Atherosclerosis—a narrowing of the coronary arteries that leads to most strokes and heart attacks—causes approximately half of all adult deaths in the Western world. But traditional risk factors, such as elevated cholesterol and cigarette smoking, account for only about half of that total. Scientists searching for a reason behind the other 50 percent began to consider infections once it became clear that inflammation—a generalized immune response against any perceived invader—also underlies the growth and destructive ruptures of the fat-laden deposits that constrict coronary arteries [see "Atherosclerosis: The New View," by Peter Libby; scientific american, May 2002].

C. pneumoniae became a prime suspect in the condition shortly after it was identified as a separate chlamydial species in 1983. It drew suspicion because of its ubiquity—more than 60 percent of adults world wide carry antibodies against it (a sign of past or ongoing infection). Support forthe hunch emerged in 1988, when physicians in Finland reported a positive correlation between the presence of these antibodies and the risk of developing coronary artery disease; other researchers identified the bacterium in clogged human arteries five years later. Since then, organizations such as the National Institutes of Health and the American Heart Association have invested millions of dollars to study the relation between C. pneumoniae and atherosclerosis.

Animal studies conducted within the past five years or so have provided some of the most convincing evidence for a link. One demonstrated, for example, that chlamydial bacteria can move from the lungs of mice to other parts of the body within white blood cells, the agents responsible for inflammation. Other research has shown that C. pneumoniae infections accelerate atherosclerosis in both mice and rabbits and that antichlamydial antibiotics can preventthat acceleration.

Experimental results such as these, though tentative, were enough to justify a handful of small clinical trials in humans. Five of these trials showed that one to three months of antibiotic treatment had a statistically significant benefit against the progression of atherosclerosis. But results were mixed as to whet her the antibiotics could actually prevent serious cardiac events. The promise for longer-term treatment was also dealt a blow by the negative outcomes of two large trials completed in 2004, each involving 4,000 volunteers who received antibiotics for one to two years.

Establishing whether a clear connection exists between C. pneumoniae infection and atherosclerosis in humans may prove difficult simply because so many other factors participate in heart disease. Exactly how troublesome such complications will be, however, remains to be seen.     —D.M.O., T.D. and P.M.B.

ARTEROSCLEROSIS & BLOCKING OXIDATIVE DAMAGE