Leucocyte telomere length and conduction system ageing

Stefan van Duijvenboden; Christopher P Nelson; Zahra Raisi-Estabragh; Julia Ramirez; Michele Orini; Qingning Wang; Nay Aung; Veryan Codd; Svetlana Stoma; Elias Allara; Angela M Wood; Emanuele Di Angelantonio; John Danesh; Nicholas C Harvey; Steffen E Petersen; Patricia B Munroe; Nilesh J Samani

doi:10.1136/heartjnl-2024-324875

Leucocyte telomere length and conduction system ageing

Heart. 2024 Dec 17:heartjnl-2024-324875. doi: 10.1136/heartjnl-2024-324875. Online ahead of print.

Authors

Stefan van Duijvenboden^#^{1

2

3}, Christopher P Nelson^#^{4

5}, Zahra Raisi-Estabragh^{2

6

7}, Julia Ramirez^{2

8

9}, Michele Orini³, Qingning Wang⁴, Nay Aung^{2

6

7}, Veryan Codd⁴, Svetlana Stoma⁴, Elias Allara^{10

11

12}, Angela M Wood^{10

11

12}, Emanuele Di Angelantonio^{10

11

12

13}, John Danesh^{10

11

12

14}, Nicholas C Harvey^{15

16}, Steffen E Petersen^{2

6

7}, Patricia B Munroe^{2

6}, Nilesh J Samani⁴

Affiliations

¹ Nuffield Department of Population Health, University of Oxford, Oxford, UK stefan.vanduijvenboden@ndph.ox.ac.uk.
² William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
³ Institute of Cardiovascular Science, UCL, London, UK.
⁴ Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
⁵ NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
⁶ NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, UK.
⁷ Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
⁸ Aragon Institute of Engineering Research, University of Zaragoza, Zaragoza, Spain.
⁹ Biomedical Research Networking Center for Bioengineering Biomaterials and Nanomedicine, University of Zaragoza, Zaragoza, Spain.
¹⁰ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹¹ Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.
¹² NIHR Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.
¹³ Health Data Science Research Centre, Human Technopole, Milan, Italy.
¹⁴ Department of Human Genetics, Wellcome Sanger Institute, Hinxton, UK.
¹⁵ MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, Hampshire, UK.
¹⁶ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.

^# Contributed equally.

PMID: 39689933
DOI: 10.1136/heartjnl-2024-324875

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.

Keywords: Electrophysiology; Epidemiology; Genetics.