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

Abstract

Background Existing research demonstrates the association of shorter leukocyte telomere length with increased risk of age‐related health outcomes including cardiovascular diseases. However, the direct causality of these relationships has not been definitively established. Cardiovascular aging at an organ level may be captured using image‐derived phenotypes of cardiac anatomy and function. Methods and Results In the current study, we use 2‐sample Mendelian randomization to assess the causal link between leukocyte telomere length and 54 cardiac magnetic resonance imaging measures representing structure and function across the 4 cardiac chambers. Genetically predicted shorter leukocyte telomere length was causally linked to smaller ventricular cavity sizes including left ventricular end‐systolic volume, left ventricular end‐diastolic volume, lower left ventricular mass, and pulmonary artery. The association with left ventricular mass ( β  =0.217, P false discovery rate =0.016) remained significant after multiple testing adjustment, whereas other associations were attenuated. Conclusions Our findings support a causal role for shorter leukocyte telomere length and faster cardiac aging, with the most prominent relationship with left ventricular mass.