Original investigation

Association between carotid diameter and the advanced glycation endproduct N^ε-Carboxymethyllysine (CML)

Marcus Baumann^1*, Tom Richart^2,3, Daniel Sollinger¹, Jaroslav Pelisek⁴, Marcel Roos¹, Tatiana Kouznetsova³, Hans-Henning Eckstein⁴, Uwe Heemann¹ and Jan A Staessen^2,3

• * Corresponding author: Marcus Baumann marcus.baumann@lrz.tum.de

Author Affiliations

¹ Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

² Genetic Epidemiology Unit, Department of Epidemiology, Maastricht University, Maastricht, the Netherlands

³ Studies Coordinating Centre, Division of Hypertension and Cardiac Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium

⁴ Department of Vascular Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

For all author emails, please log on.

Cardiovascular Diabetology 2009, 8:45 doi:10.1186/1475-2840-8-45

Published: 6 August 2009

Abstract

Background

N^ε-Carboxymethyllysine (CML) is the major non-cross linking advanced glycation end product (AGE). CML is elevated in diabetic patients and apparent in atherosclerotic lesions. AGEs are associated with hypertension and arterial stiffness potentially by qualitative changes of elastic fibers. We investigated whether CML affects carotid and aortic properties in normoglycemic subjects.

Methods

Hundred-two subjects (age 48.2 ± 11.3 years) of the FLEMENGHO study were stratified according to the median of the plasma CML level (200.8 ng/ml; 25^th percentile: 181.6 ng/ml, 75^th percentile: 226.1 ng/ml) into "high CML" versus "low CML" as determined by ELISA. Local carotid artery properties, carotid intima media thickness (IMT), aortic pulse wave velocity (PWV), blood pressure and fetuin-A were analyzed. In 26 patients after carotidectomy, CML was visualized using immunohistochemistry.

Results

According to the CML median, groups were similar for anthropometric and biochemical data. Carotid diameter was enlarged in the "high" CML group (485.7 ± 122.2 versus 421.2 ± 133.2 μm; P < 0.05), in particular in participants with elevated blood pressure and with "high" CML ("low" CML: 377.9 ± 122.2 μm and "high" CML: 514.5 ± 151.6 μm; P < 0.001). CML was associated fetuin-A as marker of vascular inflammation in the whole cohort (r = 0.28; P < 0.01) and with carotid diameter in hypertensive subjects (r = 0.42; P < 0.01). CML level had no effect on aortic stiffness. CML was detected in the subendothelial space of human carotid arteries.

Conclusion

In normoglycemic subjects CML was associated with carotid diameter without adaptive changes of elastic properties and with fetuin-A as vascular inflammation marker, in particular in subjects with elevated blood pressure. This may suggest qualitative changes of elastic fibers resulting in a defective mechanotransduction, in particular as CML is present in human carotid arteries.