A meta-analysis of the relationship between circulating microRNA-126 and coronary artery disease

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Circulating microRNA-126 (miR-126) has been implicated in vascular biology, yet evidence regarding its association with CAD remains inconsistent. Previous studies were limited by small sample sizes and methodological variability. This systematic review and meta-analysis aimed to quantify differences in circulating miR-126 levels between CAD patients and healthy controls and to explore potential sources of heterogeneity.

The search strategy was developed according to the PICO framework and adapted to database-specific controlled vocabulary (e.g.,MeSH).A comprehensive literature search was conducted across seven databases (PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP) from database inception to December 31, 2024. A supplementary search was subsequently conducted from January 1, 2025, to March 15, 2026. Eligible studies reporting circulating miR-126 levels in CAD patients and controls were included. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup and sensitivity analyses were conducted to investigate methodological and clinical sources of heterogeneity, and publication bias was evaluated.

A total of 19 studies were included. Of these, 11 provided complete overall CAD-versus-control data and were included in the primary meta-analysis, while 12 contributed subgroup-level data and were included in subgroup analyses or descriptive subgroup evidence. Circulating miR-126 levels were significantly lower in CAD patients compared with controls (SMD = - 2.51; 95% CI: -3.44 to - 1.58), with substantial heterogeneity (I² = 97.8%). Subgroup analyses indicated that heterogeneity was primarily driven by methodological differences, particularly measurement scale and normalization methods. Sensitivity analyses confirmed the robustness of the findings, with consistent direction and statistical significance across all analyses.

Circulating miR-126 is consistently reduced in CAD patients compared with healthy controls. While the magnitude of effect varies across studies, this association appears robust and biologically plausible. Future large-scale, multicenter studies using standardized measurement protocols are warranted to validate these findings and explore their potential clinical relevance.

CRD4202563309.