Association of Inflammation and Cytotoxin-Associated Gene A Positive Strains of Helicobacter Pylori in Cardiac Syndrome X Yousef Rasmi, * Sina Raeisi * and Mir H. Seyyed Mohammadzad † Departments of * Biochemistry, † Cardiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran Cardiac syndrome X (CSX) is a condition characterized by the presence of angina pectoris and a positive response to stress or radionuclide tests (thallium scan) with a normal coronary arteriogram [1]. It is found in up to 20% of angina patients undergoing angiography [2]. Despite the extensive studies, the pathogenesis of this syndrome, however, is not well known but coro- nary endothelial dysfunction has been proposed as the most important pathogenetic mechanism in CSX [3,4]. Previous studies have shown an association between viral and bacterial infections such as Helicobacter pylori (H. pylori) infection with vascular diseases such as CSX [5]. H. pylori is a gram-negative bacterium which infects the human stomach [6]. It may cause extra-intestinal manifestations some of which are functional ischemic heart disease and respiratory system disease [7,8] and has recently been associated with CSX [2]. Chronic infection of H. pylori is most probably the cause of increased production of various inflammatory metabo- lites, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) which also affect blood vessel motility and induce endothelial dysfunction [9]. IL-6 is one of the most important mediators of fever and of the acute phase response [10,11]. IL-6 has been described as ‘‘hepatocyte stimulating factor’’ and strongly stimulates hepatocytes to make acute phase proteins in response to inflammation [12]. This cyto- kine is always found in increased levels in sites of inflammation and is likely very important in a number of undescribed ways in inflammatory regulation [13,14]. The TNF-a is a cytokine involved in systemic inflam- mation [15,16]. Most organs of the body appear to be affected by TNF-a and the cytokine serves a variety of functions, many of which are not yet fully understood. In the liver, it stimulates the acute phase response [17]. Keywords Cardiac syndrome X, Helicobacter pylori, inflammation, interleukin-6, tumor necrosis factor-alpha, cytotoxin-associated gene A. Reprint requests to: Yousef Rasmi, Depart- ment of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. E-mail: rasmiy@umsu.ac.ir Abstract Background: Cardiac syndrome X (CSX) is a condition in which patients have the pain of angina despite normal coronary angiogram. Helicobacter pylori (H. pylori) infection causes chronic inflammation which may play a pathogenic role in CSX. We surveyed the association of inflammation with H. pylori and its virulent strain (cytotoxin-associated gene A positive; CagA+) infections with CSX. Material and Methods: Sixty patients with CSX (38 women ⁄ 22 men; mean age: 51.8 ± 12.3) and 60 age- and gender-matched healthy controls (39 women ⁄ 21 men; mean age: 48.9 ± 6.3) were enrolled. Plasma samples were tested for the presence of IgG antibody to H. pylori using enzyme linked immunosorbent assay (ELISA) method. IgG- positive patients were determined by the presence of IgG antibody to CagA, also by ELISA method. Also, plasma levels of interleukin-6 (IL-6) and tumor necro- sis factor-alpha (TNF-a) were measured by ELISA method. Results: Patients with CSX were detected to have significantly higher plasma IL-6 and TNF-a level in comparison with normal controls (33.6 ± 3.5 vs 3.2 ± 0.4 and 24.2 ± 2.3 vs 3.1 ± 0.4, respectively; p < 0.01). The plasma levels of these inflammatory factors in CgA+ were significantly higher than those in CagA) (CSX: IL-6: 43.05 ± 5.04 vs 23.97 ± 4.58 and TNF-a: 31.43 ± 3.13 vs 16.47 ± 2.93, Controls: IL-6: 3.52 ± 1.39 vs 2.90 ± 0.67 and TNF-a: 5.39 ± 1.17 vs 2.22 ± 0.43, respectively; p < 0.05). Conclusion: The CagA+ strain of H. pylori, can not only be a trigger, and may also have a role via chronic inflammation in the pathogenesis of CSX. Helicobacter ISSN 1523-5378 116 ª 2012 Blackwell Publishing Ltd, Helicobacter 17: 116–120