This Article  • References  • Full text PDF  • Correction  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Marja Puurunen; Matti Mänttäri, MD; Vesa Manninen, MD; Leena Tenkanen, PhD; Georg Alfthan, PhD; Christian Ehnholm, MD; Outi Vaarala, MD; Kimmo Aho, MD; Timo Palosuo, MD

Arch Intern Med. 1994;154(22):2605-2609.

Abstract
Background
Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of atherosclerosis. The purpose of the present study was to determine whether antibody against oxidized low-density lipoprotein, reported to be associated with the progression of carotid atherosclerosis, is predictive of cardiac death and nonfatal myocardial infarction.

Methods
Serum samples from 135 cases and their controls, drawn at entry from middle-aged dyslipidemic men participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil, were tested for immunoglobulin G class antibodies against oxidized low-density lipoprotein by enzyme-linked immunosorbent assay.

Results
The mean antibody level, expressed in optical density units, was significantly higher in cases than in controls (0.412 vs 0.356, P=.002). After adjustment for age, smoking, blood pressure, and high-density lipoprotein cholesterol level, there was a 2.5-fold increased risk (95% confidence interval, 1.3 to 4.9) of a cardiac end point in the highest tertile of antibody level vs the lowest tertile (P=.005 for trend).

Conclusions
Elevated levels of antibodies against oxidized low-density lipoprotein were predictive of myocardial infarction. The effect was independent of low-density lipoprotein cholesterol levels, and the joint effect was additive. Elevated antibody levels modified the effects of classic coronary risk factors.

(Arch Intern Med. 1994;154:2605-2609)

Author Affiliations
From the National Public Health Institute, Helsinki (Ms Puurunen and Drs Alfthan, Ehnholm, Vaarala, Aho, and Palosuo), the First Department of Medicine, University of Helsinki (Drs Mänttäri and Manninen), and the Helsinki Heart Study (Dr Tenkanen), Finland.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Regression of Atherosclerosis With Therapeutic Antibodies: Pipe Cleaner or Pipe Dream?
Ginsburg
J Am Coll Cardiol 2007;50:2319-2321.
FULL TEXT  

Association Between IgM Against an Aldehyde-Modified Peptide in Apolipoprotein B-100 and Progression of Carotid Disease
Fredrikson et al.
Stroke 2007;38:1495-1500.
ABSTRACT | FULL TEXT  

Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events
Tsimikas et al.
J. Lipid Res. 2007;48:425-433.
ABSTRACT | FULL TEXT  

Identification of autoantibodies in human plasma recognizing an apoB-100 LDL receptor binding site peptide
Fredrikson et al.
J. Lipid Res. 2006;47:2049-2054.
ABSTRACT | FULL TEXT  

OxLDL-IgG Immune Complexes Induce Survival of Human Monocytes
Oksjoki et al.
Arterioscler. Thromb. Vasc. Bio. 2006;26:576-583.
ABSTRACT | FULL TEXT  

Women and Ischemic Heart Disease: Pathophysiologic Implications From the Women's Ischemia Syndrome Evaluation (WISE) Study and Future Research Steps
Quyyumi
J Am Coll Cardiol 2006;47:S66-S71.
ABSTRACT | FULL TEXT  

Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure
George et al.
Eur J Heart Fail 2006;8:58-62.
ABSTRACT | FULL TEXT  

Glomerular handling of native albumin in the presence of circulating modified albumins by the normal rat kidney
Londono and Bendayan
Am. J. Physiol. Renal Physiol. 2005;289:F1201-F1209.
ABSTRACT | FULL TEXT  

Effect of Lowering of Homocysteine Levels on Inflammatory Markers: A Randomized Controlled Trial
Durga et al.
Arch Intern Med 2005;165:1388-1394.
ABSTRACT | FULL TEXT  

Humoral Immune Response Against Defined Oxidized Low-Density Lipoprotein Antigens Reflects Structure and Disease Activity of Carotid Plaques
Goncalves et al.
Arterioscler. Thromb. Vasc. Bio. 2005;25:1250-1255.
ABSTRACT | FULL TEXT  

Preclinical vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome
Jimenez et al.
Rheumatology (Oxford) 2005;44:756-761.
ABSTRACT | FULL TEXT  

Influence of age and sex on levels of anti-oxidized LDL antibodies and anti-LDL immune complexes in the general population
Tinahones et al.
J. Lipid Res. 2005;46:452-457.
ABSTRACT | FULL TEXT  

Autoantibodies Against Oxidized LDLs and Atherosclerosis in Type 2 Diabetes
Piarulli et al.
Diabetes Care 2005;28:653-657.
ABSTRACT | FULL TEXT  

Severe Periodontitis Enhances Macrophage Activation via Increased Serum Lipopolysaccharide
Pussinen et al.
Arterioscler. Thromb. Vasc. Bio. 2004;24:2174-2180.
ABSTRACT | FULL TEXT  

Are Anti-Oxidized Low-Density Lipoprotein Antibodies Pathogenic or Protective?
Shoenfeld et al.
Circulation 2004;110:2552-2558.
FULL TEXT  

Atherosclerosis and lupus
Gorman and Isenberg
Rheumatology (Oxford) 2004;43:943-945.
FULL TEXT  

ALCOHOL MISUSE INCREASES SERUM ANTIBODIES TO OXIDIZED LDL AND C-REACTIVE PROTEIN
ALHO et al.
Alcohol Alcohol 2004;39:312-315.
ABSTRACT | FULL TEXT  

Current Debates in Antiphospholipid Syndrome: The Acquired Antibody-Mediated Thrombophilia
Ozturk et al.
CLIN APPL THROMB HEMOST 2004;10:89-126.
ABSTRACT  

Antibodies to Oxidized Low-Density Lipoproteins and Angiographically Assessed Coronary Artery Disease in White Patients
Rossi et al.
Circulation 2003;108:2467-2472.
ABSTRACT | FULL TEXT  

Immunoglobulin M Type of Autoantibodies to Oxidized Low-Density Lipoprotein Has an Inverse Relation to Carotid Artery Atherosclerosis
Karvonen et al.
Circulation 2003;108:2107-2112.
ABSTRACT | FULL TEXT  

The Cardiovascular Burden of Lupus: A Complex Challenge
Schattner and Liang
Arch Intern Med 2003;163:1507-1510.
FULL TEXT  

Circulating Autoantibodies to Oxidized LDL Correlate With Impaired Coronary Endothelial Function After Cardiac Transplantation
Fang et al.
Arterioscler. Thromb. Vasc. Bio. 2002;22:2044-2048.
ABSTRACT | FULL TEXT  

Increased levels of autoantibodies against copper-oxidized low density lipoprotein, malondialdehyde-modified low density lipoprotein and cardiolipin in patients with rheumatoid arthritis
Cvetkovic et al.
Rheumatology (Oxford) 2002;41:988-995.
ABSTRACT | FULL TEXT  

No Antioxidant Effect of Combined HRT on LDL Oxidizability and Oxidative Stress Biomarkers in Treated Post-Menopausal Women
Bureau et al.
J. Am. Coll. Nutr. 2002;21:333-338.
ABSTRACT | FULL TEXT  

Are Antiphospholipid Antibodies an Independent Risk Factor for Atherosclerosis?
Bilora et al.
CLIN APPL THROMB HEMOST 2002;8:103-113.
ABSTRACT  

Role of Infectious and Immune Factors in Coronary and Cerebrovascular Arteriosclerosis
Stollberger and Finsterer
CVI 2002;9:207-215.
FULL TEXT  

Antiphospholipid syndrome
Keswani and Chauhan
JRSM 2002;95:336-342.
FULL TEXT  

Phosphorylcholine-Dependent Cross-Reactivity between Dental Plaque Bacteria and Oxidized Low-Density Lipoproteins
Schenkein et al.
Infect. Immun. 2001;69:6612-6617.
ABSTRACT | FULL TEXT  

Antibodies against oxidized LDL for non-invasive diagnosis of atherosclerotic vascular disease
de Geest and Collen
Eur Heart J 2001;22:1517-1518.
 

Correlates of Markers of Oxidative Status in the General Population
Trevisan et al.
Am J Epidemiol 2001;154:348-356.
ABSTRACT | FULL TEXT  

Antibody against oxidized low density lipoprotein may predict progression or regression of atherosclerotic coronary artery disease
Inoue et al.
J Am Coll Cardiol 2001;37:1871-1876.
ABSTRACT | FULL TEXT  

Anti-oxidized low-density-lipoprotein (OxLDL) antibodies in systemic lupus erythematosus with and without antiphospholipid syndrome
Hayem et al.
Lupus 2001;10:346-351.
ABSTRACT  

Atherosclerosis and autoimmunity
Gordon et al.
Lupus 2001;10:249-252.
ABSTRACT  

Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein
Penny et al.
J Am Coll Cardiol 2001;37:766-774.
ABSTRACT | FULL TEXT  

Clinical significance of antibody against oxidized low density lipoprotein in patients with atherosclerotic coronary artery disease
Inoue et al.
J Am Coll Cardiol 2001;37:775-779.
ABSTRACT | FULL TEXT  

Increased Autoantibodies Against Oxidized Low-Density Lipoprotein in Coronary Circulation in Patients with Coronary Spastic Angina
Ogawa et al.
ANGIOLOGY 2001;52:167-174.
ABSTRACT  

Circulating autoantibodies to oxidized cardiolipin correlate with isoprostane F2{alpha}-VI levels and the extent of atherosclerosis in ApoE-deficient mice: modulation by vitamin E
Pratico et al.
Blood 2001;97:459-464.
ABSTRACT | FULL TEXT  

Circulating Autoantibodies to Oxidized LDL Correlate With Arterial Accumulation and Depletion of Oxidized LDL in LDL Receptor-Deficient Mice
Tsimikas et al.
Arterioscler. Thromb. Vasc. Bio. 2001;21:95-100.
ABSTRACT | FULL TEXT  

Antibodies to Oxidized LDL in Relation to Intima-Media Thickness in Carotid and Femoral Arteries in 58-Year-Old Subjectively Clinically Healthy Men
Hulthe et al.
Arterioscler. Thromb. Vasc. Bio. 2001;21:101-107.
ABSTRACT | FULL TEXT  

Circulating Oxidized Low Density Lipoprotein Levels : A Biochemical Risk Marker for Coronary Heart Disease
Toshima et al.
Arterioscler. Thromb. Vasc. Bio. 2000;20:2243-2247.
ABSTRACT | FULL TEXT  

Lowering Dietary Saturated Fat and Total Fat Reduces the Oxidative Susceptibility of LDL in Healthy Men and Women
Yu-Poth et al.
J. Nutr. 2000;130:2228-2237.
ABSTRACT | FULL TEXT  

Effect of vitamin E supplementation on antibody levels against malondialdehyde modified LDL in hyperlipidemic hamsters
de Oliveira et al.
Cardiovasc Res 2000;47:567-573.
ABSTRACT | FULL TEXT  

Inflammation-mediated rheumatic diseases and atherosclerosis
MANZI et al.
Ann Rheum Dis 2000;59:321-325.
FULL TEXT  

Systemic lupus erythematosus: a model for atherogenesis?
Manzi
Rheumatology (Oxford) 2000;39:353-359.
FULL TEXT  

Antibodies to oxidised LDL
Vaarala
Lupus 2000;9:202-205.
ABSTRACT  

Autoimmunity in atherosclerosis: lessons from experimental models
George et al.
Lupus 2000;9:223-227.
ABSTRACT  

Autoantibodies Against Oxidized Low-Density Lipoprotein and Cardiolipin in Patients With Coronary Heart Disease
Erkkila et al.
Arterioscler. Thromb. Vasc. Bio. 2000;20:204-209.
ABSTRACT | FULL TEXT  

Autoantibodies Against Oxidatively Modified LDL Do Not Constitute a Risk Factor for Stroke : A Nested Case-Control Study
Ahmed et al.
Stroke 1999;30:2541-2546.
ABSTRACT | FULL TEXT  

The Role of Vitamin E in the Prevention of Heart Disease
Emmert and Kirchner
Arch Fam Med 1999;8:537-542.
ABSTRACT | FULL TEXT  

Relationship Between Lipoprotein- and Oxidation-Related Variables and Atheroma Lipid Composition in Subjects Undergoing Coronary Artery Bypass Graft Surgery
Craig et al.
Arterioscler. Thromb. Vasc. Bio. 1999;19:1512-1517.
ABSTRACT | FULL TEXT  

Atherosclerosis-related markers in systemic lupus erythematosus patients: The role of humoral immunity in enhanced atherogenesis
George et al.
Lupus 1999;8:220-226.
ABSTRACT  

Autoantibodies Against Oxidized Low Density Lipoprotein in Patients With Angiographically Verified Coronary Artery Disease
Lehtimaki et al.
Arterioscler. Thromb. Vasc. Bio. 1999;19:23-27.
ABSTRACT | FULL TEXT  

Immunization of LDL Receptor–Deficient Mice With Homologous Malondialdehyde-Modified and Native LDL Reduces Progression of Atherosclerosis by Mechanisms Other Than Induction of High Titers of Antibodies to Oxidative Neoepitopes
Freigang et al.
Arterioscler. Thromb. Vasc. Bio. 1998;18:1972-1982.
ABSTRACT | FULL TEXT  

Antiphospholipid-Protein Antibodies and Ischemic Stroke : Not Just Cardiolipin Any More
Tanne et al.
Stroke 1998;29:1755-1758.
FULL TEXT  

Antibody Titers Against Oxidized LDL Are Not Elevated in Patients With Familial Hypercholesterolemia
Hulthe et al.
Arterioscler. Thromb. Vasc. Bio. 1998;18:1203-1211.
ABSTRACT | FULL TEXT  

Prediction of Myocardial Infarction in Dyslipidemic Men by Elevated Levels of Immunoglobulin Classes A, E, and G, but Not M
Kovanen et al.
Arch Intern Med 1998;158:1434-1439.
ABSTRACT | FULL TEXT  

Review : Antiphospholipid antibodies and myocardial infarction
Vaarala
Lupus 1998;7:S132-S134.
ABSTRACT  

Antibodies Against Cardiolipin and Oxidatively Modified LDL in 50-Year-Old Men Predict Myocardial Infarction
Wu et al.
Arterioscler. Thromb. Vasc. Bio. 1997;17:3159-3163.
ABSTRACT | FULL TEXT  

Increased Oxidation of LDL in Patients With Coronary Artery Disease Is Independent From Dietary Vitamins E and C
Halevy et al.
Arterioscler. Thromb. Vasc. Bio. 1997;17:1432-1437.
ABSTRACT | FULL TEXT  

Structural Identification by Mass Spectrometry of Oxidized Phospholipids in Minimally Oxidized Low Density Lipoprotein That Induce Monocyte/Endothelial Interactions and Evidence for Their Presence in Vivo
Watson et al.
J. Biol. Chem. 1997;272:13597-13607.
ABSTRACT | FULL TEXT  

Editorial: Atherosclerosis in SLE and Hughes syndrome
Vaarala
Lupus 1997;6:489-490.
 

Atherosclerosis in LDL-receptor knockout mice is accelerated by immunization with anticardiolipin antibodies
George et al.
Lupus 1997;6:717-729.
ABSTRACT  

Circulating Autoantibodies Recognizing Peroxidase-Oxidized Low Density Lipoprotein: Evidence for New Antigenic Epitopes Formed In Vivo Independently From Lipid Peroxidation
Seccia et al.
Arterioscler. Thromb. Vasc. Bio. 1997;17:134-140.
ABSTRACT | FULL TEXT  

Autoantibodies Against Oxidized LDL Do Not Predict Atherosclerotic Vascular Disease in Non–Insulin-Dependent Diabetes Mellitus
Uusitupa et al.
Arterioscler. Thromb. Vasc. Bio. 1996;16:1236-1242.
ABSTRACT | FULL TEXT