ImportanceClonal hematopoiesis of indeterminate potential (CHIP) may contribute to the risk of atrial fibrillation (AF) through its association with inflammation and cardiac remodeling.ObjectiveTo determine whether CHIP was associated with AF, inflammatory and cardiac biomarkers, and cardiac structural changes.Design, Setting, and ParticipantsThis was a population-based, prospective cohort study in participants of the Atherosclerosis Risk in Communities (ARIC) study and UK Biobank (UKB) cohort. Samples were collected and echocardiography was performed from 2011 to 2013 in the ARIC cohort, and samples were collected from 2006 to 2010 in the UKB cohort. Included in this study were adults without hematologic malignancies, mitral valve stenosis, or previous mitral valve procedure from both the ARIC and UKB cohorts; additionally, participants without hypertrophic cardiomyopathy and congenital heart disease from the UKB cohort were also included. Data analysis was completed in 2023.ExposuresCHIP (variant allele frequency [VAF] ≥2%), common gene-specific CHIP subtypes (DNMT3A, TET2, ASXL1), large CHIP (VAF ≥10%), inflammatory and cardiac biomarkers (high-sensitivity C-reactive protein, interleukin 6 [IL-6], IL-18, high-sensitivity troponin T [hs-TnT] and hs-TnI, N-terminal pro–B-type natriuretic peptide), and echocardiographic indices.Main Outcome MeasureIncident AF.ResultsA total of 199 982 adults were included in this study. In ARIC participants (4131 [2.1%]; mean [SD] age, 76 [5] years; 2449 female [59%]; 1682 male [41%]; 935 Black [23%] and 3196 White [77%]), 1019 had any CHIP (24.7%), and 478 had large CHIP (11.6%). In UKB participants (195 851 [97.9%]; mean [SD] age, 56 [8] years; 108 370 female [55%]; 87 481 male [45%]; 3154 Black [2%], 183 747 White [94%], and 7971 other race [4%]), 11 328 had any CHIP (5.8%), and 5189 had large CHIP (2.6%). ARIC participants were followed up for a median (IQR) period of 7.0 (5.3-7.7) years, and UKB participants were followed up for a median (IQR) period of 12.2 (11.3-13.0) years. Meta-analyzed hazard ratios for AF were 1.12 (95% CI, 1.01-1.25; P = .04) for participants with vs without large CHIP, 1.29 (95% CI, 1.05-1.59; P = .02) for those with vs without large TET2 CHIP (seen in 1340 of 197 209 [0.67%]), and 1.45 (95% CI, 1.02-2.07; P = .04) for those with vs without large ASXL1 CHIP (seen in 314 of 197 209 [0.16%]). Large TET2 CHIP was associated with higher IL-6 levels. Additionally, large ASXL1 was associated with higher hs-TnT level and increased left ventricular mass index.Conclusions and RelevanceLarge TET2 and ASXL1, but not DNMT3A, CHIP was associated with higher IL-6 level, indices of cardiac remodeling, and increased risk for AF. Future research is needed to elaborate on the mechanisms driving the associations and to investigate potential interventions to reduce the risk.

中文翻译：

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TET2 和 ASXL1 中的心房颤动和克隆性造血

重要性不确定电位克隆造血 (CHIP) 可能通过其与炎症和心脏重塑的关联而增加房颤 (AF) 的风险。目的确定 CHIP 是否与 AF、炎症和心脏生物标志物以及心脏结构变化相关。设计、设置和参与者这是一项基于人群的前瞻性队列研究，对象是社区动脉粥样硬化风险 (ARIC) 研究和英国生物银行 (UKB) 队列的参与者。 ARIC 队列于 2011 年至 2013 年收集样本并进行超声心动图检查，UKB 队列于 2006 年至 2010 年收集样本。这项研究包括来自 ARIC 和 UKB 队列的没有血液恶性肿瘤、二尖瓣狭窄或既往接受过二尖瓣手术的成年人；此外，UKB 队列中没有肥厚性心肌病和先天性心脏病的参与者也被纳入其中。数据分析于2023年完成。ExposuresCHIP（变异等位基因频率[VAF]≥2%），常见基因特异性CHIP亚型（DNMT3A,TET2,ASXL1）、大 CHIP（VAF ≥10%）、炎症和心脏生物标志物（高敏 C 反应蛋白、白细胞介素 6 [IL-6]、IL-18、高敏肌钙蛋白 T [hs-TnT] 和 hs-TnI 、N 端 B 型利尿钠肽原）和超声心动图指数。主要结果指标 AF 事件。结果本研究共纳入 199 982 名成年人。在 ARIC 参与者中（4131 名 [2.1%]；平均 [SD] 年龄为 76 [5] 岁；2449 名女性 [59%]；1682 名男性 [41%]；935 名黑人 [23%] 和 3196 名白人 [77%]） ，1019 人有任何 CHIP（24.7%），478 人有大 CHIP（11.6%）。在 UKB 参与者中（195 851 [97.9%]；平均 [SD] 年龄，56 [8] 岁；108 370 名女性 [55%]；87 481 名男性 [45%]；3154 名黑人 [2%]，183 747 名白人 [ 94%]，7971 名其他种族 [4%]），11 328 名有任何 CHIP（5.8%），5189 名有大量 CHIP（2.6%）。 ARIC 参与者的中位随访时间 (IQR) 为 7.0 (5.3-7.7) 年，UKB 参与者的中位随访时间 (IQR) 为 12.2 (11.3-13.0) 年。 AF 的荟萃分析风险比为 1.12（95% CI，1.01-1.25；磷= .04) 对于有和没有大 CHIP 的参与者，1.29 (95% CI, 1.05-1.59；磷= .02) 对于那些有大的 vs 没有大的TET2CHIP（见于 197 209 中的 1340 [0.67%]）和 1.45（95% CI，1.02-2.07；磷= .04) 对于那些有大的 vs 没有大的ASXL1CHIP（参见 197 209 中的 314 [0.16%]）。大的TET2CHIP 与较高的 IL-6 水平相关。此外，大ASXL1与较高的 hs-TnT 水平和增加的左心室质量指数相关。结论和相关性大TET2和ASXL1， 但不是DNMT3A，CHIP 与较高的 IL-6 水平、心脏重塑指数和 AF 风险增加相关。未来的研究需要详细阐述驱动这些关联的机制，并调查降低风险的潜在干预措施。