Association of Helicobacter pylori infection with coronary heart disease.

The role of Helicobacter pylori (HP) as the main etiological factor in gastritis and peptic ulcer disease is undisputable. Gastric mucosal damage caused by HP involves various bacterial and host-dependent toxic substances that have been recently associated with an increased risk of coronary artery disease (CAD), possibly through the activation acute phase response and of procoagulant hemostatic factors. Recent studies showed a close and strong correlation between plasma increments of some cytokines such as IL-6 or TNFalpha and cardiovascular diseases. HP infection induces platelet activation and aggregation that could be the pathogenic explanation of the association between HP infection and CAD. The aim of this study was to determine the seroprevalence of HP infection and antibodies to CagA, an antigen that is expressed by the most virulent HP strains inducing an enhanced gastric inflammatory response, in patients undergoing routine coronary artery examination. We studied 76 patients with CAD and 81 healthy controls patients without significant change in coronary circulation. Angiograms were read by two independent experienced cardiologists blinded to the results of HP status. The presence of serum IgG antibodies to HP and to CagA and plasma interleukin-8 (IL-8) levels was measured by ELISA. In addition plasma C-reactive protein fibrinogen, total cholesterol and lipids levels were measured in all studied patients. Seropositivity to HP was found in 81.5 % of cases and in 51% of controls and the difference in prevalence was statistically significant, the odds ratio being 4.3 for Hp patients. Antibody to CagA protein was detected in 47.3% of CAD but only in 28% of healthy controls (OR = 2.3 vs OR = 10). C-reactive protein, plasma fibrinogen and total cholesterol were, respectively higher in patients with CAD than in controls. Present data show that there is significant link between CAD and HP infection. The HP infection significantly increases the risk of CAD, especially when both the anti-HP IgG and anti-CagA IgG are considered. Higher prevalence of cytotoxic HP strains might enhance the atherosclerotic process by inducing a persistent, low grade inflammatory response in arterial wall with enhanced synthesis of acute phase reactants.     

Animal models of Helicobacter pylori infection and disease

The acceptance of Helicobacter pylori as a major human pathogen has necessitated the development of animal models to help elucidate the pathogenic mechanisms of this bacterium and aid in the development of improved strategies for the treatment of gastric disease. Appropriate models, utilising a range of animal species, have been developed to examine factors such as the influence of host responses and bacterial factors in disease development and the success of new therapeutic regimens, including vaccination, to cure infection.     

Risk factors for coronary heart disease and infection with Helicobacter pylori: meta-analysis of 18 studies

Objective: To find out if chronic infection with Helicobacter pylori is correlated with risk factors for coronary heart disease. Design: Meta-analysis of 18 epidemiological studies, involving a total of 10 000 patients, that measured serum antibody titres to H pylori and risk factors for coronary heart disease. Any study published in any language before 1998 was eligible for inclusion. Results: Only small absolute differences in body mass index, blood pressure, or haematological risk factors were found between subjects who were seropositive and those who were seronegative. In those who were seropositive body mass index was slightly higher (0.37, SE 0.09) and concentrations of high density lipoprotein cholesterol were slightly lower (0.032 mmol/l, 0.008). None of the other differences were highly significant. Conclusion: Previous claims of substantial correlations between H pylori seropositivity and certain vascular risk factors were largely or wholly due to chance or the preferential publication of positive results, or both.

Key messages

• Epidemiological studies suggest that there is a weakly positive association between coronary heart disease and chronic infection with Helicobacter pylori
• A number of reports have also claimed that there are strong correlations between infection with H pylori and an increase in vascular risk factors, such as plasma fibrinogen concentrations
• Meta-analysis of 18 studies that involved 10 000 people found no strong correlations between H pylori seropositivity and vascular risk factors; previous findings of the existence of such correlations in small studies were largely or wholly due to chance or to the preferential publication of positive results

     

Helicobacter pylori infection and childhood

Pediatric-based Helicobacter?pylori research continues to contribute significantly to our understanding of both clinical and pathophysiological aspects of this infection. Here, we review the published pediatric H.?pylori literature from April 2009-March 2010. Analysis of pediatric H.?pylori strains continues to suggest that cagA(+) and cagPAI competent strains are less prevalent than in adult isolates. Studies from the Middle East report a high H.?pylori prevalence and intrafamilial transmission. Data continue to show a lack of association between H.?pylori and recurrent abdominal pain of childhood, gastroesophageal reflux disease, and growth retardation. Recent probiotic trials have not shown a benefit on H.?pylori eradication in children, while sequential therapy remains an attractive therapeutic eradication strategy in children, which requires validation in different geographic regions.     

Immunoproteomics of Helicobacter pylori infection and relation to gastric disease

The Gram negative bacterium Helicobacter pylori is a human pathogen which infects the gastric mucosa and causes an inflammatory process leading to gastritis, ulceration and cancer. A systematic, proteome based approach was chosen to detect candidate antigens of H. pylori for diagnosis, therapy and vaccine development and to investigate potential associations between specific immune responses and manifestations of disease. Sera from patients with active H. pylori infection (n = 24), a control group with unrelated gastric disorders (n = 12) and from patients with gastric cancer (n = 6) were collected and analyzed for the reactivity against proteins of the strain HP 26695 separated by two-dimensional electrophoresis. Overall, 310 antigenic protein species were recognized by H. pylori positive sera representing about 17% of all spots separated. Out of the 32 antigens most frequently recognized by H. pylori positive sera, nine were newly identified and 23 were confirmed from other studies. Three newly identified antigens which belong to the 150 most abundant protein species of H. pylori, were specifically recognized by H. pylori positive sera: the predicted coding region HP0231, serine protease HtrA (HP1019) and Cag3 (HP0522). Other antigens were recognized differently by sera from gastritis and ulcer patients, which may identify them as candidate indicators for clinical manifestations. The data from these immunoproteomic analyses are added to our public database (http://www.mpiib-berlin.mpg.de/2D-PAGE). This platform enables one to compile many protein profiles and to integrate data from other studies, an approach which will greatly assist the search for more immunogenic proteins for diagnostic assays and vaccine design.     

幽门螺杆菌感染对冠心病患者血清生化水平及颈动脉硬化的影响

目的 探讨幽门螺杆菌感染对冠心病患者血清生化水平及颈动脉硬化的影响。方法 选取150例冠心病患者,所有患者均接受14C呼气试验检查,将呼气试验阳性患者分为观察组,阴性患者分为对照组。两组患者均检测甘油三酯（TG）、胆固醇（TC）、低密度脂蛋白（LDL-C）、血清同型半胱氨酸（HCY）和血清超敏C反应蛋白（hs-CRP）水平,并接受彩色多普勒超声检查颈动脉。观察并比较两组患者血清生化水平及颈动脉情况。结果 观察组患者血清TC、LDL-C、HCY和hs-CRP水平显著高于对照组（P0.05）。观察组患者内膜厚度显著大于对照组（P0.05）。结论 冠心病患者感染幽门螺杆菌会影响脂蛋白代谢,激活炎症反应,增加冠心病患者动脉硬化发生的风险,应早期积极干预治疗。     

Helicobacter pylori infection and disease: from humans to animal models

Informative and tractable animal models that are colonized by well-defined microbial pathogens represent ideal systems for the study of complex human diseases. Helicobacter pylori colonization of the stomach is a strong risk factor for peptic ulceration and distal gastric cancer. However, gastritis has no adverse consequences for most hosts and emerging evidence suggests that H. pylori prevalence is inversely related to gastroesophageal reflux disease and allergic disorders. These observations indicate that eradication may not be appropriate for certain populations due to the potentially beneficial effects conferred by persistent gastric inflammation. Animal models have provided an invaluable resource with which to study H. pylori pathogenesis and carcinogenesis, and have permitted the development of a focused approach to selectively target human populations at high-risk of disease.Helicobacter pylori is a bacterium that colonizes gastric epithelium and represents the most common bacterial infection worldwide (Peek and Blaser, 2002). H. pylori has colonized human stomachs for over 58,000 years (Linz et al., 2007), and virtually all persons infected by this organism develop co-existing gastritis, a signature feature of which is the capacity to persist for decades. Owing to its co-evolution with humans, H. pylori can send and receive signals from gastric epithelium, allowing host and bacteria to participate in a dynamic equilibrium. However, there are biological costs to these long-term relationships.Epidemiological studies in humans and experimental infections using a variety of animal models have clearly demonstrated that sustained interactions between H. pylori and its host significantly increase the risk for peptic ulcer disease, distal gastric adenocarcinoma, and non-Hodgkin’s lymphoma of the stomach (Peek and Blaser, 2002). Eradication of H. pylori significantly decreases the risk of developing peptic ulceration or gastric adenocarcinoma in infected individuals without pre-malignant lesions (Wong et al., 2004), providing evidence that this organism influences early stages in gastric carcinogenesis. However, only a fraction of colonized persons ever develop ulcers or neoplasia, and disease risk involves well-choreographed interactions between pathogen and host, which, in turn, are dependent upon strain-specific bacterial factors and/or host characteristics.     

Does Helicobacter pylori infection contribute to gastroesophageal reflux disease?

Helicobacter pylori organisms that infect the stomach conceivably could contribute to esophageal inflammation in patients with gastroesophageal reflux disease (GERD) through any of at least three potential mechanisms: 1) by causing an increase in gastric acid secretion; 2) by spreading to infect the gastric-type columnar epithelium that occasionally can line the distal esophagus; and/or 3) by secreting noxious bacterial products into the gastric juice. Studies regarding these potential mechanisms are discussed in this report. Most investigations have found no apparent association between H. pylori infection and reflux esophagitis. Presently, infection with H. pylori does not appear to play an important role in the pathogenesis of GERD.     

Identification of a correlation between Helicobacter pylori infection and Graves' disease

Background: viral and bacterial antigens have been suspected to be able to mimic the antigenic profile of the thyroid cell membrane and to play an important role in the onset of the autoimmune diseases, such as Graves’ disease and Hashimoto thyroiditis. The Helicobacter pylori infection is worldwide diffused and is present in the developed countries up to 50% of the population. The presence of the cytotoxin‐associated gene A antigens identifies the most virulent strains of the bacterium. Previous studies have demonstrated the possible correlation between the Helicobacter pylori and Hashimoto’s thyroiditis but these results are controversial. Aims: We studied the prevalence rate of this bacterium in the Graves’ disease and two selected subgroups such as the hyperthyroid patients, at the first time of diagnosis, and the euthyroid methimazole‐treated patients. Materials and Methods: We analyzed Helicobacter pylori in fresh stool samples with an enzyme immunoassay method and the presence of cytotoxin‐associated gene A antigens with a serological test. Results: Our results show that a significative increased rate of prevalence is present in Graves' patients, when the disease is ongoing, with an overall prevalence of the strains expressing the cytotoxin‐associated gene A antigens compared to the control group. Conclusions: The association between the Helicobacter pylori and Graves’ disease suggests a possible role of this bacterium in the onset and/or the maintenance of the disease.     

Diagnosis of Helicobacter pylori infection

If we had to give a general view of the articles published in the year 2010, we should conclude that the evidence in the year 2010 suggests that, also in Helicobacter pylori diagnosis, "the devil is in the details". In this sense, different studies suggested that skipping citric acid pretreatment or local validation or reducing the (13) C-urea dose markedly decreases the accuracy of the urea breath test. The studies also implied that, even between monoclonal stool tests, there are large differences between the marketed tests. Finally, even histology does not work adequately in patients with gastric cancer or extensive areas of intestinal metaplasia. In these cases, specific gastric sites should be biopsied to improve the reliability of histology.     

Pathogenesis of Helicobacter pylori infection

Helicobacter pylori infections are thought to eventually lead to symptoms as a result of the long-lasting interactions between the bacterium and its host. Mechanisms that allow this bacterium to cause a life-long infection involve modulation of both the immune response and host cellular processes. Last year many novel findings that improve our knowledge on how H.?pylori virulence factors interact with the host were reported, but because of space limitations we can only discuss a limited number of these studies. Among those are studies on the genetic variation of genes encoding outer membrane proteins and the mimicry of host antigens, factors that alter host-cell metabolism and factors that modulate the host's immune response.