Inflammation, infection, and cardiovascular risk: how good is the clinical evidence?

Abstract

Despite substantial gains in the prevention and treatment of acute myocardial infarction, many atherothrombotic events occur among individuals without readily apparent risk factors. Several lines of basic research indicate that inflammation and perhaps chronic infection may play important roles in the initiation and progression of atherosclerosis. For example, pathological studies demonstrate that atherosclerotic lesions are heavily infiltrated with cellular components associated with inflammation, influx of neutrophils into the walls of the epicardial vessels has been demonstrated in response to acute ischemia, and sites of acute plaque rupture are preferentially associated with inflammatory components.1 2 3 4 5 6 Further, proinflammatory cytokines as well as cellular adhesion molecules involved in the attachment of monocytes to the endothelial wall appear to be critical in early atherogenesis.7 8 With regard to chronic infection, evidence of prior exposure to Chlamydia pneumoniae , cytomegalovirus, and Helicobacter pylori has been detected within human atherosclerotic tissues,9 10 11 12 13 14 and it has been hypothesized that these organisms may activate vessel-associated leukocytes or lead to a transformation of vascular smooth muscles or endothelial cells.15 In addition, animal studies suggest that infection with cytomegalovirus and perhaps other agents can lead to endothelial lesions similar to that of human atherosclerosis.16 17 From an epidemiological perspective, however, the role of inflammation and infection as potential cardiovascular risk factors is far from certain. Although several studies have reported associations between exposure to various infectious agents and prevalent coronary disease,18 19 20 21 22 23 24 25 these data derive almost exclusively from cross-sectional or retrospective studies that cannot establish a temporal relation between exposure and disease. Furthermore, it is difficult for cross-sectional and retrospective studies to exclude the possibility that observed associations are the result of inadvertent selection bias or residual confounding on the …