TY - JOUR
T1 - Plasma advanced glycation end products are associated with incident cardiovascularevents in individuals with type 2 diabetes
T2 - A Case-Cohort study with a median follow-Up of 10 years (EPIC-NL)
AU - Hanssen, Nordin M.J.
AU - Beulens, Joline W.J.
AU - Van Dieren, Susan
AU - Scheijen, Jean L.J.M.
AU - Van Der A, Daphne L.
AU - Spijkerman, Annemieke M.W.
AU - Van Der Schouw, Yvonne T.
AU - Stehouwer, Coen D.A.
AU - Schalkwijk, Casper G.
N1 - Publisher Copyright: © 2015 by the American Diabetes Association.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Experimental data suggest a role for advanced glycation end products (AGEs) in cardiovascular disease (CVD), particularly in type 2 diabetes (T2DM). However, epidemiological evidence of an association between high plasma AGEs and increased cardiovascular risk remains inconclusive. Therefore, in a case-cohort study comprising 134 cardiovascular case subjects and a random subcohort of 218 individuals (including 65 cardiovascular case subjects), all with T2DM and nested in the European Prospective Investigation into Cancer and Nutrition in the Netherlands (EPIC-NL) study, plasma levels of proteinbound Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and pentosidine were measured with liquid chromatography. AGEs were loge-transformed, combined in a z-score, and the association with incident cardiovascular eventswas analyzed with Cox proportional hazard regression, adapted for case-cohort design (Prentice method). After multivariable adjustment (sex, age, cohort status, diabetes duration, total cholesterol to HDL-cholesterol ratio, smoking, systolic blood pressure, BMI, blood pressure-, cholesterol- and glucose-lowering treatment, prior cardiovascular events, and triglycerides), higher plasma AGE z-scores were associated with higher risk of incident cardiovascular events in individuals without prior cardiovascular events (hazard ratio 1.31 [95% CI: 1.06-1.61]). A similar trend was observed in individuals withprior cardiovascular events (1.37 [0.63-2.98]). In conclusion, high plasma AGEs were associated with incident cardiovascular events in individuals with T2DM. These results underline the potential importance of AGEs in development of CVD.
AB - Experimental data suggest a role for advanced glycation end products (AGEs) in cardiovascular disease (CVD), particularly in type 2 diabetes (T2DM). However, epidemiological evidence of an association between high plasma AGEs and increased cardiovascular risk remains inconclusive. Therefore, in a case-cohort study comprising 134 cardiovascular case subjects and a random subcohort of 218 individuals (including 65 cardiovascular case subjects), all with T2DM and nested in the European Prospective Investigation into Cancer and Nutrition in the Netherlands (EPIC-NL) study, plasma levels of proteinbound Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and pentosidine were measured with liquid chromatography. AGEs were loge-transformed, combined in a z-score, and the association with incident cardiovascular eventswas analyzed with Cox proportional hazard regression, adapted for case-cohort design (Prentice method). After multivariable adjustment (sex, age, cohort status, diabetes duration, total cholesterol to HDL-cholesterol ratio, smoking, systolic blood pressure, BMI, blood pressure-, cholesterol- and glucose-lowering treatment, prior cardiovascular events, and triglycerides), higher plasma AGE z-scores were associated with higher risk of incident cardiovascular events in individuals without prior cardiovascular events (hazard ratio 1.31 [95% CI: 1.06-1.61]). A similar trend was observed in individuals withprior cardiovascular events (1.37 [0.63-2.98]). In conclusion, high plasma AGEs were associated with incident cardiovascular events in individuals with T2DM. These results underline the potential importance of AGEs in development of CVD.
UR - http://www.scopus.com/inward/record.url?scp=84919969049&partnerID=8YFLogxK
U2 - https://doi.org/10.2337/db13-1864
DO - https://doi.org/10.2337/db13-1864
M3 - Article
C2 - 24848072
SN - 0012-1797
VL - 64
SP - 257
EP - 265
JO - Diabetes
JF - Diabetes
IS - 1
ER -