‘Infectious Burden’ - New Insights into Stroke Prevention

Abstract

Atherosclerosis is a complex inflammatory disease process of the arterial vessels.1 Chronic and acute infections have been implicated as risk factors that increase the risk of stroke, myocardial infarction (MI) and other vascular events. However, no single pathogen is likely to be responsible for elevated vascular risk. Pathogens as Risk Factors for Atherosclerosis Chlamydia pneumoniaeChlamydia pneumoniae is a common respiratory pathogen believed to be responsible for approximately 10% of non-hospital-acquired pneumonias. 3 C. pneumoniae is one of the best-studied organisms believed to be associated with cardiovascular disease. Studies that have evaluated human samples of atherosclerotic lesions using electron microscopy, molecular DNA methods and immunostaining techniques have identified C. pneumoniae in coronary, carotid, aortic and popliteal plaque. 4 The majority of these studies have identified pathogen DNA or antigen only; however, a few studies have isolated viable C. pneumoniae organisms. 5,6 C. pneumoniae has been identified in both early-and late-stage fibrous plaque and, in particular, in carotid and cerebral arterial vessels. 7-9Herpesvirus FamilyHerpesviruses were initially identified as potential causes of atherosclerosis in animal models, and they have been the target of investigations into the association of infectious agents and atherosclerosis since then. 10 The most thoroughly investigated of the eight herpesvirus known to commonly infect humans are herpes simplex virus 1 (HSV1), HSV2 and cytomegalovirus (CMV). HSV1infection has been associated with accelerated atheroma formation in apolipoprotein E -/-(apoE -/-) mice, with a reduction in progression when treated with antiviral therapies. 11 HSV1 DNA has been found in some but not all samples of carotid atherosclerotic lesions. 12,13 The recurrent outbreaks associated with HSV infection and high population prevalence of exposure have made it an interesting target for epidemiological study. 'Infectious Burden' -New Insights into Stroke PreventionBrain Trauma Stroke AbstractChronic and acute infections have been implicated as risk factors that increase the risk of stroke, myocardial infarction (MI) and other vascular events. The lack of consistency among studies attempting to link exposure to infectious pathogens and stroke risk provides empirical evidence that a single pathogen is likely not responsible for stroke. Reconsidering exposure as an 'infectious burden' (IB) aligns with our understanding that the totality of pro-inflammatory agents can contribute to atherosclerosis and vascular risk. We define IB as the cumulative life-course exposure to infectious agents that elicit strong inflammatory responses and review the varied approaches to operationalising this measure.There is promising research investigating the role of acute and chronic IB suggesting that there may be a causal role of pathogens in atherosclerotic progression and plaque destabilisation to negatively affect vascular risk; however, the evidence is preliminary.