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   Table of Contents  
Year : 2012  |  Volume : 3  |  Issue : 1  |  Page : 19-21  

Frequency of Helicobacter pylori and cytotoxine associated gene A antibodies in patients with cardiac syndrome X

1 Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
2 Department of Cardiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

Date of Web Publication9-Jan-2012

Correspondence Address:
Yousef Rasmi
Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia
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DOI: 10.4103/0975-3583.91597

PMID: 22346140

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Background: Cardiac syndrome X (CSX) is a condition in which patients have the pain of angina despite normal coronary angiogram. Recently, Helicobacter pylori (H. pylori) bacteria has been associated with CSX. However, there is no obvious data about the frequency of its virulent strain (cytotoxine associated gene A: CagA) in patients with CSX. We surveyed the frequency of H. pylori and CagA antibodies in patients with cardiac syndrome X and healthy controls. Materials and Methods: Plasma samples from 100 CSX patients (61 females and 39 males; mean age: 51.8 ± 12.3 years) and 100 healthy controls (61 females and 39 males; mean age: 48.9 ± 6.3 years) were tested for the presence of IgG antibody to H. pylori using enzyme linked immunosorbent assay (ELISA) method. Also, infected patients were determined by the presence of IgG antibody to CagA by ELISA method. Statistical analysis was carried out using chi-square test and independent samples T-test. Results: Ninety two percent (92/100) of patients were anti-H. pylori positive (anti-H. pylori+), while only 56.0% (56/100) of control group were anti-H. pylori+ (P<0.01). However, prevalence of anti-CagA positive (anti- CagA+) in H. pylori infected- CSX patients and control groups were 59.8% (55/92) and 60.7% (34/56), respectively (P >0.05). Conclusion: Thus, due to the high frequency of anti-H. pylori in CSX patients, and the probable causative effect of chronic infection in vascular diseases, it is suggested that H. pylori has a probable role in the pathogenesis of CSX.

Keywords: Cardiac syndrome X, CagA, chest pain, Helicobacter pylori

How to cite this article:
Rasmi Y, Seyyed-Mohammadzad MH. Frequency of Helicobacter pylori and cytotoxine associated gene A antibodies in patients with cardiac syndrome X. J Cardiovasc Dis Res 2012;3:19-21

How to cite this URL:
Rasmi Y, Seyyed-Mohammadzad MH. Frequency of Helicobacter pylori and cytotoxine associated gene A antibodies in patients with cardiac syndrome X. J Cardiovasc Dis Res [serial online] 2012 [cited 2013 Apr 19];3:19-21. Available from:

   Introduction Top

Cardiac syndrome X (CSX) is defined by a typical angina like chest pain without flow-limiting stenoses on coronary angiography and exclusion of noncardiac chest pain. [1] There is no obvious etiology for this syndrome. [2] One to 12% of individuals with myocardial infarction who undergo coronary angiography are found to have normal coronary arteries. [3] The pathogenesis of this syndrome is not well known despite of the extensive studies. [4] Previous studies had shown an association between viral and bacterial infections with vascular diseases, such as ischemic heart disease and CSX. [5]

Helicobacter pylori
(H. pylori) is a gram-negative bacterium that causes various extra-digestive diseases, including functional vascular disorders such as primary migraine and primary Raynaud's phenomenon, as well as ischemic heart disease. [5],[6] An inflammatory response possibly due to H. pylori has been proposed as a mechanism in patients with coronary artery disease (CAD). In addition, H. pylori has been recently also associated with ischemic heart disease and CSX. [2],[3],[7],[8] H. pylori strains may be divided into at least two subgroups based on the expression or nonexpression of cytotoxin-associated gene A (CagA) and the vacuolating cytotoxin. [9],[10] The CagA has been identified as a possible marker of H. pylori virulence. [11],[12]

Our literature review did not bring up any obvious data about the frequency of CagA in patients with CSX. Hence, this study was designed to determine the frequency of anti-H. pylori and anti-CagA status in CSX patients.

   Materials and Methods Top

Study design

Patients with CSX and apparently healthy controls were studied. The CSX group consisted of 100 consecutive patients. Entry criteria were typical anginal chest pain, normal 12-lead electrocardiography (ECGs) at rest, a positive exercise ECG stress test response and normal coronary angiogram. Non-cardiac causes of chest pain such as gastrointestinal and musculoskeletal disorders were also investigated and ruled out as appropriate. Patients with diabetes mellitus were not included, as inflammatory marker levels increase in diabetes mellitus. A questionnaire was administrated to obtain general information regarding age, sex, body mass index (BMI), systolic and diastolic blood pressures. The control group consisted of 100 apparently healthy subjects. None of the control individuals had a previous history of chest pain or acute/chronic diseases. Also, none of these subjects were taking cardiac or non-cardiac medications. The study was approved by Medical Ethics Committee at Urmia University of Medical Sciences, Urmia, Iran; and all subjects gave written informed consent.

Laboratory assays

A 5-ml tri_sodium citrated blood sample was obtained from each subject and centrifuged at 2000 g for 15 minutes. Plasma was aliquoted and stored at -80°C until analysis. Specific anti-H. pylori immunoglobulin-G (IgG) positivity was determined with a commercial enzyme-linked immunosorbent assay (ELISA) kit (Glob anti-H. pylori/IgG, Milan, Italy) according to the manufacturer's instructions (sensitivity 96.5% and specificity 98.6%). Also, plasma positivity to the antigen CagA was assessed by ELISA (Dia.Pro, Milan, Italy; sensitivity and specificity >98%) in anti-H. pylori positive (anti-H. pylori+) samples.

Statistical analysis

The data were analyzed by Statistical Package for Social Sciences (SPSS) 16.0 software. Age, systolic blood pressure, diastolic blood pressure and BMI were shown as mean ± standard deviation (SD). Statistical analysis was carried out using chi-square test and independent samples T-test. P value of < 0.05 was considered statistically significant.

   Results Top

One hundred CSX patients (61 females and 39 males) were compared with 100 age and sex matched healthy controls (61 females and 39 males). Demographic and clinical characteristics of both groups are depicted in [Table 1].
Table 1: Demographic and clinical characteristics of cardiac syndrome X patients and control group

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As shown in [Table 2], anti- H. pylori+ was diagnosed in 92 (92.0%) patients with CSX and 56 (56.0%) individuals in control group (P < 0.01). Also, among CSX group, 55 patients were positive for anti- CagA (anti- CagA+) (55/92: 59.8% of anti- H. pylori+) while only 34 individuals in control group were anti- CagA+ (34/56: 60.7% of anti- H. pylori+ samples, P > 0.05).
Table 2: Frequency of anti- H. pylori and anti-CagA status in cardiac syndrome X patients and control group

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   Discussion Top

Coronary endothelial dysfunction has been proposed as pathogenetic mechanism in CSX. [1],[13],[14]

The mechanisms responsible for endothelial dysfunction in CSX patients are not well understood; [15] however, some risk factors of CAD such as obesity, hypertension, hyper-cholesterolaemia and smoking, are frequently present in these patients and may have roles. [16] Also, previous studies have suggested that chronic inflammation may contribute to endothelial dysfunction in CSX. Lanza et al., showed that two indexes of systemic inflammation, C-reactive protein and interleukin-1 receptor antagonist, increased in patients with CSX compared with well-matched healthy control subjects. Thus, this result suggested that low-grade inflammation may play a pathogenetic role in CSX patients. [7]

Recent studies have suggested a possible association of viral and bacterial infections such as H. pylori infection in the etiology of acute coronary syndromes in patients with CAD. [17] Endothelial injury due to circulating endotoxin, autoimmunity with cross-reactivity of bacterial antigens and endothelial cells are discussed as possible underlying mechanisms. [3] In addition, H. pylori has been recently associated with CSX. [2] We speculated that H. pylori may also cause endothelial dysfunction directly by affecting the structure and function of vascular endothelial cells via inflammation. [18]

H. pylori may cause chronic inflammation and enhanced immune response due to the release of some cytotoxic substances which are responsible for the systemic manifestations of H. pylori. [19] Chronic infection of H. pylori most probably causes increased production of various inflammatory metabolites, and this could also affect blood vessel motility and induce endothelial dysfunction. [20] Epithelial cell act as the most probable target in H. pylori infection, and also as major interfaces between the host and pathogens. Thus, this interaction initiates acute mucosal inflammation, and interacts with the other mucosal cell proliferation via a cytokine network. [21] These two responses may be regulated differentially following induction of cytokines in the inflammatory cascade, including tumor necrosis factor-alpha and interleukin-6. [22],[23]

Thus, with the results of our study, the possible role of H. pylori infection in the pathogenesis of CSX is suggested. This is the first study that shows anti- CagA status of H. pylori in CSX, however well designed clinical trial studies are needed to further confirm these results.

   Acknowledgments Top

This work was supported by a research grant from Research and Technology Administration, UMSU, Iran.

   References Top

1.Hurst T, Olson TH, Olson LE, Appleton CP. Cardiac syndrome X and endothelial dysfunction: New concepts in prognosis and treatment. Am J Med 2006;119:560-6.  Back to cited text no. 1
2.Eskandarian R, Malek M, Mousavi SH, Babaei M. Association of Helicobacter pylori infection with cardiac syndrome X. Singapore Med J 2006;47:704-6.  Back to cited text no. 2
3.Ammann P, Marschall S, Kraus M, Schmid L, Angehrn W, Krapf R, Rickli H. Characteristics and prognosis of myocardial infarction in patients with normal coronary arteries. Chest 2000;117:333-8.  Back to cited text no. 3
4.Li JJ, Li YS, Zhang Y, Gao Z, Li Z, Qian HY. Inflammation: A possible pathogenic link to cardiac syndrome X. Med Hypotheses 2006;66:87-91.  Back to cited text no. 4
5.Nocente R, Gentiloni N, Cremonini F, Giorgi A, Serricchio M, Santoliquido A, et al. Resolution of syndrome X after eradication of virulent CagA-positive Helicobacter pylori. South Med J 2000;93:1022-3.  Back to cited text no. 5
6.Gasbarrini A, Franceschi F, Armuzzi A, Ojetti V, Candelli M, Torre ES, et al. Extradigestive manifestations of Helicobacter pylori gastric infection. Gut 1999;45 Suppl 1:I9-12.  Back to cited text no. 6
7.Lanza GA, Sestito A, Cammarota G, Grillo RL, Vecile E, Cianci R, et al. Assessment of systemic inflammation and infective pathogen burden in patients with cardiac syndrome X. Am J Cardiol 2004;94:40-4.  Back to cited text no. 7
8.Kaski JC. Cardiac syndrome X in women: The role of oestrogen deficiency. Heart 2006;92 Suppl 3:iii5-9.  Back to cited text no. 8
9.Jafarzadeh A, Rezayati MT, Nemati M. Specific serum immunoglobulin G to H pylori and CagA in healthy children and adults (south-east of Iran). World J Gastroenterol 2007;13:3117-21.  Back to cited text no. 9
10.Yahav J, Fradkin A, Weisselberg B, Diver-Haver A, Shmuely H, Jonas A. Relevance of CagA positivity to clinical course of Helicobacter pylori infection in children. J Clin Microbiol 2000;38:3534-7.  Back to cited text no. 10
11.Kato S, Sugiyama T, Kudo M, Ohnuma K, Ozawa K, Iinuma K, et al. CagA antibodies in Japanese children with nodular gastritis or peptic ulcer disease. J Clin Microbiol 2000;38:68-70.  Back to cited text no. 11
12.Mine T. Heterogeneity in the cagA gene of Helicobacter pylori and its clinical role. J Gastroenterol 2000;35:945-6.  Back to cited text no. 12
13.Alroy S, Preis M, Barzilai M, Cassel A, Lavie L, Halon DA, et al. Endothelial cell dysfunction in women with cardiac syndrome X and MTHFR C677T mutation. Isr Med Assoc J 2007;9:321-5.  Back to cited text no. 13
14.Goon PK, Lip GY. Endothelial progenitor cells, endothelial cell dysfunction and much more observations from cardiac syndrome X. Heart 2007;93:1020-1.  Back to cited text no. 14
15.Arroyo-Espliguero R, Mollichelli N, Avanzas P, Zouridakis E, Newey VR, Nassiri DK, et al. Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X. Eur Heart J 2003;24:2006-11.  Back to cited text no. 15
16.Kaski JC. Pathophysiology and management of patients with chest pain and normal coronary arteriograms (cardiac syndrome X). Circulation 2004;109:568-72.  Back to cited text no. 16
17.Stollberger C, Finsterer J. Role of infectious and immune factors in coronary and cerebrovascular arteriosclerosis. Clin Diagn Lab Immunol 2002;9:207-15.  Back to cited text no. 17
18.Rasmi Y, Raeisi S. Possible role of Helicobacter pylori infection via microvascular dysfunction in cardiac syndrome X. Cardiol J 2009;16:585-7.  Back to cited text no. 18
19.Karatas OF, Bayrak O, Cimentepe E, Unal D. An occult risk factor for chronic prostatitis: Helicobacter pylori. Med Hypotheses 2007;69:963-4.  Back to cited text no. 19
20.Kanbay M, Kasapoglu B, Turgut F, Uz E, Bavbek N, Akcay A. Helicobacter pylori: A major risk factor for endothelial dysfunction? Med Hypotheses 2007;69:227-8.  Back to cited text no. 20
21.Stadnyk AW. Intestinal epithelial cells as a source of inflammatory cytokines and chemokines. Can J Gastroenterol 2002;16:241-6.  Back to cited text no. 21
22.Crabtree JE, Peichl P, Wyatt JI, Stachl U, Lindley IJ. Gastric interleukin-8 and IgA IL-8 autoantibodies in Helicobacter pylori infection. Scand J Immunol 1993;37:65-70.  Back to cited text no. 22
23.Gionchetti P, Vaira D, Campieri M, Holton J, Menegatti M, Belluzzi A, et al. Enhanced mucosal interleukin-6 and -8 in Helicobacter pylori-positive dyspeptic patients. Am J Gastroenterol 1994;89:883-7.  Back to cited text no. 23


  [Table 1], [Table 2]


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