Association Between Plasma microRNA Levels and Major Adverse Cardiovascular Events in Participants from an Epidemiological Cohort

Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular disease (CVD) and three-point major adverse cardiovascular events (3P-MACE): CVD death, non-fatal myocardial infarction (MI), and non-fatal stroke. The associations between plasma miRNA levels and 3P-MACE in a prospective cohort from an epidemiological study were evaluated. This nested case-control study included 479 participants: 166 cases with 3P-MACE and 313 controls matched individually for sex, exact baseline age, and region of residence. Median follow-up was 10.4 years [7.0; 11.7]. Total RNA was isolated from EDTA plasma using the miRNeasy Serum/Plasma Advanced Kit. Libraries were prepared with the QIAseq miRNA UDI Library Kit and sequenced on a NextSeq 550 (1 × 75 bp). After adjustment for six and twelve preanalytical and clinical covariates, eleven and five differentially expressed (DE) miRNAs retained significant associations with 3P-MACE or CVD death, respectively. Although these findings support plasma miRNA profiles as potential MACE biomarkers, all DE miRNAs remain exploratory. Further studies in larger independent populations with cross-validation are required before integration with traditional risk markers to predict future MACE.