Copyright
©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
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
Processing time: 135 Days and 23 Hours
ARTICLE HIGHLIGHTS
Research background
Venous thromboembolism (VTE) is a major complication in patients with inflammatory bowel disease (IBD). However, it is often underappreciated among physicians and patients. Furthermore, limited VTE risk stratification tools are available for personalized thromboprophylaxis.
Research motivation
A large IBD patient cohort is available from the UK Biobank (UKB). Its long-term clinical follow-up data and genome-wide genetic data provide a rare and efficient opportunity to address these two major challenges.
Research objectives
To estimate the prevalence of VTE complications among IBD patients and assess the performance of known and novel genetic predictors of VTE risk stratification in these patients.
Research methods
We retrospectively followed the incident VTE complication among 8465 IBD patients in the UKB. The associations of VTE with factor V leiden (FVL) mutation in the F5 gene, G20210A prothrombin gene mutation (PGM) in the F2 gene, and polygenic score (PGS) 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 complications was estimated using the area under the receiver operating characteristic curve (AUC).
Research results
The overall prevalence of VTE complication after an IBD diagnosis was 4.70%. This prevalence was comparable to that of cancer patients (4.66%) who are well-known at increased risk for VTE. A novel genetic predictor (PGS) was significantly associated with VTE risk and was independent of known genetic predictors (FVL/PGM). The AUC of differentiating VTE complication was significantly higher for PGS [0.68, 95% confidence interval (CI): 0.66-0.71] than that of FVL/PGM (0.64, 95%CI: 0.61-0.67) and was highest by combining these two genetic predictors (0.69, 95%CI: 0.66-0.71).
Research conclusions
VTE complication is common in IBD patients and is similar to that of cancer patients. Newly developed PGS provides a more informative VTE risk stratification tool than known mutations (FVL/PGM).
Research perspectives
Findings from this large study of IBD patients have potential clinical utilities. It not only highlights the significance of VTE complications in IBD patients, but also provides an informative VTE risk assessment tool for developing personalized thromboprophylaxis strategies.
