Leukocyte telomere length and circulating MiRNAs in relation to cardiovascular outcomes in older adults

Background Telomere shortening and circulating microRNAs (miRNAs) are recognized molecular hallmarks of biological aging. Both have been implicated in cardiovascular disease (CVD), yet their potential interplay and combined contribution to cardiovascular vulnerability, and potential clinical relevance in older adults remain unclear. Methods We investigated the associations of leukocyte telomere length (LTL) and five circulating miRNAs (miR-21-5p, miR-23a-3p, miR-34a-5p, miR-92a-3p, and miR-486-5p), previously linked to telomere maintenance and cardiovascular pathology, with CVD outcomes in a cohort of 624 elderly individuals (aged 60–98 years). LTL was measured in all participants, while miRNAs were quantified in a subset of 210 individuals. Logistic regression analyses adjusted for demographic and clinical covariates were applied to assess associations of LTL and miRNAs with overall CVD and specific conditions, including atrial fibrillation (AF), heart failure (HF), ischemic cardiomyopathy (ICM), and stroke. Results Shorter LTL was independently associated with higher AF risk (OR = 0.25, 95% CI 0.11–0.65, p = 0.004) but not with other CVD outcomes. In AF, miR-23a-3p and miR-92a-3p were not individually associated with risk but showed opposite directions of association when included together in fully adjusted models (miR-23a-3p protective; miR-92a-3p risk-enhancing), independently of LTL. Lower miR-92a-3p levels were also associated with stroke risk, whereas associations of miR-34a-5p with HF and miR-486-5p with ICM were attenuated after adjustment. No significant correlations were found between LTL and circulating miRNAs. Conclusions Shorter telomeres and distinct expression patterns of the analysed miRNAs were independently associated with specific cardiovascular outcomes in older adults, suggesting that these biomarkers reflect complementary molecular aspects of cardiovascular vulnerability in aging. While their addition to conventional risk factors did not significantly improve risk discrimination, they may provide mechanistic insights into biological processes underlying cardiovascular risk in aging populations.