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Combined Effects of Clonal Hematopoiesis and Carotid Stenosis on Cardiovascular Mortality
Journal of the American College of Cardiology ( IF 24.0 ) Pub Date : 2024-04-29 , DOI: 10.1016/j.jacc.2024.02.043
Roland Jäger , Matthias Hoke , Florian J. Mayer , Stefanie Boden , Cornelia Englisch , Cihan Ay , Robert Kralovics , Christoph J. Binder

The expansion of hematopoietic stem cells caused by acquired somatic mutations (clonal hematopoiesis [CH]) is a novel cardiovascular risk factor. The prognostic value of CH in patients with carotid atherosclerosis remains to be evaluated. This study assessed the prognostic significance of CH in patients with atherosclerosis as detected by ultrasound of the carotid artery. We applied deep sequencing of selected genomic regions within the genes , , and to screen for CH in 968 prospectively collected patients with asymptomatic carotid atherosclerosis evaluated by duplex sonography. We detected clonal markers at variant allele frequency ≥2% in 133 (13.7%) of 968 patients (median age 69.2 years), with increasing prevalence at advanced age. Multivariate analyses including age and established cardiovascular risk factors revealed overall presence of CH to be significantly associated with increased risk of cardiovascular death (HR: 1.50; 95% CI: 1.12-2.00; 0.007), reflected also at the single gene level. The effect of CH was more pronounced in older patients and independent of the patients’ inflammatory status as measured by high-sensitivity C-reactive protein. Simultaneous assessment of CH and degree of carotid stenosis revealed combined effects on cardiovascular mortality, depicted by a superior risk for patients with >50% stenosis and concomitant CH (adjusted HR: 1.60; 95% CI: 1.08-2.38; 0.020). CH status in combination with the extent of carotid atherosclerosis jointly predict long-term mortality. Determination of CH can provide additional prognostic information in patients with asymptomatic carotid atherosclerosis.

中文翻译:

克隆性造血和颈动脉狭窄对心血管死亡率的综合影响

由获得性体细胞突变(克隆造血[CH])引起的造血干细胞扩增是一种新的心血管危险因素。 CH 对颈动脉粥样硬化患者的预后价值仍有待评估。本研究评估了通过颈动脉超声检测发现的 CH 对动脉粥样硬化患者的预后意义。我们对基因 、 和 中选定的基因组区域进行深度测序,对前瞻性收集的 968 名无症状颈动脉粥样硬化患者进行了 CH 筛查,这些患者通过双重超声检查进行评估。我们在 968 名患者(中位年龄 69.2 岁)中的 133 名患者(中位年龄 69.2 岁)中检测到变异等位基因频率≥2% 的克隆标志物,且随着年龄的增长患病率不断增加。包括年龄和已确定的心血管危险因素在内的多变量分析显示,CH 的总体存在与心血管死亡风险增加显着相关(HR:1.50;95% CI:1.12-2.00;0.007),这也反映在单基因水平上。 CH 的效果在老年患者中更为明显,并且与通过高敏 C 反应蛋白测量的患者炎症状态无关。对 CH 和颈动脉狭窄程度的同时评估揭示了对心血管死亡率的综合影响,表现为狭窄 >50% 并伴有 CH 的患者风险较高(调整后 HR:1.60;95% CI:1.08-2.38;0.020)。 CH 状态与颈动脉粥样硬化程度相结合,共同预测长期死亡率。 CH 的测定可以为无症状颈动脉粥样硬化患者提供额外的预后信息。
更新日期:2024-04-29
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