Todorovski Angela, Wang Tzu-Fei, Sterling Evan, Collins Erin, Carrier Marc, Siegal Deborah, Kekre Natasha, Khalifé Roy, Xu Yan
Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Canada.
PLoS One. 2025 Jul 16;20(7):e0328650. doi: 10.1371/journal.pone.0328650. eCollection 2025.
Clonal hematopoiesis of indeterminate potential (CHIP) is a novel risk factor for thromboembolic events. While CHIP is linked to an increased risk of incident atherothrombosis (ATE), the link between these two conditions varies across studies. Furthermore, the association between CHIP and incident venous thromboembolism (VTE) has not yet been well characterized. Among patients with established ATE and VTE, it is still unclear how CHIP carriership influences their health outcomes. We aim to conduct a systematic review and meta-analysis to: i) determine the impact of CHIP carriership on incident ATE and VTE; and ii) evaluate the prevalence and clinical consequences of CHIP mutations among individuals with established ATE or VTE.
We will search MEDLINE, EMBASE, Scopus and CINAHL for randomized trials, cohort studies, or case control studies reporting thromboembolic events among adult CHIP carriers and non-carriers in two populations: i) individuals without prior ATE (coronary artery disease, myocardial infarction, ischemic stroke, peripheral arterial disease) or VTE (pulmonary embolism, deep vein thrombosis, superficial vein thrombosis); and ii) individuals with established ATE or VTE. Cross-sectional studies will be included to determine the prevalence of CHIP among individuals with established thromboembolic disease. The primary outcome will be incident ATE and VTE. Secondary outcomes will be: i) CHIP prevalence among individuals with established ATE or VTE; and ii) recurrent thromboembolism and treatment-associated bleeding among individuals with established ATE or VTE. We will use random-effects meta-analyses, with subgroup analyses by participant demographics, ATE and VTE risk factors, and CHIP-specific characteristics.
By understanding the prognostic impact of CHIP carriership, our findings will inform future research on CHIP's role as a predictive biomarker for ATE and VTE in the general population and among individuals with established thromboembolic disease.
This systematic review protocol was registered with the Internal Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42024539923).
不确定潜能的克隆性造血（CHIP）是血栓栓塞事件的一个新的危险因素。虽然CHIP与动脉粥样硬化血栓形成（ATE）事件风险增加有关，但这两种情况之间的联系在不同研究中有所不同。此外，CHIP与静脉血栓栓塞（VTE）事件之间的关联尚未得到充分描述。在已确诊ATE和VTE的患者中，CHIP携带者如何影响其健康结局仍不清楚。我们旨在进行一项系统评价和荟萃分析，以：i）确定CHIP携带者对ATE和VTE事件的影响；ii）评估已确诊ATE或VTE的个体中CHIP突变的患病率和临床后果。
我们将检索MEDLINE、EMBASE、Scopus和CINAHL，查找关于两组人群（即成年CHIP携带者和非携带者）中血栓栓塞事件的随机试验、队列研究或病例对照研究：i）无既往ATE（冠状动脉疾病、心肌梗死、缺血性中风、外周动脉疾病）或VTE（肺栓塞、深静脉血栓形成、浅静脉血栓形成）的个体；ii）已确诊ATE或VTE的个体。将纳入横断面研究以确定已确诊血栓栓塞性疾病个体中CHIP的患病率。主要结局将是ATE和VTE事件。次要结局将是：i）已确诊ATE或VTE的个体中CHIP的患病率；ii）已确诊ATE或VTE的个体中复发性血栓栓塞和治疗相关出血。我们将使用随机效应荟萃分析，并按参与者人口统计学、ATE和VTE危险因素以及CHIP特异性特征进行亚组分析。
通过了解CHIP携带者的预后影响，我们的研究结果将为未来关于CHIP作为一般人群和已确诊血栓栓塞性疾病个体中ATE和VTE的预测生物标志物的作用的研究提供信息。
本系统评价方案已在系统评价内部前瞻性注册库（PROSPERO，注册号CRD42024539923）注册。
