Psychological Stress Increases Risk for Peptic Ulcer, Regardless of Helicobacter pylori Infection or use of Non-steroidal Anti-inflammatory Drugs

BACKGROUND & AIMS: There is controversy over whether psychological stress contributes to development of peptic ulcers. We collected data on features of life stress and ulcer risk factors from a defined population in Denmark and compared these with findings of confirmed ulcers over the next 11-12 years.

METHODS: We collected blood samples and psychological, social, behavioral, and medical data, in 1982-1983, from a population-based sample of 3379 Danish adults without a history of ulcer participating in the World Health Organization's MONICA Study. A 0-10 point stress index scale was used to measure stress, based on concrete life stressors and perceived distress. Surviving eligible participants were re-interviewed in 1987-1988 (n=2809) and 1993-1994 (n=2410). Ulcer was diagnosed only for patients with a distinct breach in the mucosa. All diagnoses were confirmed by review of radiological and endoscopic reports. Additional cases of ulcer were detected in a search of 3379 subjects in the Danish National Patient Register.

RESULTS: Seventy-six subjects were diagnosed with ulcer. Based on the stress index scale, ulcer incidence was significantly higher among subjects in the highest tertile of stress scores (3.5%) than the lowest tertile (1.6%) (adjusted odds ratio, 2.2; 95% confidence interval [CI], 1.2-3.9; P<.01). The per-point odds ratio for the stress index (1.19; 95% CI, 1.09-1.31; P<.001) was unaffected after adjusting for the presence of immunoglobulin G antibodies against H pylori in stored sera, alcohol consumption, or sleep duration, but lower after adjusting for socioeconomic status (1.17; 95% CI, 1.07-1.29; P<.001), and still lower after further adjustments for smoking, use of non-steroidal anti-inflammatory drugs (NSAIDs), and lack of exercise (1.11; 95% CI, 1.01-1.23; P=.04). The risk for ulcer related to stress was similar among subjects who were H pylori seropositive, those who were H pylori seronegative, and those exposed to neither H pylori nor NSAIDs. On multivariable analysis, stress, socioeconomic status, smoking, H pylori infection, and use of NSAIDs were independent predictors of ulcer.

CONCLUSIONS: In a prospective study of a population-based Danish cohort, psychological stress increased the incidence of peptic ulcer, in part by influencing health risk behaviors. Stress had similar effects on ulcers associated with H pylori infection and those unrelated to either H pylori or use of NSAIDs.