BACKGROUND Calcific aortic valve disease (CAVD) is the third most common cardiovascular disease in aging populations. Despite a growing number of biomarkers having been shown to be associated with CAVD, a marker suitable for routine testing in clinical practice is still needed. Plasma cell-free DNA (cfDNA) has been suggested as a biomarker for diagnosis and prognosis in multiple diseases. In this study, we aimed to test whether cfDNA could be used as a biomarker for the diagnosis of CAVD. METHODS Serum samples were collected from 137 diagnosed CAVD patients and 180 normal controls. The amount of cfDNA was quantified by amplifying a short fragment (ALU 115) and a long fragment (ALU 247) using qPCR. The cfDNA integrity (cfDI) was calculated as the ratio of ALU247 to ALU115. The association between CAVD and cfDI was evaluated using regression analysis. RESULTS CAVD patients had increased ALU 115 fragments (median, 185.14 (416.42) vs 302.83 (665.41), p<0.05) but a decreased value of cfDI (mean, 0.50±0.25 vs 0.41±0.26, p<0.01) in their serum when compared to controls. This difference was more dramatic in non-rheumatic CAVD patients (p<0.001) vs rheumatic CAVD patients (no significant difference). Similarly, CAVD patients with bicuspid aortic valve (BAV) (p<0.01) showed a greater difference than non-BAV CAVD patients (p<0.05). Linear regression and logistic regression showed that cfDI was independently and significantly associated with the presence of CAVD (95%CI, 0.096 to 0.773, p<0.05). The ROC assay revealed that cfDI combined with clinical characteristics had a better diagnostic value than cfDI alone (AUC=0.6191, p<0.001). CONCLUSION cfDI may be a potential biomarker for diagnosis of CAVD.

中文翻译：

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血浆游离 DNA 是诊断钙化主动脉瓣疾病的潜在生物标志物。

背景技术钙化性主动脉瓣疾病（CAVD）是老龄化人群中第三大常见的心血管疾病。尽管越来越多的生物标志物已被证明与 CAVD 相关，但仍然需要适合临床实践中常规检测的标志物。血浆游离 DNA (cfDNA) 已被建议作为多种疾病诊断和预后的生物标志物。在本研究中，我们旨在测试 cfDNA 是否可以用作诊断 CAVD 的生物标志物。方法 采集 137 名确诊 CAVD 患者和 180 名正常对照者的血清样本。通过使用 qPCR 扩增短片段 (ALU 115) 和长片段 (ALU 247) 来定量 cfDNA 的量。cfDNA 完整性 (cfDI) 计算为 ALU247 与 ALU115 的比率。使用回归分析评估 CAVD 和 cfDI 之间的关联。结果 CAVD 患者血清中 ALU 115 片段增加（中位数为 185.14 (416.42) vs 302.83 (665.41)，p<0.05），但 cfDI 值降低（平均为 0.50±0.25 vs 0.41±0.26，p<0.01）。与对照相比。与风湿性 CAVD 患者相比，这种差异在非风湿性 CAVD 患者 (p<0.001) 中更为显着（无显着差异）。同样，具有二尖瓣主动脉瓣 (BAV) 的 CAVD 患者 (p<0.01) 与非 BAV CAVD 患者 (p<0.05) 相比表现出更大的差异。线性回归和逻辑回归显示，cfDI 与 CAVD 的存在独立且显着相关（95% CI，0.096 至 0.773，p<0.05）。ROC分析显示，cfDI结合临床特征比单独使用cfDI具有更好的诊断价值（AUC=0.6191，p<0.001）。结论 cfDI 可能是诊断 CAVD 的潜在生物标志物。