XII^th International Symposium on Atherosclerosis, Stockholm, Sweden. (June 25-29, 2000)
Several recent studies have pointed out that, among the different agents causing atherosclerosis, a key role is played by an autoimmune process triggered by Chlamydia pneumoniae. Antibiotics active against Chlamydia are already available for clinical practice, but large scale studies are needed to prove the efficacy of antibiotic treatment.

Stockholm, Sweden -- In one of his last papers Dr. Russell Ross described what he called the essence of the process of atherogenesis "…Atherosclerosis represents a protective, inflammatory-fibroproliferative response against the different agents that can cause the disease. If the injury continues over a long period of time, it may become excessive, and in its excess it becomes the disease itself…". The hypothesis that infectious agents and the consequent inflammatory response may lead to atherosclerosis has been considered for some time, but recently there has been a resurgence of interest in the infectious basis of coronary atherosclerosis. A workshop of the XII^th International Symposium on Atherosclerosis in Stockholm, was dedicated to this topic.

In the past, human herpesviruses and cytomegaloviruses, together with bacteria, like Helicobacter pylori and dental pathogens, have been associated with atherosclerosis and restenosis. Several recent studies have pointed out that, among the different agents causing atherosclerosis, a key role is played by an autoimmune process triggered by Chlamydia pneumoniae, reported Dr. P. Saikku (University of Oulu, Finland). Chlamydia is a small gram-negative intracellular bacterium, which is a common cause of respiratory tract infections worldwide and that is capable of multiplying in a wide range of host cells, such as smooth muscle cells, endothelial cells, and macrophages. The presence of Chlamydia in atherosclerotic lesions was demonstrated for the first time in 1992 and confirmed by different methods in over 30 studies.

As noted above, inflammation is a major factor in the pathogenesis of atherosclerosis, and Chlamydia is of particular interest as a potential stimulus of the inflammatory response. This bacterium induces cytokine production, oxidative processes, proteolysis, and autoimmunity through the heat shock protein (HSP-60). In a mouse model of atherogenesis it accelerates atherosclerosis. Furthermore, it is known that Chlamydia affects several processes involved in plaque formation and it is thought to be better associated with the progression of the lesion, than to its precipitation. Chlamydia seems to increase the atherosclerotic burden, but not the thrombotic events. However, preliminary results from recent studies have suggested that Chlamydia could be involved in the cascade of events leading to acute complications of atherosclerosis. Chlamydia is associated with intima-media thickness in carotid artery and to an atherogenic fatty acid profile in apparently healthy individuals, reported Dr L. Lind (University of Uppsala, Sweden). People with high titer of IgG against Chlamydia have a 3-fold increased risk of abdominal aortic aneurism (AAA) said Dr. D. Siscovick (University of Washington, USA).

Although 70-80% of the patients with coronary heart disease (CHD), and virtually 100% of the patient with AAA, present the bacterium in an active state, CHD requires more than just Chlamydia. Several risk factors for CHD are able to affect Chlamydia infection: age, male gender, cigarette smoking, physical inactivity, diet, and stress. On the other hand, Chlamydia itself may influence risk factors such as C reactive protein elevation, cytokine induction, plasma triglyceride, and total cholesterol elevation, and HDL reduction.

Antibiotics active against Chlamydia are already available for clinical practice. On the basis of available information, tetracycline and new macrolides are efficacious. Clinical trials have been performed with the aim of stopping Chlamydia's involvement in atherosclerosis. The ROXIS Pilot study was the first clinical trial with a primary endpoint to prove the benefit of antibiotics in coronary artery disease, said Dr E. Gurfinkel (Favaloro Foundation, Argentina). The outcome of the study showed that patients treated with roxithromycin had a significantly lower rate of combined clinical endpoints. However, after cessation of antibiotic treatment there was a rebound in inflammation and immune system activation.

In another intervention study, patients with AAA were treated for 3 months with doxicyclin and then followed for up to 12-18 months afterward, showing a reduced AAA growth.

New clinical trials are currently under way around the world, involving a total of more than 20,000 cardiac patients. These are secondary prevention studies and we will need to start primary prevention study in the near future, Dr Saikku suggested. Vaccines against Chlamydia have been tried with some success in chickens, but will be at least 50 years before results are seen in humans. "I would move macrolide from microbiology to heart disease treatment" he commented "but before doing this we have to wait for the results of these larger intervention trials". "We need confirmation by large scale studies not only to prove the efficacy of antibiotic treatment, but also to define the potential population to be treated and how long should be the optimal treatment period", concluded Dr Gurfinkel.