Chlamydia pneumoniae and atherosclerosis -- what we know and what we don't.

The clinical manifestations of atherosclerosis include coronary artery disease (CAD), stroke, abdominal aortic aneurysm and peripheral vascular disease. World-wide, CAD and stroke are the leading causes of death and disability. The recognition of atherosclerosis as an inflammatory disease in its genesis, progression and ultimate clinical manifestations has created an interesting area of vascular research. Apart from those well-known traditional risk factors for atherosclerosis, novel and potentially treatable atherosclerotic risk factors such as homocysteine (an amino acid derived from the metabolism of dietary methionine that induces vascular endothelial dysfunction) and infections have emerged. In fact, the century-old 'infectious' hypothesis of atherosclerosis has implicated a number of micro-organisms that may act as contributing inflammatory stimuli. Although cytomegalovirus, Helicobacter pylori and Chlamydia pneumoniae are the three micro-organisms most extensively studied, this review will focus on C. pneumoniae. Collaborative efforts from many disciplines have resulted in the accumulation of evidence from seroepidemiological, pathological, animal model, immunological and antibiotic intervention studies, linking C. pneumoniae with atherosclerosis. Seroepidemiological observations provide circumstantial evidence, which is weak in most prospective studies. Pathological studies have demonstrated the preferential existence of C. pneumoniae in atherosclerotic plaque tissues, while animal model experiments have shown the induction of atherosclerosis by C. pneumoniae. Finally, immunological processes whereby C. pneumoniae could participate in key atherogenic and atherothrombotic events have also been identified. Although benefits of the secondary prevention of atherosclerosis have been demonstrated in some antibiotic intervention studies, a number of negative studies have also emerged. The results of the ongoing large prospective human antibiotic intervention trials may help to finally establish if there is a causal link between C. pneumoniae infection and atherosclerosis.