To investigate the role of Helicobacter pylori, expressing the virulence marker CAGA (cytotoxin associated gene product A) in ulcer complications and its interaction with nonsteroidal anti-inflammatory drugs (NSAIDs) and other risk factors.


Case control study using conditional logistic regression analysis.


University and City Hospitals, Nottingham.


203 consecutive patients with ulcer bleeding and 203 age- and sex-matched controls.


Ulcer bleeding was more likely with positive H. pylori serology (odds ratio = 3.3, 95% CI: 1.7–6.6 for CagA positive, but only OR = 1.6, 95% CI: 0.7–3.7 for CagA negative serology), current smoking (OR 2.2, 95% CI: 1.04–4.7), aspirin ≤ 300 mg daily (OR 7.7, 95% CI: 2.8–20.6), all other nonsteroidal anti-inflammatory drugs (NSAIDs: OR 10.6, 95% CI: 3.1–35.7 for ≤ 1 defined daily dose lower and OR 22.6, 95% CI: 6.2–82.0 for higher doses) and past ulcer history (OR 5.6, 95% CI: 2.3–14.1). Aspirin ≤ 300 mg daily was used by 25.1% of patients vs. 7.4% of controls. Smoking only enhanced risk in the presence of H. pylori, with a synergistic interaction (interaction odds ratio = 4.9, 2.4–9.9, P=0.002). Conversely, risks with non-aspirin NSAIDs were reduced in the presence of H. pylori, particularly if CagA-positive (interaction odds ratio=0.21, 0.05–0.9, P=0.03).


CagA positive H. pylori infection is associated with an increased risk of ulcer bleeding. The risk from non-aspirin NSAIDs is even higher, but is less in H. pylori infected people. Low-dose aspirin is now commonly associated with ulcer bleeding.