Helicobacter pylori infection, chronic atrophic gastritis and major cardiovascular events: A population-based cohort study
Introduction
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in developed countries and has been estimated to account for 50% of all deaths in Europe [1]. Established cardiovascular risk factors do not explain all cases and emerging risk factors are intensively studied [2]. A controversially discussed emerging risk factor for ischemic heart disease and stroke is infection with the gastric bacterium Helicobacter (H.) pylori [3].
In industrialized countries 20–50% of the middle-aged population is infected with H. pylori [4]. Infection is typically acquired in early childhood and often persists throughout lifetime in the absence of specific treatments [4].
Chronic infection with H. pylori strongly increases the risk of chronic atrophic gastritis (CAG) [5]. When CAG is present, gastric mucosa functions are impaired which results among others things in a reduced secretion of pepsinogen I (PGI) and II (PGII) and malabsorption of essential metabolites like vitamin B12 [6]. CAG is associated with vitamin B12 deficiency [7], [8]; a state accompanied with high serum homocystein levels. The causal pathway from CAG to homocysteinemia has been confirmed in a recent publication [9]. The last step in the proposed causal pathway from H. pylori and CAG to CVD is the impact of homocysteinemia on the development of CVD [10], [11].
Meta-analyses of case-control and nested case-control studies published in the last three years have shown a significantly increased risk for CVD in H. pylori infected individuals, especially in those infected with cytotoxin-associated gene A (cagA) positive strains [12], [13], [14]. However, several population-based cohort studies have not observed a significant association of H. pylori infection and CVD [15], [16], [17], [18], [19]. To the best of our knowledge, no previous study has investigated the association of CAG with CVD or all-cause mortality.
Therefore, the aim of this large prospective population-based study was to investigate the association of H. pylori infection and CAG with the occurrence of myocardial infarction or stroke, cardiovascular mortality and all-cause mortality.
Section snippets
Study design
This investigation is based on the ESTHER Study [20]. In brief, 9953 subjects, aged 50–74 years at baseline, were recruited by their general practitioners during a routine health check-up between 2000 and 2002 in the German federal state Saarland and followed up for five years so far. The ESTHER Study has been approved by the ethics committees of the Medical Faculty of the University of Heidelberg and the Medical Association of Saarland and is being conducted in accordance with the declaration
Results
Characteristics of the 9953 individuals who participated in the ESTHER baseline examination are shown in Table 1. According to serology, 4977 participants (51.9%) were infected with H. pylori. In infected individuals, cagA-positive strains (n = 2604; 52.3%) were slightly more frequent than cagA-negative strains (n = 2373; 47.7%). CAG was prevalent in 541 subjects (5.7%).
During a median follow-up of 5.1 years (interquartile range 4.9–5.2 years), 540 participants died (163 from cardiovascular causes),
Discussion
To our knowledge this is the so far largest population-based cohort study that estimated the association of H. pylori infection with CVD and all-cause mortality and the first that investigated the association of CAG with these outcomes. The risk for myocardial infarction, stroke and all-cause mortality was neither increased in participants with H. pylori infection nor in those with CAG. The same applied to the association of cagA-negative H. pylori infection and CAG with cardiovascular
Conflict of interest
The authors have no conflict of interest to disclose.
Acknowledgements
The ESTHER study was funded by the Baden-Württemberg State Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany) and the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany).
References (30)
The global burden of disease: 2004 update
(2008)- et al.
Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force
Ann Intern Med
(2009) - et al.
A review of the postulated mechanisms concerning the association of Helicobacter pylori with ischemic heart disease
Helicobacter
(2007) - et al.
Helicobacter pylori infection
N Engl J Med
(2002) - et al.
Incidence of chronic atrophic gastritis: systematic review and meta-analysis of follow-up studies
Eur J Epidemiol
(2010) - et al.
Hypochlorhydria: a factor in nutrition
Annu Rev Nutr
(1989) - et al.
Serum biomarkers for atrophic gastritis and antibodies against Helicobacter pylori in the elderly: implications for vitamin B12, folic acid and iron status and response to oral vitamin therapy
Scand J Gastroenterol
(2008) - et al.
Serum vitamin B12 concentrations and atrophic gastritis in older New Zealanders
Eur J Clin Nutr
(2005) - et al.
Homocysteine levels in chronic gastritis and other conditions: relations to incident cardiovascular disease and dementia
Dig Dis Sci
(2010) - et al.
Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials
Eur Heart J
(2009)
Homocysteine, 5,10-methylenetetrahydrofolate reductase 677C > T polymorphism, nutrient intake, and incident cardiovascular disease in 24,968 initially healthy women
Clin Chem
CagA antigen of Helicobacter pylori and coronary instability: insight from a clinico-pathological study and a meta-analysis of 4241 cases
Atherosclerosis
Relationship between the cytotoxin-associated gene-A status of H pylori strains and cerebral infarction in European Caucasians and Chinese Han: a meta-analysis
World J Gastroenterol
Meta-analysis of the relationship between cytotoxin-associated gene-A and ischemic stroke subtypes
Neural Regen Res
The association of seropositivity to Helicobacter pylori. Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease: a prospective study
J Am Coll Cardiol
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2021, Heart Lung and CirculationChronic atrophic gastritis: Natural history, diagnosis and therapeutic management. A position paper by the Italian Society of Hospital Gastroenterologists and Digestive Endoscopists [AIGO], the Italian Society of Digestive Endoscopy [SIED], the Italian Society of Gastroenterology [SIGE], and the Italian Society of Internal Medicine [SIMI]
2019, Digestive and Liver DiseaseCitation Excerpt :Increased levels of homocysteine are considered a risk factor for cardiovascular diseases [58]. However, a large German serological cohort study did not observe significant associations for patients with CAG and cardiovascular disease (myocardial infarction or stroke) or mortality [59]. Another clinical cluster of autoimmune CAG is the association with autoimmune diseases, most frequently autoimmune thyroid disease and type I diabetes, less frequently vitiligo, psoriasis, coeliac disease, connective tissue disorders, and others [22,60,61].
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Equal contribution as first authors.