Helicobacter pylori infection, chronic atrophic gastritis and major cardiovascular events: A population-based cohort study

doi:10.1016/j.atherosclerosis.2011.11.029

Atherosclerosis

Volume 220, Issue 2, February 2012, Pages 569-574

https://doi.org/10.1016/j.atherosclerosis.2011.11.029 Get rights and content

Abstract

Objective

There is debate whether infection with Helicobacter (H.) pylori, the main inducer of chronic atrophic gastritis (CAG), is a risk factor for cardiovascular disease and premature mortality.

Methods

Serological measurements of H. pylori infection and pepsinogen (PG) I and II were obtained in a population-based German cohort of 9953 older adults (50–74 years). Cox regression was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for myocardial infarction, stroke, cardiovascular and all-cause mortality during five-year follow-up.

Results

According to serology, 4977 participants (51.9%) were infected with H. pylori (2604 with cytotoxin-associated gene A (cagA) strains) and 541 (5.7%) had CAG (PGI < 70 ng/mL and PGI/PGII < 3). During follow-up, 540 participants died (163 from cardiovascular causes), 170 experienced a primary myocardial infarction and 241 had a stroke. Neither cytotoxin-associated gene A (cagA) negative nor cagA positive H. pylori infections were associated with an increased risk for myocardial infarction, stroke or all-cause mortality. Intriguingly, infection with cagA positive H. pylori strains was inversely associated with cardiovascular mortality (HR, 0.62; CI: 0.41–0.94). No statistically significant associations were observed for the small group of participants with CAG, but point estimates of adjusted HRs for myocardial infarction, stroke and cardiovascular mortality were all below 1 (0.71, 0.59 and 0.65, respectively).

Conclusions

Our results do not support the hypothesis that H. pylori infection or CAG are risk factors for cardiovascular disease or mortality and instead suggest an inverse relationship of cagA positive H. pylori infection with fatal cardiovascular events.

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).

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Helicobacter pylori infection, chronic atrophic gastritis and major cardiovascular events: A population-based cohort study

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study design

Results

Discussion

Conflict of interest

Acknowledgements

The global burden of disease: 2004 update

Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force

Ann Intern Med

A review of the postulated mechanisms concerning the association of Helicobacter pylori with ischemic heart disease

Helicobacter