The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Helicobacter pylori Infection and Metabolic Disease

헬리코박터 파이로리 감염과 대사성질환

  • Kim, Hyung Hun (Department of Internal Medicine, The Catholic University of Korea College of Medicine)
  • 김형훈 (가톨릭대학교 의과대학 내과학교실)
  • Published : 2013.06.01
⟨ Previous Next ⟩

Abstract

The topic of the extragastric manifestations of Helicobacter pylori infection continues to capture the attention of many researchers all over the world. There are, in fact, several studies concerning obesity, diabetes mellitus, cardiovascular diseases, lung diseases, hematologic diseases, eye and skin diseases, hepatobiliary diseases, and neurological disorders. Among them, obesity and related disorders are hot spots in modern society. Here, we review the results of the studies about the relationship between Helicobacter pylori infection and obesity related diseases.

Keywords

References

  1. Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 1991;338:1175-1176. https://doi.org/10.1016/0140-6736(91)92035-Z
  2. Parsonnet J. Helicobacter pylori and gastric cancer. Gastroenterol Clin North Am 1993;22:89-104.
  3. Graham DY, Osato MS, Olson CA, Zhang J, Figura N. Effect of H. pylori infection and CagA status on leukocyte counts and liver function tests: extra-gastric manifestations of H. pylori infection. Helicobacter 1998;3:174-178. https://doi.org/10.1046/j.1523-5378.1998.08018.x
  4. Patel P, Mendall MA, Khulusi S, Northfield TC, Strachan DP. Helicobacter pylori infection in childhood: risk factors and effect on growth. BMJ 1994;309:1119-1123. https://doi.org/10.1136/bmj.309.6962.1119
  5. Date Y, Kojima M, Hosoda H, et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 2000;141:4255-4261. https://doi.org/10.1210/endo.141.11.7757
  6. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001;50:1714-1719. https://doi.org/10.2337/diabetes.50.8.1714
  7. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001;50:707-709. https://doi.org/10.2337/diabetes.50.4.707
  8. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001;409:194-198. https://doi.org/10.1038/35051587
  9. Andrews ZB, Liu ZW, Walllingford N, et al. UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals. Nature 2008;454:846-851. https://doi.org/10.1038/nature07181
  10. Zhao TJ, Liang G, Li RL, et al. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Proc Natl Acad Sci USA 2010;107: 7467-7472. https://doi.org/10.1073/pnas.1002271107
  11. Liew PL, Lee WJ, Lee YC, Chen WY. Gastric ghrelin expression associated with Helicobacter pylori infection and chronic gastritis in obese patients. Obes Surg 2006;16:612-619. https://doi.org/10.1381/096089206776945002
  12. Tatsuguchi A, Miyake K, Gudis K, et al. Effect of Helicobacter pylori infection on ghrelin expression in human gastric mucosa. Am J Gastroenterol 2004;99:2121-2127. https://doi.org/10.1111/j.1572-0241.2004.30291.x
  13. Mendez-Sanchez N, Pichardo-Bahena R, Vasquez-Fernandez F, et al. Effect of Helicobacter pylori infection on gastric ghrelin expression and body weight. Rev Gastroenterol Mex 2007;72:359-364.
  14. Isomoto H, Ueno H, Saenko VA, et al. Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in humans. Am J Gastroenterol 2005;100:1711-1720. https://doi.org/10.1111/j.1572-0241.2005.41492.x
  15. Nweneka CV, Prentice AM. Helicobacter pylori infection and circulating ghrelin levels - a systematic review. BMC Gastroenterol 2011;11:7. https://doi.org/10.1186/1471-230X-11-7
  16. Kawashima J, Ohno S, Sakurada T, et al. Circulating acylated ghrelin level decreases in accordance with the extent of atrophic gastritis. J Gastroenterol 2009;44:1046-1054. https://doi.org/10.1007/s00535-009-0120-0
  17. Campana D, Nori F, Pagotto U, et al. Plasma acylated ghrelin levels are higher in patients with chronic atrophic gastritis. Clin Endocrinol (Oxf) 2007;67:761-766. https://doi.org/10.1111/j.1365-2265.2007.02959.x
  18. Nwokolo CU, Freshwater DA, O'Hare P, Randeva HS. Plasma ghrelin following cure of Helicobacter pylori. Gut 2003; 52:637-640. https://doi.org/10.1136/gut.52.5.637
  19. Gokcel A, Gumurdulu Y, Kayaselcuk F, et al. Helicobacter pylori has no effect on plasma ghrelin levels. Eur J Endocrinol 2003;148:423-426. https://doi.org/10.1530/eje.0.1480423
  20. Abiko Y, Suzuki H, Masaoka T, et al. Enhanced plasma ghrelin levels in Helicobacter pylori-colonized, interleukinreceptor type 1-homozygous knockout (IL-1R1-/-) mice. World J Gastroenterol 2005;11:4148-4153. https://doi.org/10.3748/wjg.v11.i27.4148
  21. Choe YH, Lee JH, Lee HJ, et al. Ghrelin levels in gastric mucosa before and after eradication of Helicobacter pylori. Gut Liver 2007;1:132-137. https://doi.org/10.5009/gnl.2007.1.2.132
  22. Choi JY, Hahm KB. Ghrelin; influences on Helicobacter pylori-associated gastric diseases. Korean J Gastroenterol 2006;48:75-81.
  23. Lee ES, Yoon YS, Park CY, et al. Eradication of Helicobacter pylori increases ghrelin mRNA expression in the gastric mucosa. J Korean Med Sci 2010;25:265-271. https://doi.org/10.3346/jkms.2010.25.2.265
  24. Osawa H, Nakazato M, Date Y, et al. Impaired production of gastric ghrelin in chronic gastritis associated with Helicobacter pylori. J Clin Endocrinol Metab 2005;90:10-16. https://doi.org/10.1210/jc.2004-1330
  25. Ioannou GN, Weiss NS, Kearney DJ. Is Helicobacter pylori seropositivity related to body mass index in the United States? Aliment Pharmacol Ther 2005;21:765-772. https://doi.org/10.1111/j.1365-2036.2005.02369.x
  26. Cho I, Blaser MJ, François F, et al. Helicobacter pylori and overweight status in the United States: data from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 2005;162:579-584. https://doi.org/10.1093/aje/kwi237
  27. Wu MS, Lee WJ, Wang HH, Huang SP, Lin JT. A casecontrol study of association of Helicobacter pylori infection with morbid obesity in Taiwan. Arch Intern Med 2005;165: 1552-1555. https://doi.org/10.1001/archinte.165.13.1552
  28. Perdichizzi G, Bottari M, Pallio S, Fera MT, Carbone M, Barresi G. Gastric infection by Helicobacter pylori and antral gastritis in hyperglycemic obese and in diabetic subjects. New Microbiol 1996;19:149-154.
  29. Danesh J, Peto R. Risk factors for coronary heart disease and infection with Helicobacter pylori: meta-analysis of 18 studies. BMJ 1998;316:1130-1132. https://doi.org/10.1136/bmj.316.7138.1130
  30. Lane JA, Murray LJ, Harvey IM, Donovan JL, Nair P, Harvey RF. Randomised clinical trial: Helicobacter pylori eradication is associated with a significantly increased body mass index in a placebo-controlled study. Aliment Pharmacol Ther 2011;33:922-929. https://doi.org/10.1111/j.1365-2036.2011.04610.x
  31. Furuta T, Shirai N, Xiao F, Takashima M, Hanai H. Effect of Helicobacter pylori infection and its eradication on nutrition. Aliment Pharmacol Ther 2002;16:799-806. https://doi.org/10.1046/j.1365-2036.2002.01222.x
  32. Fujiwara Y, Higuchi K, Arafa UA, et al. Long-term effect of Helicobacter pylori eradication on quality of life, body mass index, and newly developed diseases in Japanese patients with peptic ulcer disease. Hepatogastroenterology 2002;49: 1298-1302.
  33. Eckel RH, Alberti KG, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2010;375:181-183. https://doi.org/10.1016/S0140-6736(09)61794-3
  34. Razzouk L, Muntner P. Ethnic, gender, and age-related differences in patients with the metabolic syndrome. Curr Hypertens Rep 2009;11:127-132. https://doi.org/10.1007/s11906-009-0023-8
  35. Bruce KD, Hanson MA. The developmental origins, mechanisms, and implications of metabolic syndrome. J Nutr 2010; 140:648-652. https://doi.org/10.3945/jn.109.111179
  36. Tereshina EV. Metabolic abnormalities as a basis for agedependent diseases and aging? state of the art. Adv Gerontol 2009;22:129-138.
  37. Bonora E, Targher G, Alberiche M, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000;23:57-63. https://doi.org/10.2337/diacare.23.1.57
  38. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004;27:1487-1495. https://doi.org/10.2337/diacare.27.6.1487
  39. Aslan M, Horoz M, Nazligul Y, et al. Insulin resistance in H pylori infection and its association with oxidative stress. World J Gastroenterol 2006;12:6865-6868. https://doi.org/10.3748/wjg.v12.i42.6865
  40. Eshraghian A, Hashemi SA, Hamidian Jahromi A, et al. Helicobacter pylori infection as a risk factor for insulin resistance. Dig Dis Sci 2009;54:1966-1970. https://doi.org/10.1007/s10620-008-0557-7
  41. Gao XY, Kuang HY, Liu XM, Duan P, Yang Y, Ma ZB. Circulating ghrelin/obestatin ratio in subjects with Helicobacter pylori infection. Nutrition 2009;25:506-511. https://doi.org/10.1016/j.nut.2008.11.002
  42. Gunji T, Matsuhashi N, Sato H, et al. Helicobacter pylori infection significantly increases insulin resistance in the asymptomatic Japanese population. Helicobacter 2009;14: 144-150.
  43. Ozdem S, Akcam M, Yilmaz A, Artan R. Insulin resistance in children with Helicobacter pylori infection. J Endocrinol Invest 2007;30:236-240. https://doi.org/10.1007/BF03347431
  44. Park SH, Jeon WK, Kim SH, et al. Helicobacter pylori eradication has no effect on metabolic and inflammatory parameters. J Natl Med Assoc 2005;97:508-513.
  45. So WY, Tong PC, Ko GT, et al. Low plasma adiponectin level, white blood cell count and Helicobacter pylori titre independently predict abnormal pancreatic beta-cell function. Diabetes Res Clin Pract 2009;86:89-95. https://doi.org/10.1016/j.diabres.2009.08.010
  46. Gen R, Demir M, Ataseven H. Effect of Helicobacter pylori eradication on insulin resistance, serum lipids and low-grade inflammation. South Med J 2010;103:190-196. https://doi.org/10.1097/SMJ.0b013e3181cf373f
  47. Polyzos SA, Kountouras J, Zavos C, Deretzi G. The association between Helicobacter pylori infection and insulin resistance: a systematic review. Helicobacter 2011;16:79-88. https://doi.org/10.1111/j.1523-5378.2011.00822.x
  48. Oldenburg B, Diepersloot RJ, Hoekstra JB. High seroprevalence of Helicobacter pylori in diabetes mellitus patients. Dig Dis Sci 1996;41:458-461. https://doi.org/10.1007/BF02282318
  49. Gasbarrini A, Ojetti V, Pitocco D, et al. Helicobacter pylori infection in patients affected by insulin-dependent diabetes mellitus. Eur J Gastroenterol Hepatol 1998;10:469-472. https://doi.org/10.1097/00042737-199806000-00006
  50. Salardi S, Cacciari E, Menegatti M, et al. Helicobacter pylori and type 1 diabetes mellitus in children. J Pediatr Gastroenterol Nutr 1999;28:307-309. https://doi.org/10.1097/00005176-199903000-00017
  51. Arslan D, Kendirci M, Kurtoglu S, Kula M. Helicobacter pylori infection in children with insulin dependent diabetes mellitus. J Pediatr Endocrinol Metab 2000;13:553-556.
  52. Senturk O, Canturk Z, Cetinarslan B, Ercin C, Hulagu S, Canturk NZ. Prevalence and comparisons of five different diagnostic methods for Helicobacter pylori in diabetic patients. Endocr Res 2001;27:179-189. https://doi.org/10.1081/ERC-100107179
  53. Quatrini M, Boarino V, Ghidoni A, Baldassarri AR, Bianchi PA, Bardella MT. Helicobacter pylori prevalence in patients with diabetes and its relationship to dyspeptic symptoms. J Clin Gastroenterol 2001;32:215-217. https://doi.org/10.1097/00004836-200103000-00006
  54. Gulcelik NE, Kaya E, Demirbas B, et al. Helicobacter pylori prevalence in diabetic patients and its relationship with dyspepsia and autonomic neuropathy. J Endocrinol Invest 2005;28:214-217. https://doi.org/10.1007/BF03345375
  55. Gentile S, Turco S, Oliviero B, Torella R. The role of autonomic neuropathy as a risk factor of Helicobacter pylori infection in dyspeptic patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 1998;42:41-48. https://doi.org/10.1016/S0168-8227(98)00088-6
  56. Persico M, Suozzo R, De Seta M, Montella F, Torella R, Gentile S. Non-ulcer dyspepsia and Helicobacter pylori in type 2 diabetic patients: association with autonomic neuropathy. Diabetes Res Clin Pract 1996;31:87-92. https://doi.org/10.1016/0168-8227(96)01207-7
  57. Quadri R, Rossi C, Catalfamo E, et al. Helicobacter pylori infection in type 2 diabetic patients. Nutr Metab Cardiovasc Dis 2000;10:263-266.
  58. Brenner H, Berg G, Frohlich M, Boeing H, Koenig W. Chronic infection with Helicobacter pylori does not provoke major systemic inflammation in healthy adults: results from a large population-based study. Atherosclerosis 1999;147: 399-403. https://doi.org/10.1016/S0021-9150(99)00210-5
  59. Anastasios R, Goritsas C, Papamihail C, Trigidou R, Garzonis P, Ferti A. Helicobacter pylori infection in diabetic patients: prevalence and endoscopic findings. Eur J Intern Med 2002;13:376. https://doi.org/10.1016/S0953-6205(02)00094-8
  60. Kozak R, Juhasz E, Horvat G, et al. Helicobacter pylori infection in diabetic patients. Orv Hetil 1999;140:993-995.
  61. Ko GT, Chan FK, Chan WB, et al. Helicobacter pylori infection in Chinese subjects with type 2 diabetes. Endocr Res 2001;27:171-177. https://doi.org/10.1081/ERC-100107178
  62. Ojetti V, Pitocco D, Ghirlanda G, Gasbarrini G, Gasbarrini A. Role of Helicobacter pylori infection in insulin-dependent diabetes mellitus. Minerva Med 2001;92:137-144.
  63. Xia HH, Talley NJ, Kam EP, Young LJ, Hammer J, Horowitz M. Helicobacter pylori infection is not associated with diabetes mellitus, nor with upper gastrointestinal symptoms in diabetes mellitus. Am J Gastroenterol 2001;96:1039-1046. https://doi.org/10.1111/j.1572-0241.2001.03604.x
  64. Stanciu OG, Trifan A, Sfarti C, Cojocariu C, Stanciu C. Helicobacter pylori infection in patients with diabetes mellitus. Rev Med Chir Soc Med Nat Iasi 2003;107:59-65.
  65. Zelenkova J, Souckova A, Kvapil M, Soucek A, Vejvalka J, Segethova J. Helicobacter pylori and diabetes mellitus. Cas Lek Cesk 2002;141:575-577.
  66. Kojecky V, Roubalik J, Bartonikova N. Helicobacter pylori in patients with diabetes mellitus. Vnitr Lek 1993;39:581-584.
  67. Pietroiusti A, Giuliano M, Magrini A, Bergamaschi A, Galante A. Cytotoxin-associated gene A strains of Helicobacter pylori represent a risk factor for the development of microalbuminuria in type 2 diabetes. Diabetes Care 2006; 29:1399-1401. https://doi.org/10.2337/dc06-0404
  68. Gasbarrini A, Ojetti V, Pitocco D, et al. Insulin-dependent diabetes mellitus affects eradication rate of Helicobacter pylori infection. Eur J Gastroenterol Hepatol 1999;11:713-716. https://doi.org/10.1097/00042737-199907000-00005
  69. Gasbarrini A, Ojetti V, Pitocco D, et al. Efficacy of different Helicobacter pylori eradication regimens in patients affected by insulin-dependent diabetes mellitus. Scand J Gastroenterol 2000;35:260-263. https://doi.org/10.1080/003655200750024119
  70. Ojetti V, Pitocco D, Bartolozzi F, et al. High rate of helicobacter pylori re-infection in patients affected by type 1 diabetes. Diabetes Care 2002;25:1485. https://doi.org/10.2337/diacare.25.8.1485
  71. Sargyn M, Uygur-Bayramicli O, Sargyn H, Orbay E, Yavuzer D, Yayla A. Type 2 diabetes mellitus affects eradication rate of Helicobacter pylori. World J Gastroenterol 2003;9:1126- 1128. https://doi.org/10.3748/wjg.v9.i5.1126
  72. Begue RE, Mirza A, Compton T, Gomez R, Vargas A. Helicobacter pylori infection and insulin requirement among children with type 1 diabetes mellitus. Pediatrics 1999;103:e83. https://doi.org/10.1542/peds.103.6.e83
  73. Solcia E, Fiocca R, Luinetti O, et al. Intestinal and diffuse gastric cancers arise in a different background of Helicobacter pylori gastritis through different gene involvement. Am J Surg Pathol 1996;20(Suppl 1):S8-22. https://doi.org/10.1097/00000478-199600001-00003
  74. Majka J, Rog T, Konturek PC, et al. Influence of chronic Helicobacter pylori infection on ischemic cerebral stroke risk factors. Med Sci Monit 2002;8:CR675-684.
  75. Chimienti G, Russo F, Lamanuzzi BL, et al. Helicobacter pylori is associated with modified lipid profile: impact on Lipoprotein(a). Clin Biochem 2003;36:359-365. https://doi.org/10.1016/S0009-9120(03)00063-8
  76. Laurila A, Bloigu A, Nayha S, Hassi J, Leinonen M, Saikku P. Association of Helicobacter pylori infection with elevated serum lipids. Atherosclerosis 1999;142:207-210. https://doi.org/10.1016/S0021-9150(98)00194-4
  77. Hoffmeister A, Rothenbacher D, Bode G, et al. Current infection with Helicobacter pylori, but not seropositivity to Chlamydia pneumoniae or cytomegalovirus, is associated with an atherogenic, modified lipid profile. Arterioscler Thromb Vasc Biol 2001;21:427-432. https://doi.org/10.1161/01.ATV.21.3.427
  78. Niemela S, Karttunen T, Korhonen T, et al. Could Helicobacter pylori infection increase the risk of coronary heart disease by modifying serum lipid concentrations? Heart 1996;75:573-575. https://doi.org/10.1136/hrt.75.6.573
  79. Feingold KR, Grunfeld C. Role of cytokines in inducing hyperlipidemia. Diabetes 1992;41(Suppl 2):97-101. https://doi.org/10.2337/diab.41.2.S97
  80. Pieniazek P, Karczewska E, Duda A, Tracz W, Pasowicz M, Konturek SJ. Association of Helicobacter pylori infection with coronary heart disease. J Physiol Pharmacol 1999;50: 743-751.
  81. Kowalski M. Helicobacter pylori (H. pylori) infection in coronary artery disease: influence of H. pylori eradication on coronary artery lumen after percutaneous transluminal coronary angioplasty: the detection of H. pylori specific DNA in human coronary atherosclerotic plaque. J Physiol Pharmacol 2001;52(1 Suppl 1):3-31.
  82. Elizalde JI, Pique JM, Moreno V, et al. Influence of Helicobacter pylori infection and eradication on blood lipids and fibrinogen. Aliment Pharmacol Ther 2002;16:577-586. https://doi.org/10.1046/j.1365-2036.2002.01202.x
  83. Adiloglu AK, Can R, Kinay O, Aridogan BC. Infection with Chlamydia pneumoniae but not Helicobacter pylori is related to elevated apolipoprotein B levels. Acta Cardiol 2005;60: 599-604. https://doi.org/10.2143/AC.60.6.2004930
  84. Scharnagl H, Kist M, Grawitz AB, Koenig W, Wieland H, Marz W. Effect of Helicobacter pylori eradication on high-density lipoprotein cholesterol. Am J Cardiol 2004;93: 219-220. https://doi.org/10.1016/j.amjcard.2003.09.045
  85. Kamada T, Hata J, Kusunoki H, et al. Eradication of Helicobacter pylori increases the incidence of hyperlipidaemia and obesity in peptic ulcer patients. Dig Liver Dis 2005; 37:39-43. https://doi.org/10.1016/j.dld.2004.07.017
  86. Chen XH, Wang JB, Wang YS, Liu ZM, Li Y. Helicobacter pylori infection enhances atherosclerosis in high-cholesterol diet fed C57BL/6 mice. Zhonghua Xin Xue Guan Bing Za Zhi 2010;38:259-263.
  87. Mach F, Sukhova GK, Michetti M, Libby P, Michetti P. Influence of Helicobacter pylori infection during atherogenesis in vivo in mice. Circ Res 2002;90:E1-4. https://doi.org/10.1161/hh0102.102270
  88. Ayada K, Yokota K, Kobayashi K, Shoenfeld Y, Matsuura E, Oguma K. Chronic infections and atherosclerosis. Ann N Y Acad Sci 2007;1108:594-602. https://doi.org/10.1196/annals.1422.062
  89. Jafarzadeh A, Esmaeeli-Nadimi A, Nemati M, Tahmasbi M, Ahmadi P. Serum concentrations of Helicobacter pylori IgG and the virulence factor CagA in patients with ischaemic heart disease. East Mediterr Health J 2010;16:1039-1044.
  90. Niccoli G, Franceschi F, Cosentino N, et al. Coronary atherosclerotic burden in patients with infection by CagApositive strains of Helicobacter pylori. Coron Artery Dis 2010;21:217-221. https://doi.org/10.1097/MCA.0b013e3283399f36
  91. Huang B, Chen Y, Xie Q, et al. CagA-positive Helicobacter pylori strains enhanced coronary atherosclerosis by increasing serum OxLDL and HsCRP in patients with coronary heart disease. Dig Dis Sci 2011;56:109-114. https://doi.org/10.1007/s10620-010-1274-6
  92. Fagoonee S, De Angelis C, Elia C, et al. Potential link between Helicobacter pylori and ischemic heart disease: does the bacterium elicit thrombosis? Minerva Med 2010;101:121-125.
  93. Heuschmann PU, Neureiter D, Gesslein M, 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 2001;32:2253-2258. https://doi.org/10.1161/hs1001.097096
  94. Whincup PH, Mendall MA, Perry IJ, Strachan DP, Walker M. Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men. Heart 1996;75:568-572. https://doi.org/10.1136/hrt.75.6.568
  95. Markus HS, Mendall MA. Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular disease and carotid atheroma. J Neurol Neurosurg Psychiatry 1998;64:104-107. https://doi.org/10.1136/jnnp.64.1.104
  96. Grau AJ, Buggle F, Lichy C, Brandt T, Becher H, Rudi J. Helicobacter pylori infection as an independent risk factor for cerebral ischemia of atherothrombotic origin. J Neurol Sci 2001;186:1-5. https://doi.org/10.1016/S0022-510X(01)00507-X
  97. Ponzetto A, Marchet A, Pellicano R, et al. Association of Helicobacter pylori infection with ischemic stroke of non-cardiac origin: the BAT.MA.N. project study. Hepatogastroenterology 2002;49:631-634.
  98. Danesh J. Coronary heart disease, Helicobacter pylori, dental disease, Chlamydia pneumoniae, and cytomegalovirus: meta-analyses of prospective studies. Am Heart J 1999; 138(5 Pt 2):S434-437. https://doi.org/10.1016/S0002-8703(99)70270-X
  99. Diomedi M, Stanzione P, Sallustio F, et al. Cytotoxinassociated Gene-A-positive Helicobacter pylori strains infection increases the risk of recurrent atherosclerotic stroke. Helicobacter 2008;13:525-531. https://doi.org/10.1111/j.1523-5378.2008.00627.x
  100. Suzuki H, Franceschi F, Nishizawa T, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection. Helicobacter 2011;16(Suppl 1):65-69. https://doi.org/10.1111/j.1523-5378.2011.00883.x