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Atherosclerosis as inflammatory disease

An article from the e-journal of the ESC Council for Cardiology Practice

Chlamydia pneumoniae causes acute respiratory infections in humans and has been associated with coronary artery disease (CAD). Clinical trials failed to demonstrate benefits from the use of antibiotic treatment in patients suffering from CAD and cannot be recommended at present.



Inflammation and vascular infection contributes to endothelial dysfunction and is thought to play an important role in atherosclerosis and its acute complications. Several large, prospective epidemiological studies have shown consistently that plasma levels of C-reactive protein (CRP, an inflammatory marker) are strong independent predictors of risk of future cardiovascular events, both in patients with a history of CAD and in apparently healthy subjects. Recently, a possible association of Chlamydia pneumoniae with CAD and other forms of vascular atherosclerosis was suspected following sero-epidemiological studies and the demonstration of these organisms in atherosclerotic plaques obtained in vivo Chlamydia pneumoniae is a worldwide distributed human pathogen causing acute respiratory diseases such as pneumonia, bronchitis, pharyngitis, and sinusitis. However, the pathogenic role of Chlamydia pneumoniae for the development of atherosclerotic vascular disease and the specificity of chlamydial effects is still poorly understood. Animal model and cell biology studies suggest that the pathogen can modulate atheroma development, including lipid- and inflammatory-related processes. Recent research demonstrates that infection with viable Chlamydia pneumoniae is not necessary to initiate atherosclerosis, since other bacterial compounds (i.e. lipopolysaccharide from Escherichia coli) also promote atheromatous lesion formation. Moreover, CRP itself promotes atherogenesis via effects on monocytes and endothelial cells.

Diagnosis of patients suffering from infection with Chlamydia pneumoniae is mainly established using serology. The micro-immunofluorescence (MIF) test is considered the gold standard for detection of Chlamydia pneumoniae antibodies, although commercially available enzyme-linked immunoassays were also shown to be sufficiently accurate.1 Increased levels of IgG were found in approximately 60% of all patients (indicating prior infection mostly during childhood or adolescence), acute infection is detected by increased levels of IgA. In addition to serological assessment, CRP testing can helpful in estimation of cardiovascular risk. The AHA/CDC recommends measuring high sensitive CRP (hs-CRP) levels in patients who - on the basis of multiple risk factor scoring with cholesterol levels, weight, level of exercise, smoking history, and presence of hypertension and diabetes - appear to have a moderately elevated risk of cardiovascular events. In these patients, an elevated CRP measurement would indicate that the risk may very well be much greater than "moderate".2

At present time, no general recommendation for the use of antibiotics in CAD patients can be made. Some preliminary antibiotic treatment trials in patients with non-ST segment elevation coronary syndrome indicated a reduction in recurrent coronary events. In the ROXIS trial (n=202) , roxithromycin appeared to extend the clinical benefit of preventing death and re-infarction for at least 6 months after initial treatment. In larger studies with patients suffering from stable CAD who are sero-positive of Chlamydia pneumoniae, such as ACADEMIC trial (n=302, azithromycin 500 mg/d for 3 days, followed by 500 mg per week for 3 months) or WIZARD trial, benefits on reduction of cardiovascular events could not be demonstrated.3 Inflammatory markers (i.e. CRP, interleukin-6) improved after long time antibiotic treatment. More recently short-term treatment with azithromycin (initially 500 mg followed by 250 mg over 4 days) failed to reduce development of recurrent events in patients with acute coronary syndrome (AZACS trial, n=1439).4

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

References


1. Vainas T, De Graaf R, Stassen FR, Kurvers HA, Grauls GE, Kitslaar PJ, Bruggeman CA. Chlamydia pneumoniae serology: comparing a commercial enzyme immunoassay and microimmunofluorescence test in patients with cardiovascular disease. Apmis. 2003;111:363-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12716394&dopt=Abstract

2. AHA/CDC panel issues recommendations on CRP testing. In:: American Heart Association Recommendations; accessed October, 6, 2003.
http://www.americanheart.org/presenter.jhtml?identifier=3007984

3. Anderson JL, Muhlestein JB, Carlquist J, Allen A, Trehan S, Nielson C, Hall S, Brady J, Egger M, Horne B, Lim T. 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 [see comments]. Circulation. 1999;99:1540-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10096928&dopt=Abstract

4. Cercek B, Shah PK, Noc M, Zahger D, Zeymer U, Matetzky S, Maurer G, Mahrer P. Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial. Lancet. 2003;361:809-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12642046&dopt=Abstract

 

Notes to editor


Dr M.G. Engelmann and Prof. S. Nikol
Munich, Münster, Germany
member of the Nucleus of the ESC Working Group on Interventional Cardiology

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.