PDF(Pubmed)
Abstract：
UNASSIGNED: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel cardiovascular disease (CVD) risk factor in individuals without acute myeloid leukemia (AML).
UNASSIGNED: The aim of this study was to examine the association between mutations associated with CHIP (CHIP-related mutations) identified in patients at AML diagnosis and the risk for cardiovascular events (CVEs).
UNASSIGNED: This was a retrospective cohort study of 623 patients with AML treated between 2015 and 2018 who underwent DNA analysis. Cause-specific hazard regression models were used to study the associations between pathogenic mutations in common CHIP-related genes (DNMT3A, TET2, ASXL1, JAK2, TP53, SRSF2, and SF3B1) and the rate of CVEs (heart failure hospitalization, acute coronary syndrome, coronary artery revascularization, ischemic stroke, venous thromboembolism, and CVD death) and between CVE development and all-cause mortality.
UNASSIGNED: Patients were 64.6 ± 15.3 years of age, 265 (42.5%) were women, and 63% had at least 1 CHIP-related mutation. Those with CHIP-related mutations were older (69.2 ± 12.3 vs 56.6 ± 16.6 years; P < 0.001) and had a greater prevalence of CVD risk factors and CVD history. In adjusted analysis, the presence of any CHIP-related mutation was associated with a higher rate of CVEs (HR: 1.74; 95% CI: 1.03-2.93; P = 0.037) among intensively treated patients (anthracycline based) but not the whole cohort (HR: 1.26; 95% CI: 0.81-1.97; P = 0.31). TP53 (HR: 4.18; 95% CI: 2.07-8.47; P < 0.001) and ASXL1 (HR: 2.37; 95% CI: 1.21-4.63; P = 0.012) mutations were associated with CVEs among intensively treated patients. Interval development of CVEs was associated with all-cause mortality (HR: 1.99; 95% CI: 1.45-2.73; P < 0.001).
UNASSIGNED: Among patients with AML treated with intensive chemotherapy, mutations in CHIP-related genes were associated with an increased risk for developing incident CVEs after AML diagnosis.
UNASSIGNED: The aim of this study was to examine the association between mutations associated with CHIP (CHIP-related mutations) identified in patients at AML diagnosis and the risk for cardiovascular events (CVEs).
UNASSIGNED: This was a retrospective cohort study of 623 patients with AML treated between 2015 and 2018 who underwent DNA analysis. Cause-specific hazard regression models were used to study the associations between pathogenic mutations in common CHIP-related genes (DNMT3A, TET2, ASXL1, JAK2, TP53, SRSF2, and SF3B1) and the rate of CVEs (heart failure hospitalization, acute coronary syndrome, coronary artery revascularization, ischemic stroke, venous thromboembolism, and CVD death) and between CVE development and all-cause mortality.
UNASSIGNED: Patients were 64.6 ± 15.3 years of age, 265 (42.5%) were women, and 63% had at least 1 CHIP-related mutation. Those with CHIP-related mutations were older (69.2 ± 12.3 vs 56.6 ± 16.6 years; P < 0.001) and had a greater prevalence of CVD risk factors and CVD history. In adjusted analysis, the presence of any CHIP-related mutation was associated with a higher rate of CVEs (HR: 1.74; 95% CI: 1.03-2.93; P = 0.037) among intensively treated patients (anthracycline based) but not the whole cohort (HR: 1.26; 95% CI: 0.81-1.97; P = 0.31). TP53 (HR: 4.18; 95% CI: 2.07-8.47; P < 0.001) and ASXL1 (HR: 2.37; 95% CI: 1.21-4.63; P = 0.012) mutations were associated with CVEs among intensively treated patients. Interval development of CVEs was associated with all-cause mortality (HR: 1.99; 95% CI: 1.45-2.73; P < 0.001).
UNASSIGNED: Among patients with AML treated with intensive chemotherapy, mutations in CHIP-related genes were associated with an increased risk for developing incident CVEs after AML diagnosis.
摘要：
未经证实：不确定潜能克隆造血（CHIP）是无急性髓性白血病（AML）个体中一种新的心血管疾病（CVD）危险因素。
UNASSIGNED：本研究的目的是检查AML诊断患者中与CHIP相关的突变（CHIP相关突变）与心血管事件（CVE）风险之间的关系。
UNASSIGNED：这是一项回顾性队列研究，纳入了2015年至2018年间接受DNA分析的623例AML患者。病因特异性风险回归模型用于研究常见CHIP相关基因(DNMT3A，TET2，ASXL1，JAK2，TP53，SRSF2和SF3B1）和CVE（心力衰竭住院率，急性冠脉综合征,冠状动脉血运重建,缺血性卒中,静脉血栓栓塞,和CVD死亡）以及CVE发展和全因死亡率之间。
未经证实：患者年龄为64.6±15.3岁，265名（42.5%）是女性，63%有至少1个CHIP相关突变。具有CHIP相关突变的患者年龄较大（69.2±12.3vs56.6±16.6岁；P<0.001），并且CVD危险因素和CVD病史的患病率更高。在调整后的分析中，在强化治疗的患者(蒽环类药物)中,任何CHIP相关突变的存在均与CVE的发生率较高相关(HR:1.74;95%CI:1.03~2.93;P=0.037),但与整个队列(HR:1.26;95%CI:0.81~1.97;P=0.31)无关.在强化治疗的患者中，TP53（HR：4.18；95％CI：2.07-8.47；P<0.001）和ASXL1（HR：2.37；95％CI：1.21-4.63；P=0.012）突变与CVE相关。CVE的间期发展与全因死亡率相关(HR:1.99;95%CI:1.45-2.73;P<0.001)。
未经证实：在接受强化化疗的AML患者中，CHIP相关基因的突变与AML诊断后发生CVE的风险增加相关.
UNASSIGNED：本研究的目的是检查AML诊断患者中与CHIP相关的突变（CHIP相关突变）与心血管事件（CVE）风险之间的关系。
UNASSIGNED：这是一项回顾性队列研究，纳入了2015年至2018年间接受DNA分析的623例AML患者。病因特异性风险回归模型用于研究常见CHIP相关基因(DNMT3A，TET2，ASXL1，JAK2，TP53，SRSF2和SF3B1）和CVE（心力衰竭住院率，急性冠脉综合征,冠状动脉血运重建,缺血性卒中,静脉血栓栓塞,和CVD死亡）以及CVE发展和全因死亡率之间。
未经证实：患者年龄为64.6±15.3岁，265名（42.5%）是女性，63%有至少1个CHIP相关突变。具有CHIP相关突变的患者年龄较大（69.2±12.3vs56.6±16.6岁；P<0.001），并且CVD危险因素和CVD病史的患病率更高。在调整后的分析中，在强化治疗的患者(蒽环类药物)中,任何CHIP相关突变的存在均与CVE的发生率较高相关(HR:1.74;95%CI:1.03~2.93;P=0.037),但与整个队列(HR:1.26;95%CI:0.81~1.97;P=0.31)无关.在强化治疗的患者中，TP53（HR：4.18；95％CI：2.07-8.47；P<0.001）和ASXL1（HR：2.37；95％CI：1.21-4.63；P=0.012）突变与CVE相关。CVE的间期发展与全因死亡率相关(HR:1.99;95%CI:1.45-2.73;P<0.001)。
未经证实：在接受强化化疗的AML患者中，CHIP相关基因的突变与AML诊断后发生CVE的风险增加相关.
