Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2023; 29(39): 5494-5502
Published online Oct 21, 2023. doi: 10.3748/wjg.v29.i39.5494
Risk assessment of venous thromboembolism in inflammatory bowel disease by inherited risk in a population-based incident cohort
Andrew S Rifkin, Zhuqing Shi, Jun Wei, Siqun Lilly Zheng, Brian T Helfand, Jonathan S Cordova, Vincent F Biank, Alfonso J Tafur, Omar Khan, Jianfeng Xu
Andrew S Rifkin, Zhuqing Shi, Jun Wei, Siqun Lilly Zheng, Brian T Helfand, Jianfeng Xu, Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, IL 60201, United States
Brian T Helfand, Jianfeng Xu, Department of Surgery, NorthShore University HealthSystem, Evanston, IL 60201, United States
Brian T Helfand, Jianfeng Xu, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, United States
Jonathan S Cordova, Vincent F Biank, Department of Pediatrics, NorthShore University HealthSystem, Evanston, IL 60201, United States
Alfonso J Tafur, Cardiovascular Institute, NorthShore University HealthSystem, Evanston, IL 60201, United States
Omar Khan, Department of Medicine, NorthShore University HealthSystem, Evanston, IL 60201, United States
Author contributions: Xu J contributed to the concept and design; Shi Z, and Wei J performed the data analysis; Rifkin AS, and Xu J drafted the manuscript; Rifkin AS, Shi Z, Wei J, Zheng SL, Helfand BT, Cordova JS, Biank VF, Tafur AJ, Khan O, and Xu J contributed to the critical revision of the manuscript for important intellectual content; Xu J performed the supervision.
Institutional review board statement: The UK Biobank was approved by North West-Haydock Research Ethics Committee (REC reference: 16/NW/0274; IRAS project ID: 200778).
Informed consent statement: Data from the UK Biobank was accessed through a Material Transfer Agreement under Application Reference Number: 50295. This study was performed in accordance with the Declaration of Helsinki.
Conflict-of-interest statement: NorthShore University HealthSystem has an agreement with GoPath Laboratories and GenomicMD for genetic tests of polygenic risk score.
Data sharing statement: The data used in this study is available in the UK Biobank, a publicly available repository. Data was accessed through a Material Transfer Agreement under Application Reference Number: 50295. For additional information, please feel free to contact the corresponding author, Jianfeng Xu, DrPH.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jianfeng Xu, MD, DrPH, Professor, Program for Personalized Cancer Care, NorthShore University HealthSystem, 1001 University Place, Evanston, IL 60201, United States. jxu@northshore.org
Received: June 5, 2023
Peer-review started: June 5, 2023
First decision: August 8, 2023
Revised: August 18, 2023
Accepted: September 28, 2023
Article in press: September 28, 2023
Published online: October 21, 2023
Abstract
BACKGROUND

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the digestive tract with increasing prevalence globally. Although venous thromboembolism (VTE) is a major complication in IBD patients, it is often underappreciated with limited tools for risk stratification.

AIM

To estimate the proportion of VTE among IBD patients and assess genetic risk factors (monogenic and polygenic) for VTE.

METHODS

Incident VTE was followed for 8465 IBD patients in the UK Biobank (UKB). The associations of VTE with F5 factor V leiden (FVL) mutation, F2 G20210A prothrombin gene mutation (PGM), and polygenic score (PGS003332) were tested using Cox hazards regression analysis, adjusting for age at IBD diagnosis, gender, and genetic background (top 10 principal components). The performance of genetic risk factors for discriminating VTE diagnosis was estimated using the area under the receiver operating characteristic curve (AUC).

RESULTS

The overall proportion of incident VTE was 4.70% in IBD patients and was similar for CD (4.46%), UC (4.49%), and unclassified (6.42%), and comparable to that of cancer patients (4.66%) who are well-known at increased risk for VTE. Mutation carriers of F5/F2 had a significantly increased risk for VTE compared to non-mutation carriers, hazard ratio (HR) was 1.94, 95% confidence interval (CI): 1.42-2.65. In contrast, patients with the top PGS decile had a considerably higher risk for VTE compared to those with intermediate scores (middle 8 deciles), HR was 2.06 (95%CI: 1.57-2.71). The AUC for differentiating VTE diagnosis was 0.64 (95%CI: 0.61-0.67), 0.68 (95%CI: 0.66-0.71), and 0.69 (95%CI: 0.66-0.71), respectively, for F5/F2 mutation carriers, PGS, and combined.

CONCLUSION

Similar to cancer patients, VTE complications are common in IBD patients. PGS provides more informative risk information than F5/F2 mutations (FVL and PGM) for personalized thromboprophylaxis.

Keywords: Inflammatory bowel disease, Venous thromboembolism, Polygenic score, Factor V leiden, Prothrombin gene mutation

Core Tip: Based on 8475 inflammatory bowel disease (IBD) patients from a population-based biobank, we showed they have an elevated risk for venous thromboembolism (VTE), with the overall proportion of incident VTE at 4.70%, similar to 4.66% observed in cancer patients. Polygenic score (PGS) is a significant predictor for VTE events, stronger than the well-known F5 factor V leiden mutation and F2 G20210A prothrombin gene mutation. The overall proportion of incident VTE is 8.53% in patients at the top 10 PGS percentile. These findings highlight the importance of VTE complications in IBD patients and provide genetic tools for personalized thromboprophylaxis.