Advanced age is the most important risk factor for atrial fibrillation (AF), however the mechanism remains unknown. Telomeres, regions of DNA that shorten with cell division, are considered reliable markers of biological aging. We sought to examine the association between leukocyte telomere length (LTL) and incident AF in a large population-based cohort using direct LTL measurements and genetic data. To further explore our findings, we compared atrial cell telomere length (ATL) and LTL in cardiac surgery patients.
METHODS AND RESULTS:
Mean LTL and the TERT rs2736100 single nucleotide polymorphism (SNP) were assessed as predictors of incident AF in the Cardiovascular Health Study (CHS). Among the surgical patients, within subject comparison of ATL versus LTL was assessed. Among 1639 CHS participants, we observed no relationship between mean LTL and incident AF prior to and after adjustment for potential confounders (adjusted hazard ratio [HR] 1.09; 95% CI: 0.92-1.29, p=0.299); chronologic age remained strongly associated with AF in the same model. No association was observed between the TERT rs2736100 SNP and incident AF (adjusted HR: 0.95; 95% CI: 0.88-1.04, p=0.265). In 35 cardiac surgery patients (26 with AF), ATL was longer than LTL (1.19 ± 0.20 versus 1.02 ± 0.25 [T/S ratio], p<0.001), a finding that remained consistent within the AF subgroup.
Our study revealed no evidence of an association between LTL and incident AF and no evidence of relative atrial cell telomere shortening in AF. Chronological aging independent of biological markers of aging is the primary risk factor for AF.