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1.  Association of helicobacter pylori infection with severity of coronary heart disease 
ARYA Atherosclerosis  2012;7(4):138-141.
There are few literatures evaluating the association between cytotoxin-associated gene A (CagA) positive strains of Helicobacter pylori (HP) and the severity of coronary heart disease (CHD). This study was designed to investigate this association.
Medical and drug history of 112 consecutive patients who were candidate for coronary angiography were taken. Fasting blood samples were obtained to measure C-reactive protein (CRP), anti Helicobacter pylori immunoglobulin G (anti-HP IgG), anti-CagA antibody (Ab) and interlukine-6 (IL6). According to angiography reports, participants were divided into patients with mild (n = 69) and with sever CHD (n = 36). To measure the association between CagA positive strains of HP with the severity of CHD, multivariate logistic regression tests were used by adjusting age, sex, history of diabetes mellitus (DM), dyslipidemia (DLP), and/or hypertension (HTN), CRP status and IL-6 level.
The analysis was concluded on 105 subjects. HP infection and CagA Ab were not significantly higher compared to the patients with severe and mild CHD (P = 0.28 and P = 0.68, respectively). Colonization of CagA positive HP did not significantly associate with severity of CHD (OR 1.05, 95% CI 0.33–3. 39).
Colonization of CagA positive HP was not an independent risk factor for severe coronary heart disease.
PMCID: PMC3413081  PMID: 23205045
Helicobacter Pylori; CagA; Coronary Heart Disease; Severity
2.  Infection with Helicobacter pylori, coronary heart disease, cardiovascular risk factors, and systemic inflammation: the Third National Health and Nutrition Examination Survey. 
BACKGROUND: Few data have been published on the association of variables of the metabolic syndrome and infection with Helicobacter pylori, a putative risk factor for cardiovascular morbidity, in large, representative samples of total populations. The null hypothesis was no association of prevalent infection with H. pylori with prevalent coronary heart disease (CHD), systemic inflammation, and variables associated with the metabolic syndrome in American men. DESIGN: Cross-sectional survey of a large national sample, the Third National Health and Nutrition Examination Survey. METHODS: Among men aged 40-74 years, the survey measured history of CHD, glycated hemoglobin percent, and concentrations of fasting serum glucose, insulin, triglycerides, HDL cholesterol, and C-reactive protein (CRP). RESULTS: Prevalence of infection with H. pylori increased with age. H. pylori infection was not correlated with serum CRP, prevalence of diagnosed diabetes mellitus, glycated hemoglobin percent, or other risk factors other than age. In diabetic men but not in all men, seropositivity was significantly associated with CHD prevalence. CONCLUSIONS: No consistent associations of H. pylon infection with diabetes prevalence or variables of the insulin resistance syndrome were found in American men aged 40-74 years. In diabetic men, H. pylori infection was associated with CHD prevalence.
PMCID: PMC2568603  PMID: 15586651
3.  Helicobacter pylori Infection and Inflammation: Implication for the Pathophysiology of Diabetes and Coronary Heart Disease in Asian Indians 
Journal of life science  2009;1(1):45-50.
Asian Indians living in the Indian subcontinent or abroad experience high rate of coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). Asian Indians are also known to suffer from various infections, particularly during their childhood. One such chronic infection is with Helicobacter pylori (H. pylori). Since H. pylori with its specific virulence factor cytotoxin-associated gene A (cagA) has been suggested to be associated with CHD, a role of this H. pylori infection was investigated in the pathogenesis of CHD in Asian Indians living in Bangladesh. H. pylori (CagA) infected subjects with CHD (HP+ve cases, n=21), and without CHD (HP+ve controls, n=20), and non-infected without CHD (HP-ve normal controls, n=21) were included in this study. Thromboxane (TXB), an index of platelet activation, was found to be significantly higher in the HP+ve cases (p=0.05), but not in the HP+ve controls (p=0.88) when compared with HP-ve controls. Analyses of lipid profiles revealed that while triglycerides, total cholesterol and LDL did not show any significant changes, HDL was significantly lower in both the HP+ve cases (p=0.0003) and controls (p=0.005). The mean fasting glucose level in the HP+ve cases was markedly increased (p>0.0001), while it was intermediate in the HP+ve controls, and lowest in the HP-ve controls. HOMA-IR values, a measure of insulin resistance, did not reflect any substantial differences between the HP+ve and HP–ve controls, but they were highly significantly different between the HP+ve cases and HP–ve controls. HOMA-B, indicating insulin secretory dysfunction (ISD), was significantly higher in both the HP+ve groups when compared with the normal controls. The data indicate that H. pylori infection is associated with impaired insulin secretion, and that a component of insulin resistance that occurs independent of H. pylori can then lead to a worsening of glucose tolerance and the development of CHD. This is the first demonstration to our knowledge that H. pylori (CagA) infection is associated with insulin secretory dysfunction in human subjects. Since many Asian Indians contract various other chronic and acute infections, it is important to investigate the role of H. pylori and other infectious agents in the pathogenesis of T2DM and CHD.
PMCID: PMC3269913  PMID: 22308070
H. pylori; Inflammation; Heart Disease; Insulin Dysfunction; Asian Indians
4.  Relation of Helicobacter pylori infection and coronary heart disease. 
British Heart Journal  1994;71(5):437-439.
BACKGROUND--There is evidence suggesting that early life experience may influence adult risk of coronary heart disease (CHD). Chronic bacterial infections have been associated with CHD. OBJECTIVE--To determine whether Helicobacter pylori, a childhood acquired chronic bacterial infection, is associated with an increased risk of coronary heart disease in later life. DESIGN--Case-control study controlling for potential confounding variables with an opportunistically recruited control group. SUBJECTS--111 consecutive cases with documented CHD were recruited from a cardiology clinic and 74 controls from a general practice health screening clinic. All were white men aged 45-65. METHODS--Serum was analysed for the presence of H pylori specific IgG antibodies by ELISA (98% sensitive and 94% specific for the presence of infection). RESULTS--59% of the cases and 39% of the controls were seropositive for H pylori (odds ratio 2.28, chi 2 7.35, p = 0.007). After adjustment by multiple logistic regression for age, cardiovascular risk factors, and current social class, the effect of H pylori was little altered (odds ratio 2.15, p = 0.03). Further adjustment for various features of the childhood environment known to be risk factors for H pylori infection only slightly weakened the association (odds ratio 1.9). H pylori seropositivity was not related to the level of risk factors in the control population. CONCLUSION--In this pilot study the association of adult coronary heart disease with H pylori seropositivity suggests that the early childhood environment may be important in determining the risk of CHD in adult life. The association needs confirmation in other better designed studies. If H pylori itself is responsible for the association, then this is of great potential importance as the infection is treatable.
PMCID: PMC483719  PMID: 8011406
5.  Significant Association between Serum Interleukin-6 and Helicobacter pylori Antibody Levels among H. pylori-Positive Japanese Adults 
Mediators of Inflammation  2013;2013:142358.
Background. Interleukin-6 (IL-6) is a multifunctional cytokine produced by many types of cells. Inflammation plays a key role in the pathogenesis of atherosclerosis that is an underlying cause of coronary heart disease (CHD). Since the 1990s, some studies have shown an association between H. pylori infection and CHD, which may be mediated by inflammation. Therefore, this study aimed to evaluate the association between serum anti-H. pylori IgG levels and serum IL-6 levels in H. pylori-infected adults. Methods. We enrolled 158 subjects who visited a clinic located in an urban area to be tested for H. pylori infection, using the 13C-urea breath test, and who were found to be infected and subsequently received eradication. Results. The geometric mean serum IL-6 level was 1.78 pg/mL for men, 1.57 pg/mL for women, and 1.64 pg/mL overall. Logarithms of serum IL-6 levels were positively correlated with logarithms of serum H. pylori IgG levels (r = 0.24, P = 0.002). In multiple linear regression analysis adjusting for sex and age, the serum IL-6 level was still significantly associated with the IgG level in all subjects (β = 0.18, P = 0.012). Conclusion. Higher H. pylori IgG levels were significantly associated with higher serum IL-6 levels among H. pylori-infected individuals.
PMCID: PMC3881527  PMID: 24453409
6.  Could Helicobacter pylori infection increase the risk of coronary heart disease by modifying serum lipid concentrations? 
Heart  1996;75(6):573-575.
OBJECTIVE: To investigate the relation between Helicobacter pylori infection and coronary heart disease (CHD). DESIGN: A case-control study. SETTING: Northern Finland (about 650,000 inhabitants). PATIENTS: 116 patients with angiographically documented CHD and 116 controls matched for age and gender randomly recruited from the register of the Finnish Social Insurance Institute. MAIN OUTCOME MEASURES: The odds ratio (OR) estimates for the association of H pylori infection with CHD. RESULTS: 64% of the CHD patients and 53% of the controls were seropositive for H pylori; the OR adjusted for age and gender was 1.5 (95% confidence interval (CI) 0.9 to 2.5). An additional adjustment for the common risk factors of CHD, including lipid concentrations, in a logistic regression analysis produced an OR estimate of 1.1 (95% CI 0.6 to 2.1). Among the controls, those who were H pylori positive had significantly (P = 0.03) higher concentrations of serum triglycerides than those who were H pylori negative: the trend among the cases was similar, but non-significant. The concentrations of HDL cholesterol tended to be lower in those who were H pylori positive than in those who were H pylori negative, among both the cases and the controls. CONCLUSIONS: The impact of H pylori infection as an independent risk factor for CHD seems to be minor. On the other hand the results are consistent with the hypothesis that H pylori infection might modify the serum lipid concentrations in a way that could increase the risk of CHD.
PMCID: PMC484379  PMID: 8697159
7.  Ectasia and Severe Atherosclerosis 
Texas Heart Institute Journal  2005;32(1):21-27.
To date, there has been no convincing evidence for an association between Chlamydia pneumoniae or Helicobacter pylori and ectasia. In this case-control study, we have investigated the association of H. pylori and C. pneumoniae seropositivity with ectasia, severe coronary atherosclerosis, and normal vessels, which were so classified by coronary angiography. We have also evaluated the influence of these infections on inflammatory markers such as high-sensitive C-reactive protein (hsCRP) and interleukin 6 (IL-6).
Of the 796 patients undergoing coronary angiography for suspected ischemic heart disease, 244 patients were recruited. Of these, 91 had normal vessels, 88 had 3 or more obstructed vessels, and 65 had ectatic vessels without atherosclerosis. Eighty-seven atherosclerotic patients (98.9%) were positive for C. pneumoniae IgG, as were 64 ectatic patients (98.5%) and 76 controls (83.5%) (P < 0.001). Forty-two atherosclerotic patients (47.7%) were positive for C. pneumoniae IgM, as were 43 ectatic patients (66.2%) and 43 controls (47.3%) (P = 0.036). Seventy-two atherosclerotic patients (81.8%) were positive for H. pylori IgA, as were 26 ectatic patients (40.0%) and 44 controls (48.4%) (P < 0.001). High-sensitive CRP levels were significantly higher in ectatic patients (5.639 mg/L) than in controls (4.390 mg/L) (P = 0.032), and IL-6 levels were significantly higher in atherosclerotic patients (33.92 U/L) than in controls (14.01 U/L) (P < 0.001). Interleukin-6 levels were higher in H. pylori seropositive patients, and hsCRP levels were higher in C. pneumoniae seropositive patients, when compared with seronegatives.
We suggest that, as in atherosclerosis, C. pneumoniae infection is related to ectasia, with raised CRP levels.
PMCID: PMC555817  PMID: 15902817
Atherosclerosis; bacterial infections/complications; biological markers; C-reactive protein; chlamydia infections/complications; Chlamydia pneumoniae; Cardiovascular diseases/etiology; dilatation, pathologic/etiology; helicobacter infections/complications; Helicobacter pylori; inflammation; interleukin-6
8.  Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs study 
BMJ : British Medical Journal  1999;319(7218):1157-1162.
To examine the association between coronary heart disease and chronic Helicobacter pylori infection.
Case-control study of myocardial infarction at young ages and study of sibling pairs with one member affected and the other not.
United Kingdom.
1122 survivors of suspected acute myocardial infarction at ages 30-49 (mean age 44 years) and 1122 age and sex matched controls with no history of coronary heart disease; 510 age and sex matched pairs of siblings (mean age 59 years) in which one sibling had survived myocardial infarction and one had no history of coronary heart disease.
Main outcome measures
Serological evidence of chronic infection with H pylori.
472 (42%) of the 1122 cases with early onset myocardial infarction were seropositive for H pylori antibodies compared with 272 (24%) of the 1122 age and sex matched controls, giving an odds ratio of 2.28 (99% confidence interval 1.80 to 2.90). This odds ratio fell to 1.87 (1.42 to 2.47; P<0.0001) after smoking and indicators of socioeconomic status were adjusted for and to 1.75 (1.29 to 2.36) after additional adjustment for blood lipid concentrations and obesity. Only 158 of the 510 pairs of siblings were discordant for H pylori status; among these, 91 cases and 67 controls were seropositive (odds ratio 1.33 (0.86 to 2.05)). No strong correlations were observed between H pylori seropositivity and measurements of other risk factors for coronary heart disease (plasma lipids, fibrinogen, C reactive protein, albumin, etc).
In the context of results from other relevant studies, these two studies suggest a moderate association between coronary heart disease and H pylori seropositivity that cannot be fully accounted for by other risk factors. But even if this association is causal and largely reversible by eradication of chronic infection, very large randomised trials would be needed to show this.
Key messagesMost previous studies of associations between chronic H pylori infection and coronary heart disease have been too small or prone to biasThis case-control study found myocardial infarction was twice as common in people infected with H pylori as in those not infectedAmong sibling pairs, myocardial infarction was about a third more common in seropositive people than those who were seronegativeThese results support a weak association between H pylori infection and coronary heart disease
PMCID: PMC28263  PMID: 10541503
9.  Chlamydia Pneumoniae and Helicobacter Pylori Serology – Importance in Patients with Coronary Heart Disease 
Materia Socio-Medica  2012;24(3):151-156.
Chronic infections in CHD are due to one or both of the organisms Chlamydia pneumoniae and Helicobacter pylori.
To examine the association between serum markers of Chlamydia pneumoniae and Helicobacter pylori infection and markers of myocardial damage. in patients with acute coronary syndrome (ACS), with chronic coronary artery disease (CAD) and in–control group.
Material and methods:
Sera were taken from a total of 153 subjects. Subjects were divided in three groups: 64 patients with ACS; 53 patients with CAD and a group of 35 conditionally healthy individuals. Analysis of patients’ sera for IgG antibodies to H. pylori and markers for myocardial damage was done on the Immulite system. The presence of specific IgG and IgA antibodies to C. pneumoniae was determined with MIF, Sero FIA (Savyon Diagnostics, Israel). Statistical analysis of data was done using the statistical program SPSS (Statistical Package for Social Sciences), version 13.
Results and discussion:
There was a high significant difference in troponin levels between the three groups of subjects (p=0.0000). Levels of creatine kinase isoenzyme (CK-MB) were highest in the ACS group (500.0 ng/mL). There was a statistically significant difference between CG subjects and ACS patients due to more frequent detection of antichlamydial IgA antibodies in patients with acute coronary syndrome. Positive serum immune response for Helicobacter pylori was 17 (53.1%) and 29 (80.6%), respectively.
Increased IgA antibody titers for C. Pneumoniae, increased CRP values as well as classic markers of myocardial damage are risk factors for coronary events.
PMCID: PMC3732349  PMID: 23922522
markers of cardiac damage; chronic infections; Chlamydia pneumoniae and Helicobacter pylori.
10.  Association between Helicobacter pylori Seropositivity and the Coronary Artery Calcium Score in a Screening Population 
Gut and Liver  2011;5(3):321-327.
Helicobacter pylori causes numerous extragastric manifestations, including coronary heart disease. The coronary artery calcification (CAC) score, measured using computed tomography (CT) has been used as a screening test for coronary atherosclerosis. This study investigated the association between H. pylori seropositivity and CAC scores in a screening population.
Patients who underwent a health checkup between October 2003 and July 2007 and who did not have a history of ischemic heart disease were enrolled in the study. Subjects were screened with a multidetector CT scan to determine the CAC score and for anti-H. pylori antibody immunoglobulin G; traditional risks for coronary heart disease were evaluated using a structured questionnaire, anthropometric measurements, and laboratory tests.
Of the 2,029 subjects enrolled (1,295 males), 1,214 (59.8%) subjects were H. pylori positive and 815 were H. pylori negative. There were no significant differences in the baseline characteristics of the seropositive and seronegative patients. When the CAC presence or absence scores were considered, multivariate analysis revealed that H. pylori seropositivity was statistically associated with the presence of CAC and that this association was stronger in the mild CAC score category.
H. pylori seropositive patients are at a higher risk for coronary atherosclerosis regardless of traditional cardiovascular risk factors. This association is particularly applicable for early coronary atherosclerosis.
PMCID: PMC3166673  PMID: 21927661
Helicobacter pylori; Seropositivity; Coronary atherosclerosis; Screening
11.  Helicobacter pylori infection is associated with decreased serum levels of high density lipoprotein, but not with the severity of coronary atherosclerosis 
The objective of this survey was to study the association between Helicobacter pylori infection and the severity of coronary atherosclerosis.
The study population consisted of 961 consecutive patients (711 males and 250 females) who underwent coronary angiography for suspected or known coronary atherosclerosis. The patients' body mass index, blood pressure, the blood lipid, blood glucose, leukocyte count (109/L), neutrophil count (109/L), and Helicobacter pylori-specific IgG antibodies were performed. Coronary angiograms were scored according to vessel score and Gensini's score.
A significant association between H. pylori infection and coronary atherosclerosis as well as its severity was not find in this cross section study (p = 0.858). And, the level distribution of vessel score (p = 0.906) and Gensini's score (p = 0.905) were similar in the seropositivity group and seronegativity group of Helicobacter pylori infection. However, the level of fasting high-density lipoprotein cholesterol (mmol/L) (p = 0.013) was significantly lower in the seropositivity group than that in the seronegativity group of Helicobacter pylori infection.
In conclusion, in the present study, a significantly correlation between Helicobacter pylori seropositivity and angiographically evaluated severity of atherosclerosis was not find. And, the present study showed a good correlation between Helicobacter pylori infection and decreased HDL cholesterol. However, the exact mechanisms need further study.
PMCID: PMC2808301  PMID: 20030806
12.  Helicobacter pylori infection is identified as a cardiovascular risk factor in Central Africans 
Helicobacter pylori is now incriminated in the pathogenesis of atherosclerosis.
To examine the importance of H. pylori infection as a cardiovascular disease (CVD) risk factor.
Two hundred five patients (128 with H. pylori infection [HP-seropositive] and 77 without) had a baseline assessment for other potential CVD risk factors and were followed prospectively for 10 years (1999–2008). They were assessed on a monthly basis for the outcomes of carotid plaque, angina pectoris, myocardial infarction, and stroke. In the HP-seropositive group, male sex and quartile 4 for IgG anti-H. pylori antibodies (anti-HP Ab) were correlated with traditional CVD risk factors, stroke, myocardial infarction, and angina pectoris.
At the baseline assessment, the levels of carotid intima-media thickness, blood fibrinogen, total cholesterol, fasting plasma glucose, and uric acid were higher in H. pylori-infected patients than in the uninfected group. Serum HDL-cholesterol was significantly lower in the HP-seropositive group. Men had higher levels of IgG anti-HP Ab, waist circumference, blood pressure, uric acid, and total cholesterol than women. Within the HP-seropositive group, individuals in quartile 4 for IgG anti-HP Ab had higher rates of elevated fibrinogen, diabetes mellitus, low high-density lipoprotein cholesterol, arterial hypertension, and high total cholesterol than those in quartile 1. After adjusting for traditional CVD risk factors, H. pylori infection was the only independent predictor of incident carotid plaque (multivariate odds ratio [OR] = 2.3, 95% confidence interval [CI]: 1.2–7.2; P < 0.0001) and incident acute stroke (multivariate OR = 3.6, 95% CI: 1.4–8.2; P < 0.0001). Within the HP-seropositive group and after adjusting for traditional CVD risk factors, male sex was the only independent predictor of incident angina pectoris (multivariate OR = 3.5, 95% CI: 1.6–16; P < 0.0001), incident acute stroke (multivariate OR = 3.2, 95% CI: 1.4–28; P < 0.0001), and acute myocardial infarction (multivariate OR = 7.2, 95% CI: 3.1–18; P < 0.0001).
Our study provides evidence for an association among known CVD risk factors, carotid plaque, stroke, and H. pylori infection. Among infected individuals, there is a significant association among severity of HP-seropositivity, male sex, and CVD. The eradication of H. pylori infection may therefore reduce the emerging burden of CVD in Africa.
PMCID: PMC3423148  PMID: 22923995
Helicobacter pylori; stroke; myocardial infarction; cardiovascular disease; carotid plaque; Africans
13.  High Prevalence of Helicobacter pylori in the Alaska Native Population and Association with Low Serum Ferritin Levels in Young Adults 
Iron deficiency anemia is a common public health problem in the Alaska Native population. Yet, a clear etiology has eluded researchers for decades. Previous studies suggested a link between Helicobacter pylori infection, gastrointestinal blood loss due to hemorrhagic gastritis, and generalized iron deficiency anemia in adult Alaska Natives. Therefore, we examined the association between the prevalence of H. pylori-specific immunoglobulin G (IgG) and serum ferritin levels, a marker of iron deficiency. A random sample of 2,080 serum samples from Alaska Native residents drawn between 1980 and 1986 from residents in 13 regions was selected, and the samples were stratified by age, sex, and region. Overall, 75% were positive for H. pylori-specific IgG. The rate of H. pylori seropositivity increased with age; by age 14 years, 78% of the residents were positive. There were no gender differences in H. pylori seropositivity. However, marked regional differences were observed. Serum ferritin levels of <12 ng/ml were found most commonly among persons <20 years of age and among women of childbearing age. A significant association between low serum ferritin levels and prevalence of H. pylori-specific IgG was found, particularly for people aged less than 20 years. H. pylori may be a factor contributing to the iron deficiency anemia in the Alaska Native population.
PMCID: PMC95979  PMID: 11063492
14.  The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: The Persian Gulf Healthy Heart Study 
The metabolic syndrome together with insulin resistance and their consequences are basic factors in pathogenesis of atherosclerosis. Chronic infections with herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), and Chlamydia pneumoniae are associated with the development of atherosclerosis and coronary heart disease. The infectious aspects of metabolic syndrome have not been investigated.
In a cross-sectional, population-based study, we used National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria in 1791 subjects, aged 25 years and over, selected by cluster random sampling in three Iranian ports in the northern Persian Gulf. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae, HSV-1, Helicobacter pylori (H. pylori) and CMV using ELISA.
In multiple logistic regression analysis, of the infectious agents, CMV [OR = 1.81 (1.05–3.10); p = 0.03], H. pylori [OR = 1.50 (1.12–2.00); p = 0.007] and Chlamydia pneumoniae [OR = 1.69 (1.27–2.25); p < 0.0001] showed a significant association with the metabolic syndrome in men and HSV-1 [OR = 1.95 (1.22–3.11); p = 0.005], H. pylori [OR = 1.45 (1.09–1.94); 0.01] and Chlamydia pneumoniae [OR = 1.65 (1.23–2.21); p = 0.001] in women.
The metabolic syndrome, which occurs very frequently in the general population, has a significant association with prior infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus and herpes simplex virus type 1. Hypothesis about participation of infection in pathogenesis of metabolic syndrome should be investigated.
PMCID: PMC1697801  PMID: 17140429
15.  The Association Between Current Helicobacter pylori Infection and Coronary Artery Disease 
The role of Helicobacter pylori (H. pylori) in the pathogenesis of coronary artery disease (CAD) is still controversial, and the relation between current H. pylori infection and CAD has not been fully examined. This study evaluated the relation between H. pylori infection as confirmed by gastroduodenoscopic biopsy and CAD.
We determined the presence of H. pylori infections, via gastroduodenoscopy, in 88 patients of the normal coronary angiographic group and also in 175 patients of the CAD group, and the latter patients had more than 50% coronary stenosis angiographically demonstrated. We excluded those patients with a history of previous H. pylori eradication and/or malignancy. A small piece of tissue from the antrum, which was obtained by gastroduodenoscopic biopsy, was stained by Warthin-starry silver stain. We defined a negative staining result that there was no stained tissue in the sample and the stained tissue was also positive for H. pylori infection.
There was no significant difference, except for gender, age, smoking and high density lipoprotein cholesterol (HDL-c), of the demographic and laboratory characteristics between the groups. Twenty seven (30.7%) patients of the normal control group and 71 (40.6%) patients of the CAD group were positive of H. pylori infection, yet there was no statistical difference. We angiographically followed up the 80 patients of the CAD group who were treated by percutaneous coronary intervention (PCI) at 6 to 9 months after their primary intervention. Twenty two (37.9%) of the 58 patients of the H. pylori negative group and 10 (45.5%) of the 22 patients of the H. pylori positive group were treated with reintervention, but reintervention was also not significantly different between the group with H. pylori infection and the group without the infection.
These data indicated that H. pylori infection had a modest influence on CAD and progressive atheroma, but the showed a tendency to increase. Further studies are needed to evaluate the relationship between H. pylori infection and CAD.
PMCID: PMC2687700  PMID: 17939331
Helicobacter pylori; Coronary artery disease
16.  Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population based study of coronary heart disease 
Heart  1999;81(3):245-247.
OBJECTIVE—To study possible associations between coronary heart disease and serological evidence of persistent infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus.
DESIGN—Population based, case-control study, nested within a randomised trial.
SETTING—Five general practices in Bedfordshire, UK.
INDIVIDUALS—288 patients with incident or prevalent coronary heart disease and 704 age and sex matched controls.
RESULTS—High concentrations of serum IgG antibodies to H pylori were present in 54% of cases v 46% of controls, with corresponding results for C pneumoniae seropositivity (33% v 33%), and cytomegalovirus seropositivity (40% v 31%). After adjustments for age, sex, smoking, indicators of socioeconomic status, and standard risk factors, the odds ratios (95% confidence intervals) for coronary heart disease of seropositivity to these agents were: 1.28 (0.93 to 1.75) for H pylori, 0.95 (0.66 to 1.36) for C pneumoniae, and 1.40 (0.96 to 2.05) for cytomegalovirus.
CONCLUSIONS—There is no good evidence of strong associations between coronary heart disease and serological markers of persistent infection with H pylori, C pneumoniae, or cytomegalovirus. To determine the existence of moderate associations between these agents and disease, however, larger scale studies will be needed that can keep residual confounders to a minimum.

 Keywords: ischaemic heart disease; Helicobacter pylori; Chlamydia pneumoniae; cytomegalovirus
PMCID: PMC1728960  PMID: 10026344
17.  Seroepidemiology of Helicobacter pylori infection in elderly people in the Beijing region, China 
AIM: To investigate seroepidemiology of cagA+ and vacA+ strains of Helicobacter pylori (H. pylori) in an elderly population in Beijing and to determine risk factors for seropositivity.
METHODS: A total of 2006 elderly persons (> 60 years) were selected using a random cluster sampling method in different parts of the Beijing area (urban, suburban and mountainous districts). Structured questionnaires were completed during home visits, including history of H. pylori infection, history of gastrointestinal diseases, diet types, hygiene habits, occupation and economic status. Blood samples (2 mL) were collected from each participant, and serum IgG antibodies to cagA, vacA and H. pylori urease antigens were measured by immunodetection.
RESULTS: The prevalence of H. pylori infection in elderly subjects was 83.4% and the type I H. pylori strain infection rate was 56%. The seroprevalence for type I H. pylori strain infection in urban and suburban districts was higher than that in the mountainous areas (P < 0.001). Elderly subjects who had previously performed manual labor or were in the young-old age group (age < 75 years) had a higher seroprevalence of H. pylori infection than those who had previously performed mental labor or were in the oldest-old age group (age ≥ 75 year) (P < 0.05). The type I H. pylori strain infection rate in the elderly with vegetarian diets was higher than in those eating high-protein foods (P < 0.001). There was no significant difference in the prevalence of H. pylori strains between male and female elderly participants (P > 0.05).
CONCLUSION: Type I H. pylori seroprevalence is higher in elderly people. The distribution of strains of H. pylori is significantly affected by age, area and dietary habits.
PMCID: PMC3974532
Elderly; Epidemiology; Helicobacter pylori; Virulence factors; Immunoblotting
18.  Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men. 
Heart  1996;75(6):568-572.
OBJECTIVE: To determine whether Helicobacter pylori, a chronic bacterial infection often acquired in childhood, is associated with increased risk of coronary heart disease and stroke later in life. DESIGN: Nested case-control study. SETTING: Prospective study of cardiovascular disease in men aged 40-59 years at entry (1978-1980) in 24 British towns. SUBJECTS: 135 cases of myocardial infarction and 137 cases of stroke occurring before December 1991; 136 controls were identified, frequency matched to cases by town and age group. METHODS: Serum samples stored at entry were analysed by an enzyme linked immunosorbent assay for the presence of H pylori specific IgG antibodies. RESULTS: 95 of the myocardial infarction cases (70%) and 93 (68%) of the stroke cases were seropositive for H pylori compared with 78 (57%) of the controls (odds ratio for myocardial infarction 1.77, 95% confidence interval (CI) 1.06 to 2.95, P = 0.03; odds ratio for stroke 1.57, 95% CI 0.95 to 2.60, P = 0.07). Helicobacter pylori infection was associated with manual social class, residence in Northern England or Scotland, cigarette smoking, higher systolic pressure and blood glucose, and a lower height-standardised forced expiratory volume in one second. Adjustment for these factors attenuated the relation between H pylori and myocardial infarction (odds ratio = 1.31, 95% CI 0.70 to 2.43, P = 0.40) and effectively abolished the relation with stroke (odds ratio = 0.96, 0.46 to 2.02, P = 0.92). The relation between helicobacter infection and fatal myocardial infarction was slightly stronger (odds ratio 2.41, 95% CI 1.13 to 5.12) but was also markedly attenuated after adjustment (1.56, 95% CI 0.68 to 3.61). CONCLUSION: In this prospective study the association between Helicobacter pylori infection and increased risk of myocardial infarction and stroke was substantially confounded by the relation between this infection, adult social class, and major cardiovascular risk factors.
PMCID: PMC484378  PMID: 8697158
19.  Predictive value of neutrophil infiltration as a marker of Helicobacter pylori infection 
AIM: To evaluate the predictive value of neutrophil infiltration as a marker of Helicobacter pylori (H. pylori) infection.
METHODS: A total of 315 patients with dyspepsia symptoms who underwent upper gastrointestinal endoscopy were enrolled in this study. Biopsies were evaluated using the updated Sydney system. The medication history of all patients in the preceding 4 wk was recorded. The diagnosis of H. pylori infection was based on 13C-urea breath test at least 4 wk after withdrawal of antisecretory drugs, antibiotics and related drugs. For the patients with subtotal gastrectomy, the diagnosis of H. pylori infection was based on anti-H. pylori immunoglobulin G (IgG) antibody. Serum anti-H. pylori IgG antibody was measured by enzyme-linked immunosorbent assays (Biohit, Finland).
RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value of neutrophil infiltration in the diagnosis of H. pylori infection were 92.3%, 83.5%, 77.4% and 94.7%, respectively. Neutrophil infiltration of gastric mucosa in the histological analysis was strongly associated with H. pylori infection (77.4% vs 5.3% in the neutrophil infiltration negative group, P = 0.000). Moderate neutrophil infiltration was more frequent in H. pylori infection when compared to mild infiltration (81.8% and 75%, respectively), but did not reach statistical significance. For those patients with negative rapid urease test, H. pylori was detected in 73.2% of patients with positive neutrophil infiltration on histology. In patients with subtotal gastrectomy, the diagnostic accuracy of neutrophil infiltration in H. pylori infection was 50%.
CONCLUSION: Neutrophil infiltration is closely associated with H. pylori and may be recognized as a sign of this infection.
PMCID: PMC3460339  PMID: 23049221
Helicobacter pylori; Histology; Neutrophil; Sensitivity; Specificity
20.  Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. 
BMJ : British Medical Journal  1995;311(7007):711-714.
OBJECTIVE--To investigate the relation between seropositivity to chronic infections with Helicobacter pylori and Chlamydia pneumoniae and both coronary heart disease and cardiovascular risk factors. DESIGN--Cross sectional study of a population based random sample of men. Coronary heart disease was assessed by electrocardiography, Rose angina questionnaire, and a history of myocardial infarction; serum antibody levels to H pylori and C pneumoniae were measured, risk factor levels determined, and a questionnaire administered. SETTING--General practices in Merton, Sutton, and Wandsworth, south London. SUBJECTS--388 white south London men aged 50-69. MAIN OUTCOME MEASURES--Evidence of coronary risk factors and infection with H pylori or C pneumoniae. RESULTS--47 men (12.1%) had electrocardiographic evidence of ischaemia or infarction. 36 (76.6%) and 18 (38.3%) were seropositive for H pylori and C pneumoniae, respectively, compared with 155 (45.5%) and 62 (18.2%) men with normal electrocardiograms. Odds ratios for abnormal electrocardiograms were 3.82 (95% confidence interval 1.60 to 9.10) and 3.06 (1.33 to 7.01) in men seropositive for H pylori and C pneumoniae, respectively, after adjustment for a range of socioeconomic indicators and risk factors for coronary heart disease. Cardiovascular risk factors that were independently associated with seropositivity to H pylori included fibrinogen concentration and total leucocyte count. Seropositivity to C pneumoniae was independently associated with raised fibrinogen and malondialdehyde concentrations. CONCLUSIONS--Both H pylori and C pneumoniae infectins are associated with coronary heart disease. These relations are not explained by a wide range of confounding factors. Possible mechanisms include an increase in risk factor levels due to a low grade chronic inflammatory response.
PMCID: PMC2550716  PMID: 7549683
21.  Heart rate variability and biomarkers of systemic inflammation in patients with stable coronary heart disease: findings from the Heart and Soul Study 
Chronic low-grade systemic inflammation is a key component in atherogenesis. Decreased heart rate variability (HRV), a strong predictor of cardiovascular events, has been associated with elevations in circulating levels of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen in apparently healthy individuals. We investigated whether decreased HRV is associated with inflammatory markers in patients with coronary heart disease (CHD).
We studied the relationship between HRV and CRP, IL-6, and fibrinogen in 862 outpatients with CHD. All participants provided fasting blood samples and underwent 24-h ambulatory monitoring to assess time-domain measures of HRV (MeanNN, SDNN, SDANN, and RMSSD). Regression analyses were adjusted for age, sex, ethnicity, body mass index, smoking, diabetes, beta blocker use, and cardiopulmonary history.
MeanNN, SDNN, and SDANN were significantly and inversely associated with CRP and IL-6 levels in age-adjusted models and after adjustment for all covariates (p ≤ 0.02). MeanNN, SDNN, and SDANN were also inversely associated with fibrinogen levels in age-adjusted models (p < 0.03), but not significantly so in multivariable-adjusted models. Reduced vagal modulation of heart rate (RMSSD) was not significantly associated with any inflammatory measures.
Reduced cardiac autonomic control is associated with increased systemic inflammation in patients with stable CHD. This relationship was largely independent of important covariates.
PMCID: PMC3207966  PMID: 20857123
Autonomic nervous system; Biomarkers; Cardiac autonomic function; Cardiovascular disease; Heart rate variability; Inflammation
22.  Human Antibody Response to Helicobacter pylori Lipopolysaccharide: Presence of an Immunodominant Epitope in the Polysaccharide Chain of Lipopolysaccharide 
Infection and Immunity  1998;66(6):3006-3011.
We have examined the antibody response to Helicobacter pylori lipopolysaccharides (LPS) in humans. We used sera from patients with gastroduodenal diseases and healthy adults infected or not infected with H. pylori. Data from the experiments for antibody binding to LPS suggested that the polysaccharide chains from many H. pylori strains showed high immunogenicity in humans. Sera from most (above 70%) H. pylori-infected individuals contained immunoglobulin G (IgG) antibodies against the polysaccharide region highly immunogenic H. pylori LPS. The IgG titers of individual serum samples that reacted strongly with highly immunogenic LPS were quite similar (r2 = 0.84 to 0.98). The results suggest wide distribution among H. pylori strains of a highly antigenic epitope in the polysaccharide moieties of their LPS. Also, the similarity in the titers of individual serum samples against highly immunogenic LPS points to the existence of epitopes sharing a common structural motif. However, some strains showed low antigenicity, even those with polysaccharide-carrying LPS. The dominant subclass of IgG that reacted with the highly immunogenic LPS was IgG2, which was preferentially raised against polysaccharide antigens. Recently, a structure that mimics that of the Lewis antigens was identified in the O-polysaccharide fraction of H. pylori LPS; however, no correlation between antigenicity of the polysaccharide chain in humans and the presence of Lewis antigens was found. The IgA and IgM titers against H. pylori LPS seemed to be mostly nonspecific and directed against lipid A. In a few cases, however, sera from individuals infected with H. pylori gave strong IgA and IgM titers against the highly immunogenic polysaccharide. In conclusion, the LPS of many H. pylori strains possess an antigenic epitope in their polysaccharide regions that is immunogenic in humans. However, our results show that the antigenic epitope is unlikely to be immunologically related to structures mimicking Lewis antigens.
PMCID: PMC108305  PMID: 9596783
23.  Seroepidemiology of Helicobacter pylori Infection in Tepehuanos Aged 15 Years and Older in Durango, Mexico 
Journal of Pathogens  2013;2013:243246.
This study aimed to determine the seroepidemiology of Helicobacter pylori infection in Tepehuanos (an indigenous ethnic group living in rural Mexico). The prevalence of anti-Helicobacter pylori IgG antibodies was examined in 156 Tepehuanos in Durango State, Mexico, using an enzyme-linked immunoassay. In addition, sociodemographic, clinical, and behavioral characteristics of Tepehuanos associated with seropositivity were investigated. In total, 103 (66%) of the 156 participants (mean age 31.03  ±  16.71 years) had Helicobacter pylori IgG antibodies. Fifty-four (52.4%) of the 103 seropositive individuals had Helicobacter pylori IgG antibody levels higher than 100 U/mL. Males and females had comparable seroprevalence of Helicobacter pylori infection and Helicobacter pylori IgG antibody levels. The seroprevalence was significantly higher in women with pregnancies than those without this obstetric characteristic. Logistic regression showed that Helicobacter pylori infection was positively associated with low education (OR = 3.37; 95% CI: 1.13–10.00; P = 0.02) and laborer occupation (OR = 2.71; 95% CI: 1.14–6.42; P = 0.02). This is the first report of seroprevalence and contributing factors for Helicobacter pylori infection in Tepehuanos and of the association of Helicobacter pylori infection with laborer occupation. Results warrants further research.
PMCID: PMC3615584  PMID: 23577260
24.  Association of Helicobacter pylori infection with the Lewis and ABO blood groups in dyspeptic patients 
Helicobacter pylori infection is a basic risk factor for chronic gastritis, and gastric carcinoma. Based on some studies, the reason is binding of H. pylori to H and Leb antigens in gastric mucosa. However, some other findings have not determined any association between the infection and these antigens. Because of this controversy and the fact that H. pylori infection and gastric adenocarcinoma are common diseases in Iran, the assessment of the association of H. pylori infection with these blood groups could be valuable.
Materials and Methods:
In a cross sectional study on 135 adult dyspeptic patients in Mashhad, Iran, from 2009 to 2010, H. pylori infection was evaluated by using the Heliprobe 14C-urea breath test and the ABO and Lewis blood group antigens were determined by the tube method. Association between the Lewis and ABO phenotypes with H. pylori infection were analysed by Fisher's exact test. A P ≤ 0.05 was considered to be significant.
68 (50.4%) patients were positive for H. pylori infection. The frequencies of the ABO, Lewis and secretion phenotypes were not significant in the infected and non-infected patients. We also did not find a significant association between Lea and Leb antigens and this infection.
We could not establish a significant association between the Lewis, ABO and secretion phenotypes with H. pylori infection. Diversity of sequences of blood group antigen b-binding adhesion (babA gene) of H. pylori may be a reason why our findings are different from other studies in other geographic areas.
PMCID: PMC3719247  PMID: 23901182
ABO blood groups; gastritis; Helicobacter pylori; Lewis blood group; secretor blood group
25.  Prevalence and risk factors of Helicobacter pylori infection in Korea: Nationwide multicenter study over 13 years 
BMC Gastroenterology  2013;13:104.
The aim of this study was to evaluate the time trend of seropositivity of Helicobacter pylori (H. pylori) over the period of 13 years in an asymptomatic Korean population, and investigate associated risk factors.
This cross-sectional nationwide multicentre study surveyed anti-H. pylori IgG antibodies in 19,272 health check-up subjects (aged [greater than and equal to]16 years) in 2011. Risk factors for H. pylori infection were investigated using logistic regression. Seropositivity in asymptomatic subjects without H. pylori eradication was compared between the years 1998 and 2005. Birth cohort effects were also evaluated.
After exclusion of subjects with a history of H. pylori eradication therapy (n = 3,712, 19.3%) and gastric symptoms (n = 4,764, 24.7%), the seroprevalence of H. pylori infection was 54.4% in 10,796 subjects. This was significantly lower than the seroprevalence of 59.6% in 2005 and that of 66.9% in 1998, and this decrease of seropositivity of H. pylori became widespread across all ages and in most areas of the country. This decreasing trend could be explained by cohort analysis. All younger birth cohorts had a lower seroprevalence of H. pylori than older birth cohorts at the same age. Decreased seroprevalence within the same birth cohorts also accounted for this phenomenon. Clinical risk factors of H. pylori infection were higher cholesterol level ([greater than and equal to] 240 mg/dl) (OR = 1.33; 95% CI = 1.14-1.54), male gender, older age, low income, and residence in a rural area.
A decreasing trend of H. pylori seroprevalence due to a birth cohort effect requires further studies on its related human host factors as well as socio-economic and hygienic factors. In addition, the relationship between H. pylori infection and high cholesterol level needs more investigation regarding underlying pathogenesis.
PMCID: PMC3702482  PMID: 23800201
Helicobacter pylori; Seroprevalence; Epidemiology; Cohort

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