Plasma levels of oxidized-low-density lipoproteins are higher in patients with unstable angina and correlated with angiographic coronary complex plaques



      To measure circulating levels of oxidized-low-density lipoproteins (ox-LDL) in patients with stable and unstable angina and controls, and to investigate their correlation with the extent of coronary artery disease (CAD) and the presence of complex plaques at coronary angiography.

      Methods and results

      Circulating ox-LDL were assessed, using ELISA, in patients with unstable angina (UA, n = 26), stable angina (SA, n = 29) and in controls (C, n = 27). All patients underwent coronary angiography. The extent of CAD was evaluated using a quantitative score, while the presence of complex, vulnerable plaques was angiographically assessed. Ox-LDL were higher in UA patients than in SA patients and in C subjects, and in SA patients than in C subjects (C, 45.6 ± 12.8 U/L; SA, 58.8 ± 11.0 U/L; UA, 73.7 ± 13.6 U/L; p < 0.001). No correlation was found with the extent of atherosclerotic disease in the coronary tree. Patients with angiographic complex lesions showed significantly higher levels of ox-LDL (68.4 ± 13.9 U/L versus 55.2 ± 16.4 U/L, p < 0.001). Multiple regression analysis showed that ox-LDL were independent predictors of the presence of complex plaques (p < 0.023).


      Ox-LDL levels are higher in unstable patients and correlate with the presence of angiographically documented complex plaques. Ox-LDL might be markers of destabilization of CAD.


      ACS (acute coronary syndrome), C (control), CAD (coronary artery disease), HDL (high-density lipoproteins), LDL (low-density lipoproteins), Ox-LDL (oxidized-low-density lipoproteins), PCI (percutaneous coronary intervention), SA (stable angina), UA (unstable angina)


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        • Falk E.
        • Shah P.K.
        • Fuster V.
        Coronary plaque disruption.
        Circulation. 1995; 92: 657-671
        • Moreno P.R.
        • Falk E.
        • Palacios I.F.
        • et al.
        Macrophage infiltration in acute coronary syndromes: implications for plaque rupture.
        Circulation. 1994; 90: 775-778
        • Van der Wal A.C.
        • Becker A.E.
        • van der Loos C.M.
        • et al.
        Site of intimal rupture or erosion if thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology.
        Circulation. 1994; 89: 36-44
        • Kovanen P.T.
        • Kaartinen M.
        • Paavonen T.
        Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction.
        Circulation. 1995; 92: 1084-1088
        • Zalai C.V.
        • Kolodziejczyk D.
        • Pilarski L.
        • et al.
        Increased circulating monocyte activation in patients with unstable coronary syndromes.
        J Am Coll Cardiol. 2001; 38: 1340-1347
        • Pearson T.A.
        • Mensah G.A.
        • Alexander R.W.
        • et al.
        Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association.
        Circulation. 2003; 107: 499-511
        • Naghavi M.
        • Libby P.
        • Falk E.
        • et al.
        From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies. Part I.
        Circulation. 2003; 108: 1664-1672
        • Idem
        From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies. Part II.
        Circulation. 2003; 108: 1772-1778
        • Zairis M.N.
        • Papadaki O.A.
        • Manousakis S.J.
        • et al.
        C-reactive protein and multiple complex coronary artery plaques in patients with primary unstable angina.
        Atherosclerosis. 2002; 164: 355-359
        • Arroyo-Espliguero R.
        • Avanzas P.
        • Cosin-Sales J.
        • et al.
        C-reactive protein elevation and disease activity in patients with coronary artery disease.
        Eur Heart J. 2004; 25: 401-408
        • Cosin-Sales J.
        • Christiansen M.
        • Kaminski P.
        • et al.
        Pregnancy-associated plasma protein A and its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), are related to complex stenosis morphology in patients with stable angina pectoris.
        Circulation. 2004; 109: 1724-1728
        • Libby P.
        • Ridker P.M.
        • Maseri A.
        Inflammation and atherosclerosis.
        Circulation. 2002; 105: 1135-1143
        • Weinbrenner T.
        • Cladellas M.
        • Covas M.I.
        • et al.
        The SOLOS Study Investigators. High oxidative stress in patients with stable coronary heart disease.
        Atherosclerosis. 2003; 168: 99-106
        • Toshima S.
        • Hasegawa A.
        • Kurabayashi M.
        • et al.
        Circulating oxidized-low-density lipoprotein levels. A biochemical risk marker for coronary heart disease.
        Arterioscl Thromb Vas Biol. 2000; 20: 2243-2247
        • Holvoet P.
        • Mertens A.
        • Verhamme P.
        • et al.
        Circulating oxidized-lDL is a useful marker for identifying patients with coronary artery disease.
        Arterioscl Thromb Vas Biol. 2001; 21: 844-848
        • Ehara S.
        • Ueda M.
        • Naruko T.
        • et al.
        Elevated levels of low-density lipoprotein show a positive relationship with the severity of acute coronary syndromes.
        Circulation. 2001; 103: 1955-1960
        • Holvoet P.
        • Vanhaecke J.
        • Janssens S.
        • et al.
        Oxidized-lDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease.
        Circulation. 1998; 98: 1487-1494
        • Tsimikas S.
        • Bergmark C.
        • Beyer R.W.
        • et al.
        Temporal increases in plasma markers of oxidized-low-density lipoprotein strongly reflect the presence of acute coronary syndromes.
        J Am Coll Cardiol. 2003; 41: 360-370
        • Monaco C.
        • Crea F.
        • Niccoli G.
        • et al.
        Autoantibodies against oxidized-low-density lipoproteins in patients with stable angina, unstable angina or peripheral vascular disease; pathophysiological implications.
        Eur Heart J. 2001; 22: 1572-1577
        • Rossi G.P.
        • Cesari M.
        • De Toni R.
        • et al.
        Antibodies to oxidized-low-density lipoproteins and angiographically assessed coronary artery disease in white patients.
        Circulation. 2003; 108: 2467-2472
        • Nishi K.
        • Itabe H.
        • Uno M.
        • et al.
        Oxidized-lDL in carotid plaques and plasma associates with plaque destabilization.
        Arterioscler Thromb Vas Biol. 2002; 22: 1649-1654
        • Braunwald E.
        Unstable angina: a classification.
        Circulation. 1989; 80: 410-414
        • Sullivan D.R.
        • Marwick T.H.
        • Freedman S.B.
        A new method of scoring coronary angiogram to reflect extent of coronary atherosclerosis and improve correlation with major risk factors.
        Am Heart J. 1990; 119: 1262-1279
        • Garcia-Moll X.
        • Coccolo F.
        • Cole D.
        • et al.
        Serum neopterin and complex stenosis morphology in patients with unstable angina.
        J Am Coll Cardiol. 2000; 35: 956-962
        • Goldstein J.A.
        • Demetriou D.
        • Grines C.L.
        • et al.
        Multiple complex coronary plaques in patients with acute myocardial infarction.
        New Engl J Med. 2000; 343: 915-922
        • Tsimikas S.
        • Witztum J.L.
        Measuring circulating oxidized-low-density lipoprotein to evaluate coronary risk.
        Circulation. 2001; 103: 1930-1932
        • Steinberg D.
        Oxidative modifications of LDL and atherogenesis.
        Circulation. 1997; 95: 1062-1071
        • Madjid M.
        • Awan I.
        • Willerson J.T.
        • et al.
        Leukocyte count and coronary heart disease: implications for risk assessment.
        J Am Coll Cardiol. 2004; 44: 1945-1956
        • Ehara S.
        • Ueda M.
        • Naruko T.
        • et al.
        Pathophysiological role of oxidized-low-density lipoprotein in plaque instability in coronary artery disease.
        J Diab Complicat. 2002; 16: 60-64
        • Alpert J.S.
        • Thygesen K.
        • Antman E.
        • et al.
        Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction.
        J Am Coll Cardiol. 2000; 36 (Erratum in: J Am Coll Cardiol. 2001;37:973): 959-969
        • Dangas G.
        • Mehran R.
        • Wallenstein S.
        • et al.
        Correlation of angiographic morphology and clinical presentation in unstable angina.
        J Am Coll Cardiol. 1997; 29: 519-525
        • Ambrose J.A.
        • Winters S.L.
        • Stern A.
        • et al.
        Angiographic morphology and the pathogenesis of unstable angina.
        J Am Coll Cardiol. 1985; 5: 609-616
        • Meuwissen M.
        • van der Wal A.C.
        • Koch K.T.
        • et al.
        Association between complex coronary artery stenosis and unstable angina and the extent of plaque inflammation.
        Am J Med. 2003; 114: 521-527
        • Katsura M.
        • Forster L.A.
        • Ferns A.A.
        • et al.
        Oxidative modification of low-density lipoprotein by human polymorphonuclear leukocytes to a form recognized by the lipoprotein scavenger pathway.
        Biochem Biophys Acta. 1994; 1213: 231-237
        • Ardans J.A.
        • Economou A.P.
        • Martinson Jr., J.M.
        • et al.
        Oxidized-low-density and high-density lipoproteins regulate the production of matrix metalloproteinase-1 and -9 by activated monocytes.
        J Leukoc Biol. 2002; 71: 1012-1018
        • Maehara A.
        • Mintz G.S.
        • Bui A.B.
        • et al.
        Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound.
        J Am Coll Cardiol. 2002; 40: 904-910
        • Hussain K.M.
        • Gould L.
        • Bharathan T.
        • et al.
        Arteriographic morphology and intracoronary thrombus in patients with unstable angina, non-Q wave myocardial infarction and stable angina pectoris.
        Angiology. 1995; 46: 181-189
        • Burke A.P.
        • Kolodgie F.D.
        • Farb A.
        • et al.
        Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression.
        Circulation. 2001; 103: 934-940