Abstract 504: Telomere-based Assessment of Biological Age in Patients with Advanced Vascular Disease

Abstract

Introduction: Ascertaining the biological age of patients with advanced vascular disease could advance risk assessment and management. The extent to which telomeres shorten in leukocytes could be a marker of biological age because it reflects the accumulation of replication stresses imposed on leukocyte progenitors. However, because of wide, genetic variability in leukocyte telomere length (TL), a single leukocyte TL measurement does not reliably indicate telomere shortening. Hypothesis: We hypothesized that the difference in length of telomeres in “non-replicating” muscle-rich tissue and that of circulating leukocytes provides a patient-specific index of telomere shortening in patients with advanced vascular disease. Methods: TL in leukocytes, skeletal muscle, and right atrial cardiac muscle were measured from 134 patients undergoing coronary or thoracic aortic surgery, using quantitative polymerase chain reaction. Relationships between leukocyte TL or the muscle-leukocyte TL difference (ΔTL) and early post-operative outcomes were tested using Cox proportional hazard and binary logistic regression analyses. Results: Telomeres in cardiac muscle and skeletal muscle were significantly longer than those in leukocytes (p<0.001) but with synchrony among these measures in an individual (p<0.001). Leukocyte TL and skeletal muscle TL inversely correlated with chronological age (p<0.001) however cardiac muscle TL did not (p=0.283). There was no relationship between leukocyte TL and either the post-operative length of stay in the intensive care unit (ICU) or major complications. However, cardiac-leukocyte ΔTL was associated with length of ICU stay (hazard ratio 1.26, p=0.043) and post-operative complications (odds ratio 3.03, p=0.029). Conclusions: Right atrium-leukocyte ΔTL provides an index of telomere shortening and may inform outcomes in patients with advanced vascular disease. This two-component telomere measurement may reflect the biological age of individuals with chronic vascular disease.