Rationale: Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth and/or a faster LTL attrition thereafter. LTL represents TL in the highly proliferative hematopoietic system, while TL in skeletal muscle (M) represents a minimally replicative tissue. Objective: We measured LTL and MTL in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD. Methods and Results: Our Discovery Cohort comprised 259 individuals aged 63±14 years (mean±SD), undergoing surgery with (n=131) or without (n=128) clinical manifestation of ASCVD. In all subjects, MTLA (MTL adjusted for muscle biopsy site) was longer than LTL and the LTL-MTLA gap similarly widened with age in ASCVD patients and controls. Age- and sex-adjusted LTL (p=0.005), but not MTLA (p=0.90), was shorter in patients with ASCVD than controls. The TL gap between leukocytes and muscle (LTL-MTLA) was wider (p=0.0003) and the TL ratio between leukocytes and muscle (LTL/MTLA) was smaller (p=0.0001) in ASCVD than in controls. Findings were replicated in a cohort comprising 143 individuals. Conclusions: This first study to apply the 'blood-and-muscle' TL model shows more pronounced LTL attrition in ASCVD patients than controls. The difference in LTL attrition was not associated with age during adulthood suggesting that increased attrition in early life is more likely to be a major explanation of the shorter LTL in ASCVD patients.Clinical Trial Registration: NCT02176941.
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 March 2020.
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#6,547,881
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Outputs of similar age from Circulation Research
#34
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Altmetric has tracked 33,779,198 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
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