We recognize that weaknesses of our study were its small size and cross-sectional design. Further, although race did not significantly differ between cases and controls, nonwhite race was more common in patients and may have confounded our results. Our study also had strengths. Because our case and control selection was embedded in a large study of preeclampsia, we were able to approach a large proportion of eligible women. Thus, selection of cases and controls was relatively unbiased. That the prevalence of C pneumoniae in this study is similar to that seen in young adults in Europe reassures us as to the generalizability of our finding.32 Further, we used a rigorous case definition for preeclampsia and well-established methods for the serological detection of C pneumoniae. However, based on this single report in a modest-sized sample, it would be premature to consider our observed link between C pneumoniae and preeclampsia to be other than an association in need of replication.
1. Lie JT. Atherosclerosis—pathology of coronary artery disease. In: Giuliani ER, Fuster V, Gersh BJ, McGoon MD, McGoon DC, eds. Cardiology: Fundamentals and practice. St. Louis: Mosby Year Book, 1987:1211–31.
2. Ridker PM, Hennekens CH, Buring JE, Rifai N. C reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836–43.
3. Redman CW, Sacks GP, Sargent IL. Preeclampsia: An excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999;180:499–506.
4. Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:5–15.
5. Kuo C-C, Campbell LA. Detection of Chlamydia pneumoniae
in arterial tissue. J Infect Dis 2000;181: Suppl 3S432–6.
6. Moazed TC, Campbell LA, Rosenfeld ME, Grayston JT, Kuo CC. Chlamydia pneumoniae
infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. J Infect Dis 1999;180:238–41.
7. Hu H, Pierce GN, Zhang G. Atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae
. J Clin Invest 1999;103:747–53.
8. Fong IW, Chiu B, Viira E, Fong MW, Jang D, Mahony J. Rabbit model for Chlamydia pneumoniae
infection. J Clin Microbiol 1997;35:48–52.
9. Saiku P, Leinonen M, Mattila K, Ekman MR, Nieminen MS, Makela PH, et al. Serological evidence of an association of a novel chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988;2:983–6.
10. Thom DH, Grayston ST, Sisovick DS, Wang SP, Weiss NS, Daling JR. Association of prior infection with Chlamydia pneumoniae
and angiographically demonstrated coronary artery disease. JAMA 1992;268:68–72.
11. Melnick SL, Shahar E, Folsom SR, Grayston JT, Sorlie PD, Wang SP, et al. Past infection by Chlamydia pneumoniae
strain TWAR and asymptomatic carotid atherosclerosis. Atherosclerosis Risk in Communities (ARIC) study investigators. Am J Med 1993;95:499–504.
12. Saikku P, Leinonen M, Tenkanen L, Linnanmaki E, Ekman MR, Manninen V, et al. Chronic Chlamydia pneumoniae
infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann Intern Med 1992;116:273–8.
13. Ridker PM, Kundsin RB, Stampfer MJ, Poulin S, Hennekens CH. Prospective study of Chlamydia pneumoniae
IgG seropositivity and risks of future myocardial infarction. Circulation 1999;99:1161–4.
14. Nieto FJ, Folsom AR, Sorlie PD, Grayston JT, Wang SP, Chambless LE. Chlamydia pneumoniae
infection and incident coronary heart disease: The Atherosclerosis Risk in Communities Study. Am J Epidemiol 1999;150:149–56.
15. Strachan DP, Carrington D, Mendall MA, Ballam L, Morris J, Butland BK, et al. Relation of Chlamydia pneumoniae
serology to mortality and incidence of ischaemic heart disease over 13 years in the Caerphilly prospective heart disease study. BMJ 1999;318:1035–40.
16. Ostergaard L, Sorensen HT, Lindholt J, Sorensen TE, Pedersen L, Eriksen T, et al. Risk of hospitalization for cardiovascular disease after use of macrolides and penicillins: A comparative prospective cohort study. J Infect Dis 2001;183:1625–30.
17. Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm AJ. Elevated Chlamydia pneumoniae
antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 1997;96:404–7.
18. Gurfinkel E, Bozovich G, Daroca A, Beck E, Mautner B. Randomized trial of roxithromycin in non-Q-wave coronary syndromes: Roxis Pilot Study. Roxis Study Group. Lancet 1997;350:404–7.
19. Teppa RJ, Ness RB, Crombleholme WR, Roberts JM. Free leptin is increased in normal pregnancy and further increased in preeclampsia. Metabolism 2000;49:1043–8.
20. National High Blood Pressure Education Program Working Group. Report on high blood pressure in pregnancy. Am J Obstet Gynecol 1990;163:1689–712.
21. Grayston JT, Kuo CC, Wang SP, Altman J. A new Chlamydia psittaci
strain, TWAR, isolated in acute respiratory tract infections. N Engl J Med 1986;315:161–8.
22. Wang S-P. The microimmunofluorescence test for Chlamydia pneumoniae
infection: Technique and interpretation. J Infect Dis 2000;181:S421–5.
23. Fong IW. Antibiotics effects in a rabbit model of Chlamydia pneumoniae
-induced athersclerosis. J Infect Dis 2000;181: Suppl 3S514–8.
24. Siscovick DS, Schwartz SM, Caps M, Wang SP, Grayston JT. Chlamydia pneumoniae and atherosclerotic risk in populations: The role of seroepidemiology. J Infect Dis 2000;181: Suppl 3417–20.
25. Herrera JA, Chaudhuri G, Lopez-Jaramillo P. Is infection a major risk factor for preeclampsia? Med Hypotheses 2001; 57:393–7.
26. Roberts JM, Cooper DW. Pathogenesis and genetics of preeclampsia. Lancet 2001;357:53–6.
27. Meekins JW, Pijnenborg R, Hanssens M, McFadyen IR, van Asshe A. A study of placental bed spiral arteries and trophoblast invasion in normal and severe preeclamptic pregnancies. Br J Obstet Gynaecol 1994;101:669–74.
28. Wick G, Perschinka H, Millonig G. Atherosclerosis as an autoimmune disease: An update. Trends Immunol 2001; 22:665–8.
29. Ness RB, Roberts JM. Heterogeneous causes constituting the single syndrome of preeclampsia: A hypothesis and its implications. Am J Obstet Gynecol 1996;175:1365–70.
30. Christen S, Hagen TM, Shigenaga MK, Ames BN. Chronic inflammation, mutation, and cancer. In: Parsonnet J, ed. Microbes and malignancy. New York: Oxford University Press, 1999:35–88.
31. Kiechl S, Lorenz E, Reindl M, Wiedermann CJ, Oberhollenzer F, Bonora E, et al. Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 2002;347:185–92.
32. Ferrari M, Poli A, Olivieri M, Tardivo S, Biasin C, Balestreri F, et al. Seroprevalence of Chlamydia pneumoniae antibodies in a young adult population sample living in Verona. European Community Respiratory Health Survey (ECRHS) Verona. Infection 2000; 28:38–41.