Epigenetic changes are a key hallmark of aging. These changes encompass age-associated shifts in DNA methylation and alterations in non-coding RNAs such as microRNAs (miRNAs), among other factors. Cardiovascular diseases (CVD) predominantly affect elderly individuals, being the leading cause of morbi-mortality worldwide. Systemic aging contributes to the development of CVD. Although several clocks based on DNA-methylation have been developed, the role of miRNAs in regulating these clocks, as well as the association with CVD and related-phenotypes, remains understudied in Mediterranean populations. Our aim was to explore the complex interplay between microRNAs, aging, and CVD using a multi-omics approach (genomics, epigenomics, transcriptomics and metabolomics). We genotyped at the genome-wide level participants in the PREDIMED-Valencia (high cardiovascular risk), PREDIMED-Plus-Valencia and the OBENUTIC studies (population-based cohort). In addition, we analyzed DNA methylation using the EPICv1 array and computed the main clocks (Horvath, GrimAge, PhenoAge, DNAm-TL, CausAge-Ying, DunedinPACE), and the DNAm-cardiovascular-risk-Westerman-score). Gene expression at the whole transcriptome was analyzed in a subsample using the Human 2.0 array, and the GeneChip™ miRNA 4.0 array was used to profile miRNA in blood. Additionally, plasma metabolomics was determined by NMR. First we analyzed at the miRNA-GWAS level the most significant SNPs in miRNA genes associated with incidence of CVD. Further we identified the target genes and analyzed SNPs, gene expression and methylation effect. In addition, we identified the miRNA signature associated with the main epigenetic clocks and DNAm-cardiovascular-risk-Westerman-score. Moreover, we obtained the most significant miRNAs in blood associated with cardiovascular risk and accelerated aging in this population.