Plasma Cell-Free DNA Is a Potential Biomarker for Diagnosis of Calcific Aortic Valve Disease
Related Experiment Video
Updated: Jul 12, 2025
Investigating Aortic Valve Calcification via Isolation and Culture of T Lymphocytes using Feeder Cells from Irradiated Buffy Coat
Published on: February 4, 2021
Wangge Ma1, Wei Zhang2, Huahua Liu3
1Department of Cardiology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China, mawangge.1991@stu.xjtu.edu.cn.
Insights
Plasma cell-free DNA integrity (cfDI) may serve as a novel biomarker for diagnosing calcific aortic valve disease (CAVD). This study found cfDI levels differed significantly between CAVD patients and healthy controls, suggesting its diagnostic potential.
Area of Science:
- Cardiovascular Medicine
- Biomarker Discovery
- Molecular Diagnostics
Background:
- Calcific aortic valve disease (CAVD) is a prevalent cardiovascular condition in aging populations.
- Current diagnostic markers for CAVD lack suitability for routine clinical practice.
- Plasma cell-free DNA (cfDNA) shows promise as a diagnostic and prognostic biomarker across various diseases.
Purpose of the Study:
- To investigate the potential of cfDNA integrity (cfDI) as a diagnostic biomarker for CAVD.
- To evaluate the association between cfDI levels and the presence of CAVD.
Main Methods:
- Serum samples from 137 CAVD patients and 180 controls were analyzed.
- Quantitative real-time PCR was used to measure cfDNA fragments (ALU 115 and ALU 247).
- cfDI was calculated as the ratio of ALU 247 to ALU 115, and regression analysis was employed.
Main Results:
- CAVD patients exhibited significantly decreased cfDI compared to controls (p < 0.01).
- The diagnostic value of cfDI was more pronounced in non-rheumatic and bicuspid aortic valve CAVD subtypes.
- cfDI was independently associated with CAVD presence (95% CI, 0.096 to 0.773; p < 0.05).
Conclusions:
- cfDI demonstrates potential as a novel biomarker for the diagnosis of CAVD.
- Combining cfDI with clinical characteristics enhances diagnostic accuracy for CAVD.
Introduction:
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 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.
Results:
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).
Conclusion:
cfDI may be a potential biomarker for diagnosis of CAVD.
