Risk of cardiovascular disease in inflammatory bowel disease

Abstract

Cardiovascular disease (CVD) can arise because of chronic inflammation and inflammatory bowel disease (IBD) is one such disease where the risk for CVD and eventual heart failure is increased considerably. The incidence of IBD, which refers to both ulcerative colitis and Crohn's disease, has been on the increase in several countries and is a potential risk factor for CVD. Although IBD can potentially cause venous thromboembolism, its significance in arterial stiffening, atherosclerosis, ischemic heart disease and myocardial infarction is only being realized now and it is currently under debate. However, several studies with large groups of patients have demonstrated the association of IBD with heart disease. It has been suggested that systemic inflammation as observed in IBD patients leads to oxidative stress and elevated levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which lead to phenotypic changes in smooth muscle cells and sets into motion a series of events that culminate in atherosclerosis and CVD. Besides the endogenous factors and cytokines, it has been suggested that due to the compromised intestinal mucosal barrier, endotoxins and bacterial lipopolysaccharides produced by intestinal microflora can enter into circulation and activate inflammatory responses that lead to atherosclerosis. Therapeutic management of IBD-associated heart diseases cannot be achieved with simple anti-inflammatory drugs such as corticosteroids and anti-TNF-α antibodies. Treatment with existing medications for CVDs, aspirin, platelet aggregation inhibitors and statins is found to be acceptable and safe. Nevertheless, further research is needed to assess their efficacy in IBD patients suffering from heart disease.

Keywords: atherosclerosis; cardiovascular disease; endothelial cells; endotoxins; inflammation; inflammatory bowel disease; lipopolysaccharide; tumor necrosis factor-α; venous thromboembolism.

Figure 1.

Mechanisms underlying the inflammation-induced arterial stiffening. Inflammation triggers oxidative stress and release and elevation of inflammatory cytokines including tumor necrosis factor-α (TNF-α). These changes lead to endothelial dysfunction, reduced nitric oxide (NO) production, elevated production of matrix metalloproteinases (MMPs), collagenase, elastases, all leading to arterial stiffening. Reduced level of NO contributes to decreased smooth muscle cell relaxation and TNF-α signaling induces the expression of osteoblast markers in smooth muscle cells, leading to calcification changes and intima thickening.

Figure 2.

Link between inflammatory bowel diseases (IBD) and coronary artery disease. Cytokines and C-reactive protein are elevated in IBD and promote atherosclerosis and cardiovascular disease through endothelial dysfunction. Hyperhomocysteinemia is another potential link between IBD and CVD. Intestinal microflora produced endotoxins including lipopolysaccharide (LPS), which cross through the leaky intestinal mucosal barrier, activate immune cells and endothelial cells, and promote events that culminate in atherosclerosis.