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(Circulation. 1998;98:1487-1494.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Oxidized LDL and Malondialdehyde-Modified LDL in Patients With Acute Coronary Syndromes and Stable Coronary Artery Disease

Paul Holvoet, PhD; Johan Vanhaecke, MD, PhD; Stefaan Janssens, MD, PhD; Frans Van de Werf, MD, PhD; ; Désiré Collen, MD, PhD

From the Center for Molecular and Vascular Biology (P.H., D.C.) and Department of Cardiology (J.V., S.J., F.V.d.W.), University of Leuven, Belgium.

Correspondence to P. Holvoet, PhD, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium. E-mail paul.holvoet{at}med.kuleuven.ac.be

Background—The association between oxidative modifications of LDL and coronary artery disease (CAD) is suspected but not established. Therefore, the association between plasma levels of oxidized LDL and malondialdehyde (MDA)-modified LDL and acute coronary syndromes and stable CAD was investigated.

Methods and Results—The study population contained 63 patients with acute coronary syndromes (45 with acute myocardial infarction and 18 with unstable angina pectoris), 35 nontransplanted patients with angiographically confirmed stable angina, 28 heart transplant patients with posttransplant CAD, 79 heart transplant patients without CAD, and 65 control subjects. After correction for age, sex, and LDL and HDL cholesterol, plasma levels of oxidized LDL and MDA-modified LDL were significantly higher in patients with CAD than in individuals without CAD (r²=0.57 and r²=0.26, respectively; both P=0.0001). Plasma levels of MDA-modified LDL were significantly higher in patients with acute coronary syndromes than in individuals with stable CAD (r²=0.65; P=0.0001) and were associated with increased levels of troponin I and C-reactive protein (r²=0.39 and r²=0.34, respectively; both P=0.0001). Plasma levels of oxidized LDL were not associated with increased levels of troponin I and C-reactive protein (r²=0.089 and r²=0.063, respectively).

Conclusions—Elevated plasma levels of oxidized LDL are associated with CAD. Elevated plasma levels of MDA-modified LDL suggest plaque instability and may be useful for the identification of patients with acute coronary syndromes.

Key Words: lipoproteins • coronary disease • angina • diagnosis • plaque

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				P. Holvoet, T. B. Harris, R. P. Tracy, P. Verhamme, A. B. Newman, S. M. Rubin, E. M. Simonsick, L. H. Colbert, and S. B. Kritchevsky Association of High Coronary Heart Disease Risk Status With Circulating Oxidized LDL in the Well-Functioning Elderly: Findings From the Health, Aging, and Body Composition Study Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1444 - 1448. [Abstract] [Full Text] [PDF]

				M. Kosch, A. Levers, M. Fobker, M. Barenbrock, R. M. Schaefer, K.-H. Rahn, and M. Hausberg Dialysis filter type determines the acute effect of haemodialysis on endothelial function and oxidative stress Nephrol. Dial. Transplant., July 1, 2003; 18(7): 1370 - 1375. [Abstract] [Full Text] [PDF]

				G. N. Fredrikson, B. Hedblad, G. Berglund, R. Alm, M. Ares, B. Cercek, K.-Y. Chyu, P. K. Shah, and J. Nilsson Identification of Immune Responses Against Aldehyde-Modified Peptide Sequences in ApoB Associated With Cardiovascular Disease Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 872 - 878. [Abstract] [Full Text] [PDF]

				G. N. Fredrikson, I. Soderberg, M. Lindholm, P. Dimayuga, K.-Y. Chyu, P. K. Shah, and J. Nilsson Inhibition of Atherosclerosis in ApoE-Null Mice by Immunization with ApoB-100 Peptide Sequences Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 879 - 884. [Abstract] [Full Text] [PDF]

				S. Kopprasch, J. Pietzsch, E. Kuhlisch, and J. Graessler Lack of Association between Serum Paraoxonase 1 Activities and Increased Oxidized Low-Density Lipoprotein Levels in Impaired Glucose Tolerance and Newly Diagnosed Diabetes Mellitus J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1711 - 1716. [Abstract] [Full Text] [PDF]

				A. Mertens, P. Verhamme, J. K. Bielicki, M. C. Phillips, R. Quarck, W. Verreth, D. Stengel, E. Ninio, M. Navab, B. Mackness, et al. Increased Low-Density Lipoprotein Oxidation and Impaired High-Density Lipoprotein Antioxidant Defense Are Associated With Increased Macrophage Homing and Atherosclerosis in Dyslipidemic Obese Mice: LCAT Gene Transfer Decreases Atherosclerosis Circulation, April 1, 2003; 107(12): 1640 - 1646. [Abstract] [Full Text] [PDF]

				M Uno, K T Kitazato, K Nishi, H Itabe, and S Nagahiro Raised plasma oxidised LDL in acute cerebral infarction J. Neurol. Neurosurg. Psychiatry, March 1, 2003; 74(3): 312 - 316. [Abstract] [Full Text] [PDF]

				M. Sanada, Y. Higashi, K. Nakagawa, M. Tsuda, I. Kodama, M. Kimura, K. Chayama, and K. Ohama A Comparison of Low-Dose and Standard-Dose Oral Estrogen on Forearm Endothelial Function in Early Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1303 - 1309. [Abstract] [Full Text] [PDF]

				R. De Caterina, F. Cipollone, F. P. Filardo, M. Zimarino, W. Bernini, G. Lazzerini, T. Bucciarelli, A. Falco, P. Marchesani, R. Muraro, et al. Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F2-Isoprostane Formation in Hypercholesterolemic Subjects: No Further Effect of Vitamin E Circulation, November 12, 2002; 106(20): 2543 - 2549. [Abstract] [Full Text] [PDF]

				S. Kopprasch, J. Pietzsch, E. Kuhlisch, K. Fuecker, T. Temelkova-Kurktschiev, M. Hanefeld, H. Kuhne, U. Julius, and J. Graessler In Vivo Evidence for Increased Oxidation of Circulating LDL in Impaired Glucose Tolerance Diabetes, October 1, 2002; 51(10): 3102 - 3106. [Abstract] [Full Text] [PDF]

				K. Nishi, H. Itabe, M. Uno, K. T. Kitazato, H. Horiguchi, K. Shinno, and S. Nagahiro Oxidized LDL in Carotid Plaques and Plasma Associates With Plaque Instability Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1649 - 1654. [Abstract] [Full Text] [PDF]

				P. Verhamme, R. Quarck, H. Hao, M. Knaapen, S. Dymarkowski, H. Bernar, J. Van Cleemput, S. Janssens, J. Vermylen, G. Gabbiani, et al. Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs Cardiovasc Res, October 1, 2002; 56(1): 135 - 144. [Abstract] [Full Text] [PDF]

				J. T. Cvetkovic, S. Wallberg-Jonsson, E. Ahmed, S. Rantapaa-Dahlqvist, and A. K. Lefvert Increased levels of autoantibodies against copper-oxidized low density lipoprotein, malondialdehyde-modified low density lipoprotein and cardiolipin in patients with rheumatoid arthritis Rheumatology, September 1, 2002; 41(9): 988 - 995. [Abstract] [Full Text] [PDF]

				G. Theilmeier, P. Verhamme, S. Dymarkowski, H. Beck, H. Bernar, M. Lox, S. Janssens, M.-C. Herregods, E. Verbeken, D. Collen, et al. Hypercholesterolemia in Minipigs Impairs Left Ventricular Response to Stress: Association With Decreased Coronary Flow Reserve and Reduced Capillary Density Circulation, August 27, 2002; 106(9): 1140 - 1146. [Abstract] [Full Text] [PDF]

				G. Theilmeier, R. Quarck, P. Verhamme, M.-L. Bochaton-Piallat, M. Lox, H. Bernar, S. Janssens, M. Kockx, G. Gabbiani, D. Collen, et al. Hypercholesterolemia impairs vascular remodelling after porcine coronary angioplasty Cardiovasc Res, August 1, 2002; 55(2): 385 - 395. [Abstract] [Full Text] [PDF]

				J. Hulthe and B. Fagerberg Circulating Oxidized LDL Is Associated With Subclinical Atherosclerosis Development and Inflammatory Cytokines (AIR Study) Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1162 - 1167. [Abstract] [Full Text] [PDF]

				K. Tanaga, H. Bujo, M. Inoue, K. Mikami, K. Kotani, K. Takahashi, T. Kanno, and Y. Saito Increased Circulating Malondialdehyde-Modified LDL Levels in Patients With Coronary Artery Diseases and Their Association With Peak Sizes of LDL Particles Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 662 - 666. [Abstract] [Full Text] [PDF]

				M. de Lorgeril, P. Salen, P. Defaye, P. Mabo, and F. Paillard Dietary prevention of sudden cardiac death Eur. Heart J., February 2, 2002; 23(4): 277 - 285. [Full Text] [PDF]

				M. Mori, H. Itabe, Y. Higashi, Y. Fujimoto, M. Shiomi, M. Yoshizumi, Y. Ouchi, and T. Takano Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum J. Lipid Res., November 1, 2001; 42(11): 1771 - 1781. [Abstract] [Full Text] [PDF]

				A. MERTENS and P. HOLVOET Oxidized LDL and HDL: antagonists in atherothrombosis FASEB J, October 1, 2001; 15(12): 2073 - 2084. [Abstract] [Full Text] [PDF]

				B. de Geest and D. Collen Antibodies against oxidized LDL for non-invasive diagnosis of atherosclerotic vascular disease Eur. Heart J., September 1, 2001; 22(17): 1517 - 1518. [PDF]

				C. Monaco, F. Crea, G. Niccoli, F. Summaria, D. Cianflone, R. Bordone, G. Bellomo, and A. Maseri Autoantibodies against oxidized low density lipoproteins in patients with stable angina, unstable angina or peripheral vascular disease; pathophysiological implications Eur. Heart J., September 1, 2001; 22(17): 1572 - 1577. [Abstract] [PDF]

				X. L. Wang, D. L. Rainwater, J. F. VandeBerg, B. D. Mitchell, and M. C. Mahaney Genetic Contributions to Plasma Total Antioxidant Activity Arterioscler Thromb Vasc Biol, July 1, 2001; 21(7): 1190 - 1195. [Abstract] [Full Text] [PDF]