Introduction: MicroRNAs (miRs) are detectable in circulation and play a role in gene regulation. Secretion of cardiac-specific or enriched miRs may reflect pathological cardiac remodeling and enhanced susceptibility to arrhythmias such as atrial fibrillation (AF). We examined associations between plasma miRs with left atrial function index (LAFI), an echocardiographic marker of pathological atrial structural and functional remodeling. We then sought to determine if plasma miRNAs associated with LAFI were related to AF.
Methods: Our analysis included 1840 Framingham Heart Study (FHS) Offspring Cohort study participants who attended Examination 8 (2005-2008), consented to undergo genomic or transcriptomic profiling, and had LAFI measured from stored echocardiographic images. We quantified expression of 340 miRNAs from plasma using high-throughput quantitative reverse-transcriptase PCR (RT-qPCR) and related plasma miRNA levels to LAFI and then AF. Models were adjusted for the CHARGE-AF risk score and Bonferroni correction for multiple testing was employed.
Results: The mean age of the FHS Offspring participants included in the analysis was 66.6±9.3 years, 54% were women, 8% had AF at the time of examination, 6% developed AF over 7 years of follow-up, and the mean LAFI was 31.2 ± 14.2. We identified 73 miRNAs that were associated with LAFI (p<0.0001). Four also were associated with AF (p<0.05): miR-106b (17.99 vs 17.31, OR 1.18), miR-26a-5p (17.58 vs 17.34, OR 1.16), miR-324a-3p (19 vs 18.60, OR 1.03), miR-20a-5p (17.08 vs 16.87, OR 1.14).
Conclusions: In a community-based cohort with moderately prevalent cardiovascular risk factors and AF, plasma levels of several miRNAs associated with heart disease were associated with LAFI and AF. Our study builds on prior work identifying miRNAs associated with AF and suggests that key miRNAs may mediate their effect through pathological left atrial structural and functional remodeling.