Circulating miR-4537 was significantly associated with incident heart failure (HR 1.31; 95% CI 1.14-1.49), while several other miRNAs exhibited age-modified associations with heart failure risk.
Cohort (n=1,897)
Are circulating microRNAs associated with incident heart failure in the general population?
Circulating miRNAs, particularly miR-4537, exhibit age-dependent associations with incident heart failure, highlighting their potential as mechanistic predictive biomarkers.
Effect estimate: HR 1.31 (95% CI 1.14-1.49)
Abstract Background Circulating microRNAs (miRNAs) have been suggested as potential promising biomarkers for heart failure (HF), but their age-dependent effects on HF risk remain unclear. Purpose We aimed to investigate associations between circulating miRNAs and incident HF in a population-based cohort, and to assess whether age modifies these associations through miRNA-age interaction analysis. Methods We analyzed plasma miRNA abundance in the population-based cohort using a targeted miRNA-sequencing approach by the HTG EdgeSeq Whole Transcriptome Assay. Of 2,083 measured miRNAs, 591 were well expressed and evaluated for association with incident HF using Cox proportional hazards models adjusted for demographic, clinical, and technical factors. Age-miRNA interactions were formally tested using likelihood ratio tests. Target genes of significant miRNAs were explored through integrated miRWalk-Enrichr pathway analyses. Results Of the 1,897 participants free of HF at baseline, mean (SD) age was 71.38 ±7.43 years. Over a median follow-up of 14.2 years, 316 HF events occurred. Model 1, adjusted only for technical variables (plate number and well position), identified 197 miRNAs associated with incident HF (FDR 0.05). After multivariable adjustment, only miR-4537 remained significantly associated with incident HF (HR= 1.31, 95% CI: 1.14-1.49). Several miRNAs, including let-7i-5p, miR-21-5p, miR-15b-5p, and miR-199a-3p, showed age-modified associations with HF risk. Predicted target genes of the identified miRNAs (n = 270) were enriched in pathways related to adrenergic signaling, apoptosis, calcium signaling, and TNF signaling, implicating remodeling and inflammatory mechanisms in HF development. Conclusions Several circulating miRNAs exhibit age-dependent associations with incident HF and highlight molecular pathways linked to cardiac remodeling and stress response. These findings may provide novel insights into the biological mechanisms of HF onset and support the potential of circulating miRNAs as mechanistic predictive biomarkers for HF in the general population.Significant interaction and main effectsFor image description, please refer to the figure legend and surrounding text. Marginal age-miRNA interaction effectsFor image description, please refer to the figure legend and surrounding text.
Farzaneh et al. (Mon,) conducted a cohort in Incident heart failure (n=1,897). Circulating microRNAs was evaluated on Incident heart failure (HR 1.31, 95% CI 1.14-1.49). Circulating miR-4537 was significantly associated with incident heart failure (HR 1.31; 95% CI 1.14-1.49), while several other miRNAs exhibited age-modified associations with heart failure risk.