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Research Article| Volume 173, ISSUE 2, P337-344, April 2004

Elevated antibody levels against Chlamydia pneumoniae, human HSP60 and mycobacterial HSP65 are independent risk factors in myocardial infarction and ischaemic heart disease

      Abstract

      The relative significance of traditional risk factors, chronic infections and autoimmune processes in the development of acute myocardial infarction (AMI) has not been fully elucidated. We compared serum IgG antibody titres to various pathogens, i.e. Chlamydia pneumoniae (Cpn), cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1), and to the potential autoantigens human heat shock protein 60 (hHSP60) and mycobacterial heat shock protein 65 (mHSP65), in serum samples obtained from patients 3–48 h after AMI (n=40) or stable effort angina (SEA, n=43), and from controls (n=46). The strongest association was observed between AMI and the elevated level of hHSP60 antibodies. The association between AMI and the level of Cpn antibodies was also significant. High levels of hHSP60 and Cpn antibodies represented independent risk factors for the development of AMI, but the simultaneous presence of high levels of antibodies to Cpn and hHSP60 suggested a joint effect on the relative risk of AMI (OR=12.0–21.1). The antibody titres to mHSP65 were higher in the SEA group than in the controls, and the simultaneous presence of high levels of Cpn and mHSP65 antibodies meant an increased risk among the SEA patients. The antibody titres to CMV or HSV-1 were similar in the three groups. In conclusion, these results demonstrate associations of AMI with high levels of anti-hHSP60 and anti-Cpn antibodies, and of SEA with the level of anti-mHSP65 antibodies, these being independent risk factors.

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      References

        • Saikku P
        • Leinonen M
        • Mattila K
        • et al.
        Serologic evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease in acute myocardial infarction.
        Lancet. 1988; 2: 983-986
        • Muhlestein J.B
        • Horne B.D
        • Carlquist J.F
        • et al.
        Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease.
        Circulation. 2000; 102: 1917-1923
        • Kiechl S
        • Egger G
        • Mayr M
        • et al.
        Chronic infections and the risk of carotid atherosclerosis prospective results from a large population study.
        Circulation. 2001; 103: 1064-1070
        • Burian K
        • Kis Z
        • Virok D
        • et al.
        Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis.
        Circulation. 2001; 103: 1503-1508
        • Danesh J
        • Wong Y
        • Ward M
        • et al.
        Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population based study of coronary heart disease.
        Heart. 1999; 81: 245-247
        • Epstein S.E
        • Zhu J
        Lack of association of infectious agents with risk of future myocardial infarction and stroke: definitive evidence disproving the infection/coronary artery disease hypothesis?.
        Circulation. 1999; 100: 1366-1368
        • Zhu J
        • Quyyumi A.A
        • Rott D
        • et al.
        Antibodies to human heat-shock protein 60 are associated with the presence and severity of coronary artery disease. Evidence for an autoimmune component of atherogenesis.
        Circulation. 2001; 103: 1071-1075
        • Xu Q
        • Willeit J
        • Marosi M
        • et al.
        Association of serum antibodies to heat shock protein 65 with carotid atherosclerosis.
        Lancet. 1993; 341: 255-259
        • Xu Q
        • Dietrich H
        • Steiner H.J
        • et al.
        Induction of atherosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65.
        Arterioscler. Thromb. 1992; 12: 789-799
        • George J
        • Shoenfeld Y
        • Afek A
        • et al.
        Enhanced fatty streak formation in C57BL/6J mice by immunization with heat shock protein-65a.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 505-510
        • Huittinen T
        • Leinonen M
        • Tenkanen L
        • et al.
        Autoimmunity to human heat shock protein 60, Chlamydia pneumoniae infection, and inflammation in predicting coronary risk.
        Arterioscler. Thromb. Vasc. Biol. 2002; 22: 431-437
        • Halvorsen D.S
        • Borvik T
        • Njolstad I
        • et al.
        Chlamydia pneumoniae IgA- and IgG antibodies in young survivers of myocardial infarction. A comparison of antibody detection by a microimmunofluorescence test and an enzyme immunoassay.
        J. Int. Med. 2002; 251: 142-147
        • Siscovick D.S
        • Schwartz S.M
        • Corey L
        • et al.
        Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults: the Cardiovascular Health Study.
        Circulation. 2000; 102: 2335-2340
        • Gattone M
        • Iacoviello L
        • Colombo M
        • et al.
        Chlamydia pneumoniae and cytomegalovirus seropositivity, inflammatory markers, and the risk of myocardial infarction at a young age.
        Am. Heart J. 2001; 142: 633-640
        • Roivainen M
        • Viik-Kajander M
        • Palosuo T
        • et al.
        Infections, inflammation, and the risk of coronary heart disease.
        Circulation. 2000; 101: 252-257
        • Zhu J
        • Nieto F.J
        • Horne B.D
        • et al.
        Prospective study of pathogen burden and risk of myocardial infarction or death.
        Circulation. 2001; 103: 45-51
        • Rupprecht H.J
        • Blankenberg S
        • Bickel C
        • et al.
        Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease.
        Circulation. 2001; 104: 25-31
        • Ridker P.M
        • Kundsin R.B
        • Stampfer M.J
        • et al.
        Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction.
        Circulation. 1999; 99: 1161-1164
        • Haider A.W
        • Wilson P.W
        • Larson M.G
        • et al.
        The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease. A prospective study.
        J. Am. Coll. Cardiol. 2002; 40: 1408-1413
        • Veres A
        • Fust G
        • Smieja M
        • et al.
        Relationship of anti-60 kDa heat shock protein and anti-cholesterol antibodies to cardiovascular events.
        Circulation. 2002; 106: 2775-2780
        • Hoppichler F
        • Lechleiter M
        • Traweger C
        • et al.
        Changes of serum antibodies to heat-shock protein 65 in coronary heart disease and acute myocardial infarction.
        Atherosclerosis. 1996; 126: 333-338
        • Prohaszka Z
        • Duba J
        • Lakos G
        • et al.
        Antibodies against human hsp60 and mycobacterial hsp65 differ in their antigen specificity and complement activating ability.
        Int. Immunol. 1999; 11: 1363-1370
        • Tanonaka K
        • Yoshida H
        • Toga W
        • et al.
        Myocardial heat shock proteins during the development of heart failure.
        Biochem. Biophys. Res. Commun. 2001; 283: 520-525
        • Schett G
        • Metzler B
        • Kleindienst R
        • et al.
        Myocardial injury leads to a release of heat shock protein (hsp) 60 and a suppression of the anti-hsp65 immune response.
        Cardiovasc. Res. 1999; 42: 685-695
        • Mahdi O.S
        • Horne B.D
        • Mullen K
        • et al.
        Serum immunoglobulin G antibodies to chlamydial heat shock protein 60 but to human and bacterial homologs are associated with coronary artery disease.
        Circulation. 2002; 106: 1659-1663
        • Mayr M
        • Metzler B
        • Kiechl S
        • et al.
        Endothelial cytotoxicity mediated by serum antibodies to heat shock proteins of Escherichia coli and Chlamydia pneumoniae: immune reactions to heat shock proteins as a possible link between infection and atherosclerosis.
        Circulation. 1999; 99: 1560-1566