Leucocyte telomere length and conduction system ageing
Leucocyte telomere length and conduction system ageing
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.
van Duijvenboden, Stefan
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Nelson, Christopher P.
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Raisi-Estabragh, Zahra
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Ramirez, Julia
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Orini, Michele
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Wang, Qingning
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Aung, Nay
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Codd, Veryan
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Stoma, Svetlana
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Allara, Elias
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Wood, Angela M.
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Di Angelantonio, Emanuele
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Danesh, John
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Harvey, Nicholas C.
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Petersen, Steffen E.
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Munroe, Patricia B.
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Samani, Nilesh J.
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van Duijvenboden, Stefan
83c9a693-2d89-43fd-b5a1-cf7b1979efa3
Nelson, Christopher P.
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Raisi-Estabragh, Zahra
43c85c5e-4574-476b-80d6-8fb1cdb3df0a
Ramirez, Julia
c58fcc6f-ec54-4b49-8741-5cc481c56dc1
Orini, Michele
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Wang, Qingning
f65fb117-c5fb-4c02-8bfa-8d1769854038
Aung, Nay
709b152d-e704-4fdc-b066-7eafaa643a0b
Codd, Veryan
18ed4108-1eb4-4702-bff1-468efae23aae
Stoma, Svetlana
2a368ba8-5b88-4548-8f25-75657327bee7
Allara, Elias
6da74d5d-2cb7-4a2d-a483-2a77593fa9d2
Wood, Angela M.
0843764d-4605-495f-9047-7af14f435d96
Di Angelantonio, Emanuele
32a4e2e1-72e5-4ee9-93f2-bd78b4a53867
Danesh, John
8804d59b-cb74-4150-8e95-3ccd81e51deb
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Petersen, Steffen E.
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Munroe, Patricia B.
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Samani, Nilesh J.
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van Duijvenboden, Stefan, Nelson, Christopher P., Raisi-Estabragh, Zahra, Ramirez, Julia, Orini, Michele, Wang, Qingning, Aung, Nay, Codd, Veryan, Stoma, Svetlana, Allara, Elias, Wood, Angela M., Di Angelantonio, Emanuele, Danesh, John, Harvey, Nicholas C., Petersen, Steffen E., Munroe, Patricia B. and Samani, Nilesh J.
(2024)
Leucocyte telomere length and conduction system ageing.
Heart.
(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.
Text
heartjnl-2024-324875.full
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Accepted/In Press date: 20 November 2024
e-pub ahead of print date: 17 December 2024
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© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.
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Local EPrints ID: 497858
URI: http://eprints.soton.ac.uk/id/eprint/497858
ISSN: 1355-6037
PURE UUID: de980064-980c-43f8-bde0-5e6fa75e327a
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Date deposited: 03 Feb 2025 17:50
Last modified: 04 Feb 2025 02:39
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Contributors
Author:
Stefan van Duijvenboden
Author:
Christopher P. Nelson
Author:
Zahra Raisi-Estabragh
Author:
Julia Ramirez
Author:
Michele Orini
Author:
Qingning Wang
Author:
Nay Aung
Author:
Veryan Codd
Author:
Svetlana Stoma
Author:
Elias Allara
Author:
Angela M. Wood
Author:
Emanuele Di Angelantonio
Author:
John Danesh
Author:
Steffen E. Petersen
Author:
Patricia B. Munroe
Author:
Nilesh J. Samani
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