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Journal of Lipid Research, Vol. 50, 342-349, February 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Circulating oxidized LDL: determinants and association with brachial flow-mediated dilation

Leonard P. van der Zwan^*, Tom Teerlink^*, Jacqueline M. Dekker, Ronald M. A. Henry, Coen D. A. Stehouwer, Cornelis Jakobs^*, Robert J. Heine^** and Peter G. Scheffer^1,*

^* Metabolic Laboratory, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands
Department of Internal Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands
^** Department of Endocrinology/Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands

Published, JLR Papers in Press, September 18, 2008.

¹ To whom correspondence should be addressed. e-mail: p.scheffer{at}vumc.nl

Circulating oxidized LDL (oxLDL) levels are strongly correlated to LDL-cholesterol (LDL-c) and apolipoprotein-B100 (apoB100), making it difficult to disentangle their independent contributions to cardiovascular risk. We explored the determinants of oxLDL and the relation between oxLDL and flow-mediated dilation (FMD) of the brachial artery to investigate whether the oxLDL/LDL-c and oxLDL/apoB100 ratios are more informative than the separate variables. FMD of the brachial artery and plasma concentrations of oxLDL, LDL-cholesterol, and apoB100 were measured in 624 men and women (age range 50 to 87 years), participating in a population-based cohort study. OxLDL was strongly correlated with apoB100 (r = 0.82, P < 0.001) and LDL-c (r = 0.67, P < 0.001). Other major independent determinants of oxLDL were sex, HDL-cholesterol, and LDL particle size. LDL-c and apoB100 concentrations were not significantly associated with FMD. After adjustment for age, sex, glucose tolerance status, and Framingham risk score, the oxLDL/apoB100 ratio was negatively related to FMD (P = 0.017). This association was weaker for the oxLDL/ LDL-c ratio (P = 0.062) and absent for oxLDL level (P = 0.27). In contrast to oxLDL, the oxLDL/apoB100 ratio, and to a lesser extent the oxLDL/LDL-c ratio, are related to a functional measure of atherosclerosis. Therefore correction of oxLDL for LDL particle number may improve the clinical usefulness of oxLDL measurement.

Supplementary key words atherosclerosis • cardiovascular risk factors • diabetes • endothelial function • vasodilation • apolipoprotein-B100 • oxidative stress

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