Department of Cardiology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China,
Department of General Practice, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Cardiology. 2024;149(2):155-162. doi: 10.1159/000534229. Epub 2023 Oct 27.
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.
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 quantitative real-time PCR. The cfDNA integrity (cfDI) was calculated as the ratio of ALU247 to ALU115. The association between CAVD and cfDI was evaluated using regression analysis.
CAVD patients had increased ALU 115 fragments (median, 185.14 (416.42) versus 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) versus 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).
cfDI may be a potential biomarker for diagnosis of CAVD.
钙化性主动脉瓣疾病（CAVD）是老龄化人群中第三大常见心血管疾病。尽管越来越多的生物标志物已被证明与 CAVD 相关，但仍需要一种适用于临床常规检测的标志物。无细胞血浆 DNA（cfDNA）已被提议作为多种疾病的诊断和预后标志物。在这项研究中，我们旨在测试 cfDNA 是否可作为 CAVD 诊断的标志物。
从 137 例确诊的 CAVD 患者和 180 例正常对照中采集血清样本。使用定量实时 PCR 扩增短片段（ALU 115）和长片段（ALU 247）来定量 cfDNA。cfDNA 完整性（cfDI）计算为 ALU247 与 ALU115 的比值。使用回归分析评估 CAVD 与 cfDI 的相关性。
与对照组相比，CAVD 患者的血清中 ALU 115 片段增加（中位数，185.14（416.42）比 302.83（665.41），p < 0.05），但 cfDI 值降低（均值，0.50 ± 0.25 比 0.41 ± 0.26，p < 0.01）。在非风湿性 CAVD 患者中差异更为显著（p < 0.001），而在风湿性 CAVD 患者中无显著差异（p > 0.05）。同样，二叶式主动脉瓣（BAV）的 CAVD 患者（p < 0.01）比非 BAV CAVD 患者（p < 0.05）差异更大。线性回归和逻辑回归显示，cfDI 与 CAVD 的存在独立且显著相关（95%CI，0.096 至 0.773，p < 0.05）。ROC 分析显示，cfDI 结合临床特征的诊断价值优于单独使用 cfDI（AUC = 0.6191，p < 0.001）。
cfDI 可能是 CAVD 诊断的潜在生物标志物。
