Psychological Stress Increases Risk for Peptic Ulcer, Regardless of Helicobacter pylori Infection or Use of Nonsteroidal 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 during 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- to 10-point stress index scale was used to measure stress on the basis of concrete life stressors and perceived distress. Surviving eligible participants were reinterviewed 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 radiologic and endoscopic reports. Additional cases of ulcer were detected in a search of all 3379 subjects in the Danish National Patient Register. Results Seventy-six subjects were diagnosed with ulcer. On the basis of 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 Helicobacter 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 nonsteroidal anti-inflammatory drugs, 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 nonsteroidal anti-inflammatory drugs. On multivariable analysis, stress, socioeconomic status, smoking, H pylori infection, and use of nonsteroidal anti-inflammatory drugs 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