(Circulation. 1995;91:23-27.)
© 1995 American Heart Association, Inc.
Articles |
Anti-Cardiolipin Antibodies and Risk of Myocardial Infarction in a Prospective Cohort of Middle-Aged Men
From the National Public Health Institute (O.V., M.P., K.A., T.P.); and the First Department of Medicine (M.M., V.M., L.T.), University of Helsinki, Finland.
Correspondence to Outi Vaarala, MD, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
Background Data concerning the relation between anti-phospholipid (aPL) antibodies and myocardial infarction in subjects without evidence of overt autoimmune disease are conflicting. All published studies have been performed on survivors of myocardial infarction or in patients with established coronary heart disease. The purpose of the present study was to determine whether the presence of aPL antibodies, namely, anti-cardiolipin (aCL) antibodies, carries a risk for myocardial infarction in a prospective cohort.
Methods and Results The sera to be studied were drawn at
entry from middle-aged dyslipidemic men (non–high-density lipoprotein
cholesterol, 
5.2 mmol/L) participating in the Helsinki Heart Study, a
5-year coronary primary prevention trial with gemfibrozil. Samples were
tested for IgG-class antibodies to cardiolipin by an ELISA. The risk
was estimated with logistic regression analysis using a nested
case-control design with 133 patients (myocardial infarction or cardiac
death) and 133 control subjects, matched for treatment
(gemfibrozil/placebo) and geographical area. The aCL antibody level, as
expressed in optical density units, was significantly higher in
patients than in control subjects (0.417 versus 0.361;
P<.005). Subjects with the antibody level in the highest
quartile of distribution had a relative risk for myocardial infarction
of 2.0 (95% confidence interval, 1.1 to 3.5) compared with the
remainder of the population. This risk was independent of confounding
factors, such as age, smoking, systolic blood pressure, low-density
lipoprotein (LDL), and high-density lipoprotein. There was a
correlation between the levels of aCL antibodies and antibodies to
oxidized LDL (r=.40, P<.001), and their joint
effect was additive for the risk.
Conclusions In a prospective cohort of healthy middle-aged men, the presence of a high aCL antibody level is an independent risk factor for myocardial infarction or cardiac death. Antibodies to cardiolipin and oxidized LDL may, at least in part, represent cross-reactive antibody populations.
Key Words: lipoproteins • antibodies • thrombosis • infarction
This article has been cited by other articles:
 |
|
 |
|
  J. Su, X. Hua, H. Concha, E. Svenungsson, A. Cederholm, and J. Frostegard Natural antibodies against phosphorylcholine as potential protective factors in SLE Rheumatology, August 1, 2008; 47(8): 1144 - 1150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Frostegard Systemic lupus erythematosus and cardiovascular disease Lupus, May 1, 2008; 17(5): 364 - 367. [Abstract] [PDF]
|
|
|
|
 |
|
 Wei Hsi Chen, Hung Sheng Lin, Yi Fen Kao, Min Yu Lan, and Jia Shou Liu Hyperhomocysteinemia Relates to the Subtype of Antiphospholipid Antibodies in Non-SLE Patients Clinical and Applied Thrombosis/Hemostasis, October 1, 2007; 13(4): 398 - 403. [Abstract] [PDF]
|
|
|
|
|
|
C. Christodoulou, S. Sangle, and D. P. D'Cruz Vasculopathy and arterial stenotic lesions in the antiphospholipid syndrome Rheumatology, June 1, 2007; 46(6): 907 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sherer, R. Gerli, B. Gilburd, E. Bartoloni Bocci, G. Vaudo, E. Mannarino, and Y. Shoenfeld Thickened carotid artery intima-media in rheumatoid arthritis is associated with elevated anticardiolipin antibodies Lupus, April 1, 2007; 16(4): 259 - 264. [Abstract] [PDF]
|
|
|
|
|
|
I. N. Bruce 'Not only...but also': factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus Rheumatology, December 1, 2005; 44(12): 1492 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shoenfeld, R. Gerli, A. Doria, E. Matsuura, M. M. Cerinic, N. Ronda, L. J. Jara, M. Abu-Shakra, P. L. Meroni, and Y. Sherer Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases Circulation, November 22, 2005; 112(21): 3337 - 3347. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Feinbloom and K. A. Bauer Assessment of Hemostatic Risk Factors in Predicting Arterial Thrombotic Events Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2043 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Frostegard Atherosclerosis in Patients With Autoimmune Disorders Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1776 - 1785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kahles, M. Humpich, H. Steinmetz, M. Sitzer, and E. Lindhoff-Last Phosphatidylserine IgG and beta-2-glycoprotein I IgA antibodies may be a risk factor for ischaemic stroke Rheumatology, September 1, 2005; 44(9): 1161 - 1165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Turiel, P. Sarzi-Puttini, R. Peretti, E. Rossi, F. Atzeni, W. Parsons, and A. Doria Thrombotic Risk Factors In Primary Antiphospholipid Syndrome: A 5-Year Prospective Study Stroke, July 1, 2005; 36(7): 1490 - 1494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jimenez, M. A. Garcia-Criado, D. Tassies, J. C. Reverter, R. Cervera, M. R. Gilabert, D. Zambon, E. Ros, C. Bru, and J. Font Preclinical vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome Rheumatology, June 1, 2005; 44(6): 756 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cederholm, E. Svenungsson, K. Jensen-Urstad, C. Trollmo, A.-K. Ulfgren, J. Swedenborg, G.-Z. Fei, and J. Frostegard Decreased Binding of Annexin V to Endothelial Cells: A Potential Mechanism in Atherothrombosis of Patients With Systemic Lupus Erythematosus Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 198 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. N Bruce Coronary heart disease (CHD) in lupus: round up the usual suspects? Lupus, August 1, 2004; 13(8): 557 - 560. [PDF]
|
|
|
|
|
|
M. A. Ozturk, I. C. Haznedaroglu, M. Turgut, and H. Goker Current Debates in Antiphospholipid Syndrome: The Acquired Antibody-Mediated Thrombophilia Clinical and Applied Thrombosis/Hemostasis, April 1, 2004; 10(2): 89 - 126. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Schattner and M. H. Liang The Cardiovascular Burden of Lupus: A Complex Challenge Arch Intern Med, July 14, 2003; 163(13): 1507 - 1510. [Full Text] [PDF]
|
|
|
|
|
|
R L Brey, J Chapman, S R Levine, G Ruiz-Irastorza, R H. Derksen, M Khamashta, and Y Shoenfeld Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002 Lupus, July 1, 2003; 12(7): 508 - 513. [Abstract] [PDF]
|
|
|
|
|
|
P. G. Vlachoyiannopoulos, P. G. Kanellopoulos, J. P. A. Ioannidis, M. G. Tektonidou, I. Mastorakou, and H. M. Moutsopoulos Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study Rheumatology, May 1, 2003; 42(5): 645 - 651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Galli, D. Luciani, G. Bertolini, and T. Barbui Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature Blood, March 1, 2003; 101(5): 1827 - 1832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. A. Ioannidis, G. E. Katsifis, E. D. Stavropoulos, M. N. Manoussakis, and H. M. Moutsopoulos Evaluation of the association of autoantibodies with mortality in the very elderly: a cohort study Rheumatology, February 1, 2003; 42(2): 357 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. L Ruberg and J. Loscalzo Prothrombotic determinants of coronary atherothrombosis Vascular Medicine, November 1, 2002; 7(4): 289 - 299. [Abstract] [PDF]
|
|
|
|
 |
|
 J. K. Pai, G. C. Curhan, C. C. Cannuscio, N. Rifai, P. M. Ridker, and E. B. Rimm Stability of Novel Plasma Markers Associated with Cardiovascular Disease: Processing within 36 Hours of Specimen Collection Clin. Chem., October 1, 2002; 48(10): 1781 - 1784. [Full Text] [PDF]
|
|
|
|
|
|
R. L. Brey, C. L. Stallworth, D. L. McGlasson, M. A. Wozniak, R. J. Wityk, B. J. Stern, M. A. Sloan, R. Sherwin, T. R. Price, R. F. Macko, et al. Antiphospholipid Antibodies and Stroke in Young Women * Editorial Comment Stroke, October 1, 2002; 33(10): 2396 - 2401. [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]
|
|
|
|
|
|
D. Erkan, Y. Yazici, M. G. Peterson, L. Sammaritano, and M. D. Lockshin A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome Rheumatology, August 1, 2002; 41(8): 924 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Levine, D. W. Branch, and J. Rauch The Antiphospholipid Syndrome N. Engl. J. Med., March 7, 2002; 346(10): 752 - 763. [Full Text] [PDF]
|
|
|
|
 |
|
 Y Sherer and Y Shoenfeld Atherosclerosis Ann Rheum Dis, February 1, 2002; 61(2): 97 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Svenungsson, K. Jensen-Urstad, M. Heimburger, A. Silveira, A. Hamsten, U. de Faire, J. L. Witztum, and J. Frostegard Risk Factors for Cardiovascular Disease in Systemic Lupus Erythematosus Circulation, October 16, 2001; 104(16): 1887 - 1893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Brey, R. D. Abbott, J. D. Curb, D. S. Sharp, G. W. Ross, C. L. Stallworth, and S. J. Kittner {beta}2-Glycoprotein 1-Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction: The Honolulu Heart Program Stroke, August 1, 2001; 32(8): 1701 - 1706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pratico, R. K. Tangirala, S. Horkko, J. L. Witztum, W. Palinski, and G. A. FitzGerald 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 Blood, January 15, 2001; 97(2): 459 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mustafa, S. Nityanand, L. Berglund, H. Lithell, and A. K. Lefvert Circulating Immune Complexes in 50-Year-Old Men as a Strong and Independent Risk Factor for Myocardial Infarction Circulation, November 21, 2000; 102(21): 2576 - 2581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bili, A. J. Moss, C. W. Francis, W. Zareba, L. F. M. Watelet, I. Sanz, f. t. T. Factors, and R. C. E. Investigators Anticardiolipin Antibodies and Recurrent Coronary Events : A Prospective Study of 1150 Patients Circulation, September 12, 2000; 102(11): 1258 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ahmed, B. Stegmayr, J. Trifunovic, L. Weinehall, G. Hallmans, and A. K. Lefvert Anticardiolipin Antibodies Are Not an Independent Risk Factor for Stroke : An Incident Case-Referent Study Nested Within the MONICA and Vasterbotten Cohort Project Stroke, June 1, 2000; 31(6): 1289 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J G Hanly and S A Smith Autoimmune antiphospholipid antibodies and cryoglobulinemia Lupus, May 1, 2000; 9(4): 264 - 270. [Abstract] [PDF]
|
|
|
|
|
|
S. MANZI, M. C. M WASKO, and S. MANZI Inflammation-mediated rheumatic diseases and atherosclerosis Ann Rheum Dis, May 1, 2000; 59(5): 321 - 325. [Full Text]
|
|
|
|
|
|
S. Manzi Systemic lupus erythematosus: a model for atherogenesis? Rheumatology, April 1, 2000; 39(4): 353 - 359. [Full Text] [PDF]
|
|
|
|
|
|
S Manzi, L H Kuller, D Edmundowicz, and K Sutton-Tyrrell Vascular imaging: changing the face of cardiovascular research Lupus, March 1, 2000; 9(3): 176 - 182. [Abstract] [PDF]
|
|
|
|
|
|
A. T. Erkkila, O. Narvanen, S. Lehto, M. I. J. Uusitupa, and S. Yla-Herttuala Autoantibodies Against Oxidized Low-Density Lipoprotein and Cardiolipin in Patients With Coronary Heart Disease Arterioscler. Thromb. Vasc. Biol., January 1, 2000; 20(1): 204 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. G. Rennke and M. Laposata Case 18-1999- A 54-Year-Old Woman with Acute Renal Failure and Thrombocytopenia N. Engl. J. Med., June 17, 1999; 340(24): 1900 - 1908. [Full Text] [PDF]
|
|
|
|
|
|
D. Pratico, D. Ferro, L. Iuliano, J. Rokach, F. Conti, G. Valesini, G. A. FitzGerald, and F. Violi Ongoing Prothrombotic State in Patients With Antiphospholipid Antibodies: A Role for Increased Lipid Peroxidation Blood, May 15, 1999; 93(10): 3401 - 3407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Harats, J. George, Y. Levy, M.A. Khamashta, G.R.V. Hughes, and Y. Shoenfeld Atheroma: links with antiphospholipid antibodies, Hughes syndrome and lupus QJM, January 1, 1999; 92(1): 57 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Lehtimaki, S. Lehtinen, T. Solakivi, M. Nikkila, O. Jaakkola, H. Jokela, S. Yla-Herttuala, J. S. Luoma, T. Koivula, and T. Nikkari Autoantibodies Against Oxidized Low Density Lipoprotein in Patients With Angiographically Verified Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., January 1, 1999; 19(1): 23 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tanne, D. A. Triplett, and S. R. Levine Antiphospholipid-Protein Antibodies and Ischemic Stroke : Not Just Cardiolipin Any More Stroke, September 1, 1998; 29(9): 1755 - 1758. [Full Text] [PDF]
|
|
|
|
|
|
P. T. Kovanen, M. Manttari, T. Palosuo, V. Manninen, and K. Aho Prediction of Myocardial Infarction in Dyslipidemic Men by Elevated Levels of Immunoglobulin Classes A, E, and G, but Not M Arch Intern Med, July 13, 1998; 158(13): 1434 - 1439. [Abstract] [Full Text]
|
|
|
|
|
|
L. Iuliano, D. Pratico, D. Ferro, V. Pittoni, G. Valesini, J. Lawson, G. A. FitzGerald, and F. Violi Enhanced Lipid Peroxidation in Patients Positive for Antiphospholipid Antibodies Blood, November 15, 1997; 90(10): 3931 - 3935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wu, S. Nityanand, L. Berglund, H. Lithell, G. Holm, and A. K. Lefvert Antibodies Against Cardiolipin and Oxidatively Modified LDL in 50-Year-Old Men Predict Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 3159 - 3163. [Abstract] [Full Text]
|
|
|
|
|
|
A. P. Burke, A. Farb, G. T. Malcom, Y.-h. Liang, J. Smialek, and R. Virmani Coronary Risk Factors and Plaque Morphology in Men with Coronary Disease Who Died Suddenly N. Engl. J. Med., May 1, 1997; 336(18): 1276 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. George and Y. Shoenfeld The anti-phospholipid (Hughes) syndrome: a crossroads of autoimmunity and atherosclerosis Lupus, January 1, 1997; 6(7): 559 - 560. [PDF]
|
|
|
|
|
|
J. George, A. Afek, B. Gilburd, Y. Levy, M. Blank, J. Kopolovic, D. Harats, and Y. Shoenfeld Atherosclerosis in LDL-receptor knockout mice is accelerated by immunization with anticardiolipin antibodies Lupus, January 1, 1997; 6(9): 717 - 729. [Abstract] [PDF]
|
|
|
|
|
|
S. S. Pierangeli, X. W. Liu, G. Anderson, J.H. Barker, and E.N. Harris Thrombogenic Properties of Murine Anti-Cardiolipin Antibodies Induced by ß2 Glycoprotein 1 and Human Immunoglobulin G Antiphospholipid Antibodies Circulation, October 1, 1996; 94(7): 1746 - 1751. [Abstract] [Full Text]
|
|
|
|
|
|
M. Hojnik, J. George, L. Ziporen, and Y. Shoenfeld Heart Valve Involvement (Libman-Sacks Endocarditis) in the Antiphospholipid Syndrome Circulation, April 15, 1996; 93(8): 1579 - 1587. [Abstract] [Full Text]
|
|