Relations Between Autoantibodies Against Oxidized Low-Density Lipoprotein, Inflammation, Subclinical Atherosclerosis, and Cardiovascular Disease in Rheumatoid Arthritis

MIKE J.L. PETERS, VOKKO P. van HALM, MICHAEL T. NURMOHAMED, JAN DAMOISEAUX, JAN WILLEM COHEN TERVAERT, JOS W.R. TWISK, BEN A.C. DIJKMANS, and ALEXANDRE E. VOSKUYL

ABSTRACT.

Objective. Rheumatoid arthritis (RA) is associated with an unexplained increased cardiovascular risk. Autoantibodies recognizing oxidized low-density lipoprotein (oxLDL-ab) are associated with atherosclerosis in the general population and have been reported in several autoimmune diseases. We investigated relations between oxLDL-ab, inflammation, subclinical atherosclerosis, and cardiovascular disease (CVD) in patients with RA.

Methods. In a nested case-control study, serum concentrations of oxLDL-ab were measured in 140 RA patients. Ultrasound examination of the carotid artery [i.e., carotid intima-media thickness (CIMT)] was performed in a third of these patients. Correlations were calculated for oxLDL-ab, C-reactive protein (CRP), and high-density lipoprotein (HDL) cholesterol. Regression analyses were used to examine associations between oxLDL-ab and prevalent CVD, and oxLDL-ab and CIMT.

Results. OxLDL-ab were positively correlated with CRP (r = 0.33, p < 0.001) and negatively correlated with HDL cholesterol (r = –0.28, p = 0.001). An indication for interaction was found (p = 0.09), suggesting that inflammation modifies the relation between HDL cholesterol and oxLDL-ab. OxLDL-ab were independently associated with intimal thickening, but not associated with prevalent CVD.

Conclusion. OxLDL-ab were strongly related with the degree of inflammation and may predispose to a higher risk for CVD, as they were independently associated with subclinical atherosclerosis in patients with RA. (First Release June 15 2008; J Rheumatol 2008;35:1495–9)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
CARDIOVASCULAR DISEASE
INFLAMMATION
CHOLESTEROL

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From the Department of Rheumatology, VU University Medical Center, Amsterdam; Department of Rheumatology, Jan van Breemen Institute, Amsterdam; Department of Internal Medicine, VU University Medical Center, Amsterdam; Department of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht; and Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.

M.J.L. Peters, MD; V.P. van Halm, MD, Department of Rheumatology, VU University Medical Center; M.T. Nurmohamed, MD, PhD, Department of Rheumatology, Jan van Breemen Institute, Department of Internal Medicine, VU University Medical Center; J. Damoiseaux, PhD; J.W. Cohen Tervaert, MD, PhD, Department of Clinical and Experimental Immunology, University Hospital Maastricht; J.W.R. Twisk, PhD, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; B.A.C. Dijkmans, MD, PhD, Department of Rheumatology, VU University Medical Center, Department of Rheumatology, Jan van Breemen Institute; A.E. Voskuyl, MD, PhD, Department of Rheumatology, VU University Medical Center.

Address reprint requests to Dr. A.E. Voskuyl, VU University Medical Center, Department of Rheumatology, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: ae.voskuyl@vumc.nl

Accepted for publication March 24, 2008.

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