Published Online
on March 15, 2007

A more recent version of this article appeared on May 1, 2007

This Article Full Text (PDF) All Versions of this Article: 38/5/1495    most recent STROKEAHA.106.474577v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fredrikson, G. N. Articles by Nilsson, J. Search for Related Content PubMed PubMed Citation Articles by Fredrikson, G. N. Articles by Nilsson, J. Related Collections Risk Factors

Submitted on October 9, 2006
Revised on December 5, 2006
Accepted on December 11, 2006

Association Between IgM Against an Aldehyde-Modified Peptide in Apolipoprotein B-100 and Progression of Carotid Disease

Gunilla Nordin Fredrikson PhD^*; Bo Hedblad MD, PhD; Göran Berglund MD, PhD; Ragnar Alm BSI; Jan-Åke Nilsson BSI; Alexandru Schiopu MD, PhD; Prediman K. Shah MD; and Jan Nilsson MD, PhD

From the Department of Clinical Sciences (G.N.F., B.H., G.B., R.A., J.-A.N., A.S., J.N.), Malmö University Hospital, Lund University, Malmö, Sweden; the Department of Biomedical Laboratory Science (G.N.F.), Malmö University, Sweden; and the Atherosclerosis Research Center and Division of Cardiology (P.K.S.), Cedars-Sinai Medical Center and David Geffen School of Medicine at UCLA School of Medicine, Los Angeles, Calif.

^* To whom correspondence should be addressed. E-mail: Gunilla.Nordin_Fredrikson{at}med.lu.se.

Background and Purpose--Autoantibodies against antigens in oxidized low-density lipoprotein are common in people; experimental studies suggest that these immune responses have a functional role in the disease process. The aim of this study was to evaluate the relationship between the immune response against one defined oxidized low-density lipoprotein antigen, the aldehyde-modified peptide corresponding amino acids 3136 and 3155 (MDA-p210) in apolipoprotein (apo) B-100, and progression of carotid intima media thickness (IMT).

Methods--IgM and IgG against MDA-p210 were determined by enzyme-linked immunosorbent assay at baseline and after 12 months of treatment with placebo, metoprolol, fluvastatin, or metoprolol/fluvastatin in 751 individuals participating in the BCAPS. Carotid IMT was assessed by ultrasonography at baseline and after 18 and 36 months of treatment.

Results--Antibody levels did not change in response to treatment, but high baseline MDA-p210 IgM levels were associated with a more rapid progression of carotid disease both at 18 (r=0.09, P<0.05) and 36 months (r=0.12, P<0.005). At 36 months, the difference in IMT progression rate per year between those with high MDA-p210 IgM levels and those with low was 0.011 mm (95% CI=0.005 to 0.018 mm, P<0.0001). Treatment with fluvastatin markedly decreased the progression of IMT among subjects with high but not with low MDA-p210 IgM levels. There was no association between MDA-p210 IgG and carotid IMT progression.

Conclusions--IgM against the aldehyde-modified peptide corresponding amino acids 3136 and 3155 in apo B-100 is common in subjects with asymptomatic carotid disease, and high levels are associated with a more rapid progression of carotid IMT. The observation that the effect of fluvastatin was restricted to subjects with high MDA-p210 IgM levels may reflect the increased rate of disease progression in this group.

Key words: atherosclerosis • carotid arteries • echocardiography • immune system • lipoproteins

This article has been cited by other articles:

				A. E. Fraley, G. G. Schwartz, A. G. Olsson, S. Kinlay, M. Szarek, N. Rifai, P. Libby, P. Ganz, J. L. Witztum, S. Tsimikas, et al. Relationship of oxidized phospholipids and biomarkers of oxidized low-density lipoprotein with cardiovascular risk factors, inflammatory biomarkers, and effect of statin therapy in patients with acute coronary syndromes: Results from the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) trial. J. Am. Coll. Cardiol., June 9, 2009; 53(23): 2186 - 2196. [Abstract] [Full Text] [PDF]

				P. Sjogren, G. N. Fredrikson, A. Samnegard, C.-G. Ericsson, J. Ohrvik, R. M. Fisher, J. Nilsson, and A. Hamsten High plasma concentrations of autoantibodies against native peptide 210 of apoB-100 are related to less coronary atherosclerosis and lower risk of myocardial infarction Eur. Heart J., September 2, 2008; 29(18): 2218 - 2226. [Abstract] [Full Text] [PDF]

				B. Ky, A. Burke, S. Tsimikas, M. L. Wolfe, M. G. Tadesse, P. O. Szapary, J. L. Witztum, G. A. FitzGerald, and D. J. Rader The Influence of Pravastatin and Atorvastatin on Markers of Oxidative Stress in Hypercholesterolemic Humans J. Am. Coll. Cardiol., April 29, 2008; 51(17): 1653 - 1662. [Abstract] [Full Text] [PDF]