Letter to the Editor: Helicobacter pylori eradication in chronic aspirin users - a gastrointestinal strategy with cardiovascular implications?

Abstract

The prospective cohort study by Semeya et al provides important insights into the relationship among Helicobacter pylori (H. pylori) infection, peptic ulcer bleeding (PUB), and cardiovascular (CV) disease progression in chronic low-dose aspirin users. Persistent H. pylori infection was independently associated with increased risks of both PUB and short-term CV progression. Notably, successful eradication reduced the incidence of PUB from 11.9% to 3.7% and was associated with fewer CV events. Although the observational design limits causal inference, these findings suggest that H. pylori status may represent a modifiable factor in integrated gastrointestinal and CV risk management. Although randomized trials are needed, the data support considering H. pylori screening in selected high-risk aspirin users.

Key Words: Helicobacter pylori; Low-dose aspirin; Peptic ulcer bleeding; Cardiovascular disease; Eradication therapy

Core Tip: Persistent Helicobacter pylori (H. pylori) infection in chronic low-dose aspirin users may represent more than a gastrointestinal risk factor. In the prospective cohort study by Semeya et al, persistent infection was associated not only with increased peptic ulcer bleeding but also with short-term cardiovascular (CV) progression, whereas successful eradication was linked to fewer bleeding and CV events. These findings raise the possibility that H. pylori status may function as a modifiable component within an integrated gastrointestinal-CV risk framework. Although causality cannot be established from observational data, the study highlights the potential value of considering H. pylori assessment in selected high-risk aspirin users and emphasizes the need for randomized trials to clarify its CV implications.

TO THE EDITOR

The prospective cohort study by Semeya et al[1] evaluating the relationship among Helicobacter pylori (H. pylori) infection, peptic ulcer bleeding (PUB), and cardiovascular (CV) progression in chronic low-dose aspirin users addresses a clinically meaningful and previously underexplored area. The independent association of persistent H. pylori infection with both PUB and short-term CV progression is particularly compelling. Notably, successful eradication was associated with a reduction in PUB incidence from 11.9% to 3.7%, corresponding to an approximate 69% relative risk reduction and providing a robust signal supporting gastroprotection. Moreover, the lower rates of CV events observed among patients with successful eradication suggest that H. pylori management may merit consideration beyond the narrow scope of gastrointestinal bleeding prevention and within a broader integrated gastrointestinal-CV risk framework[1]. Nonetheless, the definition of CV progression may encompass a heterogeneous composite endpoint and should therefore be interpreted with appropriate caution. In addition, the moderate eradication rate reported in the study likely reflects real-world challenges related to increasing antimicrobial resistance[1].

The marked reduction in PUB observed in the study is consistent with the well-established gastroprotective effect of H. pylori eradication in chronic aspirin users[2]. However, the higher rates of CV progression among patients with persistent infection suggest a systemic biological interaction extending beyond local gastrointestinal mucosal injury[2,3]. Accumulating evidence indicates that H. pylori infection is associated with systemic inflammation and a prothrombotic state[2-5].

In particular, studies suggesting that CagA-positive strains may be associated with endothelial dysfunction, atherosclerotic plaque progression, and increased atherothrombotic risk further strengthen the biological plausibility of this relationship[6]. Within this context, persistent H. pylori infection in chronic aspirin users, who often already exhibit a proinflammatory and prothrombotic profile, may represent an additional modifiable factor contributing to CV vulnerability[4].

H. pylori infection is not confined to localized mucosal inflammation but may also trigger a systemic low-grade chronic inflammatory response. Elevated levels of interleukin-6, tumor necrosis factor-α, and C-reactive protein have been reported in infected individuals, and this cytokine profile may adversely affect endothelial function. Sustained inflammatory activation can impair nitric oxide bioavailability and disrupt vascular reactivity, thereby contributing to endothelial dysfunction[7-9]. Furthermore, evidence suggests that H. pylori infection may be associated with enhanced platelet activation and an increased propensity for aggregation[4,7]. Elevated fibrinogen levels and a procoagulant milieu may, in turn, increase susceptibility to thrombotic events, particularly in individuals with underlying atherosclerotic disease. The reported association of CagA-positive strains with endothelial injury and accelerated atherosclerotic plaque progression further reinforces the coherence of this proposed biological pathway[4,7,10].

Within this context, the clinical scenario observed in chronic aspirin users may reflect a form of biological tension. Although aspirin has antiplatelet properties, chronic H. pylori infection may stimulate prothrombotic and inflammatory pathways, thereby offsetting some of the preventive effects of aspirin. Accordingly, the observed reduction in CV progression following successful eradication may not be explained solely by a decrease in bleeding risk but may also reflect broader modulation of inflammatory and thrombotic processes[11]. The present findings should not be interpreted as grounds for immediate changes in clinical practice[12].

Nevertheless, systematic assessment of H. pylori status may represent a reasonable approach in selected higher-risk individuals, including older patients, those with established CV disease, a prior history of peptic ulcer, concomitant antithrombotic therapy, or an elevated risk of gastrointestinal bleeding[12,13]. Current gastroenterology guidelines already recommend testing for and eradicating H. pylori in patients with a history of ulcer disease or an increased bleeding risk; the present data may prompt consideration of these recommendations within a broader CV context[14,15].

Within this framework, eradication strategies should be considered not solely as a means of bleeding prophylaxis but also as part of a comprehensive assessment integrating both gastrointestinal and CV risk. In patients at the intersection of cardiology and gastroenterology, multidisciplinary risk stratification may facilitate more individualized clinical decision-making. Importantly, proton pump inhibitors (PPIs) remain a cornerstone of gastrointestinal protection in chronic aspirin users; however, H. pylori eradication should be viewed as complementary rather than alternative to PPI therapy[1,12]. This complementary role may reflect distinct but synergistic mechanisms: PPIs primarily reduce gastric acid exposure and mucosal injury, whereas H. pylori eradication targets the underlying inflammatory and infectious components, thereby potentially offering additive protection in high-risk patients.

Further clarification of the impact of eradication on CV outcomes will require randomized studies. The current evidence is best interpreted as a clinically meaningful signal warranting careful patient selection and further investigation, rather than as grounds for immediate changes in practice.

It is essential to acknowledge that the observational nature of the study precludes definitive causal inference. Although multivariable adjustment and sensitivity analyses were performed, residual or unmeasured confounding cannot be entirely excluded. This may particularly relate to differences in baseline CV risk profiles, indication bias associated with aspirin use, variability in adherence to eradication therapy, and concomitant medication use. Furthermore, the relatively short duration of CV follow-up may limit conclusions regarding long-term atherothrombotic outcomes.

In conclusion, these findings support a shift from isolated gastroprotection toward an integrated gastrointestinal-CV risk paradigm in chronic aspirin users. Although causality cannot be established, H. pylori infection emerges as a potentially modifiable factor influencing both bleeding and CV outcomes. These observations highlight the need for individualized risk assessment and further prospective studies to clarify the broader clinical implications.