Background: The less aggressive natural history and lower genetic predisposition in elderly-onset inflammatory bowel disease (EO-IBD) suggest a unique disease pathophysiology in the elderly. Given the theoretical role of intestinal microvascular ischemia in IBD pathogenesis, we aimed to assess if peripheral arterial disease increases the risk of EO-IBD.
Methods: We conducted a case-control study using a national medical claims and pharmacy database from Source Healthcare Analytics LLC, containing data from January 2008 to December 2012. Incident cases of EO-IBD were defined as: 1) ≥60 years old, 2) ≥3 ICD-9 codes for either Crohn's Disease (CD) or Ulcerative Colitis (UC) in 2012, and 3) no IBD-related prescriptions or IBD ICD-9 codes for patients between 2008 and 2011. EO-IBD patients with a history of ischemic colitis were excluded. Controls had no IBD-related medications, IBD ICD-9 codes, IBD-associated autoimmune disease or ischemic colitis. Controls were matched to cases by age group, gender, race and geographic location. Patients were determined to have peripheral arterial disease (PAD) if they had one or more of the following ICD-9 codes on or before the first IBD code: 440.2–440.4, 443.89, 443.9. Conditional logistic regression was performed to assess the association of PAD with EO-IBD. All models were adjusted for age, vascular risk factors and diseases (diabetes, hypertension, hyperlipidemia, obesity, coronary artery disease, cerebrovascular disease) and medications previously associated with new-onset IBD (statins, antibiotics and hormone therapy).
Results: In the analysis, 3846 EO-IBD cases (CD =1479, UC =2097, IBD-U =270) and 19,222 controls were included. Baseline characteristics and the distribution of vascular comorbidities between cases and controls are shown in Table 1.
After controlling for vascular and medication confounders, PAD was significantly associated with an increased risk of EO-IBD (OR 1.52, 95% CI 1.36–1.71, p<0.001). The risk was greater in elderly-onset UC patients (OR 1.61, 95% CI 1.39–1.87, p<0.001) compared to elderly-onset CD patients (OR 1.37, 95% CI 1.13–1.68, p=0.002). To address the potential misclassification of ischemic colitis as IBD, a subgroup analysis of ulcerative pancolitis patients was performed which also suggested an association between PAD and EO-IBD (OR 1.38, 95% CI 0.94–2.01, p=0.10).
Conclusions: PAD was associated with an increased risk of EO-IBD suggesting that vascular factors may contribute to EO-IBD pathogenesis.