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Clinical Chemistry 48: 1631, 2002;
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(Clinical Chemistry. 2002;48:1631.)
© 2002 American Association for Clinical Chemistry, Inc.

Letters

Macrolide Treatment Does Not Influence Serum Homocysteine in Chlamydia pneumoniae-seropositive Patients Suffering from Atherosclerosis

Georg Schulthess1a, Peter Wiesli1 and Friedrich E. Maly2

1 Department of Internal Medicine Medical Policlinic and,
2 Institute of Clinical Chemistry, University Hospital, CH-8091 Zurich, Switzerland

aAuthor for correspondence. Fax 41-1-255-4567; e-mail georg.schulthess{at}dim.usz.ch.


To the Editor:

Both chronic infection with Chlamydia pneumoniae and hyperhomocysteinemia are assumed to increase the atherosclerotic risk (1)(2). Recently, we reported that C. pneumoniae seropositivity is linked with hyperhomocysteinemia in male patients suffering from established atherosclerosis (3). However, the nature of the relationship between the two risk factors is still elusive.

To further investigate the relationship between C. pneumoniae seropositivity and hyperhomocysteinemia, we randomly assigned 40 C. pneumoniae-seropositive men suffering from peripheral arterial occlusive disease to receive either roxithromycin (300 mg daily) or placebo for 1 month. We selected elderly men (71.3 ± 8.4 years) with a high prevalence of smoking (>80%) and at high risk of undergoing progression of atherosclerotic disease as the study population. Exclusion criteria were diabetes mellitus, malignant neoplasia, chronic inflammatory disorders, and renal insufficiency. Testing for antibodies against C. pneumoniae was performed by a microimmunofluorescence assay (MRL). C. pneumoniae seropositivity was defined as an IgG titer >=1:128. Fasting serum homocysteine was determined by HPLC (Bio-Rad) at baseline, at the end of the treatment period, and 6 months after the study medication was ended. As shown in Table 1 , homocysteine concentrations, which were moderately increased in both study groups, were not influenced by antibiotic treatment. However, roxithromycin treatment had a substantial (beneficial) effect on the clinical course of peripheral arterial occlusive disease and on carotid plaque size in these patients (4).


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  		Table 1. Influence of roxithromycin treatment on serum homocysteine.1

Macrolide treatment, although preventing progression of the atherosclerotic disease, had no influence on homocysteine concentrations. This finding makes it improbable that C. pneumoniae infection directly causes hyperhomocysteinemia. The following two hypotheses provide more probable explanations for the association between C. pneumoniae seropositivity and hyperhomocysteinemia: either (a) chronic endovascular infection with C. pneumoniae causes, at least in advanced atherosclerosis, irreversible cell injury that is responsible for persistent hyperhomocysteinemia by an as yet unknown mechanism; or (b) preexisting hyperhomocysteinemia, possibly accompanied by decreased methionine concentrations, represents a metabolic niche favoring chronic infection with C. pneumoniae. In vitro, the growth of C. pneumoniae is known to be enhanced in media depleted of lysine and methionine (5).


References

  1. Saikku 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;2:983-986.[ISI][Medline] [Order article via Infotrieve]
  2. Welch GN, Loscalzo J. Homocysteine and atherothrombosis [Review]. N Engl J Med 1998;338:1042-1050.[Free Full Text]
  3. Wiesli P, Maly FE, Meniconi A, Czerwenka W, Hoffmann U, Vetter W, et al. Chlamydia pneumoniae seropositivity and hyperhomocysteinemia are linked in patients with atherosclerosis. Clin Chem 2001;47:1304-1306.[Free Full Text]
  4. Wiesli P, Czerwenka W, Meniconi A, Maly FE, Hoffmann U, Vetter W, et al. Roxithromycin treatment prevents progression of peripheral arterial occlusive disease in Chlamydia pneumoniae seropositive men: a randomized, double-blind, placebo-controlled trial. Circulation 2002;105:2646-2652.[Abstract/Free Full Text]
  5. Kuo CC, Grayston JT. Amino acid requirements for growth of Chlamydia pneumoniae in cell cultures: growth enhancement by lysine or methionine depletion. J Clin Microbiol 1990;28:1098-1100.[Abstract/Free Full Text]




This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schulthess, G.
Right arrow Articles by Maly, F. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schulthess, G.
Right arrow Articles by Maly, F. E.
Related Collections
Right arrow Lipids, Lipoproteins, and Cardiovascular Risk Factors

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