs to be significantly associated with CVD in an older cohort, but not in a healthier middle-aged to older population that had lower systemic inflammation and lower baseline AGE concentrations. In the general population, AGEs may exert detrimental cardiovascular effects only at higher levels over longer cumulative exposure.
Inhibitors of Advanced Glycation End Products (AGEs): Potential Utility for the Treatment of Cardiovascular Disease
