Enhanced atherogenesis and altered high density lipoprotein in patients with Crohn's disease

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Journal of Lipid Research, Vol. 48, 2640-2646, December 2007Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Enhanced atherogenesis and altered high density lipoprotein in patients with Crohn's disease

Sander I. van Leuven1,*, Hezemans, Johannes H. Levels, Snoek, Pieter C. Stokkers, G. Kees Hovingh*, J. P. Kastelein*, S. Stroes*, de Groot* and Daan W. Hommes

* Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Published, JLR Papers in Press, September 22, 2007.

1 To whom correspondence should be addressed. e-mail: s.i.vanleuven@...

A chronic inflammatory state is a risk factor for accelerated atherogenesis. The aim of our study was to explore whether Crohn's disease (CD), characterized by recurrent inflammatory episodes, is also associated with accelerated atherogenesis. In 60 CD patients and 122 matched controls, carotid intima media thickness (IMT), a validated marker for the burden and progression of atherosclerosis, was assessed ultrasonographically. Additional subgroup analyses, including plasma levels of acute phase reactants and HDL protein profiling, were performed in 11 consecutive patients with CD in remission, 10 patients with active CD, and 15 healthy controls. Carotid IMT in patients with CD was increased compared with healthy volunteers: 0.71 (0.17) versus 0.59 (0.14) mm (P < 0.0001), respectively. In the subgroup analysis, HDL levels in controls and patients in remission were identical [(1.45 (0.48) and 1.40 (0.46) mmol/l; P = 0.797], whereas HDL during exacerbation was profoundly reduced: 1.02 (0.33) (P = 0.022). HDL from patients with active CD and CD patients in remission was characterized by a reduced ability to attenuate oxidation compared with controls (P = 0.008 and P = 0.024 respectively). Patients with CD have increased IMT compared with matched controls, indicative of accelerated atherogenesis. The changes during CD exacerbation in terms of HDL concentration and composition imply a role for impaired HDL protection in these patients.

Supplementary key words atherosclerosis • inflammation • endothelium