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Date of Award

1-1-2002

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Health Research Methodology

Supervisor

Charles H. Goldsmith

Abstract

Human atherosclerosis is a disease of the blood vessel wall caused by an interplay between inflammatory, thrombotic, and lipid factors. A contributing or causal role for infection in that inflammatory response was first proposed in the 19th century, and with the advent of more sophisticated diagnostic techniques, a new search for a microbiologic etiology of human atherosclerosis has been rekindled. In this thesis, I examine methods for investigating whether infections contribute to human atherosclerotic cardiovascular disease. I explore three different technologies: serology (measuring antibody), inflammatory markers (as risk markers and as surrogates for infections), and the direct measurement of bacterial or viral DNA in the bloodstream. I examine three different study designs: cross-sectional, case-control, and cohort. Chlamydia pneumoniae , an obligate intracellular bacterium, is the primary focus of these studies. In addition, cytomegalovirus and other infections are included as controls, with the a priori expectation that these other infections would not be related to cardiovascular disease. We found a relationship between cardiovascular disease and C. pneumoniae antibody status in a small case-control study, but found no independent association in a large, prospective study. Inflammatory markers were measured in the prospective study, and were associated with cardiovascular events, yet no clear association between inflammation and infection was found. However, in developing methods for directly detecting bacterial and viral DNA in the bloodstream, we found that serology itself was not associated with current detection of bacterial DNA. Furthermore, we found a strong relationship between C. pneumoniae and smoking, and conclude that future studies need to examine the interaction between infection, inflammation, and smoking status.

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