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无既往心脏病变的慢性肾脏病患者的不确定潜能克隆性造血与心血管风险

Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Risk in Patients with Chronic Kidney Disease without Previous Cardiac Pathology.

作者信息

Kislikova Maria, Lopez Maria Ana Batlle, Salinas Francisco Javier Freire, Blanco José Antonio Parra, Molina Maria Pilar García-Berbel, Fernandez Alejandro Aguilera, Haces Vicente Celestino Piñera, Unzueta Maria Teresa García, Hernández Adalberto Benito, Millan Juan Carlos Ruiz San, Rodrigo Calabia Emilio

机构信息

Immunopathology Group, Nephrology Department, Marqués de Valdecilla University Hospital-IDIVAL, 39009 Santander, Spain.

Hematology Department, Marqués de Valdecilla University Hospital-IDIVAL, 39009 Santander, Spain.

出版信息

Life (Basel). 2023 Aug 24;13(9):1801. doi: 10.3390/life13091801.

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the clonal expansion of hematopoietic stem cells carrying certain genes associated with an increased risk of hematological malignancies. Our study analyzes the influence of CHIP on the risk of heart disease and cardiovascular events in a population with chronic kidney disease (CKD). A total of 128 patients were prospectively followed up for 18 months to detect major cardiovascular events (MACE). To detect the presence of silent heart disease, troponin I, NT-Pro-BNP, and coronary calcification were measured. A massive sequencing was performed to detect CHIP. A total of 24.2% of the patients presented CHIP, including that which was only pathogenic. The most frequently affected gene was TET2 (21.1%). Using multivariate logistic regression analysis, the presence of CHIP was not related to coronary calcification (OR 0.387, 95% CI 0.142-1.058, = 0.387), nor was it related to troponin I or NT-Pro-BNP. A total of nine patients developed major cardiovascular events. Patients with CHIP did not have a higher risk of major cardiovascular events, although patients with DNMT3A did have a higher risk (HR 6.637, 95% CI 1.443-30.533, = 0.015), independent of other variables. We did not find that CHIP was associated with a greater risk of silent heart disease or cardiovascular events, although those affected by DNMT3a, analyzed independently, were associated with a greater number of cardiovascular events.

摘要

不确定潜能的克隆性造血(CHIP)由携带某些与血液系统恶性肿瘤风险增加相关基因的造血干细胞克隆性扩增所定义。我们的研究分析了CHIP对慢性肾脏病(CKD)人群中心脏病风险和心血管事件的影响。总共128例患者被前瞻性随访18个月以检测主要心血管事件(MACE)。为检测隐匿性心脏病的存在,检测了肌钙蛋白I、N末端脑钠肽原(NT-Pro-BNP)和冠状动脉钙化情况。进行大规模测序以检测CHIP。总共24.2%的患者存在CHIP,包括仅具有致病性的CHIP。最常受影响的基因是TET2(21.1%)。使用多因素逻辑回归分析,CHIP的存在与冠状动脉钙化无关(比值比[OR]0.387,95%置信区间[CI]0.142 - 1.058,P = 0.387),也与肌钙蛋白I或NT-Pro-BNP无关。共有9例患者发生了主要心血管事件。CHIP患者发生主要心血管事件的风险并不更高,尽管DNMT3A基因变异的患者确实有更高风险(风险比[HR]6.637,95%CI 1.443 - 30.533,P = 0.015),且独立于其他变量。我们没有发现CHIP与隐匿性心脏病或心血管事件的更高风险相关,尽管独立分析显示,受DNMT3a影响的患者与更多心血管事件相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3208/10532913/935d58fe15d5/life-13-01801-g001.jpg

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