Telomere length dynamics do not predict subclinical atherosclerosis progression over a six-year period

Subclinical atherosclerosis (SA) burden and progression are independently associated with all-cause mortality. However, monitoring SA progression requires reliable and cost-effective biomarkers. While leukocyte telomere length (LTL) attrition has been linked to cardiovascular disease and mortality, it remains uncertain whether changes in LTL over time can predict SA progression. In this study, we conducted a longitudinal study to assess whether accelerated LTL attrition is associated with SA progression over a 6-year period in healthy middle-aged individuals. LTL was measured by high-throughput quantitative fluorescence in-situ hybridization in peripheral-blood leukocyte samples obtained 6 years apart from a sub-cohort of 1068 Progression of Early Subclinical Atherosclerosis (PESA)-study participants. SA was assessed by 3D vascular ultrasound in the carotid and femoral territories. Associations were evaluated using linear and logistic regression models. LTL parameters at baseline and after 6 years showed a positive correlation, but no significant associations were found between changes in LTL and changes in plaque volume over 6 years, either in the total sample or when stratified by sex. Likewise, no significant associations were found between LTL changes and the odds of SA progression over a 6-year period. Similar results were found when considering short telomere load changes. These findings suggest limited utility of LTL dynamics as an early biomarker for SA progression in healthy middle-aged individuals.