Background The mechanism and medical treatment target for degenerative aortic valve disease, including aortic stenosis, is not well studied. In this study, we investigated the effect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aortic valve sclerosis (AVS), a calcified aortic valve without significant stenosis. Methods Participants with AVS (valves ≥2 mm thick, high echogenicity, and a peak transaortic velocity of <2.5 m/sec) and an age- and sex-matched control group were enrolled. Twenty-four CHIP genes with common variants in cardiovascular disease were used to generate a next-generation sequencing panel. The primary endpoint was the CHIP detection rate between the AVS and control groups. Inverse-probability treatment weighting (IPTW) analysis was performed to adjust for differences in baseline characteristics. Results From April 2020 to April 2022, 187 participants (125 with AVS and 62 controls) were enrolled; the mean age was 72.6±8.5 yrs, and 54.5% were male. An average of 1.3 CHIP variants was observed. CHIP detection, defined by a variant allele frequency (VAF) of ≥0.5%, was similar between the groups. However, the AVS group had larger CHIP clones: 49 (39.2%) participants had a VAF of ≥1% (vs. 13 [21.0%] in the control group; P=0.020), and 25 (20.0%) had a VAF of ≥2% (vs. 4 [6.5%]; P=0.028). AVS is independently associated with a VAF of ≥1% (adjusted odds ratio: 2.44, 95% confidence interval: 1.11-5.36; P=0.027). This trend was concordant and clearer in the IPTW cohort. Conclusions Participants with AVS more commonly had larger CHIP clones than age- and sex-matched controls. Further studies are warranted to identify causality between AVS and CHIP.

中文翻译：

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主动脉瓣硬化与不确定潜力的克隆造血之间的关联。


背景 退行性主动脉瓣疾病（包括主动脉瓣狭窄）的机制和药物治疗目标尚未得到很好的研究。在这项研究中，我们调查了不确定电位克隆造血 （CHIP） 对主动脉瓣硬化症 （AVS） 发展的影响，主动脉瓣硬化症是一种钙化的主动脉瓣，没有明显的狭窄。方法 纳入 AVS （瓣膜 ≥2 mm 厚、回声高、经主动脉峰速度 <2.5 m/sec） 参与者和年龄和性别匹配的对照组。使用在心血管疾病中具有常见变异的 24 个 CHIP 基因生成下一代测序面板。主要终点是 AVS 组和对照组之间的 CHIP 检出率。进行逆概率处理加权 （IPTW） 分析以调整基线特征的差异。结果 从 2020 年 4 月到 2022年4月，共招募了 187 名参与者 （125 名 AVS 和 62 名对照）;平均年龄为 72.6±8.5 岁，其中 54.5% 为男性。平均观察到 1.3 个 CHIP 变体。由变异等位基因频率 （VAF） 定义的 CHIP 检测为 ≥0.5%）在两组之间相似。然而，AVS 组的 CHIP 克隆更大：49 名 （39.2%） 参与者的 VAF 为 ≥1%（对照组为 13 名 [21.0%];P=0.020），25 例 （20.0%） 的 VAF 为 ≥2% （vs. 4 [6.5%];P=0.028）。AVS 与 ≥1% 的 VAF 独立相关（调整后比值比：2.44,95% 置信区间：1.11-5.36;P=0.027）。这一趋势在 IPTW 队列中更加一致且清晰。结论 与年龄和性别匹配的对照组相比，AVS 参与者更常具有更大的 CHIP 克隆。需要进一步的研究来确定 AVS 和 CHIP 之间的因果关系。