Abstract
Objectives
There is cross-sectional evidence that CagA antigen produced by Helicobacter pylori is associated with coronary heart disease, stroke, atrial fibrillation (AF) and microalbuminuria,
but no large-scale longitudinal studies have been conducted in diabetic patients.
We aimed to determine whether cytotoxin-associated gene-A (CagA) seropositivity is
independently associated with important vascular outcomes in type 2 diabetes.
Methods
We studied 1179 type 2 patients from a well characterized community-based cohort who
had available sera from baseline assessment between 1993 and 1996, and follow-up for
incident events to end-June 2007. H. pylori IgG and CagA antibodies at baseline were measured by validated ELISA. Multiple logistic/linear
regression analysis and Cox proportional hazards modelling were used to determine
independent baseline associates of prevalent and incident complications, respectively,
including H. pylori/CagA serostatus.
Results
At baseline, 62.0% of patients were H. pylori seropositive and 37.7% were both H. pylori and CagA seropositive. CagA seropositivity was not independently associated with
prevalent coronary heart disease (CHD), cerebrovascular disease (CVD), peripheral
arterial disease or AF at baseline (P > 0.41), but there was a significant inverse association with ln(urinary albumin:creatinine)
(P = 0.033). There were no independent associations between CagA seropositivity and incident
CHD/CVD or progression to microalbuminuria (P > 0.20). During follow-up, 480 patients (40.7%) died, 246 (50.2%) from cardiovascular
causes. After adjustment for other variables, CagA seropositivity was weakly protective
against cardiovascular death (P = 0.024).
Conclusion
CagA seropositivity is not a risk factor for chronic vascular complications of type
2 diabetes. Assay of CagA antibodies does not contribute significantly to clinical
management outside gastroenterological indications.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Modulation of Helicobacter pylori induced interleukin-8 synthesis in gastric epithelial cells mediated by cag PAI encoded VirD4 homologue.J Clin Pathol. 1999; 52: 653-657
- Detection of Helicobacterpylori in human carotid arteries.Stroke. 2001; 32: 385-391
- Inflammation and infections as risk factors for ischemic stroke.Stroke. 2003; 34: 2518-2532
- Cytotoxin-associated gene-A-seropositive virulent strains of Helicobacter pylori and atherosclerotic diseases: a systematic review.Chin Med J (Engl). 2008; 121: 946-951
- Frequency of Helicobacter pylori seropositivity and C-reactive protein increase in atrial fibrillation in patients undergoing coronary angiography.Am J Cardiol. 2008; 101: 848-851
- Helicobacter pylori and atrial fibrillation: absence of correlations.J Cardiovasc Med (Hagerstown). 2009; 10: 4-5
- Cytotoxin-associated gene-A bearing strains of Helicobacter pylori and atrial fibrillation due to ischemic origin: is there a link?.Eur J Cardiovasc Prev Rehabil. 2007; 14: 518-520
- Diabetes mellitus and Helicobacter pylori infection.Nutrition. 2000; 16: 407-410
- Helicobacter pylori and hepatitis A virus infections and the cardiovascular risk profile in patients with diabetes mellitus: results of a population-based study.Eur J Cardiovasc Prev Rehabil. 2004; 11: 471-476
- Antiplatelet therapy, Helicobacter pylori infection and complicated peptic ulcer disease in diabetes: the Fremantle Diabetes Study.Diabet Med. 2009; 26: 70-75
- Cytotoxin-associated gene A strains of Helicobacter pylori represent a risk factor for the development of microalbuminuria in type 2 diabetes.Diabetes Care. 2006; 29: 1399-1401
- Cross-reactivity of anti-CagA antibodies with vascular wall antigens: possible pathogenic link between Heli-cobacter pylori infection and atherosclerosis.Circulation. 2002; 106: 430-434
- Microalbuminuria as predictor of vascular disease in non-diabetic subjects, Islington Diabetes Survey.Lancet. 1988; 2: 530-533
- Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus.Lancet. 1992; 340: 319-323
- Autoantibodies to glutamic acid decarboxylase in diabetic patients from a multi-ethnic Australian community: the Fremantle Diabetes Study.Diabet Med. 2000; 17: 667-674
- Predictors, consequences and costs of diabetes-related lower extremity amputation complicating type 2 diabetes: the Fremantle Diabetes Study.Diabetologia. 2006; 49: 2634-2641
- A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in Renal Disease Study Group.Ann Inter Med. 1999; 130: 461-470
- A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy.Diabetes Care. 1994; 17: 1281-1289
- Verbeek AL Evaluation of commercially available Helicobacter pylori serology kits: a review.J Clin Microbiol. 1998; 36: 2803-2809
- Serum antibodies anti-H. pylori and anti-CagA: a comparison between four different assays.J Clin Lab Anal. 1999; 13: 194-198
- Population-based linkage of health records in Western Australia: development of a health services research linked database.Aust N Z J Public Health. 1999; 23: 453-459
UKPDS Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998:352:837-53.
- Helicobacter pylori infection in diabetic patients: prevalence and endoscopic findings.Eur J Intern Med. 2002; 13: 376-379
- Virulence factor genotypes of Helicobacter pylori affect cure rates of eradication therapy.Arch Immunol Ther Exp (Warsz). 2009; 57: 45-56
- Helicobacter pylori infection, the cytotoxin gene A strain, and carotid artery intima-media thickness.J Cardiovasc Risk. 2002; 9: 1-6
- Is Helicobacter pylori a cause of atrial fibrillation?.Future Cardiol. 2006; 2: 429-439
- Permanent atrial fibrillation in patients without structural heart disease is not associated with signs of infection by Chlamydia pneumoniae and Helicobacter pylori.Acta Cardiol. 2008; 63: 479-484
Kowalski M. Helicobacter pylori (H. pylori) infection in coronary artery disease: influence of H. pylori eradication on coronary artery lumen after percutaneous transluminal coronary angioplasty. The detection of H. pylori specific DNA in human coronary atherosclerotic plaque. J Physiol Pharmacol 2001:52:3-31.
- Effect of treatment for Chlamydia pneu-moniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA).Circulation. 2002; 106: 1219-1223
- Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.Lancet. 2004; 364: 937-952
Article info
Publication history
Published online: June 09, 2010
Accepted:
May 10,
2010
Received in revised form:
May 5,
2010
Received:
April 10,
2010
Identification
Copyright
© 2012 Published by Elsevier Inc.
