Hyperhomocysteinemia and the Risk of Thromboembolism and Atherosclerosis in IBD

Abstract

Purpose: Patients with inflammatory bowel disease (IBD) have an increased risk of thromboembolism (TE). Hyperhomocysteinemia has been shown to be an independent, modifiable risk factor for thrombosis and atherosclerosis. We determined if there is an association between elevated homocysteine levels and vascular complications in IBD patients. Methods: This was a retrospective observational study of IBD patients (N = 951) followed in a tertiary center over a 5-year period. Demographic information, type of IBD (Crohn's Disease (CD) or Ulcerative Colitis (UC), number and distribution of TE events were recorded. TE events included arterial and venous thromboses, pulmonary emboli (PE) and ischemic cerebrovascular accidents (CVA) following radiographic confirmation. Atherosclerotic disease included coronary and peripheral vascular disease. Hyperhomocysteinemia was defined as a total homocysteine (tHcy) concentration of > 14 micromoles per liter (μmol/L). IBD patients with no documented TE or atherosclerosis served as the control group for the case-control study. Results: TE events were identified in 92 out of 951 (9.7%) IBD patients, including, 79 patients with arterial or venous thrombi and 13 patients with ischemic CVAs. In the control group, hyperhomocysteinemia was identified in 7 out of 60 (11.7%) patients. Sixty-one patients with TE had tHcy levels measured as part of the hypercoagulability evaluation, and out of these only 4 patients (6.6%) had elevated tHcy concentrations (P= 0.33 vs control group). Two patients with arterial or venous thrombi and 2 patients with cerebrovascular disease demonstrated hyperhomocysteinemia. Coronary or peripheral vascular disease was identified in 33 out of 951 (3.5%) IBD patients. Twenty-three patients had measured homocysteine levels, and out of these 8 (34.8%) had elevated tHcy levels (P= 0.02 vs control group). Mean tHcy concentration in the control group was 9.91 ± 0.53 μmol/L which was similar to the mean tHcy concentration (8.74 ± 0.35 μmol/L) in the TE group (P= 0.09). However, IBD patients with atherosclerotic disease had a significantly higher mean tHcy concentration (12.69 ± 1.11 μmol/L) compared to IBD controls (P= 0.004). Conclusion: In our study, there was no correlation between hyperhomocysteinemia and risk of thromboembolism in our cohort of IBD patients. However, one third of IBD patients with atherosclerotic disease had elevated tHcy concentrations. Hyperhomocysteinemia did not appear to play a major role in TE complications in IBD. Prophylactic use of folic acid and cobalamin supplements may be warranted in IBD patients at risk for atherosclerotic disease.