Bendix Samarta Witarto, Visuddho Visuddho, Fan Maitri Aldian, Maxwell Salvador Surya Atmaja, Melissa Valentina Ariyanto, Andro Pramana Witarto, Citrawati Dyah Kencono Wungu, Hendri Susilo, Mochamad Yusuf Alsagaff, Mohammad Saifur Rohman
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. © 2023 The Authors
Medical Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia; Department of Cardiology and Vascular Medicine, Universitas Airlangga Hospital, Surabaya, Indonesia; Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia; Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Brawijaya, Malang, Indonesia