Overall, it seems most likely that the contribution of C. pneumoniae to coronary artery disease is more accurately reflected by the extensive prospective serological studies, (which indicate a weak association), rather than by the pathology studies, which indicate an extremely strong association, which, were it true, should by now be self-evident from other data.
In terms of temporality it is feasible that C. pneumoniae might be a cause or significant exacerbating factor in atherosclerosis, as the organism is found in cardiovascular tissue relatively early in life, in teenage persons [Taylor-Robinson & Thomas, 1998]. Evidence of a biological gradient is more controversial. This laboratory found little association between the distribution of C. pneumoniae DNA within an individual and the severity of atheromatous disease [Thomas et al., 1999]. However others have reported such differences [see C. pneumoniae dectection].
In terms of coherence and analogy, experimental studies at the cellular level and in animals certainly suggest mechanisms by which C. pneumoniae might cause atherosclerosis or precipitate coronary heart disease as a result of persisting local antigenic stimulation. Many of these effects seem to be attributable to the inflammatory and immunomodulatory effects of lipopolysaccharide and are thus unlikely to be specific to C. pneumoniae. The extent to which infection might trigger lipid core formation in atheromatous plaque or cause actual plaque rupture and thrombosis leading to acute coronary heart disease has not been adequately researched. For reviews on the role of C. pneumoniae in coronary artery disease see Kalayoglu et al., 2002; Ngeh et al., 2002; Leinonen & Saikku., 2002.
Atheromatous plaque is commonly colonised with C. pneumoniae and this organism, among others, is thereby associated with coronary artery disease. Studies in animals have shown the potential of C. pneumoniae to exacerbate coronary heart disease, but there is little evidence as to whether this has any clinical significance in human disease. Future research needs to focus on the possibility that C. pneumoniae and other chronic bacterial pathogens may trigger acute coronary events, such as plaque rupture. Unfortunately, the present antibiotic trials may prove to lack sufficient power to answer these key issues and one major clinical trial has been abandoned for lack of positive results. In the overall context of risk factors for coronary artery disease it seems likely that the importance of C. pneumoniae and other bacteria as a trigger may be relatively small. Nevertheless coronary heart disease is an extremely common cause of death. Moreover any effect of bacterial infections on heart disease are potentially preventable. Even a small role for bacterial infections could be very significant in public health terms and as Leinonen and Saikku 2002 point out, the ultimate proof of a causal relationship would be the demonstration that C. pneumoniae vaccination can prevent disease. Meanwhile we can settle for clear demonstrated benefit of antibiotic in preventing coronary artery disease over a substantial follow up period. It is vital that the relationship of infection to coronary artery disease continues to be an active area for medical research.
Data on the role of C. pneumoniae on other chronic diseases are sparse and, frequently, contradictory. It is therefore premature to draw any firm conclusions in this area.
[MEW] August 2004
NEXT: Chronic infections index
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