Blood-based circulating microRNAs as diagnostic biomarkers for subclinical carotid atherosclerosis: A systematic review and meta-analysis with bioinformatics analysis

Background: Atherosclerosis in carotid arteries can remain clinically undetected in its early development until an acute cerebrovascular event such as stroke emerges. Recently, microRNAs (miRNAs) circulating in blood have emerged as potential diagnostic biomarkers, but their performance in detecting subclinical carotid atherosclerosis has yet to be systematically researched.Aim: To investigate the diagnostic performance of circulating miRNAs in detecting subclinical carotid atherosclerosis.Methods: We systematically searched five electronic databases from inception to July 23, 2022. Subclinical carotid atherosclerosis was defined using carotid intima-media thickness (CIMT). Diagnostic accuracy parameters and correlation coefficients were pooled. A gene network visualisation and enrichment bioinformatics analysis were additionally conducted to search for potential target genes and pathway regulations of the miRNAs.Results: Fifteen studies (15 unique miRNAs) comprising 2542 subjects were identified. Circulating miRNAs had a pooled sensitivity of 85% (95% CI 80%-89%), specificity of 84% (95% CI 78%-88%), positive likelihood ratio of 5.19 (95% CI 3.97-6.80), negative likelihood ratio of 0.18 (95% CI 0.13-0.23), diagnostic odds ratio of 29.48 (95% CI 21.15-41.11), and area under the summary receiver operating characteristic curve of 0.91 (95% CI 0.88-0.93), with a strong correlation to CIMT (pooled coefficient 0.701; 95% CI 0.664-0.731). Bioinformatics analysis revealed a major role of the miRNAs, as shown by their relation with CCND1, KCTD15, SPARC, WWTR1, VEGFA genes, and multiple pathways involved in the pathogenesis of carotid atherosclerosis.Conclusion: Circulating miRNAs had excellent accuracy in detecting subclinical carotid atherosclerosis, suggesting their utilisation as novel diagnostic tools.