Table of Contents
Epidemiology Research International
Volume 2014 (2014), Article ID 735378, 9 pages
http://dx.doi.org/10.1155/2014/735378
Review Article

The Infection Hypothesis Revisited: Oral Infection and Cardiovascular Disease

1Institute of Oral Biology, Dental Faculty, University of Oslo, PB 1052 Blindern, 0316 Oslo, Norway
2Institute of Basic Medical Sciences, Medical Faculty, University of Oslo, PB 1110 Blindern, 0317 Oslo, Norway

Received 29 June 2014; Revised 22 September 2014; Accepted 23 September 2014; Published 21 October 2014

Academic Editor: Jaume Marrugat

Copyright © 2014 Lise Lund Håheim. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. World Health Organization, http://www.who.int/research/en/.
  2. P. E. Petersen and H. Ogawa, “Strengthening the prevention of periodontal disease: the WHO approach,” Journal of Periodontology, vol. 76, no. 12, pp. 2187–2193, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. J. Chen, S. L. T. Normand, Y. Wang, E. E. Drye, G. C. Schreiner, and H. M. Krumholz, “Recent declines in hospitalizations for acute myocardial infarction for medicare fee-for-service beneficiaries: progress and continuing challenges,” Circulation, vol. 121, no. 11, pp. 1322–1328, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. L. L. Håheim, I. Holme, I. Hjermann, P. Leren, and S. Tonstad, “Trends in the incidence of acute myocardial infarction and stroke: a 21-year follow-up of the Oslo study,” Scandinavian Cardiovascular Journal, vol. 38, no. 4, pp. 216–221, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. L. B. Goldstein, R. Adams, M. J. Alberts et al., “Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council,” Stroke, vol. 37, no. 6, pp. 1583–1633, 2006, Erratum in Stroke, vol. 38, no. 1, p. 207, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. http://www.escardio.org/Pages/index.aspx.
  7. J. A. Berliner, M. Navab, A. M. Fogelman et al., “Atherosclerosis: basic mechanisms: oxidation, inflammation, and genetics,” Circulation, vol. 91, no. 9, pp. 2488–2496, 1995. View at Publisher · View at Google Scholar · View at Scopus
  8. R. Ross, “Aterosclerosis—an inflammatory disease,” The New England Journal of Medicine, vol. 340, pp. 115–126, 1999. View at Publisher · View at Google Scholar
  9. P. Libby, P. M. Ridker, and G. K. Hansson, “Inflammation in atherosclerosis: From pathophysiology to practice,” Journal of the American College of Cardiology, vol. 54, no. 23, pp. 2129–2138, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Kerrigan and D. Cox, “Biological mechanisms: platelets and bacteria—current scientific evidence and methods of analyses,” in Oral Infections and Cardiovascular Disease, vol. 6, chapter 6, pp. 45–66, Bentham Science, New York, NY, USA, 2011. View at Google Scholar
  11. S. O'Connor, C. Taylor, L. A. Campbell, S. Epstein, and P. Libby, “Potential infectious etiologies of atherosclerosis: a multifactorial perspective,” Emerging Infectious Diseases, vol. 7, no. 5, pp. 780–788, 2001. View at Publisher · View at Google Scholar · View at Scopus
  12. G. Dahlén, N.-E. Fiehn, I. Olsen, and U. Dahlgren, Oral Microbiology and Immunology, Munksgaard, Copenhagen, Denmark, 2012.
  13. P. I. Eke, B. A. Dye, L. Wei, G. O. Thornton-Evans, and R. J. Genco, “Prevalence of periodontitis in adults in the united states: 2009 and 2010,” Journal of Dental Research, vol. 91, no. 10, pp. 914–920, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. B. J. Paster, I. Olsen, J. A. Aas, and F. E. Dewhirst, “The breadth of bacterial diversity in the human periodontal pocket and other oral sites,” Periodontology, vol. 42, no. 1, pp. 80–87, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. B. Grinde and I. Olsen, “The role of viruses in oral disease,” Journal of Oral Microbiology, vol. 2, article 2127, 2010. View at Publisher · View at Google Scholar
  16. M. Enersen, “Risk factors for periodontal disease,” in Oral Infections and Cardiovascular Disease, chapter 5, Bentham Science, New York, NY, USA, 2011. View at Google Scholar
  17. F. DeStefano, R. F. Anda, H. S. Kahn, D. F. Williamson, and C. M. Russell, “Dental disease and risk of coronary heart disease and mortality,” British Medical Journal, vol. 306, no. 6879, pp. 688–691, 1993. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Rautemaa, A. Lauhio, M. P. Cullinan, and G. J. Seymour, “Oral infections and systemic disease—an emerging problem in medicine,” Clinical Microbiology and Infection, vol. 13, no. 11, pp. 1041–1047, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. G. J. Seymour, P. J. Ford, M. P. Cullinan, S. Leishman, and K. Yamazaki, “Relationship between periodontal infections and systemic disease,” Clinical Microbiology and Infection, vol. 13, supplement 4, pp. 3–10, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. X. Li, K. M. Kolltveit, L. Tronstad, and I. Olsen, “Systemic diseases caused by oral infection,” Clinical Microbiology Reviews, vol. 13, no. 4, pp. 547–558, 2000. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Engebretson and T. Kocher, “Evidence that periodontal treatment improves diabetes outcomes: a systematic review and meta-analysis,” Journal of Clinical Periodontology, vol. 40, no. 14, pp. S153–S163, 2013. View at Publisher · View at Google Scholar · View at Scopus
  22. W. S. Borgnakke, P. V. Ylöstalo, G. W. Taylor, and R. J. Genco, “Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence,” Journal of Clinical Periodontology, vol. 40, no. 14, pp. S135–S152, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Ide and P. N. Papapanou, “Epidemiology of association between maternal periodontal disease and adverse pregnancy outcomes—Systematic review,” Journal of Clinical Periodontology, vol. 40, supplement 14, pp. S181–S194, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. B. S. Michalowicz, A. Gustafsson, V. Thumbigere-Math, and K. Buhlin, “The effects of periodontal treatment on pregnancy outcomes,” Journal of Clinical Periodontology, vol. 40, no. 14, pp. S195–S208, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. A. A. Bahekar, S. Singh, S. Saha, J. Molnar, and R. Arora, “The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis,” American Heart Journal, vol. 154, no. 5, pp. 830–837, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Fedele, W. Sabbah, N. Donos, S. Porter, and F. D'Aiuto, “Common oral mucosal diseases, systemic inflammation, and cardiovascular diseases in a large cross-sectional US survey,” The American Heart Journal, vol. 161, no. 2, pp. 344–350, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Kebschull, R. T. Demmer, and P. N. Papapanou, “‘Gum bug, leave my heart alone!’—epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis,” Journal of Dental Research, vol. 89, no. 9, pp. 879–902, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Helfand, D. I. Buckley, M. Freeman et al., “Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force,” Annals of Internal Medicine, vol. 151, no. 7, pp. 496–507, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. L. L. Håheim, Oral Infections and Cardiovascular Disease, Bentham Science Publishers, New York, NY, USA, 2011.
  30. M. S. Tonetti and T. E. van Dyke, “Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases,” Journal of Clinical Periodontology, vol. 40, no. 14, pp. S24–S29, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. F. J. Nieto, “Infections and atherosclerosis: new clues from an old hypothesis?” American Journal of Epidemiology, vol. 148, no. 10, pp. 937–948, 1998. View at Publisher · View at Google Scholar · View at Scopus
  32. K. Mattila, “Dental infections and cardiovascular disease—the early findings,” in Oral Infections and Cardiovascular Disease, chapter 1, pp. 3–7, Bentham Science, New York, NY, USA, 2011. View at Google Scholar
  33. M. C. Herzberg and M. W. Weyer, “Dental plaque, platelets, and cardiovascular diseases,” Annals of Periodontology, vol. 3, no. 1, pp. 151–160, 1998. View at Publisher · View at Google Scholar · View at Scopus
  34. G. Toverud, L. Rubal, and D. G. Wiehl, “The influence of war and postwar conditions on the teeth of Norwegian school children,” Milbank Memorial Fund Quarterly, vol. 39, pp. 489–539, 1961. View at Publisher · View at Google Scholar
  35. G. Toverud, “The influence of war and post-war conditions on the teeth of Norwegian school children. III. Discussion of food supply and dental condition in Norway and other European countries,” The Milbank Memorial Fund Quarterly, vol. 35, no. 4, pp. 373–459, 1957. View at Publisher · View at Google Scholar
  36. Statistics Norway, http://www.ssb.no/en/forside;jsessionid=F735889A891792F079DEF53DAB5626EB.kpld-as-prod03.
  37. K. Rothman, Epidemiology.: An Introduction, Oxford University Press, Oxford, UK, 2nd edition, 2012.
  38. A. B. Hill, “The environment and disease: association or causation?” Proceedings of the Royal Society of Medicine, vol. 58, pp. 295–300, 1965. View at Google Scholar · View at Scopus
  39. K. Joshipura, J. C. Zevallos, and C. S. Ritchie, “Strength of evidence relating periodontal disease and atherosclerotic disease,” Compendium of Continuing Education in Dentistry, vol. 30, no. 7, pp. 430–439, 2009. View at Google Scholar · View at Scopus
  40. W. B. Grant and B. J. Boucher, “Are hill's criteria for causality satisfied for vitamin D and periodontal disease?” Dermato-Endocrinology, vol. 2, no. 1, pp. 30–36, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. S. Yusuf and S. Anand, “Deciphering the causes of cardiovascular and other complex diseases in populations: achievements, challenges, opportunities, and approaches,” Progress in Cardiovascular Diseases, vol. 53, no. 1, pp. 62–67, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Hyman, “The importance of assessing confounding and effect modification in research involving periodontal disease and systemic diseases,” Journal of Clinical Periodontology, vol. 33, no. 2, pp. 102–103, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. M. J. Pencina, R. B. D'Agostino, M. G. Larson, J. M. Massaro, and R. S. Vasan, “Predicting the 30-year risk of cardiovascular disease: the framingham heart study,” Circulation, vol. 119, no. 24, pp. 3078–3084, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. G. J. Linden and M. C. Herzberg, “Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases,” Journal of Clinical Periodontology, vol. 40, no. 14, pp. S20–S23, 2013. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Desvarieux, R. T. Demmer, T. Rundek et al., “Relationship between periodontal disease, tooth loss, and carotid artery plaque: the oral infections and vascular disease epidemiology study (INVEST),” Stroke, vol. 34, no. 9, pp. 2120–2125, 2003. View at Publisher · View at Google Scholar · View at Scopus
  46. R. T. Demmer, P. N. Papapanou, D. R. Jacobs, and M. Desvarieux, “Evaluating clinical periodontal measures as surrogates for bacterial exposure: the Oral Infections and Vascular Disease Epidemiology Study (INVEST),” BMC Medical Research Methodology, vol. 10, article 2, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. K. Buhlin, A. Gustafsson, K. Andersson, J. Håkansson, and B. Klinge, “Validity and limitations of self-reported periodontal health,” Community Dentistry and Oral Epidemiology, vol. 30, no. 6, pp. 431–437, 2002. View at Publisher · View at Google Scholar · View at Scopus
  48. K. Divaris, K. L. Monda, K. E. North et al., “Exploring the genetic basis of chronic periodontitis: a genome-wide association study,” Human Molecular Genetics, vol. 22, no. 11, pp. 2312–2324, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. T. E. van Dyke and A. J. van Winkelhoff, “Infection and inflammatory mechanisms,” Journal of Clinical Periodontology, vol. 40, no. 14, pp. S1–S7, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. L. Lund Håheim, I. Olsen, P. Nafstad, P. Schwarze, and K. S. Rønningen, “Antibody levels to single bacteria or in combination evaluated against myocardial infarction,” Journal of Clinical Periodontology, vol. 35, no. 6, pp. 473–478, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. J. D. Beck, P. Eke, G. Heiss et al., “Periodontal disease and coronary heart disease: a reappraisal of the exposure,” Circulation, vol. 112, no. 1, pp. 19–24, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. I. Olsen, “Oral bacteria in cardiovascular diseases,” in Oral Infections and Cardiovascular Disease, chapter 5, pp. 35–44, Bentham Science Publishers, New York, NY, USA, 2011. View at Google Scholar
  53. E. Kozarov, “Bacterial invasion of vascular cell types: vascular infectology and atherogenesis,” Future Cardiology, vol. 8, no. 1, pp. 123–138, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. N.-E. Fiehn, E. Gutschik, T. Larsen, and J. M. Bangsborg, “Identity of streptococcal blood isolates and oral isolates from two patients with infective endocarditis,” Journal of Clinical Microbiology, vol. 33, no. 5, pp. 1399–1401, 1995. View at Google Scholar · View at Scopus
  55. N.-E. Fiehn, T. Larsen, N. Christiansen, P. Holmstrup, and T. V. Schroeder, “Identification of periodontal pathogens in atherosclerotic vessels,” Journal of Periodontology, vol. 76, no. 5, pp. 731–736, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. V. I. Haraszthy, J. J. Zambon, M. Trevisan, M. Zeid, and R. J. Genco, “Identification of periodontal pathogens in atheromatous plaques,” Journal of Periodontology, vol. 71, no. 10, pp. 1554–1560, 2000. View at Publisher · View at Google Scholar · View at Scopus
  57. H. K. Kuramitsu, I.-C. Kang, and M. Qi, “Interactions of porphyromonas gingivalis with host cells: implications for cardiovascular diseases,” Journal of Periodontology, vol. 74, no. 1, pp. 85–89, 2003. View at Publisher · View at Google Scholar · View at Scopus
  58. L. Reyes, D. Herrera, E. Kozarov, S. Roldán, and A. Progulske-Fox, “Periodontal bacterial invasion and infection: contribution to atherosclerotic pathology,” Journal of Clinical Periodontology, vol. 40, no. 14 supplement, pp. S30–S50, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. S. S. Chukkapalli, M. F. Rivera, I. M. Velsko et al., “Invasion of oral and aortic tissues by oral spirochete Treponema denticola in ApoE-/- mice causally links periodontal disease and atherosclerosis,” Infection and Immunity, vol. 82, no. 5, pp. 1959–1967, 2014. View at Publisher · View at Google Scholar · View at Scopus
  60. T. Maekawa, N. Takahashi, K. Tabeta et al., “Chronic oral infection with porphyromonas gingivalis accelerates atheroma formation by shifting the lipid profile,” PLoS ONE, vol. 6, no. 5, Article ID e20240, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. M. F. Rivera, J.-Y. Lee, M. Aneja et al., “Polymicrobial infection with major periodontal pathogens induced periodontal disease and aortic atherosclerosis in hyperlipidemic ApoEnull mice,” PLoS ONE, vol. 8, no. 2, Article ID e57178, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. S. P. Engebretson, I. B. Lamster, M. S. V. Elkind et al., “Radiographic measures of chronic periodontitis and carotid artery plaque,” Stroke, vol. 36, no. 3, pp. 561–566, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Desvarieux, R. T. Demmer, T. Rundek et al., “Periodontal microbiota and carotid intima-media thickness: the Oral Infections and Vascular Disease Epidemiology Study (INVEST),” Circulation, vol. 111, no. 5, pp. 576–582, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Desvarieux, R. T. Demmer, D. R. Jacobs Jr. et al., “Periodontal bacteria and hypertension: the oral infections and vascular disease epidemiology study (INVEST),” Journal of Hypertension, vol. 28, no. 7, pp. 1413–1421, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Desvarieux, R. T. Demmer, D. R. Jacobs, P. N. Papapanou, R. L. Sacco, and T. Rundek, “Changes in clinical and microbiological periodontal profiles relate to progression of carotid intima-media thickness: the oral infections and vascular disease epidemiology study,” Journal of the American Heart Association, vol. 2, Article ID e000254, 2013. View at Publisher · View at Google Scholar
  66. K. Miyaki, K. Masaki, M. Naito et al., “Periodontal disease and atherosclerosis from the viewpoint of the relationship between community periodontal index of treatment needs and brachial-ankle pulse wave velocity,” BMC Public Health, vol. 6, article 131, 2006. View at Publisher · View at Google Scholar · View at Scopus
  67. T. Wu, M. Trevisan, R. J. Genco, K. L. Falkner, J. P. Dorn, and C. T. Sempos, “Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen,” The American Journal of Epidemiology, vol. 151, no. 3, pp. 273–282, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. P. M. Ridker, S. S. Bassuk, and P. P. Toth, “C-reactive protein and risk of cardiovascular disease: evidence and clinical application,” Current Atherosclerosis Reports, vol. 5, no. 5, pp. 341–349, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. E. T. H. Yeh and R. P. Palusinski, “C-reactive protein: the pawn has been promoted to queen,” Current Atherosclerosis Reports, vol. 5, no. 2, pp. 101–105, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. B. Noack, R. J. Genco, M. Trevisan, S. Grossi, J. J. Zambon, and E. de Nardin, “Periodontal infections contribute to elevated systemic C-reactive protien level,” Journal of Periodontology, vol. 72, no. 9, pp. 1221–1227, 2001. View at Publisher · View at Google Scholar · View at Scopus
  71. J. K. Pai, T. Pischon, J. Ma et al., “Inflammatory markers and the risk of coronary heart disease in men and women,” The New England Journal of Medicine, vol. 351, no. 25, pp. 2599–2610, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. L. Lund Håheim, P. Nafstad, I. Olsen, P. Schwarze, and K. S. Rønningen, “C-reactive protein variations for different chronic somatic disorders,” Scandinavian Journal of Public Health, vol. 37, no. 6, pp. 640–646, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. P. J. Pussinen, M. Jauhiainen, T. Vilkuna-Rautiainen et al., “Periodontitis decreases the antiatherogenic potency of high density lipoprotein,” Journal of Lipid Research, vol. 45, no. 1, pp. 139–147, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. R. Griffiths and S. Barbour, “Lipoproteins and lipoprotein metabolism in periodontal disease,” Clinical Lipidology, vol. 5, no. 3, pp. 397–411, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. H. A. Schenkein and B. G. Loos, “Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases,” Journal of Clinical Periodontology, vol. 40, no. 14, pp. S51–S69, 2013. View at Publisher · View at Google Scholar · View at Scopus
  76. P. M. Ridker, E. Danielson, F. A. H. Fonseca et al., “Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein,” The New England Journal of Medicine, vol. 359, no. 21, pp. 2195–2207, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. F. D’Aiuto, M. Orlandi, and J. C. Gunsolley, “Evidence that periodontal treatment improves biomarkers and CVD outcomes,” Journal of Clinical Periodontology, vol. 40, no. 14, pp. S85–S105, 2013. View at Publisher · View at Google Scholar · View at Scopus
  78. J. L. Ebersole, M. A. Taubman, D. J. Smith, D. E. Frey, A. D. Haffajee, and S. S. Socransky, “Human serum antibody responses to oral microorganisms. IV. Correlation with homologous infection,” Oral Microbiology and Immunology, vol. 2, no. 2, pp. 53–59, 1987. View at Publisher · View at Google Scholar · View at Scopus
  79. A. Moura Foz, G. Alexandre Romito, C. Manoel Bispo et al., “Periodontal therapy and biomarkers related to cardiovascular risk,” Minerva Stomatologica, vol. 59, no. 5, pp. 271–283, 2010. View at Google Scholar · View at Scopus
  80. B. Hoen and X. Duval, “Infective endocarditis,” New England Journal of Medicine, vol. 369, no. 8, p. 785, 2013. View at Publisher · View at Google Scholar · View at Scopus
  81. M. H. Thornhill, M. J. Dayer, J. M. Forde et al., “Impact of the NICE guideline recommending cessation of antibiotic prophylaxis for prevention of infective endocarditis: before and after study,” British Medical Journal, vol. 342, no. 7807, Article ID d2392, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. C. de Oliveira, R. Watt, and M. Hamer, “Toothbrushing, inflammation, and risk of cardiovascular disease: results from Scottish Health Survey,” BMJ: British Medical Journal, vol. 340, Article ID c2451, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. T. Dietrich, M. Jimenez, E. A. K. Kaye, P. S. Vokonas, and R. I. Garcia, “Age-dependent associations between chronic periodontitis/edentulism and risk of coronary heart disease,” Circulation, vol. 117, no. 13, pp. 1668–1674, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. R. G. Watt, G. Tsakos, C. de Oliveira, and M. Hamer, “Tooth loss and cardiovascular disease mortality risk—results from the Scottish Health Survey,” PLoS ONE, vol. 7, no. 2, Article ID e30797, 2012. View at Publisher · View at Google Scholar · View at Scopus
  85. L. A. Mucci, C.-C. Hsieh, P. L. Williams et al., “Do genetic factors explain the association between poor oral health and cardiovascular disease? A prospective study among Swedish twins,” The American Journal of Epidemiology, vol. 170, no. 5, pp. 615–621, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. T. H. Howell, P. M. Ridker, U. A. Ajani, C. H. Hennekens, and W. G. Christen, “Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians,” Journal of the American College of Cardiology, vol. 37, no. 2, pp. 445–450, 2001. View at Publisher · View at Google Scholar · View at Scopus
  87. P. P. Hujoel, M. Drangsholt, C. Spiekerman, and T. A. DeRouen, “Periodontal disease and coronary heart disease risk,” Journal of the American Medical Association, vol. 284, no. 11, pp. 1406–1410, 2000. View at Publisher · View at Google Scholar · View at Scopus
  88. B. Söder, L. J. Jin, B. Klinge, and P.-Ö. Söder, “Periodontitis and premature death: a 16-year longitudinal study in a Swedish urban population,” Journal of Periodontal Research, vol. 42, no. 4, pp. 361–366, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. T. Wu, M. Trevisan, R. J. Genco, J. P. Dorn, K. L. Falkner, and C. T. Sempos, “Periodontal disease and risk of cerebrovascular disease: the First National Health and Nutrition Examination Survey and its follow-up study,” Archives of Internal Medicine, vol. 160, no. 18, pp. 2749–2755, 2000. View at Publisher · View at Google Scholar · View at Scopus
  90. K. J. Joshipura, H.-C. Hung, E. B. Rimm, W. C. Willett, and A. Ascherio, “Periodontal disease, tooth loss, and incidence of ischemic stroke,” Stroke, vol. 34, no. 1, pp. 47–52, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Jimenez, E. A. Krall, R. I. Garcia, P. S. Vokonas, and T. Dietrich, “Periodontitis and incidence of cerebrovascular disease in men,” Annals of Neurology, vol. 66, no. 4, pp. 505–512, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. S. Sen, R. Sumner, J. Hardin et al., “Periodontal disease and recurrent vascular events in stroke/transient ischemic attack patients,” Journal of Stroke and Cerebrovascular Diseases, vol. 22, no. 8, pp. 1420–1427, 2013. View at Publisher · View at Google Scholar · View at Scopus
  93. Y.-L. Lee, H.-Y. Hu, N. Huang, D.-K. Hwang, P. Chou, and D. Chu, “Dental prophylaxis and periodontal treatment are protective factors to ischemic stroke,” Stroke, vol. 44, no. 4, pp. 1026–1030, 2013. View at Publisher · View at Google Scholar · View at Scopus
  94. H. C. Hung, W. Willett, A. Merchant, B. A. Rosner, A. Ascherio, and K. J. Joshipura, “Oral health and peripheral arterial disease,” Circulation, vol. 107, no. 8, pp. 1152–1157, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. T. Dietrich, P. Sharma, C. Walter, P. Weston, and J. Beck, “The epidemiological evidence behind the association between periodontitis and incident atherosclerotic cardiovascular disease,” Journal of Clinical Periodontology, vol. 40, supplement 14, pp. S70–S85, 2013, Erratum in Journal of Clinical Periodontology, vol. 40, supplement 14, pp. S210–S215, 2013. View at Publisher · View at Google Scholar · View at Scopus
  96. R. Tuominen, A. Reunanen, M. Paunio, I. Paunio, and A. Aromaa, “Oral health indicators poorly predict coronary heart disease deaths,” Journal of Dental Research, vol. 82, no. 9, pp. 713–718, 2003. View at Publisher · View at Google Scholar · View at Scopus
  97. G. J. Linden, A. Lyons, and F. A. Scannapieco, “Periodontal systemic associations: review of the evidence,” Journal of Clinical Periodontology, vol. 40, no. 14, pp. S8–S19, 2013. View at Publisher · View at Google Scholar · View at Scopus
  98. S. Offenbacher, J. D. Beck, K. Moss et al., “Results from the Periodontitis and Vascular Events (PAVE) study: a pilot multicentered, randomized, controlled trial to study effects of periodontal therapy in a secondary prevention model of cardiovascular disease,” Journal of Periodontology, vol. 80, no. 2, pp. 190–201, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. M. P. Gabay, R. Jain, J. F. Feliu, and A. Marcotte, “Role of antibiotics for the prevention of cardiovascular disease,” Annals of Pharmacotherapy, vol. 36, no. 10, pp. 1629–1636, 2002. View at Publisher · View at Google Scholar · View at Scopus