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Chlamydia pneumoniae and Atherosclerosis following Carotid Endarterectomy

Published online by Cambridge University Press:  02 December 2014

Babak S. Jahromi
Affiliation:
Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, ON Section of Neurosurgery, University of Chicago, Chicago IL USA
Michael D. Hill
Affiliation:
Pathology, St. Michael's Hospital, University of Toronto, Toronto, ON Department of Clinical Neurosciences, University of Calgary, Calgary, AB
Kate Holmes
Affiliation:
Department of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, ON
Stuart Hutchison
Affiliation:
Department of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, ON
William S. Tucker
Affiliation:
Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, ON
Brian Chiu
Affiliation:
Pathology, St. Michael's Hospital, University of Toronto, Toronto, ON Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada
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Abstract

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Background:

Seroepidemiological studies have shown an association between raised antibody titres against Chlamydia pneumoniae, and carotid atherosclerosis or stroke. However, direct evidence for a causal link between arterial infection with C. pneumoniae and carotid disease remains weak. We hypothesized that long-term follow-up of patients with pathologically-proven arterial C. pneumoniae infection might provide further insight into the role of C. pneumoniae in carotid atherosclerosis.

Methods:

We followed a cohort of 70 carotid endarterectomy patients for ipsilateral restenosis, contralateral progression, and all-cause mortality (four year median follow-up period). All patients had presence or absence of C. pneumoniae in their carotid plaques documented by immunohistochemistry after endarterectomy. A survival function was generated and the log-rank test was used to assess the difference in survival between subjects with and without documented chlamydial infection in their plaque.

Results:

Baseline demographic and cardiovascular risk factors were similar between the two groups, and survival analysis demonstrated no difference (p>0.05) in all-cause mortality, or all-cause mortality combined with restenosis and progression.

Conclusion:

Our data finds no causal role for C. pneumoniae in restenosis or progression of carotid disease or mortality in this patient population with advanced carotid atherosclerosis.

Résumé:

RÉSUMÉ:Introduction:

Des études séroépidémiologiques ont montré une association entre un taux élevé d'anticorps contre C. pneumoniae et l'athérosclérose carotidienne ou l'accident vasculaire cérébral. Cependant, les preuves directes qu'il existe un lien causal entre l'infection artérielle à C. pneumoniae et la maladie carotidienne demeurent faibles. Nous avons émis l'hypothèse que le suivi à long terme de patients porteurs d'une infection artérielle à C. pneumoniae prouvée en anatomopathologie pourrait fournir d'autres indices sur le rôle de C. pneumoniae dans l'athérosclérose carotidienne.

Méthodes:

Nous avons suivi une cohorte de 70 patients ayant subi une endartérectomie carotidienne, pour resténose ipsilatérale, progression contralatérale et mortalité toute cause (suivi médian de quatre ans). Chez tous les patients, la présence ou l'absence de C. pneumoniae dans les plaques carotidiennes a été documenté par immunohistochimie après l'endartérectomie. La différence dans la survie entre les sujets avec et sans infection à C. pneumoniae dans leurs plaques a été évaluée en générant une fonction de survie et en utilisant le test du log-rank.

Résultats:

Les données démographiques et les facteurs de risque étaient similaires entre les deux groupes et l'analyse de survie n'a pas montré de différence (p > 0,05) dans la mortalité toute cause ou la mortalité toute cause combinée à la resténose et à la progression.

Conclusions:

Nos données ne sont pas en faveur d'un rôle causal de C. pneumoniae dans la resténose ou la progression de la maladie carotidienne ou dans la mortalité dans cette population de patients porteurs d'athérosclérose carotidienne sévère.

Type
Research Article
Copyright
Copyright © The Canadian Journal of Neurological 2003

References

1. Saikku, P, Leinonen, M, Mattila, K, et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988;2:983986.Google Scholar
2. Jackson, LA, Campbell, LA, Schmidt, RA, et al. Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma: evaluation of the innocent bystander hypothesis. Am J Pathol 1997;150:1785-–790.Google Scholar
3. Vink, A, Poppen, M, Schoneveld, AH, et al. Distribution of Chlamydia pneumoniae in the human arterial system and its relation to the local amount of atherosclerosis within the individual. Circulation 2001;103:16131617.Google Scholar
4. Melnick, SL, Shahar, E, Folsom, AR, et al. Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Am J Med 1993;95:499504.Google Scholar
5. Espinola-Klein, C, Rupprecht, HJ, Blankenberg, S, et al. Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection? Stroke 2000;31:21272133.Google Scholar
6. Schmidt, C, Hulthe, J, Wikstrand, J, et al. Chlamydia pneumoniae seropositivity is associated with carotid artery intima-media thickness. Stroke 2000;31:15261531.Google Scholar
7. Kawamoto, R, Doi, T, Tokunaga, H, Konishi, I. An association between an antibody against Chlamydia pneumoniae and common carotid atherosclerosis. Intern Med 2001;40:208213.CrossRefGoogle ScholarPubMed
8 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;103:10641070.CrossRefGoogle ScholarPubMed
9. Sander, D, Winbeck, K, Klingelhofer, J, Etgen, T, Conrad, B. Enhanced progression of early carotid atherosclerosis is related to Chlamydia pneumoniae (Taiwan acute respiratory) seropositivity. Circulation 2001;103:13901395.Google Scholar
10. Wimmer, ML, Sandmann-Strupp, R, Saikku, P, Haberl, RL. Association of chlamydial infection with cerebrovascular disease. Stroke 1996;27:22072210.Google Scholar
11. Cook, PJ, Honeybourne, D, Lip, GY, et al. Chlamydia pneumoniae antibody titers are significantly associated with acute stroke and transient cerebral ischemia: the West Birmingham Stroke Project. Stroke 1998;29:404410.Google Scholar
12. Fagerberg, B, Gnarpe, J, Gnarpe, H, Agewall, S, Wikstrand, J. Chlamydia pneumoniae but not cytomegalovirus antibodies are associated with future risk of stroke and cardiovascular disease: a prospective study in middle-aged to elderly men with treated hypertension. Stroke 1999;30:299305.CrossRefGoogle Scholar
13. Elkind, MS, Lin, IF, Grayston, JT, Sacco, RL. Chlamydia pneumoniae and the risk of first ischemic stroke : The Northern Manhattan Stroke Study. Stroke 2000;31:15211525.Google Scholar
14. LaBiche, R, Koziol, D, Quinn, TC, et al. Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque. Stroke 2001;32:855860.CrossRefGoogle ScholarPubMed
15. Jackson, LA, Campbell, LA, Kuo, CC, et al. Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen. J Infect Dis 1997;176:292295.Google Scholar
16. Maass, M, Krause, E, Engel, PM, Kruger, S. Endovascular presence of Chlamydia pneumoniae in patients with hemodynamically effective carotid artery stenosis. Angiology 1997;48:699706.CrossRefGoogle ScholarPubMed
17. Esposito, G, Blasi, F, Allegra, L, et al. Demonstration of viable Chlamydia pneumoniae in atherosclerotic plaques of carotid arteries by reverse transcriptase polymerase chain reaction. Ann Vasc Surg 1999;13:421425.Google Scholar
18. Nadrchal, R, Makristathis, A, Apfalter, P, et al. Detection of Chlamydia pneumoniae DNA in atheromatous tissues by polymerase chain reaction.Wien Klin Wochenschr 1999;111:153156.Google ScholarPubMed
19. Berger, M, Schroder, B, Daeschlein, G, et al. Chlamydia pneumoniae DNA in non-coronary atherosclerotic plaques and circulating leukocytes. J Lab Clin Med 2000;136:194200.Google Scholar
20. Gibbs, RG, Sian, M, Mitchell, AW, et al. Chlamydia pneumoniae does not influence atherosclerotic plaque behavior in patients with established carotid artery stenosis. Stroke 2000;31:29302935.Google Scholar
21. Valassina, M, Migliorini, L, Sansoni, A, et al. Search for Chlamydia pneumoniae genes and their expression in atherosclerotic plaques of carotid arteries. J Med Microbiol 2001;50:228232.Google Scholar
22. Grayston, JT, Kuo, CC, Coulson, AS, et al. Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery. Circulation 1995;92:33973400.Google Scholar
23. Chiu, B, Viira, E, Tucker, W, Fong, IW. Chlamydia pneumoniae, cytomegalovirus, and herpes simplex virus in atherosclerosis of the carotid artery. Circulation 1997;96:21442148.CrossRefGoogle ScholarPubMed
24. Yamashita, K, Ouchi, K, Shirai, M, et al. Distribution of Chlamydia pneumoniae infection in the athersclerotic carotid artery. Stroke 1998;29:773738.CrossRefGoogle ScholarPubMed
25. Jackson, WF, Blair, KL. Characterization and function of Ca(2+)- activated K+ channels in arteriolar muscle cells. Am J Physiol 1998;274:H27-H34.Google Scholar
26. Campbell, WB, Deeter, C, Gauthier, KM, et al. 14,15- Dihydroxyeicosatrienoic acid relaxes bovine coronary arteries by activation of K(Ca) channels. Am J Physiol Heart Circ Physiol 2002;282:H1656-H1664.Google Scholar
27. Apfalter, P, Loidl, M, Nadrchal, R, et al. Isolation and continuous growth of Chlamydia pneumoniae from arterectomy specimens. Eur J Clin Microbiol Infect Dis 2000;19:305308.Google Scholar
28. Paterson, DL, Hall, J, Rasmussen, SJ, Timms, P. Failure to detect Chlamydia pneumoniae in atherosclerotic plaques of Australian patients. Pathology 1998;30:169172.Google Scholar
29. Glader, CA, Stegmayr, B, Boman, J, et al. Chlamydia pneumoniae antibodies and high lipoprotein(a) levels do not predict ischemic cerebral infarctions. Results from a nested case- control study in Northern Sweden. Stroke 1999;30:20132018.CrossRefGoogle Scholar
30. Coles, KA, Plant, AJ, Riley, TV, et al. Lack of association between seropositivity to Chlamydia pneumoniae and carotid atherosclerosis. Am J Cardiol 1999;84:825828.Google Scholar
31. Markus, HS, Sitzer, M, Carrington, D, Mendall, MA, Steinmetz, H. Chlamydia pneumoniae infection and early asymptomatic carotid atherosclerosis. Circulation 1999;100:832837.CrossRefGoogle ScholarPubMed
32. Maass, M, Bartels, C, Kruger, S, et al. Endovascular presence of Chlamydia pneumoniae DNA is a generalized phenomenon in atherosclerotic vascular disease. Atherosclerosis 1998;140(Suppl1):S25–S30.CrossRefGoogle ScholarPubMed
33. Maass, M, Gieffers, J, Krause, E, et al. Poor correlation between microimmunofluorescence serology and polymerase chain reaction for detection of vascular Chlamydia pneumoniae infection in coronary artery disease patients. Med Microbiol Immunol (Berl) 1998;187:103106.Google Scholar
34. Dowell, SF, Peeling, RW, Boman, J, et al. Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada). Clin Infect Dis 2001;33:492503.Google Scholar
35. Taylor, DC, Strandness, DE Jr. Carotid artery duplex scanning. J Clin Ultrasound 1987;15:635644.Google Scholar
36. Zoccali, C, Benedetto, FA, Mallamaci, F, et al. Inflammation is associated with carotid atherosclerosis in dialysis patients. Creed Investigators. Cardiovascular Risk Extended Evaluation in Dialysis Patients. J Hypertens 2000;18:12071213.CrossRefGoogle ScholarPubMed
37. Apfalter, P, Blasi, F, Boman, J, et al. Multicenter comparison trial of DNA extraction methods and PCR assays for detection of Chlamydia pneumoniae in endarterectomy specimens. J Clin Microbiol 2001;39:519524.CrossRefGoogle ScholarPubMed
38. Meijer, A, Roholl, PJ, Gielis-Proper, SK, Ossewaarde, JM. Chlamydia pneumoniae antigens, rather than viable bacteria, persist in atherosclerotic lesions. J Clin Pathol 2000;53:911916.Google Scholar
39. Zhu, J, Nieto, FJ, Horne, BD, et al. Prospective study of pathogen burden and risk of myocardial infarction or death. Circulation 2001;103:4551.Google Scholar
40. Gurfinkel, E, Bozovich, G, Daroca, A, Beck, E, Mautner, B. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot Study. ROXIS Study Group. Lancet 1997;350:404407.Google Scholar
41. Gupta, S, Leatham, EW, Carrington, D, et al. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 1997;96:404407.Google Scholar
42. Anderson, JL, Muhlestein, JB, Carlquist, J, et al. Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study. Circulation 1999;99:15401547.Google Scholar
43. Lattimer, CR, Burnand, KG. Recurrent carotid stenosis after carotid endarterectomy. Br J Surg 1997;84:12061219.Google Scholar
44. Frericks, H, Kievit, J, van Baalen, JM, van Bockel JH. Carotid recurrent stenosis and risk of ipsilateral stroke: a systematic review of the literature. Stroke 1998;29:244250.CrossRefGoogle ScholarPubMed