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The increasing incidence of thromboembolic events among hospitalized patients with inflammatory bowel disease SreyRam Kuy, Anahita Dua, Rohit Chappidi, Gary Seabrook, Kellie R Brown, Brian Lewis, Peter J Rossi and Cheong J Lee Vascular published online 1 July 2014 DOI: 10.1177/1708538114541799 The online version of this article can be found at: http://vas.sagepub.com/content/early/2014/06/30/1708538114541799
Published by: http://www.sagepublications.com
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Vascular OnlineFirst, published on July 1, 2014 as doi:10.1177/1708538114541799
Original Article
The increasing incidence of thromboembolic events among hospitalized patients with inflammatory bowel disease
Vascular 0(0) 1–5 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1708538114541799 vas.sagepub.com
SreyRam Kuy1, Anahita Dua2,3, Rohit Chappidi4, Gary Seabrook2, Kellie R Brown2, Brian Lewis2, Peter J Rossi2 and Cheong J Lee2
Abstract Background: We performed a national population-based study examining the incidence of both venous and arterial thromboembolic events in patients hospitalized with inflammatory bowel disease over the past decade. Methods: A retrospective cross-sectional analysis using the Nationwide Inpatient Sample Database was performed. Patients hospitalized with Crohn’s disease and ulcerative colitis were identified using ICD-9 codes. The incidence of clinically relevant venous thromboembolic events and arterial thromboembolic events including myocardial infarction, visceral ischemia, cerebrovascular accidents, and peripheral arterial events was examined. Results: During the study period, 461,415 hospitalized inflammatory bowel disease patients were identified. Among these patients, 28,820 had a diagnosis of a thromboembolic event (overall prevalence of 6%). The incidence of thromboembolic events in patients with inflammatory bowel disease rose from 5.65% in 2000 to 7.17% by 2009. There were 18,270 (3.96%) patients who had an arterial thrombotic event, the most common being myocardial infarction (50%), followed by visceral ischemia (25%), and cerebrovascular incidents (22%). There were 11,083 (2.4%) patients identified to have had a venous thrombotic event, with the most common manifestation being deep vein thrombosis (77%), pulmonary embolism (32%), and portal vein thrombosis (3.9%). Conclusion: An increasing incidence of thromboembolic event in patients with inflammatory bowel disease was observed over the past decade. Interestingly, there were more arterial thrombotic events in comparison to venous thrombotic events.
Keywords Inflammatory bowel disease, thromboembolic events, arterial embolic events, venous embolic events
thromboembolism. Epidemiologic data are lacking in cataloging the incidence of such thromboembolic
Introduction Thromboembolic events (TEEs) are significant extraintestinal manifestations of inflammatory bowel disease (IBD).1,2 Studies have shown that venous thromboembolic events (VTE) is three to four times more common in people with Crohn’s disease (CD) and ulcerative colitis (UC) when compared to healthy controls regardless of whether IBD pathology is quiescent or in an active state.1,2 The impact of IBD patient’s procoagulant state, however, has not been well correlated to the potentially critical arterial thromboembolic events (ATEs) that this patient cohort may encounter including myocardial infarction (MI), embolic stroke, and peripheral
1 Overton Brooks Veterans Affairs Medical Center and Louisiana State University at Shreveport, USA 2 Division of Vascular Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA 3 Center for Translational Injury Research (CeTIR), Department of Surgery, University of Texas-Houston, Houston, TX, USA 4 Department of Internal Medicine, Loyola University, Chicago, IL, USA
Corresponding author: Cheong J Lee, Division of Vascular Surgery, Department of Surgery, Medical College of Wisconsin, 9200 W Wisconsin Avenue, Milwaukee, WI 53226, USA. Email: [email protected]
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phenomenon among IBD patients.3 While the magnitude and the impact of VTEs amongst IBD patients have been published using administrative databases, a national population study reviewing the trends in the overall incidence of TEEs, inclusive of ATEs, in US patients with IBD has not been performed. The objective of this study was to determine the incidence of TEEs in hospitalized patients with IBD over the last decade in the US and delineate the most frequent venous and arterial TEE that occur in this vulnerable cohort.
Methods A retrospective cross-sectional analysis of hospital discharge data for 2000–2009, utilizing the Health Care Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database, a stratified 20% sample of all inpatient admissions to non-federal, acute care hospitals maintained by the Agency for Healthcare Research and Quality (AHRQ), was performed. The HCUP-NIS is the largest all-payer inpatient database in the US with records from approximately eight million hospital stays recorded annually. Developed through a Federal-State-Industry partnership sponsored by the AHRQ, HCUP data inform decision making at the national, state, and community levels. Information in the database is entered automatically and hence is subject to small variances in data collection. It has been validated as an accurate database in multiple studies and contains more than 100 clinical and non-clinical data elements for each hospital stay. This study received exemption from the Institutional Review Board at our institution because data were deidentified.
Patient identification Records were limited to hospitalized patients with a diagnosis of UC or CD, identified using ICD-9 codes (556.0, 556.1, 556.2, 556.3, 556.4, 556.5, 556.6, 556.8, 556.9, 555.0, 555.1, 555.2, 555.9). ICD-9 diagnosis codes were used to identify patients with a diagnosis of thromboembolism. VTEs were defined as deep vein thrombosis (DVT), pulmonary embolism (PE), and portal vein thrombosis. Arterial thromboembolic events were defined as MI, embolic stroke, and mesenteric ischemia and other abdominal arterial embolic phenomenon and included peripheral thromboembolic events to the extremities and other arteries.
Variables Year was the primary independent variable of interest. Patient-level covariates included age, gender,
and race/ethnicity (white, black, Hispanic, other, as coded in HCUP-NIS). Clinical covariates included admission urgency (elective vs. non-elective) and insurance status (private, Medicaid, Medicare, self-pay). Hospital level variables included hospital location, region, and teaching status. The outcome of interest was TEEs in patients with IBD.
Statistical analysis Data analysis and management were performed using SAS version 9.1 (Cary, NC, USA). Statistical significance was set at a probability value of p < 0.05.
Results Over the 10-year period, 461,415 patients with IBD were identified, of which 28,820 (6%) patients were identified to have had a TEE. Table 1 depicts the number of IBD admissions by year and the annual incidence of TEE within this cohort. During this period, the number of admissions in patients with IBD rose from 34,300 in 2000 to 58,468 in 2009. In addition, the incidence of TEE in 2000 was 5.65% but rose to 7.17% by 2009. Demographic factors associated with increased incidence of TEE are listed in Table 2. Older age, male gender, emergency admissions, and transfers were found to have an increased predisposition to have a TEE. In the subgroup of patients who developed TEE, 18,270 (3.96%) were observed to have had an ATE. Table 3 depicts the observed distribution of ATE based on type of event and anatomic location.
Table 1. National trends in the incidence of thromboembolic events in patients with IBD in the US, 2000–2009.
Year
Number of IBD admissions
Number of thromboembolic events
Incidence (%)
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
34,300 36,504 40,126 43,056 45,677 46,299 46,600 49,832 60,553 58,468
1937 2172 2436 2519 2676 2767 2832 3093 4197 4191
5.65 5.95 6.07 5.85 5.86 5.98 6.08 6.21 6.93 7.17
IBD: inflammatory bowel disease.
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The most common ATE was a MI (50.34%), followed by mesenteric ischemic events (25.12%), and embolic stroke (21.84%). The prevalence of peripheral ATE (lower and upper extremity, other, and thoracic) was relatively low in comparison ranging from 0.2 to 2.8% of the total ATE. There were 11,083 patients (2.4% of IBD patients) who suffered a VTE during this observational period. The most common manifestation of VTE was DVT (77%), followed by PE (32%) and portal vein thrombosis (3.9%). Table 4 depicts the distribution of the type of VTE observed in patients with IBD.
Discussion A thromboembolic event incurs a profound increase in lifetime morbidity and mortality and the increased risk of developing a TEE when diagnosed IBD has been firmly established and is postulated to be multifactorial.1–5 For one, fibrinolytic activity has been shown to
Table 2. Demographic differences between IBD patients with and without TEE.
Older Males Emergency admit Transfer Private insurance
IBD with TEE
IBD without TEE
p value
62 years 46% 86% 9% 35%
49 years 42% 77% 4% 50%
The increasing incidence of thromboembolic events among hospitalized patients with inflammatory bowel disease SreyRam Kuy, Anahita Dua, Rohit Chappidi, Gary Seabrook, Kellie R Brown, Brian Lewis, Peter J Rossi and Cheong J Lee Vascular published online 1 July 2014 DOI: 10.1177/1708538114541799 The online version of this article can be found at: http://vas.sagepub.com/content/early/2014/06/30/1708538114541799
Published by: http://www.sagepublications.com
Additional services and information for Vascular can be found at: Email Alerts: http://vas.sagepub.com/cgi/alerts Subscriptions: http://vas.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Jul 1, 2014 What is This?
Downloaded from vas.sagepub.com at UZH Hauptbibliothek / Zentralbibliothek Zürich on July 8, 2014
XML Template (2014) [25.6.2014–5:09pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/VASJ/Vol00000/140043/APPFile/SG-VASJ140043.3d
(VAS)
[1–5] [PREPRINTER stage]
Vascular OnlineFirst, published on July 1, 2014 as doi:10.1177/1708538114541799
Original Article
The increasing incidence of thromboembolic events among hospitalized patients with inflammatory bowel disease
Vascular 0(0) 1–5 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1708538114541799 vas.sagepub.com
SreyRam Kuy1, Anahita Dua2,3, Rohit Chappidi4, Gary Seabrook2, Kellie R Brown2, Brian Lewis2, Peter J Rossi2 and Cheong J Lee2
Abstract Background: We performed a national population-based study examining the incidence of both venous and arterial thromboembolic events in patients hospitalized with inflammatory bowel disease over the past decade. Methods: A retrospective cross-sectional analysis using the Nationwide Inpatient Sample Database was performed. Patients hospitalized with Crohn’s disease and ulcerative colitis were identified using ICD-9 codes. The incidence of clinically relevant venous thromboembolic events and arterial thromboembolic events including myocardial infarction, visceral ischemia, cerebrovascular accidents, and peripheral arterial events was examined. Results: During the study period, 461,415 hospitalized inflammatory bowel disease patients were identified. Among these patients, 28,820 had a diagnosis of a thromboembolic event (overall prevalence of 6%). The incidence of thromboembolic events in patients with inflammatory bowel disease rose from 5.65% in 2000 to 7.17% by 2009. There were 18,270 (3.96%) patients who had an arterial thrombotic event, the most common being myocardial infarction (50%), followed by visceral ischemia (25%), and cerebrovascular incidents (22%). There were 11,083 (2.4%) patients identified to have had a venous thrombotic event, with the most common manifestation being deep vein thrombosis (77%), pulmonary embolism (32%), and portal vein thrombosis (3.9%). Conclusion: An increasing incidence of thromboembolic event in patients with inflammatory bowel disease was observed over the past decade. Interestingly, there were more arterial thrombotic events in comparison to venous thrombotic events.
Keywords Inflammatory bowel disease, thromboembolic events, arterial embolic events, venous embolic events
thromboembolism. Epidemiologic data are lacking in cataloging the incidence of such thromboembolic
Introduction Thromboembolic events (TEEs) are significant extraintestinal manifestations of inflammatory bowel disease (IBD).1,2 Studies have shown that venous thromboembolic events (VTE) is three to four times more common in people with Crohn’s disease (CD) and ulcerative colitis (UC) when compared to healthy controls regardless of whether IBD pathology is quiescent or in an active state.1,2 The impact of IBD patient’s procoagulant state, however, has not been well correlated to the potentially critical arterial thromboembolic events (ATEs) that this patient cohort may encounter including myocardial infarction (MI), embolic stroke, and peripheral
1 Overton Brooks Veterans Affairs Medical Center and Louisiana State University at Shreveport, USA 2 Division of Vascular Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA 3 Center for Translational Injury Research (CeTIR), Department of Surgery, University of Texas-Houston, Houston, TX, USA 4 Department of Internal Medicine, Loyola University, Chicago, IL, USA
Corresponding author: Cheong J Lee, Division of Vascular Surgery, Department of Surgery, Medical College of Wisconsin, 9200 W Wisconsin Avenue, Milwaukee, WI 53226, USA. Email: [email protected]
Downloaded from vas.sagepub.com at UZH Hauptbibliothek / Zentralbibliothek Zürich on July 8, 2014
XML Template (2014) [25.6.2014–5:09pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/VASJ/Vol00000/140043/APPFile/SG-VASJ140043.3d
(VAS)
[1–5] [PREPRINTER stage]
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phenomenon among IBD patients.3 While the magnitude and the impact of VTEs amongst IBD patients have been published using administrative databases, a national population study reviewing the trends in the overall incidence of TEEs, inclusive of ATEs, in US patients with IBD has not been performed. The objective of this study was to determine the incidence of TEEs in hospitalized patients with IBD over the last decade in the US and delineate the most frequent venous and arterial TEE that occur in this vulnerable cohort.
Methods A retrospective cross-sectional analysis of hospital discharge data for 2000–2009, utilizing the Health Care Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database, a stratified 20% sample of all inpatient admissions to non-federal, acute care hospitals maintained by the Agency for Healthcare Research and Quality (AHRQ), was performed. The HCUP-NIS is the largest all-payer inpatient database in the US with records from approximately eight million hospital stays recorded annually. Developed through a Federal-State-Industry partnership sponsored by the AHRQ, HCUP data inform decision making at the national, state, and community levels. Information in the database is entered automatically and hence is subject to small variances in data collection. It has been validated as an accurate database in multiple studies and contains more than 100 clinical and non-clinical data elements for each hospital stay. This study received exemption from the Institutional Review Board at our institution because data were deidentified.
Patient identification Records were limited to hospitalized patients with a diagnosis of UC or CD, identified using ICD-9 codes (556.0, 556.1, 556.2, 556.3, 556.4, 556.5, 556.6, 556.8, 556.9, 555.0, 555.1, 555.2, 555.9). ICD-9 diagnosis codes were used to identify patients with a diagnosis of thromboembolism. VTEs were defined as deep vein thrombosis (DVT), pulmonary embolism (PE), and portal vein thrombosis. Arterial thromboembolic events were defined as MI, embolic stroke, and mesenteric ischemia and other abdominal arterial embolic phenomenon and included peripheral thromboembolic events to the extremities and other arteries.
Variables Year was the primary independent variable of interest. Patient-level covariates included age, gender,
and race/ethnicity (white, black, Hispanic, other, as coded in HCUP-NIS). Clinical covariates included admission urgency (elective vs. non-elective) and insurance status (private, Medicaid, Medicare, self-pay). Hospital level variables included hospital location, region, and teaching status. The outcome of interest was TEEs in patients with IBD.
Statistical analysis Data analysis and management were performed using SAS version 9.1 (Cary, NC, USA). Statistical significance was set at a probability value of p < 0.05.
Results Over the 10-year period, 461,415 patients with IBD were identified, of which 28,820 (6%) patients were identified to have had a TEE. Table 1 depicts the number of IBD admissions by year and the annual incidence of TEE within this cohort. During this period, the number of admissions in patients with IBD rose from 34,300 in 2000 to 58,468 in 2009. In addition, the incidence of TEE in 2000 was 5.65% but rose to 7.17% by 2009. Demographic factors associated with increased incidence of TEE are listed in Table 2. Older age, male gender, emergency admissions, and transfers were found to have an increased predisposition to have a TEE. In the subgroup of patients who developed TEE, 18,270 (3.96%) were observed to have had an ATE. Table 3 depicts the observed distribution of ATE based on type of event and anatomic location.
Table 1. National trends in the incidence of thromboembolic events in patients with IBD in the US, 2000–2009.
Year
Number of IBD admissions
Number of thromboembolic events
Incidence (%)
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
34,300 36,504 40,126 43,056 45,677 46,299 46,600 49,832 60,553 58,468
1937 2172 2436 2519 2676 2767 2832 3093 4197 4191
5.65 5.95 6.07 5.85 5.86 5.98 6.08 6.21 6.93 7.17
IBD: inflammatory bowel disease.
Downloaded from vas.sagepub.com at UZH Hauptbibliothek / Zentralbibliothek Zürich on July 8, 2014
XML Template (2014) [25.6.2014–5:09pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/VASJ/Vol00000/140043/APPFile/SG-VASJ140043.3d
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Kuy et al.
3
The most common ATE was a MI (50.34%), followed by mesenteric ischemic events (25.12%), and embolic stroke (21.84%). The prevalence of peripheral ATE (lower and upper extremity, other, and thoracic) was relatively low in comparison ranging from 0.2 to 2.8% of the total ATE. There were 11,083 patients (2.4% of IBD patients) who suffered a VTE during this observational period. The most common manifestation of VTE was DVT (77%), followed by PE (32%) and portal vein thrombosis (3.9%). Table 4 depicts the distribution of the type of VTE observed in patients with IBD.
Discussion A thromboembolic event incurs a profound increase in lifetime morbidity and mortality and the increased risk of developing a TEE when diagnosed IBD has been firmly established and is postulated to be multifactorial.1–5 For one, fibrinolytic activity has been shown to
Table 2. Demographic differences between IBD patients with and without TEE.
Older Males Emergency admit Transfer Private insurance
IBD with TEE
IBD without TEE
p value
62 years 46% 86% 9% 35%
49 years 42% 77% 4% 50%
