Cardiovascular complications in inflammatory bowel disease

Abstract

Over the past years, a growing number of studies have indicated that patients suffering from inflammatory bowel disease (IBD) have an increased risk of developing cardiovascular disease. Both are chronic inflammatory diseases and share certain pathophysiological mechanisms that may influence each other. High levels of cytokines, C-reactive protein (CRP), and homocysteine in IBD patients may lead to endothelial dysfunction, an early sign of atherosclerosis. IBD patients, in general, do not show the typical risk factors for cardiovascular disease but changes in lipid profiles similar to the ones seen in cardiovascular events have been reported recently. Higher levels of coagulation factors frequently occur in IBD which may predispose to arterial thromboembolic events. Finally, the gut itself may have an impact on atherogenesis during IBD through its microbiota. Microbial products are released from the inflamed mucosa into the circulation through a leaky barrier. The induced rise in proinflammatory cytokines could contribute to endothelial damage, artherosclerosis and cardiovascular events. Although large retrospective studies favor a link between IBD and cardiovascular diseases, the mechanisms behind still remain to be determined.

Fig. 1. Abnormalities in the coagulation cascade in inflammatory bowel diseases(IBD)

Aberrant levels of coagulation factors are found in IBD patients that may lead to hypercoagulability. The coagulation cascade can be devided in an intrinsic, extrinsic and common pathway. Fibrinolysis (Fibrinolytic system) and thrombin generation (Thrombin-generating system) takes also part in the coagulation system [4]. Within the extrinsic pathway, higher levels of factor VIIa has been been found in IBD patients vs. quiescent patients [69] while in the intrinsic pathway, Factors XIa and IXa were found elevated in ulcerative colitis (UC) patients vs. patients with inactive UC [69]. Additionally, Factors Va and Xa of the common pathway showed higher levels in active vs. inactive UC [69]. Within the thrombin generating system, prothrombin fragments 1+2 (F1+2) and the thrombin-antithrombin complex (TAT) were also significantly elevated in IBD patients vs. patients in quiescent phase [69] whereas thrombin inhibitor antithrombin III was decreased [70]. Within the fibrinolytic system, inhibitor of plasminogen activator-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were increased while tissue plasminogen activator (tPA) was decreased in IBD patients vs. healthy controls [71, 72, 94] suggesting promotion of prothrombotic mechanisms in IBD.

Fig. 2. Potential factors linking inflammatory bowel diseases (IBD) with cardiovascular disease

Cytokines, C-reactive protein (CRP) and LDL-cholesterol are increased in patients with IBD and may promote atherogenesis and cardiovascular disease. Decreased levels of HDL-cholesterol observed in IBD patients and impaired HDL functionality may contribute as well. A further characteristic of IBD is a leaky mucosal barrier. Microbial products and endotoxins could translocate through the colon mucosa and enter the circulation to directly activate immune cells and endothelial cells thus contributing to atherosclerosis. IBD patients also exhibit high levels of homocysteine and coagulation factors known to be implicated in atherosclerosis and thrombus formation.