Coronary macrovascular and microvascular involvement and their association with distinct circulating microRNA...

Circulating microRNAs (miRNAs) may represent promising candidate biomarkers of chronic coronary syndrome (CCS). Nevertheless, their relationship with patterns of coronary dysfunction remains underexplored. This study aims to identify plasma miRNA profiles associated with macrovascular and/or microvascular patterns of coronary dysfunction.

Prospective, multicenter cohort study that enrolled consecutive patients with chest pain of presumed coronary origin who were referred for invasive physiological evaluation, which included measurement of fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR). Based on FFR and IMR values, patients were categorized into four groups: normal coronary indices; isolated microvascular dysfunction; isolated macrovascular dysfunction; and combined macrovascular and microvascular dysfunction. miRNA profiling was performed using RT-qPCR. An unsupervised hierarchical clustering approach was applied to identify miRNA-based clusters (miRNotypes).

128 patients were included and were distributed across study groups as follows: 37.5% normal coronary indices, 23.4% isolated microvascular dysfunction, 19.5% isolated macrovascular dysfunction; and 19.5% combined macro- and microvascular dysfunction. Plasma miRNA profiles in patients with isolated macrovascular dysfunction differed significantly from those with normal indices and microvascular dysfunction. miR-21-5p and miR-92a-3p were independently associated with coronary macrovascular dysfunction. Incorporating a 3-miRNA signature (miR-17-5p, miR-21-5p, miR-92a-3p) was associated with improved reclassification metrics when added to a clinical model (IDI = 0.082, p-value = 0.002; NRI = 0.576, p-value<0.001). Unsupervised clustering revealed three distinct plasma miRNotypes associated with specific patterns of coronary dysfunction.

In patients with suspected CCS, circulating miRNA profiles differ between patterns of coronary involvement. Plasma miRNA-based molecular phenotyping could potentially complement existing clinical tools aiding in the identification of coronary macrovascular dysfunction.