Int J Med Sci 2022; 19(3):446-459. doi:10.7150/ijms.67094 This issue


Diagnostic value of circRNAs as effective biomarkers in human cardiovascular disease: an updated meta-analysis

Zhexiao Zhang1,2*, Runmin Guo1*, Yuhui Wang3*, Hairong Huang2, Jie Liu2, Chenfei Wang2, Hongfu Wu4✉, Tangbin Zou1,2✉*

1. Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, China.
2. Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China.
3. Department of Surgery, the Third Affiliated Hospital of Guangdong Medical University (Longjiang Hospital of Shunde District), Foshan, China.
4. Key Laboratory of Stem Cell and Regenerative Tissue Engineering, Guangdong Medical University, Dongguan, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Zhang Z, Guo R, Wang Y, Huang H, Liu J, Wang C, Wu H, Zou T. Diagnostic value of circRNAs as effective biomarkers in human cardiovascular disease: an updated meta-analysis. Int J Med Sci 2022; 19(3):446-459. doi:10.7150/ijms.67094. Available from

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Graphic abstract

Background: A growing body of literature has demonstrated that circular RNAs (circRNAs) are the potential biomarkers in human cardiovascular disease (CVD). Therefore, a meta-analysis based on current studies was accomplished to appraise the role of circRNAs in the diagnostic of CVD patients.

Methods: Studies before October 30, 2021, were searched using PubMed, EMBASE, the Web of Science, and Cochrane Library. The diagnostic odds ratio (DOR) with a confidence interval (CI) of 95% was used to investigate the associations between circRNAs and CVDs.

Results: A total of 27 eligible articles were selected, including 47 studies, with 6833 participants meeting the criteria standard constrain. The pooled overall sensitivity and specificity for circRNAs expression profile in differentiating CVD patients from controls (non-CVDs or healthy subjects) were 0.81 (95%CI 0.78-0.83) and 0.74 (95%CI 0.68-0.78), respectively; the overall positive likelihood ratio was 3.1 (95%CI 2.5-3.7); the negative likelihood ratio was 0.26 (95%CI 0.22-0.31); the overall diagnostic odds ratio corresponding to an area under the curve of 0.85 (95%CI 0.81-0.88) was 12 (95%CI 9-16). Subgroup analysis indicated that the serum rather than blood has higher diagnostic accuracy. Likewise, meta-regression analysis demonstrated that the specimen, detection method, sample size, and publication year were the main sources of heterogeneity. Sensitivity analysis and Deeks' funnel plot revealed that our results are relatively robust.

Conclusions: Our evidence-based analysis results suggested that circRNAs provide higher diagnostic accuracy in the prediction of CVDs. Thus, circRNAs might be potential biomarkers in CVDs.

Keywords: circRNAs, cardiovascular disease, diagnosis, biomarker, meta-analysis