Patients, respectively, reported that the risk of MI in IBD patients

Patients, respectively, reported that the risk of MI in IBD patients was comparable to matched IBD-free controls [7,8]. However, a Canadian study of 8,000 IBD patients showed an increased risk of ischaemic heart disease (RR 1.26 [1.11?.44]), whereas increased risk of stroke was only significant among CD patients (RR 1.26 [1.04?.53]) [24]. In addition, in a cohort of 8,000 patients with CD from the UK General Practice Research Database, an increased risk of stroke in patients ,50 years 1655472 (odds ratio 2.93 [1.44?.98]) was observed, but no increased overall risk of stroke among older patients [6]. Moreover, a retrospective single-center cohort study of around 350 IBD patients found an increased risk of coronary artery disease [25]. The current results add considerably to the existing literature by demonstrating a significantly increased risk of MI, stroke, and cardiovascular death in a large and unselected population of patients with IBD. A novel finding was that the risk was related to IBD activity with highest risk during flares and periods of persistent activity, while in remission periods the risk of MI and stroke was only marginally increased and in the latter periods the risk of cardiovascular death was comparable to the reference population. In agreement with our results, a study from the same nationwide population published during the preparation of our manuscript also reported an increased risk of ischaemic heart disease including MI in patients with IBD, with particularly high risk in the first 3 months after IBD diagnosis and in patients with a history of treatment with oral corticosteroids [26]. Importantly, that study did not examine the risk of stroke and cardiovascular death, and did not specifically explore the risk associated with different activity of IBD as done in the present study. Moreover, the primary outcome of that study, i.e. ischaemic heart disease, has not been validated in the Danish National Patient Register. These differences notwithstanding, the results clearly suggest that the systemic inflammatory burden in subjects with IBD may be an important determinant of atherothrombotic risk. In agreement with this contention, a disease severity-dependent increased risk of MI and stroke has also been found in patients with other chronic inflammatory diseases, including rheumatoid arthritis and psoriasis [27,28].Atherosclerosis is a chronic inflammatory disease characterized by inflammation both in the arterial wall and systemically in the body, and atherothrombotic disease is associated with increased inflammation as exemplified by elevated levels of C-reactive protein [2,29,30]. Indeed, the inflammatory state TBHQ site involves many unspecific mechanisms including release of MedChemExpress Dimethylenastron cytokines and other mediators (including tumor necrosis factor alpha, interleukin-1, and platelet activating factor) which may contribute to shifting the hemostatic balance towards a prothrombotic state [2]. IBD is also characterized by an inappropriate immuno-inflammatory activation, and the pathophysiological processes in the colonic wall in patients with IBD share many features with the processes in the arterial wall during progression of atherosclerosis and, ultimately, atherosclerotic plaque rupture and thrombosis [12,31?5]._ENREF_21_ENREF_21 Reports that IBD is associated with subclinical atherosclerosis, including endothelial dysfunction and increased carotid intima-media thickness, together with atherogenic alterations of the lipid profile, lend addi.Patients, respectively, reported that the risk of MI in IBD patients was comparable to matched IBD-free controls [7,8]. However, a Canadian study of 8,000 IBD patients showed an increased risk of ischaemic heart disease (RR 1.26 [1.11?.44]), whereas increased risk of stroke was only significant among CD patients (RR 1.26 [1.04?.53]) [24]. In addition, in a cohort of 8,000 patients with CD from the UK General Practice Research Database, an increased risk of stroke in patients ,50 years 1655472 (odds ratio 2.93 [1.44?.98]) was observed, but no increased overall risk of stroke among older patients [6]. Moreover, a retrospective single-center cohort study of around 350 IBD patients found an increased risk of coronary artery disease [25]. The current results add considerably to the existing literature by demonstrating a significantly increased risk of MI, stroke, and cardiovascular death in a large and unselected population of patients with IBD. A novel finding was that the risk was related to IBD activity with highest risk during flares and periods of persistent activity, while in remission periods the risk of MI and stroke was only marginally increased and in the latter periods the risk of cardiovascular death was comparable to the reference population. In agreement with our results, a study from the same nationwide population published during the preparation of our manuscript also reported an increased risk of ischaemic heart disease including MI in patients with IBD, with particularly high risk in the first 3 months after IBD diagnosis and in patients with a history of treatment with oral corticosteroids [26]. Importantly, that study did not examine the risk of stroke and cardiovascular death, and did not specifically explore the risk associated with different activity of IBD as done in the present study. Moreover, the primary outcome of that study, i.e. ischaemic heart disease, has not been validated in the Danish National Patient Register. These differences notwithstanding, the results clearly suggest that the systemic inflammatory burden in subjects with IBD may be an important determinant of atherothrombotic risk. In agreement with this contention, a disease severity-dependent increased risk of MI and stroke has also been found in patients with other chronic inflammatory diseases, including rheumatoid arthritis and psoriasis [27,28].Atherosclerosis is a chronic inflammatory disease characterized by inflammation both in the arterial wall and systemically in the body, and atherothrombotic disease is associated with increased inflammation as exemplified by elevated levels of C-reactive protein [2,29,30]. Indeed, the inflammatory state involves many unspecific mechanisms including release of cytokines and other mediators (including tumor necrosis factor alpha, interleukin-1, and platelet activating factor) which may contribute to shifting the hemostatic balance towards a prothrombotic state [2]. IBD is also characterized by an inappropriate immuno-inflammatory activation, and the pathophysiological processes in the colonic wall in patients with IBD share many features with the processes in the arterial wall during progression of atherosclerosis and, ultimately, atherosclerotic plaque rupture and thrombosis [12,31?5]._ENREF_21_ENREF_21 Reports that IBD is associated with subclinical atherosclerosis, including endothelial dysfunction and increased carotid intima-media thickness, together with atherogenic alterations of the lipid profile, lend addi.