Rs (C02A, C02B, C02C), non-loop diuretics (C02DA, C02L, C03A, C03B, C03D, C03E, C03X, C07C, C07D, C08G, C09BA, C09DA, C09XA52), vasodilators (C02DB, C02DD, C02DG), b blockers (C07), calcium channel blockers (C07F, C08, C09BB, C09DB), and renin-angiotensin system inhibitors (C09). Similarly we defined diabetes by either the hospital diagnosis (E10 14) or use of glucose-lowering Calcitonin (salmon) web agents (A10). All information on cardiovascular medication and co-morbidity were continually updated throughout the follow-up period.Study population – Cohort entry and follow-upIn the present matched cohort study we defined IBD cases as all individuals aged 15 years who received a first diagnosis of IBD, i.e. CD (K50 and 563.01) or UC (K51 and 569.04+563.01), during the period 1996?009 in combination with a dispensed prescription for pharmacological IBD treatment, including one or more of the following 23727046 agents (ATC codes): 5-aminosalicylic acid (A07EC02), sulfasalazine (A07EC01), oral corticosteroids (H02AB06), budesonide (A07EA), azathioprine (L04AX01), P7C3 6mercaptopurine (L01BB02) and methotrexate (L01BA01) within one year before the time of diagnosis and hereafter. The index dates of IBD cases were the date of IBD ICD-10 code and drug prescription, whichever came last. Initiation of biological treatment with anti-tumor necrosis factor-a (TNF) agents was defined by the Danish procedural code (BHJ18A). Surgery for IBD was defined by procedure codes (KJF [colon and small intestine], KJG and KJH [perianal area] in combination with IBD-diagnosis). The IBD diagnoses in the National Patient Registry have been found to be accurate [19]. Patients with a diagnosis of IBD, MI or stroke prior to index date were excluded. Also, individuals with a history of prescribed IBD medication (apart from corticosteroids) more than a year prior to IBD diagnosis were excluded. Each IBD patient was matched with 10 controls from the general population at time of inclusion according to age and gender. Controls with a history of MI, stroke or IBD diagnoses were excluded as well. Study subjects were followed from inclusion (index date) until MI, stroke, emigration, death or end of follow-up. Patients with aStudy endpointsThe following endpoints (ICD-10 codes) were used: MI (I21?I22), stroke (I60 61, I63 64), cardiovascular death (I00 99) and a secondary composite endpoint of MI, stroke and cardiovascular death. The stroke and MI codes have previously been validated in the National Patient Register [20,21].Statistical analysisBaseline characteristic were summarized as means with standard deviations for continuous variables and frequencies and percentages for categorical variables. Incidence rates (IRs) are presented per 1000 person-years. To estimate rate ratios (RRs) and 95 confidence intervals (CIs) for MI, stroke, cardiovascular death, and the composite endpoint, we fitted multivariable Poisson regression models in patients with IBD using the matched controls as reference. The models were adjusted for confounding factors,Active IBD and Risk of Atherothrombotic DiseaseFigure 1. Example of disease activity periods and hospitalizations in apatient with inflammatory bowel disease (IBD) throughout the study period. doi:10.1371/journal.pone.0056944.gincluding socioeconomic status, and gender. Age, co-morbidity, use of cardiovascular medication (antihypertensive treatment, statins, loop diuretics, vitamin K antagonists), lipid-lowering agents, glucose-lowering medication, and IBD disease activity.Rs (C02A, C02B, C02C), non-loop diuretics (C02DA, C02L, C03A, C03B, C03D, C03E, C03X, C07C, C07D, C08G, C09BA, C09DA, C09XA52), vasodilators (C02DB, C02DD, C02DG), b blockers (C07), calcium channel blockers (C07F, C08, C09BB, C09DB), and renin-angiotensin system inhibitors (C09). Similarly we defined diabetes by either the hospital diagnosis (E10 14) or use of glucose-lowering agents (A10). All information on cardiovascular medication and co-morbidity were continually updated throughout the follow-up period.Study population – Cohort entry and follow-upIn the present matched cohort study we defined IBD cases as all individuals aged 15 years who received a first diagnosis of IBD, i.e. CD (K50 and 563.01) or UC (K51 and 569.04+563.01), during the period 1996?009 in combination with a dispensed prescription for pharmacological IBD treatment, including one or more of the following 23727046 agents (ATC codes): 5-aminosalicylic acid (A07EC02), sulfasalazine (A07EC01), oral corticosteroids (H02AB06), budesonide (A07EA), azathioprine (L04AX01), 6mercaptopurine (L01BB02) and methotrexate (L01BA01) within one year before the time of diagnosis and hereafter. The index dates of IBD cases were the date of IBD ICD-10 code and drug prescription, whichever came last. Initiation of biological treatment with anti-tumor necrosis factor-a (TNF) agents was defined by the Danish procedural code (BHJ18A). Surgery for IBD was defined by procedure codes (KJF [colon and small intestine], KJG and KJH [perianal area] in combination with IBD-diagnosis). The IBD diagnoses in the National Patient Registry have been found to be accurate [19]. Patients with a diagnosis of IBD, MI or stroke prior to index date were excluded. Also, individuals with a history of prescribed IBD medication (apart from corticosteroids) more than a year prior to IBD diagnosis were excluded. Each IBD patient was matched with 10 controls from the general population at time of inclusion according to age and gender. Controls with a history of MI, stroke or IBD diagnoses were excluded as well. Study subjects were followed from inclusion (index date) until MI, stroke, emigration, death or end of follow-up. Patients with aStudy endpointsThe following endpoints (ICD-10 codes) were used: MI (I21?I22), stroke (I60 61, I63 64), cardiovascular death (I00 99) and a secondary composite endpoint of MI, stroke and cardiovascular death. The stroke and MI codes have previously been validated in the National Patient Register [20,21].Statistical analysisBaseline characteristic were summarized as means with standard deviations for continuous variables and frequencies and percentages for categorical variables. Incidence rates (IRs) are presented per 1000 person-years. To estimate rate ratios (RRs) and 95 confidence intervals (CIs) for MI, stroke, cardiovascular death, and the composite endpoint, we fitted multivariable Poisson regression models in patients with IBD using the matched controls as reference. The models were adjusted for confounding factors,Active IBD and Risk of Atherothrombotic DiseaseFigure 1. Example of disease activity periods and hospitalizations in apatient with inflammatory bowel disease (IBD) throughout the study period. doi:10.1371/journal.pone.0056944.gincluding socioeconomic status, and gender. Age, co-morbidity, use of cardiovascular medication (antihypertensive treatment, statins, loop diuretics, vitamin K antagonists), lipid-lowering agents, glucose-lowering medication, and IBD disease activity.
