A blood-based microRNA signature may reveal coronary plaque instability without invasive imaging. In two independent Indian cohorts totaling 31 CAD patients and 12 controls, miR-664a-3p — measured from peripheral blood mononuclear cells — was significantly downregulated in CAD (log2 fold-change ≈ −1.02 to −1.04, p<0.01 at both sites). Critically, lower miR-664a-3p expression correlated inversely with both total plaque burden and necrotic core volume, the very features that define rupture-prone vulnerable plaques. ROC analysis yielded AUCs of 0.842 and 0.881 across sites, suggesting meaningful discriminative power. Pathway enrichment linked miR-664a-3p targets to IL-17 and TNF inflammatory signaling, mechanistically connecting PBMC immune activation to plaque vulnerability.
This is noteworthy because identifying high-risk plaques currently requires intravascular ultrasound with virtual histology — expensive, operator-dependent, and invasive. A validated blood miRNA biomarker could transform risk stratification, especially in resource-limited settings. The IL-17/TNF pathway connection aligns with growing evidence that systemic immune dysregulation drives local plaque inflammation, reinforcing the immune-atherosclerosis axis. However, the cohort is very small (n=43 total), limiting statistical confidence and generalizability beyond South Asian populations. The cross-sectional design prevents causal inference, and replication in larger, ethnically diverse prospective cohorts is essential. As a preprint posted on medRxiv and not yet peer-reviewed, these findings should be treated as preliminary — analytical choices and effect sizes may shift after independent scrutiny. Still, the dual-site replication of both direction and magnitude is an encouraging signal worth tracking.
