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

Abstract

ImportanceLonger 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.ObjectiveTo evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypesDesign, Setting, and ParticipantsThis 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.ExposureLTL.Main Outcomes and MeasuresCardiovascular imaging traits and HF.ResultsOf 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 RelevanceIn 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.

Leukocyte Telomere Length and Cardiac Structure and Function: A Mendelian Randomization Study

“…Importantly, our study confirms the previously reported causal association between LTL and LVM 16 using 2‐sample MR, which is less susceptible to bias compared with 1‐sample MR. Similarly to Aung et al, 16 who reported a nominally significant effect between LTL and LV stroke volume, there were also significant associations between LTL and LV end‐diastolic and end‐systolic volume, but these did not survive multiple testing correction.…”

“…A recent study used MR to examine the association between LTL and 7 CMR metrics. 16 The findings indicate that shorter LTL was associated with reduced left ventricular (LV) mass (LVM), reduced LV stroke volume, reduced global ventricular volume, and reduced overall ventricular size. However, only the reduction in LVM would survive multiple testing correction across the 7 explored traits.…”

“… 18 Therefore, a 2‐sample MR, where there is no overlap between the samples of the exposure and the outcome and which avoids such biases, can be used to substantiate these findings. Finally, Aung et al 16 focused on the most common CMR metrics. However, there are further metrics, such as ejection fraction, which are of broad interest and can be explored using available GWAS summary statistics in a 2‐sample MR framework.…”

Pre‐diagnostic free androgen and estradiol levels influence heart failure risk in both women and men: A prospective cohort study in the UK Biobank

“…We considered whether the observed associations between FAI, FEI, and HF risk among women and men could be potentially driven by correlations with some noteworthy biomarkers that were previously found to be related to risk of HF (online supplementary Table S3). 23,26 Among men and women, we found that FAI and FEI had low correlations with LTL, overall BHS and its constituent biomarkers.…”

Precision Measurement of Telomere Length as a Future Guide to Improve CVD Interventions

“…In a recent JAMA Cardiology publication, Aung et al performed a large population-based cross-sectional cardiovascular study of middle-aged White adults. The authors reported larger left ventricular mass, volume, and size with longer LTL, which was in turn associated with lower risk of incident heart failure.…”