Abstract
Several observational studies have suggested an association between periodontitis and cerebral ischemia. This meta-analysis aimed to investigate whether this link exists, and if so, the degree to which it is significant. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline for systematic review was used. The search strategy included using electronic databases and hand searching works published up to March 2015. MEDLINE via PubMed, EMBASE, Proceedings Web of Science and Current Contents Connect were searched by two independent reviewers. Case-control, cross-sectional or cohort studies including patients with measures of periodontitis and ischemic stroke were eligible to be included in the analysis. Quality assessments of selected studies were performed. From a total of 414 titles and abstracts, 57 potentially relevant full text papers were identified. After inclusion criteria were applied, 8 studies were included in the present systematic review (5 case-control and 3 cohort studies). Although it was not the intention, cross-sectional studies were excluded due to eligibility criteria were not accomplished. Therefore, meta-analyses were conducted with data retrieved from the 8 studies included. These meta-analyses showed statistically significant association between periodontitis and ischemic stroke in both cohort pooled relative risks at 2.52 (1.77–3.58), and case-control studies pooled relative risks at 3.04 (1.10–8.43). In conclusion, the present meta-analysis demonstrated an association between periodontitis and ischemic stroke. However, well-designed prospective studies should be carried out to provide robust evidence of the link between both diseases. In regards to ischemic stroke subtypes, further case-control studies should be carried out to investigate whether there is any association between the different subtypes of cerebral infarcts and periodontitis.
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References
Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics—2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006;113:85–151.
Vila-Córcoles A, Forcadell MJ, de Diego C, et al. Incidence and mortality of ischaemic stroke among people 60 years or older in the region of Tarragona, Spain [article in Spanish]. Rev Esp Salud Publica. 2015;89:597–605.
López-Espuela F, Pedrera-Zamorano JD, Jiménez-Caballero PE, et al. Functional status and disability in patients after acute stroke: a longitudinal study. Am J Crit Care. 2016;25:144–51.
Díaz-Guzmán J, Egido JA, Gabriel-Sánchez R, Barberá-Comes G, Fuentes-Gimeno B, Fernández-Pérez C. IBERICTUS study investigators of the stroke project of the spanish cerebrovascular diseases study group. Cerebrovasc Dis. 2012;34:272–81.
Kelly BM, Pangilinan PH Jr, Rodriguez GM. The stroke rehabilitation paradigm. Phys Med Rehabil Clin N Am. 2007;18:631–50.
Pihlstrom B, Michalowicz B, Johnson N. Periodontal diseases. Lancet. 2005;366:1809–20.
Albandar JM, Rams TE. Global epidemiology of periodontal diseases: an overview. Periodontol 2000. 2002;29:7–10.
Elter JR, Offenbacher S, Toole JF, Beck JD. Relationship of periodontal disease and edentulism to stroke/TIA. J Dent Res. 2003;82:998–1001.
You Z, Cushman M, Jenny NS, Howard G. REGARDS. Tooth loss, systemic inflammation, and prevalent stroke among participants in the reasons for geographic and racial difference in stroke (REGARDS) study. Atherosclerosis. 2009;203:615–9.
Beck J, Garcia R, Heiss G, Vokonas PS, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol. 1996;67:1123–37.
Wu T, Trevisan M, Genco RJ, Dorn JP, Falkner KL, Sempos CT. Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study. Arch Intern Med. 2000;160:2749–55.
Jimenez M, Krall EA, Garcia RI, Vokonas PS, Dietrich T. Periodontitis and incidence of cerebrovascular disease in men. Ann Neurol. 2009;66:505–12.
Grau AJ, Becher H, Ziegler CM, et al. Periodontal disease as a risk factor for ischemic stroke. Stroke. 2004;35:496–501.
Dörfer CE, Becher H, Ziegler CM, et al. The association of gingivitis and periodontitis with ischemic stroke. J Clin Periodontol. 2004;31:396–401.
Sim SJ, Kim HD, Moon JY, et al. Periodontitis and the risk for non-fatal stroke in Korean adults. J Periodontol. 2008;79:1652–8.
Pradeep AR, Hadge P, Arjun Raju P, Shetty SR, Guruprasad CN. Periodontitis as a risk factor for cerebrovascular accident: a case-control study in the Indian population. J Periodontal Res. 2010;45:223–8.
Lafon A, Tala S, Ahossi V, Perrin D, Giroud M, Béjot Y. Association between periodontal disease and non-fatal ischemic stroke: a case-control study. Acta Odontol Scand. 2014;72:687–93.
Leira Y, Blanco M, Blanco J, Castillo J. Association between periodontal disease and cerebrovascular disease. A review of the literature [article in Spanish]. Rev Neurol. 2015;60:29–38.
Schenkein HA, Loos BG. Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases. J Clin Periodontol. 2013;40(Suppl. 14):51–69.
Janket SK, Baird AE, Chuang SK, Jones JA. Meta-analysis of periodontal disease and risk of coronary heart disease and stroke. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95:559–69.
Khader YS, Albashaireh ZS, Alomari MA. Periodontal diseases and the risk of coronary heart and cerebrovascular diseases: a meta-analysis. J Periodontol. 2004;75:1046–53.
Sfyroeras GS, Roussas N, Saleptsis VG, Argyriou C, Giannoukas AD. Association between periodontal disease and stroke. J Vasc Surg. 2012;55:1178–84.
Lafon A, Pereira B, Dufour T, et al. Periodontal disease and stroke: a meta-analysis of cohort studies. Eur J Neurol. 2014;21:1155–61.
Armitage GC. Development of classification system for periodontal diseases and conditions. Ann Periodontol. 1999;4:1–6.
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62:1–34.
Kokotailo RA, Hill MD. Coding of stroke and stroke risk factors for using international classification for diseases, revisions 9 and 10. Stroke. 2005;36:1776–81.
Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definition for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment. Stroke. 1993;24:35–41.
Takkouche B, Cadarso-Suárez C, Spiegelman D. Evaluation of old and new tests of heterogeneity in epidemiologic meta-analysis. Am J Epidemiol. 1999;150:206–15.
Costa-Bouzas J, Takkouche B, Cadarso-Suárez C, Spiegelman D, Hepi MA. HEpiMA: a software for the identification of heterogeneity in meta-analysis. Comput Methods Programs Biomed. 2001;64:101–7.
Epidat: programa para análisis epidemiolóxico de datos. Versión 4.1, outubro 2014. Consellería de Sanidade, Xunta de Galicia, España; Organización Panamericana da saúde (OPS-OMS); Universidade CES, Colombia. Dispoñible en: http://dxsp.sergas.es.
Balshem H, Helfand M, Schünemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401–6.
Abnet CC, Qiao YL, Dawsey SM, Dong ZW, Taylor PR, Mark SD. Tooth loss is associated with increased risk of total death and death from upper gastrointestinal cancer, heart disease, and stroke in a Chinese population-based cohort. Int J Epidemiol. 2005;34:467–74.
Heitmann BL, Gamborg M. Remaining teeth, cardiovascular morbidity and death among adult Danes. Prev Med. 2008;47:156–60.
Tu YK, Galobardes B, Smith GD, McCarron P, Jeffreys M, Gilthorpe MS. Associations between tooth loss and mortality patterns in the Glasgow Alumni Cohort. Heart. 2007;93:1098–103.
Choe H, Kim YH, Park JW, Kim SY, Lee SY, Jee SH. Tooth loss, hypertension and risk for stroke in a Korean population. Atherosclerosis. 2009;203:550–6.
Joshipura KJ, Hung HC, Rimm EB, Willett WC, Ascherio A. Periodontal disease, tooth loss, and incidence of ischemic stroke. Stroke. 2003;34:47–52.
Howell TH, Ridker PM, Ajani UA, Hennekens CH, Christen WG. Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians. J Am Coll Cardiol. 2001;37:445–50.
Yu YH, Chasman DI, Buring JE, Rose L, Ridker PM. Cardiovascular risks associated with incident and prevalent periodontal disease. J Clin Periodontol. 2015;42:21–8.
Pearce N, Checkoway H, Kriebel D. Bias in occupational epidemiology studies. Occup Environ Med. 2007;64:562–8.
Delgado-Rodríguez M, Llorca J. Bias. J Epidemiol Commun Health. 2004;58:635–41.
Fahey MT, Forbes AB, Hodge AM. Correcting for the bias caused by exposure measurement error in epidemiological studies. Respirology. 2014;19:979–84.
Lee YL, Hu HY, Huang N, Hwang DK, Chou P, Chu D. Dental prophylaxis and periodontal treatment are protective factors to ischemic stroke. Stroke. 2013;44:1026–30.
Acknowledgments
Y. Leira is recipient of a fellowship from Health Research Institute of Santiago de Compostela (IDIS). Furthermore, we thank Dr. Zhiying You (Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, United States) for providing additional information about his study.
Funding
This study has been partially supported by grants from Instituto de Salud Carlos III (PI13/02027), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS (RD12/0014), Xunta de Galicia (Consellería Educación GRC2014/027) and the European Union program FEDER. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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To qualify for authorship, we indicate the contribution of each author to this manuscript: Leira, Y: conception and design, acquisition of data, analysis and interpretation of data, drafting the article, revising it critically for important intellectual content and final approval of the version to be published. Seoane, J: conception and design, acquisition of data, analysis and interpretation of data, revising the article critically for important intellectual content and final approval of the version to be published. Blanco, M; Rodríguez-Yáñez, M: revising the article critically for important intellectual content and final approval of the version to be published. Takkouche, B: analysis and interpretation of data, revising the article critically for important intellectual content and final approval of the version to be published. Blanco, J; Castillo, J: conception and design, revising the article critically for important intellectual content and final approval of the version to be published.
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Leira, Y., Seoane, J., Blanco, M. et al. Association between periodontitis and ischemic stroke: a systematic review and meta-analysis. Eur J Epidemiol 32, 43–53 (2017). https://doi.org/10.1007/s10654-016-0170-6
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DOI: https://doi.org/10.1007/s10654-016-0170-6