Comorbidities affect risk of nonvariceal upper gastrointestinal bleeding

The incidence of upper gastrointestinal bleeding (GIB) has not been reduced despite the decreasing incidence of peptic ulcers, strategies to eradicate Helicobacter pylori infection, and prophylaxis against ulceration from nonsteroidal anti-inflammatory drugs. Other factors might therefore be involved in the pathogenesis of GIB. Patients with GIB have increasing nongastrointestinal comorbidity, so we investigated whether comorbidity itself increased the risk of GIB.

We conducted a matched case-control study using linked primary and secondary care data collected in England from April 1, 1997 through August 31, 2010. Patients older than 15 years with nonvariceal GIB (n = 16,355) were matched to 5 controls by age, sex, year, and practice (n = 81,636). All available risk factors for GIB were extracted and modeled using conditional logistic regression. Adjusted associations with nongastrointestinal comorbidity, defined using the Charlson Index, were then tested and sequential population attributable fractions calculated.

Comorbidity had a strong graded association with GIB; the adjusted odds ratio for a single comorbidity was 1.43 (95% confidence interval [CI]: 1.35-1.52) and for multiple or severe comorbidity was 2.26 (95% CI: 2.14%-2.38%). The additional population attributable fraction for comorbidity (19.8%; 95% CI: 18.4%-21.2%) was considerably larger than that for any other measured risk factor, including aspirin or nonsteroidal anti-inflammatory drug use (3.0% and 3.1%, respectively).

Nongastrointestinal comorbidity is an independent risk factor for GIB, and contributes to a greater proportion of patients with bleeding in the population than other recognized risk factors. These findings could help in the assessment of potential causes of GIB, and also explain why the incidence of GIB remains high in an aging population.