Infection and Risk of Ischemic Stroke

Paganini-Hill, A.; Lozano, Edward; Fischberg, Glenn M; Barreto, Maria Perez; Rajamani, Kumar; Ameriso, Sebastián F.; Heseltine, Peter N. R.; Fisher, Mark

doi:10.1161/01.str.0000053451.28410.98

Cited by 83 publications

(59 citation statements)

References 32 publications

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“…Several observational clinical studies have reported associations between preceding common infections (mainly respiratory tract infections) and ischemic stroke (Grau et al 2010). The reported prevalence of preceding infection, and timing prior to index stroke varies considerably between these studies, and one study found no difference in the prevalence of recent infection between cases and controls (Paganini-Hill et al 2003). In the largest study, based on the UK General Practice Research…”

Section: The Immune System and Strokementioning

confidence: 99%

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Smith

Lawrence

Rodriguez‐Grande

et al. 2013

J Neuroimmune Pharmacol

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Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome.Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infectionsimilar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches.

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Section: The Immune System and Strokementioning

confidence: 99%

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Smith

Lawrence

Rodriguez‐Grande

et al. 2013

J Neuroimmune Pharmacol

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“…29 Our data suggest that atrial fibrillation partially explains the infection-stroke association, consistent with previous reports of an association between acute infection and an increased risk of cardioembolic stroke. 12,30 Studies have also shown that acute infection is associated with stroke due to large-vessel atherothromboembolism. 12 Interestingly, cardioembolic strokes and largeartery infarcts are ischemic stroke types that are more common in whites compared with blacks.…”

mentioning

confidence: 99%

Acute infection contributes to racial disparities in stroke mortality

2014

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Objective: It is unknown whether racial differences in exposure to acute precipitants of stroke, specifically infection, contribute to racial disparities in stroke mortality.Methods: Among participants in the nationally representative Health and Retirement Study with linked Medicare data (1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007), we conducted a case-crossover study employing withinperson comparisons to study racial/ethnic differences in the risks of death and hospitalization from ischemic stroke following acute infection.Results: There were 964 adults hospitalized for ischemic stroke. Acute infection increased the 30-day risks of ischemic stroke death (5.82-fold) and ischemic stroke hospitalization (1.87-fold). Acute infection was a more potent trigger of acute ischemic stroke death in non-Hispanic blacks (odds ratio [OR] 39.21; 95% confidence interval [CI] 9.26-166.00) than in nonHispanic whites (OR 4.50; 95% CI 3.14-6.44) or Hispanics (OR 5.18; 95% CI 1.34-19.95) (race-by-stroke interaction, p 5 0.005). When adjusted for atrial fibrillation, infection remained more strongly associated with stroke mortality in blacks (OR 34.85) than in whites (OR 3.58) and Hispanics (OR 3.53). Acute infection increased the short-term risk of incident stroke similarly across racial/ethnic groups. Infection occurred often before stroke death in non-Hispanic blacks, with 70% experiencing an infection in the 30 days before stroke death compared to a background frequency of 15%.Conclusions: Acute infection disproportionately increases the risk of stroke death for nonHispanic blacks, independently of atrial fibrillation. Stroke incidence did not explain this finding. Acute infection appears to be one factor that contributes to the black-white disparity in stroke mortality. Significant racial disparities in stroke mortality persist in the United States and are widening. [1][2][3] Non-Hispanic blacks have a greater risk of dying from stroke than non-Hispanic whites, and the excess risk of stroke death increased 55% for men and 26% for women from 1979 to 2006. 2While much attention has focused on the role of differences in vascular risk factors or health behaviors in these racial disparities, 2,4 less attention has focused on whether racial differences in exposure to acute precipitants of stroke, so-called triggers, might contribute to racial differences in stroke mortality.Acute infection may precipitate stroke. 5 However, confounding by vascular risk factors or social class may bias estimates, leading to false-positive associations between infection and stroke.6 Given that randomized controlled trials of infection precipitating stroke are unfeasible, observational study designs that minimize confounding, such as a case-crossover study in which each person serves as his or her own control, can be used.7-9 Two case-crossover studies 10,11 suggest that acute infection is a trigger of incident stroke, yet another does not. 12From the

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“…Furthermore, poststroke infections affect clinical outcome (164). Respiratory-and urinary tract infections are the most common types of infection preceding stroke after adjustment for age and conventional vascular risk factors (165,166).…”

Section: Systemic Inflammation and Infection: The Need For Appropriatmentioning

confidence: 99%

Modeling Risk Factors and Confounding Effects in Stroke

2016

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Most research to date has used experimental models in rodents which fail to mimic the underlying causes of stroke in patients or the primary confounding factors. Available data indicate that factors such as atherosclerosis, hypertension, obesity, diabetes, age, and inflammation have a major influence on outcome. These findings suggest that we need to rethink the preclinical data that are required before selection of candidate interventions for clinical trials in stroke.

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Infection and Risk of Ischemic Stroke

Cited by 83 publications

References 32 publications

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Acute infection contributes to racial disparities in stroke mortality

Modeling Risk Factors and Confounding Effects in Stroke

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