Chronic infection and coronary artery disease.

Coronary artery disease resulting from atherosclerosis causes more deaths in the Western world than any other disease. 88 Atherosclerosis results from the progressive buildup of plaque, which consists of a combination of lipids, smooth muscle cells, inflammatory cells, and extracellular matrix, within the intima of an artery. 103 As the plaque matures, the intimal cap that covers the atherosclerotic material has the potential to rupture. 118 Acute thrombosis can then result in unstable angina, myocardial infarction, or death. 109 Although much is known about the pathologic process whereby atherosclerotic plaque develops, in many cases, the underlying cause remains unclear. Certain risk factors associated with the development of atherosclerosis are well defined, including diabetes mellitus, hypertension, hyperlipidemia, tobacco abuse, and a positive family history. 26 These risk factors, however, combine to account for only about 50% of the observed incidents of atherosclerosis. 122 Additionally, these risk factors generally are only associations, and the exact mechanism by which they may contribute to the development of atherosclerosis is not known. Atherosclerosis is a common disease, but its incidence has not been constant. In the United States, the death rate from coronary artery disease began to increase in the 1950s, peaked in about 1963, and has been declining since. 43,72 Potential explanations for the falling incidence over the past 30 years include improved medications, altered lifestyles, and a reduction in smoking. An alternative explanation may be that atherosclerosis is following the course of a prolonged infectious epidemic. Some have also noted that the beginning of the decline in atherosclerosis-related deaths corresponds with the start of the common use of antibiotics. The question whether infections can cause diffuse and chronic arterial lesions has been debated for many years. Only more recently, however, has evidence regarding specific associations between atherosclerosis and a number of infectious agents been determined. In this article, the reported associations between atherosclerosis and a number of infectious agents are reviewed and presently available knowledge regarding potential mechanisms whereby these agents may play a causative role in atherosclerosis is reported.