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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

Karly C. Sourris1, 2 / Jasmine G. Lyons1 / Sonia L. Dougherty1 / Vibhasha Chand1, 2 / Nora E. Straznicky1 / Markus P. Schlaich1 / Mariee T. Grima1 / Mark E. Cooper1, 2 / Bronwyn A. Kingwell1, 2 / Maximilian P.J. de Courten3 / Josephine M. Forbes1, 2, 4 / 1, 5

1Baker IDI Heart and Diabetes Institute, Melbourne, Australia

2Departments of Medicine, Immunology and Physiology, Monash University, Australia

3Copenhagen School of Global Health, Copenhagen University, Denmark

4Glycation and Diabetes, Mater Medical Research Institute, South Brisbane, Australia

5Department of Biomedical Sciences, Copenhagen University, Denmark

Corresponding author: A/Prof. Barbora de Courten, MD, PhD, MPH, FRACP, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, 3004, VIC, Australia, Phone: +61 3 85321353, Fax: +61 3 85321111, E-mail:

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 52, Issue 1, Pages 129–138, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/cclm-2012-0850, March 2013

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Background: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective was to characterize the relationship between serum AGEs, CLAIS and other risk factors for CV disease in normotensive non-diabetic individuals.

Methods: We measured body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid and glucose profile in 44 non-diabetic volunteers (17 female, 27 males). Carboxymethyl-lysine (CML) was measured by ELISA as a marker for circulating AGEs and NF-κB p65 activity as an inflammatory marker by DNA-binding in peripheral blood mononuclear cells lysates (PBMC).

Results: Plasma CML concentrations were related to diastolic blood pressure (r=−0.51, p<0.01) independently of age, sex, BMI and WHR (p<0.05). Diastolic blood pressure was also related to NF-κB activity in PBMC (r=0.47, p<0.01) before and after adjustment for age, sex, BMI and WHR (p<0.05). Plasma CML concentrations were related to the pulse pressure before (r=0.42; p<0.05) and after adjustment for age, sex, BMI and waist (p<0.05). Neither CML nor NF-κB activity were related to systolic blood pressure (both p=ns). Plasma CML concentrations were not associated with plasma lipid or glucose concentrations (all p=ns).

Conclusions: Plasma AGE levels and NF-κB activity in PBMC were independent determinants of diastolic and pulse pressure in healthy normotensive individuals. This association suggests a role for AGEs in the etiology of hypertension, possibly via the initiation of CLAIS and aortic stiffening.

Keywords: advanced glycation end products; alkaline phosphatase; blood pressure; central obesity; chronic low-grade inflammation; NF-κB activity

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