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The effect of azithromycin and Chlamydophila pneumoniae infection on expansion of small abdominal aortic aneurysms: a prospective randomised double-blind trial
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
Uppsala University, Units outside the University.
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2009 (English)In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 50, no 1, 23-29 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The aim of the study was to evaluate the effect of azithromycin on the expansion rate of small abdominal aortic aneurysms (AAAs), and to determine whether or not a correlation exists between serological markers for Chlamydophilia pneumonia (Cpn) infection and AAA expansion. METHODS: Nine vascular centers were included and 259 patients were invited to participate. Ten patients declined and 2 patients had chronic kidney failure, leaving a total of 247 patients. Inclusion criteria were: AAA 35-49 mm and age <80 years. Patients were randomized to receive either azithromycin (Azithromax, Pfizer Inc, New York, NY) 600 mg once daily for 3 days and then 600 mg once weekly for 15 weeks, or placebo in identical tablets. The ultrasound scans were performed in a standardized way within a month before inclusion and every 6 months for a minimum follow-up time of 18 months. Cpn serology was analyzed in blood samples taken at inclusion and 6 months later. Serum was analyzed for Cpn IgA and IgG antibodies by microimmunofluorescence (MIF). Computed tomography (CT) scans were done in 66 patients at inclusion and at 1 year for volume calculations. RESULTS: Thirty-four patients were excluded, ie, could not be followed for 18 months, 20 in the placebo group and 16 in the active treatment group. A total of 211 patients had at least two measurements and all were analyzed in an intention-to-treat analysis. Detectable IgA against Cpn was found in 115 patients and detectable IgG against Cpn in 160 patients. No statistically significant differences were found between the groups regarding median expansion rate measured by ultrasound scan (0.22 cm/year, interquartile range [IQR]: 0.09 to 0.34 in the placebo group vs 0.22, IQR: 0.12 to 0.36 in the treatment group, P = .85). Volume calculation did not change that outcome (10.4 cm(3)/year in the placebo group vs 15.9 cm(3)/year in the treatment group, P = .61). No correlation was found between serological markers for Cpn infection and the expansion rate. Patients taking statins in combination with acetylsalicylic acid (ASA) had significantly reduced expansion rate compared to patients who did not take statins or ASA, 0.14 cm/year vs 0.27 cm/year, P < .001. CONCLUSION: Azithromycin did not have any effect on AAA expansion. No correlation was found between serological markers for Cpn and AAA expansion, indicating no clinical relevance for Cpn testing in AAA surveillance. However, a significant reduction in AAA expansion rate was found in patients treated with a combination of ASA and statins.

Place, publisher, year, edition, pages
2009. Vol. 50, no 1, 23-29 p.
Keyword [en]
Abdominal aortic aneurysm, Chlamydophila pneumoniae, inflammation, statin, expansion, randomised clinical trial, MMP-9, IL-6, CRP, azithromycin
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-108598DOI: 10.1016/j.jvs.2008.12.048ISI: 000267498500004PubMedID: 19563951OAI: oai:DiVA.org:uu-108598DiVA: diva2:236650
Available from: 2009-09-24 Created: 2009-09-24 Last updated: 2017-12-13Bibliographically approved
In thesis
1. The Role of Chlamydophila Pneumoniae in the Inflammatory Response and Expansion of Abdominal Aortic Aneurysms
Open this publication in new window or tab >>The Role of Chlamydophila Pneumoniae in the Inflammatory Response and Expansion of Abdominal Aortic Aneurysms
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Abdominal aortic aneurysm (AAA) is a common disease that develops gradually over several years and is characterised by weakening and dilatation of the aortic wall. AAAs also demonstrates a marked inflammatory infiltrate throughout the aortic wall. Chlamydophila pneumoniae (C. pneumoniae), is a common bacterium. About 50% of the population has been infected in adolescence. Thirteen studies report the presence of either C. pneumoniae or its antigens in 35-100% of AAA specimens.

The overall aim of this thesis was to evaluate the possible role of C. pneumoniae in inflammatory response and expansion of AAA from a clinical point of view.

In paper I, viable C. pneumoniae was detected in a majority of 26 patients with AAA having open surgery. Patients operated for AAA had higher C. pneumoniae antibodies titers than controls. In paper II, 247 patients were randomised in a double-blind trial, to evaluate the effect of azithromycin on the expansion of small AAAs. No such effect was seen and there was no correlation between C. pneumoniae antibody titers and AAA expansion. In paper III, 42 patients with AAA were compared to 100 age- and sex matched controls with normal aortas. C. pneumoniae antibodies were analysed in plasma samples obtained at screening, and in samples from a study conducted 5-15 (mean 12) years previously on the same population. There was no significant difference between the groups. In paper IV, were 211 patients were analysed, we could not find an association between levels in plasma of three markers of inflammation (IL-6, MMP-9 and CRP) and AAA expansion. A significant reduction in AAA expansion rate was found in patients treated with a combination of ASA and statins.

In conclusion, viable C. pneumoniae is found at the scene of the crime, but we were unable to reverse or halt expansion of AAA with antibiotic treatment. C. pneumoniae antibody titers cannot be used, to detect small AAA, or to evaluate AAA expansion. From a clinical point of view, based on the methods and analyses used in this thesis, the role of C. pneumoniae in the inflammatory response and expansion of abdominal aortic aneurysms is limited.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 85 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 485
Keyword
Abdominal aortic aneurysm, Chlamydophila pneumoniae, inflammation, aspirin, statin, expansion, randomised clinical trial
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-108867 (URN)978-91-554-7617-5 (ISBN)
Public defence
2009-11-06, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2009-10-16 Created: 2009-10-01 Last updated: 2009-10-16Bibliographically approved

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