Chlamydia pneumonia: An innocent bystander or a major mediator of inflammation in the development of coronary artery disease?

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide in which inflammation is an important but poorly understood factor in the development of atherosclerosis. Several risk factors for CAD, including hypertension, dyslipidemia, tobacco abuse, diabetes, and positive family history, have been well documented but do not completely explain how inflammation contributes to the progression of atherosclerosis. There is growing evidence that microbial infections and immunologic mechanisms could be implicated as possible inflammatory mediators in the pathogenesis of atherosclerosis.1 In one study looking at inflammatory and infectious markers for angiographic CAD and myocardial infarction, the authors found that C-reactive protein, an inflammatory marker, is elevated 2-fold in patients with CAD and 4-fold in patients with acute myocardial infarction, although the stimulus for elevated C-reactive protein levels was unclear.2 There have been several meta-analyses and prospective studies looking specifically at Chlamydia pneumonia as a possible inflammatory mediator by evaluating DNA and immunoglobulin-A and G serology, although causality was not established.3, 4

In the current issue of Heart & Lung, Pesonen et al5, 6 advanced the theory that microbial infections such as C. pneumonia may potentially play a major role in the pathogenesis of CAD by invoking an inflammatory process leading to atherosclerosis. The authors used a novel quantitative enzyme immunoassay for lipopolysaccharide-binding protein as a capture molecule for the measurement of chlamydial lipopolysaccharide (cLPS) concentrations in patients with acute myocardial infarction and unstable angina. They hypothesized that the presence of cLPS is a risk factor for future coronary events.

By using this new quantitative enzyme immunoassay for cLPS, the authors demonstrated that serum cLPS concentrations correlated significantly with C-reactive protein levels and seem to be a marker of a chronic inflammatory process possibly lending to the development of atherosclerosis. In addition, the presence of cLPS in the serum indicated active, productive C. pneumonia infection, whereas the presence of C. pneumonia antibodies only demonstrated that the patient had been exposed to C. pneumonia in the past. The authors postulated that high levels of cLPS during an acute coronary syndrome suggest the liberation of cLPS from damaged tissue with active infection, which was supported by an additional finding that cLPS was found in more than 20% of atherosclerotic carotid plaques obtained from patients with symptomatic carotid stenosis. The authors concluded that this study supports the hypothesis that C. pneumonia bacteria play a role as a risk factor for the development of CAD and seem to be a risk factor for a secondary event.

This study supports the growing view that chronic C. pneumonia infection leading to inflammation may be an important but poorly understood risk factor in the development of atherosclerosis and that CAD may be a risk factor for a secondary event. Additional studies to move the thesis forward that inflammation plays a role in the development of atherosclerosis, specifically looking at C. pneumonia as a mediator of the inflammatory cascade, are obligatory in determining causality.