Abstract
The occurrence of stroke in populations is incompletely explained by traditional vascular risk factors. Data from several case–control studies and one large study using case series methodology indicate that recent infection is a temporarily acting, independent trigger factor for ischemic stroke. Both bacterial and viral infections, particularly respiratory tract infections, contribute to this association. A causal role for infection in stroke is supported by a graded temporal relationship between these conditions, and by multiple pathophysiological pathways linking infection and inflammation, thrombosis, and stroke. Furthermore, observational studies suggest that influenza vaccination confers a preventive effect against stroke. Case–control and prospective studies indicate that chronic infections, such as periodontitis, chronic bronchitis and infection with Helicobacter pylori, Chlamydia pneumoniae or Cytomegalovirus, might increase stroke risk, although considerable variation exists in the results of these studies, and methodological issues regarding serological results remain unresolved. Increasing evidence indicates that the aggregate burden of chronic and/or past infections rather than any one single infectious disease is associated with the risk of stroke. Furthermore, genetic predispositions relating to infection susceptibility and the strength of the inflammatory response seem to codetermine this risk. Here, we summarize and analyze the evidence for common acute and chronic infectious diseases as stroke risk factors.
Key Points
-
Acute bacterial and viral infections (mainly respiratory infections) transiently increase the risk of ischemic stroke—an effect mainly observed during the first week after infection onset
-
The association between acute infection and stroke is not dependent on particular microbial agents but, rather, results from the inflammatory response to infection, which induces a procoagulant state
-
Periodontitis, chronic bronchitis, and infection with Helicobacter pylori or Chlamydia pneumoniae might be associated with an increase in stroke risk; however, whether such chronic infections are causally related to stroke remains undetermined
-
The aggregate burden of chronic persistent infections and/or past infections rather than one single infectious disease seems to be associated with stroke risk
-
Observational studies suggest that influenza vaccination has a protective effect against stroke
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kelly-Hayes, M. et al. Temporal patterns of stroke onset. The Framingham Study. Stroke 26, 1343–1347 (1995).
Rothwell, P. M., Wroe, S. J., Slattery, J. & Warlow, C. P. Is stroke incidence related to season or temperature? The Oxfordshire Community Stroke Project. Lancet 347, 934–936 (1996).
Freud, S. Die infantile Cerebrallähmung 1–327 (Holder, Wien, 1897).
Marie, S. Infantile cerebral hemiparesis and infectious diseases [French]. Progrès Méd. 13, 167–169 (1885).
Bickerstaff, E. R. Aetiology of acute hemiplegia in childhood. Br. Med. J. 2, 82–87 (1964).
Hindfelt, B. & Nilsson, O. Brain infarction in young adults (with particular reference to pathogenesis). Acta Neurol. Scand. 55, 145–157 (1977).
Syrjänen, J., Valtonen, V. V., Iivanainen, M., Kaste, M. & Huttunen, J. K. Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients. Br. Med. J. (Clin. Res. Ed.) 296, 1156–1160 (1988).
Grau, A. J. et al. Recent bacterial and viral infection is a risk factor for cerebrovascular ischemia: clinical and biochemical studies. Neurology 50, 196–203 (1998).
Grau, A. J. et al. Recent infection as a risk factor for cerebrovascular ischemia. Stroke 26, 373–379 (1995).
Bova, I. Y., Bornstein, N. M. & Korczyn, A. D. Acute infection as a risk factor for ischemic stroke. Stroke 27, 2204–2206 (1996).
Macko, R. F. et al. Precipitants of brain infarction. Roles of preceding infection/inflammation and recent psychological stress. Stroke 27, 1999–2004 (1996).
Nagaraja, D. et al. Preceding infection as a risk factor of stroke in the young. J. Assoc. Physicians India 47, 673–675 (1999).
Nencini, P., Sarti, C., Innocenti, R., Pracucci, G. & Inzitari, D. Acute inflammatory events and ischemic stroke subtypes. Cerebrovasc. Dis. 15, 215–221 (2003).
Paganini-Hill, A. et al. Infection and risk of ischemic stroke: differences among stroke subtypes. Stroke 34, 452–457 (2003).
Clayton, T. C., Thompson, M. & Meade, T. W. Recent respiratory infection and risk of cardiovascular disease: case–control study through a general practice database. Eur. Heart J. 29, 96–103 (2008).
Zurru, M. C. et al. Recent respiratory infection predicts atherothrombotic stroke: case–control study in a Buenos Aires healthcare system. Stroke 40, 1986–1990 (2009).
Smeeth, L. et al. Risk of myocardial infarction and stroke after acute infection or vaccination. N. Engl. J. Med. 351, 2611–2618 (2004).
Eickhoff, T. C., Sherman, I. L. & Serfling, R. E. Observations on excess mortality associated with epidemic influenza. JAMA 176, 776–782 (1961).
Gordon, T. & Thom, T. The recent decrease in CHD mortality. Prev. Med. 4, 115–125 (1975).
Soltero, I., Liu, K., Cooper, R., Stamler, J. & Garside, D. Trends in mortality from cerebrovascular diseases in the United States, 1960 to 1975. Stroke 9, 549–558 (1978).
Field, T. S., Zhu, H., Tarrant, M., Mitchell, J. R. & Hill, M. D. Relationship between supra-annual trends in influenza rates and stroke occurrence. Neuroepidemiology 23, 228–235 (2004).
Curwen, M. Excess winter mortality: a British phenomenon. Health Trends 22, 169–175 (1990).
Grau, A. J. et al. Clinical and biochemical analysis in infection-associated stroke. Stroke 26, 1520–1526 (1995).
Grau, A. J. et al. Lack of evidence for pulmonary venous thrombosis in cryptogenic stroke: a magnetic resonance angiography study. Stroke 33, 1416–1419 (2002).
Grau, A. J. et al. Association of cervical artery dissection with recent infection. Arch. Neurol. 56, 851–856 (1999).
Guillon, B. et al. Infection and the risk of spontaneous cervical artery dissection: a case–control study. Stroke 34, e79–e81 (2003).
Schievink, W. I., Wijdicks, E. F. & Kuiper, J. D. Seasonal pattern of spontaneous cervical artery dissection. J. Neurosurg. 89, 101–103 (1998).
Paciaroni, M. et al. Seasonal variability in spontaneous cervical artery dissection. J. Neurol. Neurosurg. Psychiatry 77, 677–679 (2006).
Genius, J., Dong-Si, T., Grau, A. P. & Lichy, C. Postacute C-reactive protein levels are elevated in cervical artery dissection. Stroke 36, e42–e44 (2005).
Jørgensen, H. S., Reith, J., Pedersen, P. M., Nakayama, H. & Olsen, T. S. Body temperature and outcome in stroke patients. Lancet 348, 193 (1996).
Ameriso, S. F., Wong, V. L., Quismorio, F. P. Jr & Fisher, M. Immunohematologic characteristics of infection-associated cerebral infarction. Stroke 22, 1004–1009 (1991).
McColl, B. W., Rothwell, N. J. & Allan, S. M. Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1- and neutrophil-dependent mechanisms. J. Neurosci. 27, 4403–4412 (2007).
Grau, A. J. et al. Fever and infection early after ischemic stroke. J. Neurol. Sci. 171, 115–120 (1999).
Rosenzweig, H. L. et al. Endotoxin preconditioning prevents cellular inflammatory response during ischemic neuroprotection in mice. Stroke 35, 2576–2581 (2004).
Grayston, J. T., Kuo, C. C., Wang, S. P. & Altman, J. A new Chlamydia psittaci strain, TWAR, isolated in acute respiratory tract infections. N. Engl. J. Med. 315, 161–168 (1986).
Urra, X., Obach, V. & Chamorro, A. Stroke induced immunodepression syndrome: from bench to bedside. Curr. Mol. Med. 9, 195–202 (2009).
Epstein, S. E., Zhu, J., Najafi, A. H. & Burnett, M. S. Insights into the role of infection in atherogenesis and in plaque rupture. Circulation 119, 3133–3141 (2009).
Wimmer, M. L., Sandmann-Strupp, R., Saikku, P. & Haberl, R. L. Association of chlamydial infection with cerebrovascular disease. Stroke 27, 2207–2210 (1996).
Cook, P. J. et al. Chlamydia pneumoniae antibody titers are significantly associated with acute stroke and transient cerebral ischemia: the West Birmingham Stroke Project. Stroke 29, 404–410 (1998).
Glader, C. A. et al. Chlamydia pneumoniae antibodies and high lipoprotein(a) levels do not predict ischemic cerebral infarctions. Results from a nested case–control study in Northern Sweden. Stroke 30, 2013–2018 (1999).
Fagerberg, B., Gnarpe, J., Gnarpe, H., Agewall, S. & Wikstrand, J. Chlamydia pneumoniae but not cytomegalovirus antibodies are associated with future risk of stroke and cardiovascular disease: a prospective study in middle-aged to elderly men with treated hypertension. Stroke 30, 299–305 (1999).
Elkind, M. S., Lin, I. F., Grayston, J. T. & Sacco, R. L. Chlamydia pneumoniae and the risk of first ischemic stroke: the Northern Manhattan Stroke Study. Stroke 31, 1521–1525 (2000).
Heuschmann, P. U. et al. Association between infection with Helicobacter pylori and Chlamydia pneumoniae and risk of ischemic stroke subtypes: results from a population-based case–control study. Stroke 32, 2253–2258 (2001).
Madre, J. G. et al. Association between seropositivity to Chlamydia pneumoniae and acute ischaemic stroke. Eur. J. Neurol. 9, 303–306 (2002).
Tanne, D. et al. Prospective study of Chlamydia pneumoniae IgG and IgA seropositivity and risk of incident ischemic stroke. Cerebrovasc. Dis. 16, 166–170 (2003).
Ngeh, J., Gupta, S., Goodbourn, C., Panayiotou, B. & McElligott, G. Chlamydia pneumoniae in elderly patients with stroke (C-PEPS): a case–control study on the seroprevalence of Chlamydia pneumoniae in elderly patients with acute cerebrovascular disease. Cerebrovasc. Dis. 15, 11–16 (2003).
Anzini, A. et al. Chlamydia pneumoniae infection in young stroke patients: a case–control study. Eur. J. Neurol. 11, 321–327 (2004).
Johnsen, S. P. et al. Chlamydia pneumoniae seropositivity and risk of ischemic stroke: a nested case–control study. Eur. J. Epidemiol. 20, 59–65 (2005).
Elkind, M. S. et al. Seropositivity to Chlamydia pneumoniae is associated with risk of first ischemic stroke. Stroke 37, 790–795 (2006).
Piechowski-Jozwiak, B., Mickielewicz, A., Gaciong, Z., Berent, H. & Kwiecinski, H. Elevated levels of anti-Chlamydia pneumoniae IgA and IgG antibodies in young adults with ischemic stroke. Acta Neurol. Scand. 116, 144–149 (2007).
Bandaru, V. C. et al. Chlamydia pneumoniae antibodies in various subtypes of ischemic stroke in Indian patients. J. Neurol. Sci. 272, 115–122 (2008).
Lin, T. M. et al. The association of C (–260)→ T polymorphism in CD14 promoter and Chlamydia pneumoniae infection in ischemic stroke patients. Am. J.Clin. Pathol. 130, 595–601 (2008).
Alamowitch, S., Labreuche, J., Touboul, P. J., Eb, F. & Amarenco, P. Chlamydia pneumoniae seropositivity in aetiological subtypes of brain infarction and carotid atherosclerosis: a case control study. J. Neurol. Neurosurg. Psychiatry 79, 147–151 (2008).
Bandaru, V. C., Boddu, D. B., Laxmi, V., Neeraja, M. & Kaul, S. Seroprevalence of Chlamydia pneumoniae antibodies in stroke in young. Can. J. Neurol. Sci. 36, 725–730 (2009).
Apfalter, P. Chlamydia pneumoniae, stroke, and serological associations: anything learned from the atherosclerosis–cardiovascular literature or do we have to start over again? Stroke 37, 756–758 (2006).
Lindsberg, P. J. & Grau, A. J. Inflammation and infections as risk factors for ischemic stroke. Stroke 34, 2518–2532 (2003).
Prager, M. et al. Chlamydia pneumoniae in carotid artery atherosclerosis: a comparison of its presence in atherosclerotic plaque, healthy vessels, and circulating leukocytes from the same individuals. Stroke 33, 2756–2761 (2002).
Muller, J. et al. Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in healthy control subjects and patients with diabetes mellitus, acute coronary syndrome, stroke, and arterial hypertension. Scand. J. Infect. Dis. 35, 704–712 (2003).
Maass, M. et al. Poor correlation between microimmunofluorescence serology and polymerase chain reaction for detection of vascular Chlamydia pneumoniae infection in coronary artery disease patients. Med. Microbiol. Immunol. 187, 103–106 (1998).
Andraws, R., Berger, J. S. & Brown, D. L. Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials. JAMA 293, 2641–2647 (2005).
Illoh, K. O., Illoh, O. C., Feseha, H. B. & Hallenbeck, J. M. Antibiotics for vascular diseases: a meta-analysis of randomized controlled trials. Atherosclerosis 179, 403–412 (2005).
Luchsinger, J. A., Pablos-Mendez, A., Knirsch, C., Rabinowitz, D. & Shea, S. Antibiotic use and risk of ischemic stroke in the elderly. Am. J. Med. 111, 361–366 (2001).
Sander, D., Winbeck, K., Klingelhofer, J., Etgen, T. & Conrad, B. Progression of early carotid atherosclerosis is only temporarily reduced after antibiotic treatment of Chlamydia pneumoniae seropositivity. Circulation 109, 1010–1015 (2004).
McColl, K. E. Clinical practice. Helicobacter pylori infection. N. Engl. J. Med. 362, 1597–1604 (2010).
Ameriso, S. F., Fridman, E. A., Leiguarda, R. C. & Sevlever, G. E. Detection of Helicobacter pylori in human carotid atherosclerotic plaques. Stroke 32, 385–391 (2001).
Cremonini, F., Gabrielli, M., Gasbarrini, G., Pola, P. & Gasbarrini, A. The relationship between chronic H. pylori infection, CagA seropositivity and stroke: meta-analysis. Atherosclerosis 173, 253–259 (2004).
Pietroiusti, A. et al. Cytotoxin-associated gene-A-positive Helicobacter pylori strains are associated with atherosclerotic stroke. Circulation 106, 580–584 (2002).
Preusch, M. R. et al. Association between cerebral ischemia and cytotoxin-associated gene-A-bearing strains of Helicobacter pylori. Stroke 35, 1800–1804 (2004).
Zhang, S., Guo, Y., Ma, Y. & Teng, Y. Cytotoxin-associated gene-A-seropositive virulent strains of Helicobacter pylori and atherosclerotic diseases: a systematic review. Chin. Med. J. (Engl.) 121, 946–951 (2008).
De Bastiani, R. et al. High prevalence of Cag-A positive H. pylori strains in ischemic stroke: a primary care multicenter study. Helicobacter 13, 274–277 (2008).
Diomedi, M. et al. Cytotoxin-associated gene-A-positive Helicobacter pylori strains infection increases the risk of recurrent atherosclerotic stroke. Helicobacter 13, 525–531 (2008).
Janket, S. J., Baird, A. E., Chuang, S. K. & Jones, J. A. Meta-analysis of periodontal disease and risk of coronary heart disease and stroke. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 95, 559–569 (2003).
Chiu, B. Multiple infections in carotid atherosclerotic plaques. Am. Heart J. 138, S534–S536 (1999).
Grau, A. J. et al. Periodontal disease as a risk factor for ischemic stroke. Stroke 35, 496–501 (2004).
Sim, S. J. et al. Periodontitis and the risk for non-fatal stroke in Korean adults. J. Periodontol. 79, 1652–1658 (2008).
Desvarieux, M. et al. Gender differences in the relationship between periodontal disease, tooth loss, and atherosclerosis. Stroke 35, 2029–2035 (2004).
Jimenez, M., Krall, E. A., Garcia, R. I., Vokonas, P. S. & Dietrich, T. Periodontitis and incidence of cerebrovascular disease in men. Ann. Neurol. 66, 505–512 (2009).
Pussinen, P. J. et al. Antibodies to periodontal pathogens and stroke risk. Stroke 35, 2020–2023 (2004).
Pussinen, P. J., Alfthan, G., Jousilahti, P., Paju, S. & Tuomilehto, J. Systemic exposure to Porphyromonas gingivalis predicts incident stroke. Atherosclerosis 193, 222–228 (2007).
Mustapha, I. Z., Debrey, S., Oladubu, M. & Ugarte, R. Markers of systemic bacterial exposure in periodontal disease and cardiovascular disease risk: a systematic review and meta-analysis. J. Periodontol. 78, 2289–2302 (2007).
D'Aiuto, F. et al. Periodontal infections cause changes in traditional and novel cardiovascular risk factors: results from a randomized controlled clinical trial. Am. Heart J. 151, 977–984 (2006).
Tonetti, M. S. et al. Treatment of periodontitis and endothelial function. N. Engl. J. Med. 356, 911–920 (2007).
Grau, A. J. et al. Association between acute cerebrovascular ischemia and chronic and recurrent infection. Stroke 28, 1724–1729 (1997).
Grau, A. J. et al. Association of symptoms of chronic bronchitis and frequent flu-like illnesses with stroke. Stroke 40, 3206–3210 (2009).
Kiechl, S. et al. Active and passive smoking, chronic infections, and the risk of carotid atherosclerosis: prospective results from the Bruneck Study. Stroke 33, 2170–2176 (2002).
Elkind, M. S. Infectious burden: a new risk factor and treatment target for atherosclerosis. Infect. Disord. Drug Targets 10, 84–90 (2010).
Nieto, F. J. et al. Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis. Circulation 94, 922–927 (1996).
Espinola-Klein, C. et al. Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection? Stroke 31, 2127–2133 (2000).
Kis, Z. et al. Chronic infections and genetic factors in the development of ischemic stroke. New Microbiol. 30, 213–220 (2007).
Yi, L., Lin, J. Y., Gao, Y., Feng, Z. J. & Wang, D. X. Detection of human cytomegalovirus in the atherosclerotic cerebral arteries in han population in China. Acta Virol. 52, 99–106 (2008).
Saetta, A., Fanourakis, G., Agapitos, E. & Davaris, P. S. Atherosclerosis of the carotid artery: absence of evidence for CMV involvement in atheroma formation. Cardiovasc. Pathol. 9, 181–183 (2000).
Ridker, P. M., Hennekens, C. H., Stampfer, M. J. & Wang, F. Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke. Circulation 98, 2796–2799 (1998).
Espinola-Klein, C. et al. Impact of infectious burden on progression of carotid atherosclerosis. Stroke 33, 2581–2586 (2002).
Ngeh, J. & Goodbourn, C. Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila in elderly patients with stroke (C-PEPS, M-PEPS, L-PEPS): a case–control study on the infectious burden of atypical respiratory pathogens in elderly patients with acute cerebrovascular disease. Stroke 36, 259–265 (2005).
Corrado, E. et al. Markers of inflammation and infection influence the outcome of patients with baseline asymptomatic carotid lesions: a 5-year follow-up study. Stroke 37, 482–486 (2006).
Elkind, M. S. et al. Infectious burden and risk of stroke: the northern Manhattan study. Arch. Neurol. 67, 33–38 (2010).
Elkind, M. S. et al. Infectious burden and carotid plaque thickness: the northern Manhattan study. Stroke 41, e117–e122 (2010).
Szklo, M. et al. Individual pathogens, pathogen burden and markers of subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis. J. Cardiovasc. Med. (Hagerstown) 10, 747–751 (2009).
Galobardes, B., Smith, G. D. & Lynch, J. W. Systematic review of the influence of childhood socioeconomic circumstances on risk for cardiovascular disease in adulthood. Ann. Epidemiol. 16, 91–104 (2006).
Gussekloo, J., Schaap, M. C., Frölich, M., Blauw, G. J. & Westendorp, R. G. C-reactive protein is a strong but nonspecific risk factor of fatal stroke in elderly persons. Arterioscler. Thromb. Vasc. Biol. 20, 1047–1051 (2000).
Kiechl, S. et al. Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation 103, 1064–1070 (2001).
McColl, B. W., Allan, S. M. & Rothwell, N. J. Systemic infection, inflammation and acute ischemic stroke. Neuroscience 158, 1049–1061 (2009).
Grau, A. J. et al. Leukocyte count as an independent predictor of recurrent ischemic events. Stroke 35, 1147–1152 (2004).
Ogata, K. et al. Thrombosis-inducing activity in plasma of patients with acute respiratory tract infection disappears after treatment. Respiration 58, 176–180 (1991).
van der Poll, T. et al. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N. Engl. J. Med. 322, 1622–1627 (1990).
Cermak, J. et al. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 82, 513–520 (1993).
Esmon, C. T., Taylor, F. B. Jr & Snow, T. R. Inflammation and coagulation: linked processes potentially regulated through a common pathway mediated by protein C. Thromb. Haemost. 66, 160–165 (1991).
Lourbakos, A. et al. Activation of protease-activated receptors by gingipains from Porphyromonas gingivalis leads to platelet aggregation: a new trait in microbial pathogenicity. Blood 97, 3790–3797 (2001).
Macko, R. F. et al. Impairments of the protein C system and fibrinolysis in infection-associated stroke. Stroke 27, 2005–2011 (1996).
Zeller, J. A., Lenz, A., Eschenfelder, C. C., Zunker, P. & Deuschl, G. Platelet-leukocyte interaction and platelet activation in acute stroke with and without preceding infection. Arterioscler. Thromb. Vasc. Biol. 25, 1519–1523 (2005).
Gustafsson, C., Blomback, M., Britton, M., Hamsten, A. & Svensson, J. Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. Stroke 21, 47–51 (1990).
Ross, R. Atherosclerosis—an inflammatory disease. N. Engl. J. Med. 340, 115–126 (1999).
Mayr, M., Kiechl, S., Willeit, J., Wick, G. & Xu, Q. Infections, immunity, and atherosclerosis: associations of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis. Circulation 102, 833–839 (2000).
De Palma, R. et al. Patients with acute coronary syndrome show oligoclonal T-cell recruitment within unstable plaque: evidence for a local, intracoronary immunologic mechanism. Circulation 113, 640–646 (2006).
Keller, T. T. et al. Selective expansion of influenza A virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques. Stroke 39, 174–179 (2008).
Niessner, A. et al. Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-alpha. Circulation 114, 2482–2489 (2006).
Wiesel, J. The affection of arterial vessels during acute infections [German]. Zeitschr. f. Heilkunde 27, 262–294 (1906).
Somer, T. & Finegold, S. M. Vasculitides associated with infections, immunization, and antimicrobial drugs. Clin. Infect. Dis. 20, 1010–1036 (1995).
Pesonen, E., Paakkari, I. & Rapola, J. Infection-associated intimal thickening in the coronary arteries of children. Atherosclerosis 142, 425–429 (1999).
Liuba, P., Persson, J., Luoma, J., Yla-Herttuala, S. & Pesonen, E. Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media. Eur. Heart J. 24, 515–521 (2003).
Charakida, M. et al. Endothelial response to childhood infection: the role of mannose-binding lectin (MBL). Atherosclerosis 208, 217–221 (2010).
Hallenbeck, J. M. et al. Stroke risk factors prepare rat brainstem tissues for modified local Shwartzman reaction. Stroke 19, 863–869 (1988).
Siren, A. L. et al. Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Stroke 23, 1643–1650 (1992).
Flex, A. et al. Proinflammatory genetic profiles in subjects with history of ischemic stroke. Stroke 35, 2270–2275 (2004).
Markus, H. S. et al. Genetic and acquired inflammatory conditions are synergistically associated with early carotid atherosclerosis. Stroke 37, 2253–2259 (2006).
Hegele, R. A., Ban, M. R., Anderson, C. M. & Spence, J. D. Infection-susceptibility alleles of mannose-binding lectin are associated with increased carotid plaque area. J. Investig. Med. 48, 198–202 (2000).
Eickhoff, T. C. & Robinson, R. Q. Influenza surveillance, United States, 1960. Public Health Rep. 76, 1099–1106 (1961).
Housworth, J. & Langmuir, A. D. Excess mortality from epidemic influenza, 1957–1966. Am. J. Epidemiol. 100, 40–48 (1974).
Lavallee, P., Perchaud, V., Gautier-Bertrand, M., Grabli, D. & Amarenco, P. Association between influenza vaccination and reduced risk of brain infarction. Stroke 33, 513–518 (2002).
Grau, A. J. et al. Influenza vaccination is associated with a reduced risk of stroke. Stroke 36, 1501–1506 (2005).
Nichol, K. L. et al. Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. N. Engl. J. Med. 348, 1322–1332 (2003).
Davis, M. M. et al. Influenza vaccination as secondary prevention for cardiovascular disease: a science advisory from the American Heart Association/American College of Cardiology. J. Am. Coll. Cardiol. 48, 1498–1502 (2006).
Brassard, P., Bourgault, C., Brophy, J., Kezouh, A. & Suissa, S. Antibiotics in primary prevention of stroke in the elderly. Stroke 34, e163–e166 (2003).
Pleiner, J. et al. Simvastatin prevents vascular hyporeactivity during inflammation. Circulation 110, 3349–3354 (2004).
Steiner, S. et al. Simvastatin blunts endotoxin-induced tissue factor in vivo. Circulation 111, 1841–1846 (2005).
Author information
Authors and Affiliations
Contributions
A. J. Grau, researched the data for the article, provided substantial contributions to discussions of the content, and wrote the article. C. Urbanek and F. Palm researched the data for the article, provided substantial contributions to discussions of the content, and contributed equally to review and editing of the manuscript before submission.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Grau, A., Urbanek, C. & Palm, F. Common infections and the risk of stroke. Nat Rev Neurol 6, 681–694 (2010). https://doi.org/10.1038/nrneurol.2010.163
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrneurol.2010.163
This article is cited by
-
Secrets and lies of host–microbial interactions: MHC restriction and trans-regulation of T cell trafficking conceal the role of microbial agents on the edge between health and multifactorial/complex diseases
Cellular and Molecular Life Sciences (2024)
-
Research progress of different components of PM2.5 and ischemic stroke
Scientific Reports (2023)
-
Hospitalisation for lower respiratory tract infection is associated with an increased incidence of acute myocardial infarction and stroke in tropical Northern Australia
Scientific Reports (2021)
-
A case-based systematic review on the SARS-COVID-2-associated cerebrovascular diseases and the possible virus routes of entry
Journal of NeuroVirology (2021)
-
Acute cerebral infarction with adenomyosis in a patient with fever: a case report
BMC Neurology (2020)