Abstract
BACKGROUND: Deterioration of the cardiac conduction system is an important manifestation of cardiac ageing. Cellular ageing is accompanied by telomere shortening and telomere length (TL) is often regarded as a marker of biological ageing, potentially adding information regarding conduction disease over and above chronological age. We therefore sought to evaluate the association between leucocyte telomere length (LTL) on two related, but distinct aspects of the cardiac conduction system: ECG measures of conduction (PR interval and QRS duration) and incident pacemaker implantation in a large population-based cohort. METHODS: In the UK Biobank, we measured PR interval and QRS duration from signal-averaged ECG waveforms in 59 868 and 62 266 participants, respectively. Incident pacemaker implantation was ascertained using hospital episode data from 420 071 participants. Associations with LTL were evaluated in (Cox) multivariable regression analyses adjusted for potential confounders. Putative causal effects of LTL were investigated by mendelian randomisation (MR). RESULTS: Mean PR interval and QRS duration were 144.2 ms (± 20.4) and 92.3 ms (± 7.8), respectively, and there were 7169 (1.7%) incident pacemaker implantations, during a median follow-up period of 13.6 (IQR 1.5) years. LTL was significantly associated with PR interval (0.19 ms (95% CI: 0.03 to 0.35), per 1 SD shorter LTL, p=0.021), but not QRS duration. After adjusting for age, sex and cardiovascular risk factors, shorter LTL remained associated with an increased risk for incident pacemaker implantation (HR per SD decrease in LTL: 1.03 (95% CI: 1.01 to 1.06), p=0.012). MR analysis showed a trend towards an association of shorter LTL with longer PR interval and higher risk of pacemaker implantation but was likely to be underpowered. CONCLUSIONS: Shorter LTL was significantly, and possibly causally, associated with prolongation of atrioventricular conduction and pacemaker implantation, independent of traditional cardiovascular risk factors. Our findings support further research to explore the role of ageing on cardiac conduction beyond chronological age.