Chronic Chlamydia pneumoniae Infection as a Risk Factor for Coronary Heart Disease in the Helsinki Heart Study

doi:10.1059/0003-4819-116-4-273

Chronic Chlamydia pneumoniae Infection as a Risk Factor for Coronary Heart Disease in the Helsinki Heart Study

Pekka Saikku, MD, PhD;
Maija Leinonen, PhD;
Leena Tenkanen, MSc;
Eila Linnanmäki, MSc;
Marja-Riitta Ekman, MD;
Vesa Manninen, MD, PhD;
Matti Mänttäri, MD, PhD;
M. Heikki Frick, MD, PhD; and
Jussi K. Huttunen, MD, PhD

Abstract

▪ Objective: To investigate in the prospective Helsinki Heart Study, whether chronic Chlamydia pneumoniae infection, indicated by elevated antibody titers against the pathogen, chlamydial lipopolysaccharide-containing immune complexes, or both, is a risk factor for coronary heart disease.

▪ Design and Setting: The Helsinki Heart Study was a randomized, double-blind, 5-year clinical trial to test the efficacy of gemfibrozil in reducing the risk for coronary heart disease. Participants were randomized to receive either gemfibrozil (2046 patients) or placebo (2035 patients). Fatal and nonfatal myocardial infarction and sudden cardiac death were the main study end points. Serum samples were collected at 3-month intervals from all patients.

▪ Patients: One hundred forty cardiac events occurred during the follow-up period. Serum samples from 103 case patients obtained 3 to 6 months before a cardiac end point were matched with those from controls for time point, locality, and treatment. Samples were tested for markers of chronic chlamydial infection.

▪ Measurements: Immunoglobulin A (IgA) and G (IgG) antibodies to C. pneumoniae were measured using the microimmunofluorescence method. Lipopolysaccharide-containing immune complexes were measured using two antigen-specific enzyme immunoassays, the lipopolysaccharide-capture and immunoglobulin M (lgM)-capture methods.

▪ Main Results: Using a conditional logistic regression model, odds ratios for the development of coronary heart disease were 2.7 (95% Cl, 1.1 to 6.5) for elevated lgA titers, 2.1 (Cl, 1.1 to 3.9) for the presence of immune complexes, and 2.9 (Cl, 1.5 to 5.4) for the presence of both factors. If we adjusted for other coronary heart disease risk factors such as age, hypertension, and smoking, the corresponding values would be 2.3 (Cl, 0.9 to 6.2), 1.8 (Cl, 0.9 to 3.6), and 2.6 (Cl, 1.3 to 5.2), respectively.

▪ Conclusion: The results suggest that chronic C. pneumoniae infection may be a significant risk factor for the development of coronary heart disease.

Article and Author Information

From the University of Helsinki, the National Public Health Institute, Helsinki; and the University of Tampere, Tampere, Finland. For current author addresses, see end of text.
Grant Support: By grants from the Medical Council, Academy of Finland, Sigrid Juselius Foundation (P.S.), and the Meilahti Foundation.
Requests for Reprints: Pekka Saikku, MD, PhD, Department of Virology, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland.
Current Author Addresses: Drs. Saikku and Ekman and Ms. Linnanmäki: Department of Virology, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland.

Drs. Leinonen and Huttunen: National Public Health Institute, Mannerheimintie 166, SF 00300 Helsinki, Finland.

Ms. Tenkanen: Department of Public Health, University of Tampere, P.O. Box 607, SF 33101 Tampere, Finland.

Drs. Mänttäri, Manninen, and Frick: First Department of Medicine, Helsinki University Central Hospital, Haartmaninkatu 4, SF-00290 Helsinki, Finland.