The aim of this investigation was to determine the seroprevalence of H. pylori in patients with coronary artery disease
(CAD). Patients with coronary artery disease (n=90) and control group (n=90) were enrolled into this randomized,
multi-centre study. CAD risk factors analyzed included age, male gender, diabetes mellitus, systemic hypertension, cigarette
smoking, hypercholesterolemia and socioeconomic status. The results of this study showed a higher seroprevalence
of Helicobacter pylori infection in patients with CAD compared to controls (78,8% versus 58,3%, p<0.05). However, Helicobacter
pylori seropositivity was not associated with coronary artery risk factors (smoking, body mass index, diabetes
mellitus, hypertension, total cholesterol and socioeconomic status) either in the whole study population or in the patients
and control subjects analyzed separately (P>0.05). Further study are needed to clarify the precise role of Helicobacter
pylori infection on the development of coronary artery disease

Aleksandar Včev

Alen Ružić

Anamarija Mrđen

Branko Radanović

Dario Nakić

Dubravko Božić

Ivan Soldo

Jerko Barbić

Jure Mirat

Marko Matijević

Sanja Balen

Valentina Matijević

Viktor Peršić

English

Hrčak - Portal of scientific journals of Croatia

Coll. Antropol. 31 (2007) 3: 757–760Original scientific paperHelicobacter Pylori Infection andCoronary Artery DiseaseAleksandar V~ev1, Dario Naki}2, Anamarija Mr|en3, Jure Mirat4, Sanja Balen5, Alen Ru`i}6,Viktor Per{i}6, Ivan Soldo7, Marko Matijevi}1, Jerko Barbi}1, Valentina Matijevi}1, Dubravko Bo`i}1and Branko Radanovi}81 Department of Internal Medicine, School of Medicine, University »J.J. Strossmayer« Osijek, Osijek, Croatia2 Department of Internal Medicine, General Hospital »Zadar«, Zadar, Croatia3 Department of Neurology, General Hospital »Zadar«, Zadar, Croatia4 Department of Internal Medicine, General Hospital »Sveti Duh«, Zagreb, Croatia5 Department of Transfusiology, School of Medicine, University of Rijeka, Rijeka, Croatia6 Special Hospital »Thalassotherapia«, Opatija, Croatia7 Department of Infectology, School of Medicine, University »J.J. Strossmayer« Osijek, Osijek, Croatia8 Department of Neurology, School of Medicine, University »J.J. Strossmayer« Osijek, Osijek, CroatiaA B S T R A C TThe aim of this investigation was to determine the seroprevalence of H. pylori in patients with coronary artery disease(CAD). Patients with coronary artery disease (n=90) and control group (n=90) were enrolled into this randomized,multi-centre study. CAD risk factors analyzed included age, male gender, diabetes mellitus, systemic hypertension, ciga-rette smoking, hypercholesterolemia and socioeconomic status. The results of this study showed a higher seroprevalenceof Helicobacter pylori infection in patients with CAD compared to controls (78,8% versus 58,3%, p<0.05). However, Heli-cobacter pylori seropositivity was not associated with coronary artery risk factors (smoking, body mass index, diabetesmellitus, hypertension, total cholesterol and socioeconomic status) either in the whole study population or in the patientsand control subjects analyzed separately (P>0.05). Further study are needed to clarify the precise role of Helicobacterpylori infection on the development of coronary artery disease.Key words: Helicobacter pylori infection, coronary artery disease-CADIntroductionHelicobacter pylori, a gram-negative, microaerophilicspiral bacterium, has been found to infect the gastric mu-cosa of over half the world s population1. Helicobacterpylori gastritis is associated with the development of pep-tic ulcer, gastric adenocarcinoma and gastric MALT lym-phoma2. Helicobacter pylori infection may induce a chro-nic systemic inflammatory status of low degree, whichmay have repercussions for the whole organism. Sys-temic indices of inflammation, such as levels of poly-morphs and monocytes, are increased in H. pylori-in-fected dyspeptic patients, and many vasoactive substancesand cellular mediators, such as cytokines, which are pro-duced in the gastric mucosa in response to H. pylori in-fection, may be transported in the blood-stream and pro-mote an inflammatory response in organs distant fromthe stomach3,4.Several preliminary reports have suggested that chro-nic infections by H. pylori, as well as other chronic infec-tions, may be associated with atherosclerosis and vascu-lar diseases5,6. However, most prospective studies havenot confirmed the association between chronic infectionsand coronary disease7–10. Furthermore, H. pylori infec-tion is associated with several confounding factors, par-ticularly low social class, which are also related to higherincidence of vascular diseases5.757Received for publication June 29, 2007The aim of this investigation was to determine theseroprevalence of H. pylori in patients with coronary ar-tery disease.Materials and MethodsPatients with coronary artery disease (n=90) andcontrol group (n=90) were enrolled into this random-ized, multi-centre study.All subjects had given informed consent to inclusionin the study and the research was carried out in accor-dance with the principles of the Declaration of Helsinki.The diagnosis of coronary artery disease (CAD) re-quired the presence of one of following: a history of coro-nary artery bypass graft surgery, a history of myocardialinfarction or a history of percutaneous transluminal cor-onary stent. Exclusion criteria were: prior H. pylori erad-ication therapy, consumption of acid-suppressive drugsor antibiotics in the preceding 12 months, history ofvagotomy or operations on the upper gastrointestinaltract and a known history of gastrointestinal pathology.CAD risk factors analyzed included age, male gender,diabetes mellitus, systemic hypertension, cigarette smok-ing, hypercholesterolemia and socioeconomic status. Weused occupational status as the socioeconomic status in-dicator. Patients were considered to have systemic hyper-tension if they had received the diagnosis with an arte-rial pressure>140/90 mm Hg or were being treated withantihypertensive medications or dietary modification. Ahistory of past and current smoking of each patient wasobtained. Patients who had stopped smoking >20 yearsago and who were <30 years of age when they stoppedwere considered not to have smoking as a risk factor. Pa-tients were considered to have diabetes mellitus if theyhad a fasting plasma glucose >6.4 mmol/L, were takinginsulin or oral hypoglycemic agents or had previously re-ceived such treatment, or were currently using dietarymodification to control the condition. Patients were con-sidered to have hyperlipidemia if they had a serum cho-lesterol value >5.2 mmol/L or were receiving cholesterol-lowering treatment.Potential control subjects were excluded if they exhib-ited one or more of the following: a known history ofCAD, a known history of gastrointestinal pathology, chestpain and dyspnea, prior Helicobacter pylori eradicationtherapy, consumption of acid-suppressive drugs or anti-biotics in the preceding 12 months, a history of vagotomyor operations on the upper gastrointestinal tract or aknown history of gastrointestinal pathology. We selected90 controls from among the healthy subjects and match-ed them with the patients for sex, age and coronary ar-tery risk factors.All subjects enrolled (CAD patients and controls) un-derwent an enzyme-linked Immulite (chemiluminescent)analyzer IgG serologic test for H. pylori diagnosis (Diag-nostic Products Corp., Los Angeles, CA, USA), in accor-dance with the manufacturer s guidelines. This kit has asensitivity of 97% and a specificity of 98.%.Results are presented as mean ±SD (standard devia-tion). Statistical analysis was carried out using SPSSsoftware (Statistical Package for the Social Sciences, ver-sion 11.0, SPSS Inc., Chicago, IL,USA) and chi-squareand Student t-tests. A value of P<0.05 was consideredstatistically significant.ResultsIn Table 1. are listed demographic data on the pati-ents and controls. There was no significant difference inage, sex or coronary artery risk factors between the twogroups, but the prevalence of seropositivity for Helico-bacter pylori was higher in patients compared to controls(78,8% versus 58,3%, P<0.05). However, Helicobacterpylori seropositivity was not associated with coronary ar-tery risk factors (smoking, body mass index, diabetesmellitus, hypertension, total cholesterol and socioeco-nomic status) either in the whole study population or inthe patients and control subjects analyzed separately(P>0.05) as reported in Tables 2 and 3.DiscussionSince 1994, a considerable number of studies havebeen performed on the correlation between Helicobacterpylori infection and ischaemic heart disease. The exactA. V~ev et al.: Helicobacter Pylori Infection and Coronary Artery Disease, Coll. Antropol. 31 (2007) 3: 757–760758TABLE 1DEMOGRAPHIC DATA OF PATIENTS AND CONTROL GROUPPatients (n=90) Controls (n=90) value*Age (mean years) 49.2 50.8 NSMale (%) 67.5 68.7 NSHypertension (%) 59.6 55.8 NSwidctlparSmoking (%) 67.2 62.9 NSDiabetes mellitus (%) 19.7 15.2 NSBody mass index (kg/m2) 29.5 26.2 NSTotal cholesterol (mmol/L) 6.9 5.1 NSSocioeconomic status (high, %) 45.7 49.1 NSSeropositivity to Helicobacter pylori IgG antibody (%) 78.8 55.5 P<0.05*NS, P>0.05pathogenetic role of H. pylori infection in atherosclerosisis still a matter of debate, and the process that underliesthis association is also unclear.Epidemiological and molecular studies as well as someeradicating trials gave conflicting results.Mendall et al.5 in 1994 reported a higher prevalence ofH. pylori infections in patients with ischaemic heart dis-ease (IHD). This finding has since been verified by sev-eral other authors. Danesh et al.11 showed evidence ofstrong association between IHD and serological markersof persistent infection sustained by H. pylori. These re-sults were confirmed by other studies in which higherlevels of anti H. pylori antibodies were found in patientswith IHD or who had died of myocardial infarction (MI)than in normal controls12,13. Pasceri et al.14 have demon-strated a higher prevalence of either H. pylori infectionor CagA-positive strains in patients with IHD than incontrols. Singh et al.15 in a similar study, found a preva-lence of H. pylori CagA-positive strains in 52% of theIHD patients compared to 43% of the controls. The asso-ciation remained significant even after the adjustmentfor blood pressure values, body mass indeks, plasma con-centrations of low-density lipoprotein and high-densitylipoprotein cholesterol, history of hypertension and dia-betes, statin treatment and socioeconomic status. Ko-walski et al.16 reported a higher prevalence of H. pyloriinfection in patients with unstable angina or MI as wellas an evidence of H. pylori-related DNA in atheroscle-rotic lesions of 47,8% patients with coronary heart dis-ease.Some epidemiological study did not show any clearcorrelation between H. pylori infection and IHD17,18. Nosignificant association was found concering H. pylori in-fection among patients with angiographically document-ed coronary artery disease19–21, and in patients with highrisk of restenosis after coronary intervention22. In Ko-enig et al.23 and Whincup et al.24 studies none of the in-flammatory markers (CRP, fibrinogen, plasma viscosityor leucocyte counts) was significantly different in pa-tients with H. pylori infection and in controls, thus deny-ing any positive correlation between those events.Kowalski et al.25 proved that H. pylori eradication sig-nificantly attenuates the reduction in coronary artery lu-men in patients with coronary artery disease after per-cutaneous coronary angioplasty, possibly by reducing theeffect of proinflammatory cytokines. Another study26 hasevaluated the effect of the eradication of H. pylori infec-tion on the plasma levels of total cholesterol, LDL choles-A. V~ev et al.: Helicobacter Pylori Infection and Coronary Artery Disease, Coll. Antropol. 31 (2007) 3: 757–760759TABLE 2MAIN CLINICAL FEATURES OF CAD PATIENTS WITH AND WITHOUT HELICOBACTER PYLORI INFECTIONHelicobacter pylori statusSeropositivity(n=71)Seronegativity(n=19)P value*Age (years) 50.1+9 48.6+6 NSMen (%) 67.9 66.7 NSSmoker (%) 67.5 66.1 NSDiabetes mellitus 20.1 19.1 NSTotal cholesterol > 5,2mmol/L (%) 59.6 55.7 NSSocioeconomic status (high,%) 43.9 47.8 NSData are presented as mean+SD or percentage of patients.*NS, P>0.05TABLE 3MAIN CLINICAL FEATURES OF CONTROL SUBJECTS WITH AND WITHOUT HELICOBACTER PYLORI INFECTIONHelicobacter pylori statusSeropositivity(n=50)Seronegativity(n=40)P value*Age (years) 50.1+7 49.6+9 NSMen (%) 69.5 67.9 NSSmoker (%) 63.4 62.6 NSDiabetes mellitus 20.3 19.1 NSTotal cholesterol > 5,2 mmol/L (%) 50.6 48.7 NSSocioeconomic status (high, %) 48.9 49.8 NSData are presented as mean+SD or percentage of patients.*NS, P>0.05terol, fibrinogen and IL-8. In particular, all those factorswere significantly decreased after the administration ofthe eradicating treatment.Other studies did not confirm any beneficial effect ofthe eradicating treatment on the known risk for ischa-emic heart disease. Schweeger et al.27 demonstrated thatsuccessful eradication of H. pylori do not determine anychange in either fibrinogen or other proteins of the acutephase levels. Stone et al.28 did not find any correlationbetween eradication of H. pylori infection and risk fac-tors for ischaemic heart disease.In conclusion, the results of this study showed ahigher seroprevalence of Helicobacter pylori infection inpatients with CAD compared to controls (78,8% versus58,3%, p<0.05). However, Helicobacter pylori seropo-sitivity was not associated with coronary artery risk fac-tors (smoking, body mass index, diabetes mellitus, hyper-tension, total cholesterol and socioeconomic status) eitherin the whole study population or in the patients and con-trol subjects analyzed separately (P>0.05). Further studyare needed to clarify the precise role of Helicobacterpylori infection on the development of coronary arterydiseaseR E F E R E N C E S1. POUNDER RE, Aliment Pharmacol Ther, 9 Suppl (1996) 33. — 2.MARSHALL BJ, Am J Gastroenterol, 89 Suppl (1994 S116. — 3. GRA-HAM DY, OSATO MS, OLSON CA, ZHANG J, FIGURA N, Helicobacter,3 (1998) 174. — 4. PERRI F, R.. CLEMANTE R, FESTA V, CHECCHIADE AMBROSIO C, QUITADAMO M, FUSILLO M, GROSSI E, ANDRI-ULI A, Ital J Gastroenterol Hepatol, 31 (1999) 290. — 5. MENDALL MA,GOGGIN PM, MOLINEAUX N, Br Heart J, 71 (1994) 437. — 6. DA-NESH J, COLLINS R, PETO R, Lancet, 350 (1997) 430. — 7. WHINCUPP, MENDALL MA, PERRY IJ, Heart, 75 (1996) 568. — 8. WALD NJ, LAWMR, MORRIS JK, BMJ, 315 (1997) 1199. — 9. FOLSOM AM, NIETO JF,SORLIE P, Circulation, 98 (1998) 845. — 10. HAIDER AW, WILSONPWF, LARSON MG, J Am Coll Cardiol, 40 (2002) 1408. — 11. DANESH J,WONG Y, WARD M, MUIR J, Heart, 81 (1999) 245. — 12. ALKOUT AM,RAMSAY EJ, MACKENZIE DA, FEMS Immunol Med Microbiol, 29(2002) 271. — 13. PELLICANO R, MAZZARELLO MG, MORELLONI S,Int J Clin Lab Res, 29 (1999) 141. — 14. PASCERI V, CAMMAROTA G,PATTI G, Circulation, 97 (1998) 1675. — 15. SINGH RK, MCMAHONAD, PATEL H, Heart, 88 (2002) 43. — 16.KOWALSKI M, REES W,KONTUREK PC, Dig Liver Dis, 34 (2002) 398. — 17. ZITO F, DI CA-STELNUOVO A, D ORAZIO A, Thromb Haemost, 82 (1999) 14. — 18.HOFFMEISTER A, ROTHENBACHER D, BODE G, Arterioscler ThrombVasc Biol, 21 (2001) 427. — 19. TASI CJ, HUANG TY, Dig Dis Sci, 45(2000) 1227. — 20. STOLLBERGER C, MOLZER G, FINSTERER J, ClinDiagn Lab Immunol, 8 (2001) 997. — 21. CARLSSON J, MIKETI] S,BROM J, ROSS R, BACHMANN H, TEBBE U, Int J Cardiol, 73 (2000)165. — 22. SCHIELE F, BATUR MK, SERONDE MF, MENEVEAU N,SEWOKE P, BASSIGNOT A, Heart, 85 (2001) 304. — 23. KOENIG W,ROTHENBACHER D, HOFFMEISTER A, MILLER M, BODE G, AD-LER G, Circulation, 100 (1999) 2326. — 24. WHINCUP P, DANESH J,WALKER M, LENNON L, THOMSON A, APPLEBY P, Circulation, 101(2000) 1647. — 25. KOWALSKI M, KONTUREK PC, PIENIAZEK P,KARCZEWSKA E, KLUCZKA A, GROVE R, Dig Liver Dis, 33 (2001) 222.— 26. MAJKA J, ROG T, KONTUREK PC, BIELANSKI W, KOWALSKIM, Med Sci Monit, 8 (2002) CR675. — 27. SCHWEEGER I, FITSCHA P,SINZINGER H, Tromb Res, 97 (2000) 411. — 28. STONE AF, MENDALLMA, KASKI JC, EDGER TM, RISLEY P, POLONIECKI J, Circulation,106 (2002) 1219.A. V~evDepartment of Internal Medicine, School of Medicine, University »J.J. Strossmayer» Osijek, J. Huttlera 4,31000 Osijek, Croatiae-mail: vcev.aleksandarºkbo.hrHELICOBACTER PYLORI INFEKCIJA I KORONARNA ARTERIJSKA BOLESTS A @ E T A KCilj ovog rada je bio odrediti seroprevalenciju Helicobacter pylori infekcije u bolesnika s koronarnom arterijskombole{}u. U ovu randomiziranu multicentri~nu studiju uklju~eno je 90 bolesnika s koronarnom arterijskom bole{}u i 90zdravih osoba u kontrolnoj skupini. Analizirani su rizi~ni ~imbenici za koronarnu arterijsku bolest i to: dob, spol, pu-{enje, prekomjerna tjelesna te`ina, arterijska hipertenzija, ukupni kolesterol u krvi, {e}erna bolest i socioekonomskistatus ispitanika. Rezultati su pokazali statisti~ki zna~ajnu ve}u seroprevalenciju H. pylori infekcije u bolesnika s koro-narnom arterijskom bole{}u nego u ispitanika kontrolne skupine (79,1% nasuprot 58,3%, P<0,05). Me|utim, H. pyloriseropozitivnost nije bila udru`ena s ~imbenicima rizika za koronarnu arterijsku bolest gledaju}i ukupan broj ispitanika(n=180) ili gledaju}i posebno bolesnike, a posebno ispitanike u kontrolnoj skupini (P>0,05). Potrebne su budu}e stu-dije kako bi se precizno odredila uloga H. pylori infekcije u nastanku koronarne arterijske bolestiA. V~ev et al.: Helicobacter Pylori Infection and Coronary Artery Disease, Coll. Antropol. 31 (2007) 3: 757–760760

Helicobacter Pylori Infection and Coronary Artery Disease

HRČAK - Portal of Croatian Scientific and Professional Journals

The aim of this investigation was to determine the seroprevalence of H.pylori in patients with coronary artery disease (CAD).Patients with coronary artery disease (n=90) were enrolled into this randomized, multicentric study. CAD risk factors analyzed included age, male gender, diabetes mellitus, systemic hypertension, cigarette smoking, hypercholesterolemia and socioeconomic status. The results of the study showed a higher seroprevalence of Helicobacter pylori infection in patients with CAD compared to controls (78.8% versus 58.3%, p>0.05). However, Helicobacter Pylori seropositivity was not associated with coronary artery risk factors (smoking, body mass index, diabetes mellitus, hypertension, total cholesterol and socioeconomic status)either in the whole study population or in the patients and control subjects analyzed separately (P>0.05.). Further study is needed to clarify the precise role of Helicobacter pylori infection on the development of coronary artery disease

Helicobacter Pylori Infection and Coronary Artery Disease

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