Journal of Vascular Surgery
Volume 50, Issue 1 , Pages 23-29 , July 2009

The effect of azithromycin and Chlamydophilia pneumonia infection on expansion of small abdominal aortic aneurysms - A prospective randomized double-blind trial

  • Lars Karlsson, MD

      Affiliations

    • Institution of Surgical Sciences, Section of Vascular Surgery, Uppsala University Hospital, Uppsala, Gävle, Sweden
    • Department of Surgery, Gävle County Hospital, Gävle, Sweden
    • Corresponding Author InformationReprint requests: Lars Karlsson, MD, Department of Surgery, Gävle County Hospital, S-80187 Gävle, Sweden
  • ,
  • Judy Gnarpe, PhD

      Affiliations

    • Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada
  • ,
  • David Bergqvist, MD, PhD, FRCS

      Affiliations

    • Institution of Surgical Sciences, Section of Vascular Surgery, Uppsala University Hospital, Uppsala, Gävle, Sweden
  • ,
  • Johan Lindbäck, MSc

      Affiliations

    • Uppsala Clinical Research Centre, Section of Statistics, Uppsala, Gävle, Sweden
  • ,
  • Håkan Pärsson, MD, PhD

      Affiliations

    • Institution of Surgical Sciences, Section of Vascular Surgery, Uppsala University Hospital, Uppsala, Gävle, Sweden
    • Department of Surgery, Helsingborg County Hospital, Helsingborg, Sweden

Received 1 October 2008 ,Accepted 21 December 2008.

References 

  1. Wills A, Thompson MM, Crowther M, Sayers RD, Bell PR. Pathogenesis of abdominal aortic aneurysms - cellular and biochemical mechanisms. Eur J Vasc Endovasc Surg. 1996;12:391–400
  2. Vine N, Powell JT. Metalloproteinases in degenerative aortic disease. Clin Sci (Lond). 1991;81:233–239
  3. Kuo CC, Grayston JT, Campbell YA, Goo R, Wissler W, Benditt EP. Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old). Proc Natl Acad Sci USA. 1995;92:6911–6914
  4. Juvonen J, Juvonen T, Laurila A, Alakärppä H, Lounatmaa K, Surcel HM, et al. Demonstration of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms. J Vasc Surg. 1997;25:499–505
  5. Karlsson L, Gnarpe J, Nääs J, Olsson G, Lindholm J, Steen B, et al. Detection of viable Chlamydia pneumoniae in abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2000;19:630–635
  6. Vink A, Poppen M, Schoneveld AH, Roholl PJ, de Kleijn DP, Borst C, 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;103:1613–1617
  7. Tomasi TB, Grey HM. Structure and function of immunoglobulin A. Prog Allergy. 1972;16:181–213
  8. Falck G, Gnarpe J, Gnarpe H. Persistent Chlamydia pneumoniae infection in a Swedish family. Scand J Infect Dis. 1996;28:271–273
  9. Lindholt JS, Ashton HA, Scott RA. Indicators of infection with Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysms. J Vasc Surg. 2001;34:212–215
  10. Fong IW, Chiu B, Viira E, Jang D, Fong MW, Peeling R, et al. Can an antibiotic (macrolide) prevent Chlamydia pneumoniae- induced atherosclerosis in a rabbit model?. Clin Diagn Lab Immunol. 1999;6:891–894
  11. Tambiah J, Powell JT. Chlamydia pneumoniae antigens facilitate experimental aortic dilatation: prevention with azithromycin. J Vasc Surg. 2002;36:1011–1017
  12. Mosorin M, Juvonen J, Biancari F, Satta J, Surcel HM, Leinonen M, et al. Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study. J Vasc Surg. 2001;34:606–610
  13. Vammen S, Lindholt JS, Ostergaard L, Fasting H, Henneberg EW. Randomized double-blind controlled trial of roxithromycin for prevention of abdominal aortic aneurysm expansion. Br J Surg. 2001;88:1066–1072
  14. Tiran A, Gruber HJ, Grainer WF, Wagner AH, Van Leeuwen EB, Tiran B. Aspirin inhibits Chlamydia pneumoniae-induced nuclear factor-kappa B activation, cytokine expression, and bacterial development in human endothelial cells. Arterioscler Thromb Vasc Biol. 2002;22:1075–1080
  15. Kalyanasundaram A, Elmore JR, Manazer JR, Golden A, Franklin DP, et al. Simvastatin suppresses experimental aortic aneurysm expansion. J Vasc Surg. 2006;43:117–124
  16. Gnarpe J, Sparr A, Nääs J, Lundbäck A. Serological analysis of specific IgA to Chlamydia pneumoniae: increased sensitivity of IgA antibody detection using prolonged incubation and high antigen concentration. APMIS. 2000;108:357–362
  17. Gnarpe J, Nääs J, Lundbäck A. Comparison of a new commercial EIA kit and the microimmunofluorescence technique for determination of IgG and IgA antibodies to Chlamydia pneumoniae. APMIS. 2000;108:819–824
  18. R Development Core Team (2008). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org.
  19. Tambiah J, Franklin IJ, Trendell-Smith N, Peston D, Powell JT. Provocation of experimental aortic inflammation and dilatation by inflammatory mediators and Chlamydia pneumoniae. Br J Surg. 2001;88:935–940
  20. Contopoulos-Ioannidis DG, Ioannidis JP, Chew P, Lau J. Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for lower respiratory tract infections. J Antimicrob Chemother. 2001;48:691–703
  21. Parchure N, Zouridakis EG, Kaski JC. Effect of azithromycin treatment on endothelial function in patients with coronary artery disease and evidence of Chlamydia pneumoniae infection. Circulation. 2002;105:1298–1303
  22. Grayston JT, Campbell LA, Kuo CC, Mordhorst CH, Saikku P, Thom D, et al. A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR. J Infect Dis. 1990;161:618–625
  23. Gaydos CA, Summersgill JT, Sahney NN, Ramirez JA, Quinn TC. Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells. Infect Immun. 1996;64:1614–1620
  24. Schett G, Xu Q, Amberger A, Van der Zee R, Recheis H, Willeit J, et al. Autoantibodies against heat shock protein 60 mediate endothelial cytotoxicity. J Clin Invest. 1995;96:2569–2577
  25. Wiedeman JA, Kaul R, Heuer LS, Thao NN, Pinkerton KE, Wenman WM. Tobacco smoke induces persistent infection of Chlamydia pneumoniae in HEp-2 cells. Microb Pathog. 2004;37:141–148
  26. Gieffers J, Rupp J, Gebert A, Solbach W, Klinger M. First-choice antibiotics at subinhibitory concentrations induce persistence of Chlamydia pneumoniae. Antimicrob Agents Chemother. 2004;48:1402–1405
  27. Lederle FA, Nelson DB, Joseph AM. Smokers‘ relative risk for aortic aneurysm compared with other smoking-related diseases: a systematic review. J Vasc Surg. 2003;38:329–334
  28. MacSweeney ST, Ellis M, Worrell PC, Greenhalgh RM, Powell JT. Smoking and growth rate of small aortic aneurysms. Lancet. 1994;344:651–652
  29. The UK Small Aneurysm Trial Participants. Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. Lancet. 1998;352:1649–1655
  30. Brady AR, Thompson SG, Fowkes FG, Greenhalgh RM, Powell JT The UK Small Aneurysm Trial Participants. Abdominal aortic aneurysm expansion: risk factors and time intervals for surveillance. Circulation. 2004;110:16–21
  31. Lindholt JS, Heegaard NH, Vammen S, Fasting H, Henneberg EW, Heickendorff L. Smoking, but not lipids, lipoprotein(a) and antibodies against oxidised LDL, is correlated to the expansion of abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2001;21:51–56
  32. Sukhija R, Aronow WS, Yalamanchili K, Sinha N, Babu S. Prevalence of coronary artery disease, lower extremity peripheral arterial disease, and cerebrovascular disease in 110 men with an abdominal aortic aneurysm. Am J Cardiol. 2004;94:1358–1359
  33. Schlösser FJ, Tangelder MJ, Verhagen HJ, van der Heijden GJ, Muhs BE, van der Graaf Y, et al. J Vasc Surg. 2008;47:1127–1133
  34. Schouten O, van Laanen JH, Boersma E, Vidakovic R, Feringa HH, Dunkelgrün M, et al. Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth. Eur J Vasc Endovasc Surg. 2006;32:21–26
  35. Evans J, Powell JT, Schwalbe E, Loftus IM, Thompson MM. Simvastatin attenuates the activity of matrix metalloproteinase-9 in aneurysmal aortic tissue. Eur J Vasc Endovasc Surg. 2007;34:302–303
  36. Franklin IJ, Walton LJ, Brown L, Greenhalgh RM, Powell JT. Vascular surgical society of Great Britain and Ireland: non steroidal anti-inflammatory drugs to treat abdominal aortic aneurysm. Br J Surg. 1999;86:707
  37. 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;30:299–305

 The Research was supported by grants from County of Gävleborg Research and Development Center (FoU), Gore Swedish Research Foundation, Pfizer AB Sweden, Schyberg medical research fund, and Zoega medical research fund. We thank Prof Martin Björck for initial funding for the CT scans.

 Competition of interest: none.

PII: S0741-5214(08)02287-8

doi: 10.1016/j.jvs.2008.12.048

Journal of Vascular Surgery
Volume 50, Issue 1 , Pages 23-29 , July 2009