{"title":"Frailty, Genetic Risk, and Long-Term Risk of Venous Thromboembolism: Insight From a UK Biobank Study.","authors":"Jiatang Xu,Qiushi Ren,Yangfan Su,Liling Lin,Runnan Shen,Kai Huang","doi":"10.1002/ajh.27753","DOIUrl":null,"url":null,"abstract":"Frailty is more prevalent among venous thromboembolism (VTE) patients. However, the relationship between long-term VTE risk and frailty remained unexplored. This study included 315 523 participants recruited from UK Biobank between 2006 and 2010. Frailty status of participants at recruitment was evaluated by physical frailty and frailty index. The association between frailty and long-term risk of VTE was assessed through Cox proportional models. After excluded participants without genetic data, we further explored the interaction and joint effect between frailty and genetic risk in 258 461 participants. Mediation analyses were performed to investigate whether frailty mediates the association between cancer, obesity, and VTE. Results revealed significant associations between frailty and increased risk of VTE (physical frailty: HR, 1.63; 95% CI, 1.49-1.78; frailty index: HR, 1.66; 95% CI, 1.53-1.78). Participants with high genetic risk and frailty exhibited the highest VTE risk (physical frailty: HR, 3.83; 95% CI, 3.22-4.55; frailty index: HR, 3.96; 95% CI, 3.41-4.62). Frailty and genetic risk exhibited a significant additive interaction, with a relative excess risk due to interaction (RERI) of 0.76 in the physical frailty cohort, and a RERI of 1.11 in the frailty index cohort. Frailty mediated approximately 14% of the association between cancer and VTE, and 9% of the association between obesity and VTE. In conclusion, frailty is significantly associated with an increased long-term risk of VTE in the general population. Combining frailty and genetic risk can assist in the identification of high-risk VTE populations. Also, frailty significantly mediates the association between cancer, obesity, and VTE.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 1","pages":""},"PeriodicalIF":10.1000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ajh.27753","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Frailty is more prevalent among venous thromboembolism (VTE) patients. However, the relationship between long-term VTE risk and frailty remained unexplored. This study included 315 523 participants recruited from UK Biobank between 2006 and 2010. Frailty status of participants at recruitment was evaluated by physical frailty and frailty index. The association between frailty and long-term risk of VTE was assessed through Cox proportional models. After excluded participants without genetic data, we further explored the interaction and joint effect between frailty and genetic risk in 258 461 participants. Mediation analyses were performed to investigate whether frailty mediates the association between cancer, obesity, and VTE. Results revealed significant associations between frailty and increased risk of VTE (physical frailty: HR, 1.63; 95% CI, 1.49-1.78; frailty index: HR, 1.66; 95% CI, 1.53-1.78). Participants with high genetic risk and frailty exhibited the highest VTE risk (physical frailty: HR, 3.83; 95% CI, 3.22-4.55; frailty index: HR, 3.96; 95% CI, 3.41-4.62). Frailty and genetic risk exhibited a significant additive interaction, with a relative excess risk due to interaction (RERI) of 0.76 in the physical frailty cohort, and a RERI of 1.11 in the frailty index cohort. Frailty mediated approximately 14% of the association between cancer and VTE, and 9% of the association between obesity and VTE. In conclusion, frailty is significantly associated with an increased long-term risk of VTE in the general population. Combining frailty and genetic risk can assist in the identification of high-risk VTE populations. Also, frailty significantly mediates the association between cancer, obesity, and VTE.
期刊介绍:
The American Journal of Hematology offers extensive coverage of experimental and clinical aspects of blood diseases in humans and animal models. The journal publishes original contributions in both non-malignant and malignant hematological diseases, encompassing clinical and basic studies in areas such as hemostasis, thrombosis, immunology, blood banking, and stem cell biology. Clinical translational reports highlighting innovative therapeutic approaches for the diagnosis and treatment of hematological diseases are actively encouraged.The American Journal of Hematology features regular original laboratory and clinical research articles, brief research reports, critical reviews, images in hematology, as well as letters and correspondence.