Plasma advanced glycation endproducts are associated with incident cardiovascular events in individuals with type 2 diabetes: a case-cohort study with a median follow-up of 10 years (EPIC-NL)
- Nordin M.J Hanssen1,
- Joline W.J Beulens2,
- Susan van Dieren2,
- Jean L.J.M. Scheijen1,
- Daphne L. van der A3,
- Annemieke M.W. Spijkerman3,
- Yvonne T. van der Schouw2,
- Coen D.A Stehouwer1 and
- Casper G. Schalkwijk1⇑
- 1CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands
- Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht
- 3The Netherlands 3The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Corresponding author: Casper G. Schalkwijk,
Experimental data suggest a role for advanced glycation endproducts (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 cases and a random subcohort of 218 individuals (including 65 cardiovascular cases), all with T2DM and nested in the EPIC-NL study, plasma levels of protein-bound Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL) and pentosidine were measured with liquid-chromatography. AGEs were loge-transformed, combined in a z-score and the association with incident cardiovascular events was analysed 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, (HR: 1.31 (95%CI: 1.06-1.61)). A similar trend was observed in individuals with prior cardiovascular events (HR: 1.37 (95%CI: 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.
- Received December 10, 2013.
- Accepted May 1, 2014.
- © 2014 by the American Diabetes Association.
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