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, Samani Nilesh J
Nuffield Department of Population Health, University of Oxford, Oxford, UK
William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Heart. 2025 Mar 13;111(7):314-320. doi: 10.1136/heartjnl-2024-324875.
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.
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).
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.
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.
心脏传导系统的退化是心脏衰老的重要表现。细胞衰老伴随着端粒缩短,端粒长度(TL)常被视为生物衰老的标志物,可能会提供超出实际年龄的关于传导疾病的信息。因此,我们试图在一个基于人群的大型队列中评估白细胞端粒长度(LTL)与心脏传导系统两个相关但不同方面之间的关联:心电图传导测量指标(PR间期和QRS时限)以及起搏器植入事件。
在英国生物银行中,我们分别从59868名和62266名参与者的信号平均心电图波形中测量了PR间期和QRS时限。使用420071名参与者的医院病历数据确定起搏器植入事件。在针对潜在混杂因素进行调整的(Cox)多变量回归分析中评估与LTL的关联。通过孟德尔随机化(MR)研究LTL的假定因果效应。
平均PR间期和QRS时限分别为144.2毫秒(±20.4)和92.3毫秒(±7.8),在中位随访期13.6年(四分位间距1.5年)内有7169例(1.7%)起搏器植入事件。LTL与PR间期显著相关(LTL每缩短1个标准差,PR间期延长0.19毫秒(95%置信区间:0.03至0.35),p = 0.021),但与QRS时限无关。在调整年龄、性别和心血管危险因素后,较短的LTL仍与起搏器植入事件风险增加相关(LTL每降低1个标准差的风险比:1.03(95%置信区间:1.01至1.06),p = 0.012)。MR分析显示较短的LTL与较长的PR间期和较高的起搏器植入风险之间存在关联趋势,但可能因效能不足而无法确定。
较短的LTL与房室传导延长和起搏器植入显著相关,且可能存在因果关系,独立于传统心血管危险因素。我们的研究结果支持进一步研究以探索衰老在实际年龄之外对心脏传导的作用。