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. 2023 Sep 1;8(9):808-815.
doi: 10.1001/jamacardio.2023.2167.

Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure

Nay Aung  1   2   3 , Qingning Wang  4   5 , Stefan van Duijvenboden  1   2   6 , Richard Burns  7 , Svetlana Stoma  4 , Zahra Raisi-Estabragh  1   2   3 , Selda Ahmet  3 , Elias Allara  8   9   10 , Angela Wood  8   9   10   11   12   13 , Emanuele Di Angelantonio  8   9   10   11   12   14 , John Danesh  8   9   10   11   12   15 , Patricia B Munroe  1   2 , Alistair Young  7 , Nicholas C Harvey  16   17 , Veryan Codd  4 , Christopher P Nelson  4 , Steffen E Petersen  1   2   3 , Nilesh J Samani  4
Affiliations

Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure

Nay Aung et al. JAMA Cardiol. .

Abstract

Importance: Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear.

Objective: To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.

Design, setting, and participants: This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023.

Exposure: LTL.

Main outcomes and measures: Cardiovascular imaging traits and HF.

Results: Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume.

Conclusions and relevance: In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Danesh has received grants from the British Heart Foundation during the conduct of the study; serves on scientific advisory boards for AstraZeneca, Novartis, Sanofi, and UK Biobank; is an honorary consultant for Cambridge University Hospital NHS Foundation Trust; and is a member of the Wellcome Trust Sanger Institute, Medical Research Council International Advisory Group, Medical Research Council High Throughput Science ‘Omics Panel, and Wellcome Sanger Institute outside the submitted work. Dr Harvey has received personal fees from UCB, Amgen, and Kyowa Kirin outside the submitted work. Dr Codd has received grants from the Medical Research Council during the conduct of the study. Dr Petersen has received personal fees from Circle Cardiovascular Imaging outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Sample Selection Flowchart
CMR indicates cardiovascular magnetic resonance; LA, left atrial; LVM, left ventricular mass; LVMVR, left ventricle mass to end-diastolic volume ratio; LVSV, left ventricular stroke volume; LTL, leukocyte telomere length; RA, right atrial; RVSV, right ventricular stroke volume; UKB, UK Biobank; WBC, white blood cell count.
Figure 2.
Figure 2.. Longitudinal Association Between Leukocyte Telomere Length (LTL) and Incident Heart Failure
BMI indicates body mass index; HR, hazard ratio.
Figure 3.
Figure 3.. Mendelian Randomization Associations Between Leukocyte Telomere Length (LTL) and Cardiac Imaging Traits and Heart Failure (HF)
LA, left atrial; LV indicates left ventricular; LVSV, left ventricular stroke volume; MR, mendelian randomization; RVSV, right ventricular stroke volume.
See this image and copyright information in PMC

References

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