Infection with Chlamydia pneumoniae as a cause of coronary heart disease: the hypothesis is still untested.

Abstract

We are convinced that Chlamydia pneumoniae research has been unfavorably affected by the negative results of antibiotic treatment trials for the secondary prevention of late-stage coronary heart disease (CHD) (O'Connor et al. , 2003; Cannon et al. , 2005; Grayston et al. , 2005). There is a widespread belief that the clinical trials showed that C. pneumoniae has no role in atherosclerotic disease. This flawed causal inference from these trials has contributed to slowing much-needed research on C. pneumoniae. It has also resulted in a nearly complete loss of momentum for research on the infection-based response to injury hypothesis as a key factor in the initiation and progression of CHD. ### Box 1 Chlamydia pneumoniae had been considered a possible cause of atherosclerosis. That antibiotics failed to prevent secondary coronary events in patients with established coronary artery disease has been erroneously interpreted as ruling out a causative role for C. pneumoniae . This misinterpretation has had a chilling effect on C. pneumoniae research. Our concern has been confirmed by the sharp drop in published reports (PubMed citations) on C. pneumoniae since 2005. From 1999 to 2005, approximately 375 papers were published each year. There has been a 62% drop from that number with 143 being listed for 2013. The antibiotic treatment trials were not etiologic studies. No inference regarding the role of C. pneumoniae in the cause of atherosclerosis can properly be made from the trials. A prior publication stated that the study design for these trials precluded proving or disproving a role for C. pneumoniae in the initiation or progression of atherosclerosis, and predicted an overreaction to either negative or positive results (Grayston 2000). All subjects of these trials had established coronary artery disease with mostly advanced disease. Most had had a myocardial infarction (MI). The trials studied whether antibiotics could prevent …