This Article Full Text Full Text (PDF) All Versions of this Article: 107/20/2566    most recent 01.CIR.0000068338.17948.22v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huittinen, T. Articles by Saikku, P. Search for Related Content PubMed PubMed Citation Articles by Huittinen, T. Articles by Saikku, P. Pubmed/NCBI databases Substance via MeSH Related Collections Risk Factors

(Circulation. 2003;107:2566.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Synergistic Effect of Persistent Chlamydia pneumoniae Infection, Autoimmunity, and Inflammation on Coronary Risk

Tiina Huittinen, MSc; Maija Leinonen, PhD; Leena Tenkanen, PhD; Hanna Virkkunen, MSc; Matti Mänttäri, MD, FESC; Timo Palosuo, MD, PhD; Vesa Manninen, MD, PhD; Pekka Saikku, MD, PhD

From the National Public Health Institute, Oulu (T.H., M.L.) and Helsinki (T.P.); the Helsinki Heart Study (L.T., H.V.) and the Department of Medicine, Helsinki University Central Hospital (M.M., V.M.), Helsinki; and the Department of Medical Microbiology, University of Oulu, Oulu (P.S.), Finland.

Correspondence to Tiina Huittinen, National Public Health Institute, Aapistie 1, PO box 310, FIN-90101 Oulu, Finland. E-mail tiina.huittinen{at}ktl.fi

Background— Given the role of chronic infections, autoimmunity, and inflammation in atherosclerosis, we studied the joint effect of chronic Chlamydia pneumoniae infection, persistently elevated human heat-shock protein 60 (hHsp60) antibodies, and C-reactive protein (CRP) on coronary risk.

Methods and Results— The participants for this prospective nested case-control study were obtained from the Helsinki Heart Study, during which 241 nonfatal myocardial infarctions or coronary deaths occurred among 4081 dyslipidemic middle-aged men. Serum samples taken at baseline and 3 to 6 months before the coronary events that occurred during the 8.5-year period were analyzed for antibodies to C pneumoniae and hHsp60 and the CRP concentration. Compared with persistently low levels, the risk of coronary events was 2-fold for persistently elevated immunocomplex (IC)-bound and/or serum IgA antibodies to C pneumoniae (OR, 1.96; 95% CI, 1.14 to 3.36) and also for serum IgA antibodies to hHsp60 (OR, 2.11; 95% CI, 1.08 to 4.13). The risks associated with elevated antibodies were much higher when CRP was also elevated. Compared with low or transiently elevated levels, the risk of coronary events, with adjustment for age and smoking, was 4.5-fold for persistently elevated CRP and C pneumoniae IC/IgA antibodies together (OR, 4.47; 95% CI, 1.84 to 10.83) and was similar for CRP and hHsp60 IgA antibodies together (OR, 4.36; 95% CI, 1.53 to 12.39).

Conclusions— Persistently but not transiently elevated C pneumoniae IC/IgA and hHsp60 IgA antibodies, especially when present together with an elevated CRP level, predicted coronary events.

Key Words: coronary disease • risk factors • infection • inflammation

This article has been cited by other articles:

				I. Volanen, K. Kallio, M. Saarinen, M. J. Jarvisalo, R. Vainionpaa, T. Ronnemaa, J. Viikari, J. Marniemi, O. Simell, and O. T. Raitakari Arterial Intima-Media Thickness in 13-Year-Old Adolescents and Previous Antichlamydial Antimicrobial Use: A Retrospective Follow-up Study Pediatrics, September 1, 2008; 122(3): e675 - e681. [Abstract] [Full Text] [PDF]

				A. Palikhe, M.-L. Lokki, P. Saikku, M. Leinonen, M. Paldanius, M. Seppanen, V. Valtonen, M. S. Nieminen, and J. Sinisalo Association of Chlamydia pneumoniae Infection with HLA-B*35 in Patients with Coronary Artery Disease Clin. Vaccine Immunol., January 1, 2008; 15(1): 55 - 59. [Abstract] [Full Text] [PDF]

				H. K. Park, E.-C. Park, S. W. Bae, M. Y. Park, S. W. Kim, H. S. Yoo, M. Tudev, Y. H. Ko, Y.-H. Choi, S. Kim, et al. Expression of Heat Shock Protein 27 in Human Atherosclerotic Plaques and Increased Plasma Level of Heat Shock Protein 27 in Patients With Acute Coronary Syndrome Circulation, August 29, 2006; 114(9): 886 - 893. [Abstract] [Full Text] [PDF]

				I. Volanen, M. J. Jarvisalo, R. Vainionpaa, M. Arffman, K. Kallio, S. Angle, T. Ronnemaa, J. Viikari, J. Marniemi, O. T. Raitakari, et al. Increased Aortic Intima-Media Thickness in 11-Year-Old Healthy Children With Persistent Chlamydia pneumoniae Seropositivity Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 649 - 655. [Abstract] [Full Text] [PDF]

				Q. Xiao, K. Mandal, G. Schett, M. Mayr, G. Wick, F. Oberhollenzer, J. Willeit, S. Kiechl, and Q. Xu Association of Serum-Soluble Heat Shock Protein 60 With Carotid Atherosclerosis: Clinical Significance Determined in a Follow-Up Study Stroke, December 1, 2005; 36(12): 2571 - 2576. [Abstract] [Full Text] [PDF]

				D H Birnie, L E Vickers, W S Hillis, J Norrie, and S M Cobbe Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain Heart, September 1, 2005; 91(9): 1148 - 1153. [Abstract] [Full Text] [PDF]

				M. Paldanius, A. Bloigu, M. Alho, M. Leinonen, and P. Saikku Prevalence and Persistence of Chlamydia pneumoniae Antibodies in Healthy Laboratory Personnel in Finland Clin. Vaccine Immunol., May 1, 2005; 12(5): 654 - 659. [Abstract] [Full Text] [PDF]

				R. Mitusch, J. Luedemann, W. G. Wood, K. Berger, U. Schminke, M. Suter, C. Kessler, U. John, J. Rupp, M. Kentsch, et al. Asymptomatic Carotid Atherosclerosis Is Associated With Circulating Chlamydia pneumoniae DNA in Younger Normotensive Subjects in a General Population Survey Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 386 - 391. [Abstract] [Full Text] [PDF]

				B. Ludewig, P. Krebs, and E. Scandella Immunopathogenesis of atherosclerosis J. Leukoc. Biol., August 1, 2004; 76(2): 300 - 306. [Abstract] [Full Text] [PDF]

				D. Sander, K. Winbeck, J. Klingelhofer, T. Etgen, and B. Conrad Progression of Early Carotid Atherosclerosis Is Only Temporarily Reduced After Antibiotic Treatment of Chlamydia pneumoniae Seropositivity Circulation, March 2, 2004; 109(8): 1010 - 1015. [Abstract] [Full Text] [PDF]