Inflammatory bowel disease and cardiovascular diseases: a concise review

Abstract

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality despite aggressive treatment of traditional risk factors. Chronic inflammation plays an important role in the initiation and progression of CVDs. Inflammatory bowel disease (IBD) is a systemic state of inflammation exhibiting increased levels of pro-inflammatory cytokines including tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. Importantly, IBD is associated with increased risk for CVDs especially in women and young adults, including coronary artery disease, stroke, thromboembolic diseases, and arrhythmias. Potential mechanisms underlying the increased risk for CVDs in IBD patients include increased levels of inflammatory cytokines and oxidative stress, altered platelet function, hypercoagulability, decreased numbers of circulating endothelial progenitor cells, endothelial dysfunction, and possible interruption of gut microbiota. Although IBD does not appear to exacerbate the traditional risk factors for CVDs, including hypertension, hyperlipidaemia, diabetes mellitus, and obesity, aggressive risk stratifications are important for primary and secondary prevention of CVDs for IBD patients. Compared to 5-aminosalicylates and corticosteroids, anti-TNF-α therapy in IBD patients was consistently associated with decreasing cardiovascular events. In the absence of contraindications, low-dose aspirin and statins appear to be beneficial for IBD patients. Low-molecular-weight heparin is also recommended for patients who are hospitalized with acute IBD flares without major bleeding risk. A multidisciplinary team approach should be considered for the management of IBD patients.

Keywords: Cardiovascular medications; Inflammatory bowel disease; Ischaemic arterial disease; Venous thromboembolism.

Graphical Abstract

Figure 1

Schematic diagram showing the relationship between inflammatory bowel disease and increased risk of arterial diseases together with potential mechanisms. A variety of pro-inflammatory cytokines including tumour necrosis factor-α, interleukin-6, interleukin-1β, interleukin-8, interleukin-12, and Calprotectin are produced in inflammatory bowel disease patients. Patients with inflammatory bowel disease also exhibit a decrease in the number of circulating endothelial progenitor cells, endothelial dysfunction, and possible interruption of gut microbiota, as well as increase in neutrophil extracellular traps, leading to atherosclerosis and related diseases including stroke, coronary artery disease, and peripheral artery disease. CAD, coronary artery disease; cIMT, carotid intima-media thickness; CRP, C-reactive protein; EPC, endothelial progenitor cell; FMD, brachial artery flow-mediated dilation; IBD, inflammatory bowel disease; IL, interleukin; NETs, neutrophil extracellular traps; PAD, peripheral artery disease; PAT, pulse arterial tonometry indices; PWV, pulse wave velocity; ROS, reactive oxygen species; SAA, serum amyloid A; TNF-α, tumour necrosis factor-α.

Figure 2

Schematic diagram showing the relationship between inflammatory bowel disease and increased risk of venous thromboembolic events and potential mechanisms. In inflammatory bowel disease patients, significant platelet alterations, hypercoagulability, endothelial dysfunction, increase in neutrophil extracellular traps, and possible interruption of gut microbiota could increase the risk of venous thromboembolic events and pulmonary embolism. CDI, Clostridium difficile infection; DVT, deep venous thromboembolism; EC, endothelial cell; EPCR, endothelial protein C receptor; F2, prothrombin G20210A; F5, Factor V Leiden; IBD, inflammatory bowel disease; NETs, neutrophil extracellular traps; PE, pulmonary embolism; TFPI, tissue factor pathway inhibitor; TM, thrombomodulin.