Re: Chlamydia pneumoniae Does Not Influence Atherosclerotic Plaque Behavior in Patients With Established Carotid Artery Stenosis
To the Editor:
We read the interesting paper of Gibbs et al.1 We believe that, just as in other cases, the inflammatory response to infection probably plays a significant role.2 The basic incentive in writing this letter is to underline the following assertion that results from the original idea of the authors to check the rhythm of emboli by means of transcranial Doppler ultrasonography (TCD).
The fact that most patients without Chlamydia pneumoniae infection present with a cerebral episode does not discard the relationship between infection from C pneumoniae and embolization. It is simply the reporting of the results, which the authors suggest, that the plaques can be influenced by C pneumoniae infection, because wherever we find C pneumoniae infection we discover more embolic episodes.
The conclusion which results from the interpretation of Table 2 of Gibbs et al (although not documented in our experience, however) is that a correlation probably exists between C pneumoniae infection and plaques (soft, or not taking under consideration that many embolic episodes do not provoke many cerebral episodes as well in the C pneumoniae-positive group), despite the fact that the discovery of the rhythm of emboli with TCD had not resulted in an increase in the number of cerebral episodes. The reasoning that there may likely exist some kind of increased correlation between soft plaques and C pneumoniae infection results from the interpretation of the table. More investigation of the carotid plaque with ultrasonography is required, however, with an adjunct TCD, for better corroboration of the final result.
In our work, an attempt was made to combine the recent or chronic disease due to C pneumoniae, as shown from the results of the titers of immunoglobulin (Ig)G and IgM. Our results were as follows3,4: 20 of 35 (57.1%) of the patients had an increased IgG titer of antibodies; 2 patients had high IgG and IgM antibody titers and were PCR positive, while both were symptomatic. It should be noted that we had also examined samples of thyroid artery in all of the patients in whom C pneumoniae was not traced in the arteries. Sixty-five percent of the 20 patients with increased IgG antibody titer were symptomatic; in the subgroup of 8 patients with IgG and IgM antibodies (recent disease), 85% were symptomatic; and in the subgroup with active disease (IgG+IgM+polymerase chain reaction [PCR]), both patients were symptomatic. Moreover, we examined the quality of the atheromatous plaque with use of color-coded duplex sonography; however, we were not able to connect the soft plaques of type I and II with the symptomatic patients, while the majority of the symptomatic patients had plaques of the III, IV, and V type. The basic conclusion is that there was a high affinity between recent disease and signs of C pneumoniae in the plaques when PCR was used. In our work, we concluded that the symptomatic patients, in the majority of the cases, were seropositive.
In any case, there is no etiological connection between the systematic disease arising from C pneumoniae, as shown by the titer of the antibodies, and the specific localization on the carotid plaque.
More studies focused on this matter might connect the titer of the antibodies and carotid stenosis, or, better still, the influence of the ratio in the presence of cerebral episodes.
Gibbs RGJ, Sian M, Mitchell AWM, Greenhalgh RM, Davies AH, Carey N. Chlamydia pneumoniae does not influence atherosclerotic plaque behavior in patients with established carotid artery stenosis. Stroke. 2000; 31: 2930–2935.
Mozaed TC, Juo CC, Grayston JT, Campbell LA. Murine models of Chlamydia pneumoniae infection and atherosclerosis. J Infect Dis. 1997; 175: 883–890.
K. Katsenis E, Kouskouni L, Kolokotronis PB, Dimakakos . The significance of Chlamydia pneumoniae in symptomatic carotid stenosis. J Angiology. 2000; 52: 1–5.
Katsenis K, Kouskouni E, Kolokotronis L, Arapoglou B, Kotsis T, Papadimitriou L, Dimakakos PB. Chlamydia pneumoniae infection and the atherosclerotic carotid disease.In: Proceedings of the European Chapter of the IUA; May 26–30, 1999; Rhodes,Greece.
We thank the authors for their comments, and were interested in their hypothesis that C pneumoniae is more likely to be found in soft, lipid-rich plaques compared with harder fibrous plaques. Ultrasound assessment of plaque density was not a factor assessed in this work, so any comment is conjectural. However, we disagree with their interpretation of the results presented. Soft plaques have been reported to be more likely to embolize and cause cerebral ischemia than hard plaques. If there were an association between C pneumoniae and soft plaque content, the results would have been biased in such a way that C pneumoniae would have been more likely to be associated with embolization and infarction. This was manifestly not the case; if the results had shown a significant correlation between embolization, infarction and C pneumoniae DNA, then plaque content would have had to be analyzed to ensure it was not a confounding factor. Whether C pneumoniae has a causal or disease-modifying effect has yet to be established. We suggest that if the case is proven, the underlying mechanisms in atherogenesis or alteration of plaque behavior are likely to be at the subcellular level, and interpretation of plaque content either by ultrasound or histology is unlikely to shed light on cause and effect.