Brain Trauma Stroke ‘Infectious Burden’ – New Insights into Stroke Prevention Jorge M Luna1 and Mitchell SV Elkind2
1. Graduate Research Assistant, and Doctoral Candidate; 2. Associate Professor of Neurology, Associate Chairman of Neurology, and Associate Professor of Epidemiology, Columbia University College of Physicians and Surgeons and Joseph Mailman School of Public Health, Columbia University
Abstract
Chronic 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.
Keywords
Stroke, atherosclerosis, cerebral thrombosis, cerebral infarction, infection, infectious burden, Chlamydia pneumoniae, Helicobacter pylori, herpesviruses, risk factors, epidemiology
Disclosure: The authors have no conflicts of interest to declare. Received: 3 June 2010 Accepted: 30 June 2010 Citation: European Neurological Review, 2010;5(1):34–8 Correspondence: Mitchell SV Elkind, Neurological Institute, Box 182, 710 West 168 Street, New York, NY 10032, US. E:
mse13@columbia.edu
Atherosclerosis is a complex inflammatory disease process of the arterial vessels.1
More likely, the
Herpesvirus Family
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.2
combined effect of long-term exposure to multiple pathogens, or ‘infectious burden’ (IB), is more relevant to the study of vascular disease and stroke. The role of infections in vascular disease may also extend to acute precipitants of vascular events. This article reviews the postulated mechanisms of infection-induced vascular damage, host determinants of infection-mediated vascular effects and clinical evidence linking individual and composite measures of IB and stroke risk, and also provides a review of recent research evaluating intervention strategies.
Pathogens as Risk Factors for Atherosclerosis Chlamydia pneumoniae Chlamydia pneumoniae is a common respiratory pathogen believed to be responsible for approximately 10% of non-hospital-acquired pneumonias.3
Herpesviruses 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). HSV1 infection has been associated with accelerated atheroma formation in apolipoprotein E-/- (apoE-/-) mice, with a reduction in progression when treated with antiviral therapies.11
some but not all samples of carotid atherosclerotic lesions.12,13
HSV1 DNA has been found in The
recurrent outbreaks associated with HSV infection and high population prevalence of exposure have made it an interesting target for epidemiological study.11
For CMV, evidence for involvement in
vascular disease has been garnered from polymerase chain reaction (PCR) detection of CMV DNA in atherosclerotic lesions. For example, Hendrix et al. found CMV DNA in 90% of advanced atherosclerotic lesions compared with only 50% of control patients with no or minimal atherosclerosis.14
The complete CMV genome has been
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
identified in asymptomatic individuals, indicating persistent latent stage within the host cells.14,15
Additional evidence of CMV causing a
vasculopathy is derived from the evidence of association of CMV and advanced progression of atherosclerosis and vasculopathy in heart- transplant recipients.16
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.7–9
34
Helicobacter pylori Helicobacter pylori is a bacterium responsible for inflammation of the stomach lining, ulceration and stomach cancer. H. pylori has been found at higher rates in carotid endarterectomy plaque
© TOUCH BRIEFINGS 2010
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