Investigating the relationship between the leukocyte telomere length and the incidence of atrial fibrillation: a study utilizing data from the UK Biobank

Abstract Background Atrial fibrillation (AF) is a common cardiac arrhythmia linked to a higher risk of stroke, heart failure, and death. Telomeres are DNA-protein complexes located at the end of chromosomes, and telomere length is known to be associated with biological aging and age-related disease. However, the relationship between leukocyte telomere length (LTL) and AF has been inconsistent in the literature. This study aims to clarify the relationship between LTL and AF risk using UK Biobank data and to examine the link between AF and both biological and chronological aging. Methods The UK Biobank cohort of 502,421 participants aged 40-70 was recruited across 22 UK centers from 2006-2010. After excluding i) missing values (n=32,219), ii) previous AF history (n=6,746) and iii) valvular heart disease (n=3,204), a total of 460,252 participants without AF (median age, 58.0 [interquartile range (IQR), 50.0–64.0] years; 208,543 [45.3%] male) were included. Participants were categorized into four groups based on the LTL, as determined by the adjusted T/S ratio from whole blood test. To investigate the intermediate phenotype prior to the onset of atrial fibrillation, we compared each group with LA maximum volume, LA minimum volume, LA stroke volume, and LA ejection fraction. Throughout the follow-up period, new-onset atrial fibrillation was documented. Survival analysis was conducted using Kaplan-Meier analysis and Cox proportional regression analysis. Results Among 460,252 participants without AF, the new-onset AF group had more comorbidities and lower mean LTL. Groups with shorter LTL tend to be older, and new-onset AF is more prevalent in these groups. Additionally, the incidence of comorbidities is generally higher in the groups with shorter LTL. It was observed that as the LTL shortens, the LA stroke volume decreases. The Kaplan-Meier curve demonstrated that shorter LTL correlated with increased new-onset AF risk. (Log-rank P < 0.001) However, upon examination through a multivariable univariate Cox proportional regression analysis, telomere length did not show as an independent risk factor for new-onset AF. (aHR 1.00, 95% CI 1.00-1.00, P=0.099, Adjusted T/S ratio). Conclusion Even though the incidence of AF increased as LTL shortened, there was no relationship between LTL and new-onset AF when the covariate was adjusted.