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(ɛ)-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.
['Kizer|Jorge R|JR|', 'Benkeser|David|D|', 'Arnold|Alice M|AM|', 'Ix|Joachim H|JH|', 'Mukamal|Kenneth J|KJ|', 'Djousse|Luc|L|', 'Tracy|Russell P|RP|', 'Siscovick|David S|DS|', 'Psaty|Bruce M|BM|', 'Zieman|Susan J|SJ|']
D000368:Aged D000418:Albumins D000959:Antihypertensive Agents D001794:Blood Pressure D002318:Cardiovascular Diseases D015331:Cohort Studies D003327:Coronary Disease D003404:Creatinine D005260:Female D005919:Glomerular Filtration Rate D017127:Glycation End Products, Advanced D006801:Humans D007118:Immunoassay D015994:Incidence D008239:Lysine D008297:Male D018384:Oxidative Stress D016016:Proportional Hazards Models D020521:Stroke D016896:Treatment Outcome
Carboxymethyl-lysine Coronary heart disease Stroke Older adults Aging Advanced glycation endproducts