title: Short Telomere Load, Telomere Length, and Subclinical Atherosclerosis: The PESA Study.
abstract: Leucocyte telomere length (LTL) shortening is associated with cardiovascular ischemic events and mortality in humans, but data on its association with subclinical atherosclerosis are scarce. Whether the incidence and severity of subclinical atherosclerosis are associated with the abundance of critically short telomeres, a major trigger of cellular senescence, remains unknown.
  
  
  
  The authors conducted a cross-sectional exploration of the association between subclinical atherosclerosis burden and both average LTL and the abundance of short telomeres (%LTL<3 kb).
  
  
  
  Telomere length was assessed by high-throughput quantitative fluorescence in situ hybridization in circulating leukocytes from 1,459 volunteers without established cardiovascular disease (58% men, 40 to 54 years of age) from the PESA (Progression of Early Subclinical Atherosclerosis) study. Subclinical atherosclerosis was evaluated by coronary artery calcium scan and 2-dimensional/3-dimensional ultrasound in different aortic territories. Statistical significance of differences among multiple covariates was assessed with linear regression models. Independent associations of telomere parameters with plaque presence were evaluated using general linear models.
  
  
  
  In men and women, age was inversely associated with LTL (Pearson's r = -0.127, p < 0.001) and directly with %LTL<3 kb (Pearson's r = 0.085; p = 0.001). Short LTL reached statistical significance as a determinant of total and femoral plaque in men, but not in women. However, this association was not sustained after adjustment for age or additional adjustment for cardiovascular risk factors. No significant independent association was found between %LTL<3 kb and plaque burden. Serum-oxidized low-density lipoprotein levels were directly associated with %LTL<3 kb in men (p = 0.008) and women (p < 0.001).
  
  
  
  In a cross-sectional study of a middle-aged population, average LTL and short telomere load are not significant independent determinants of subclinical atherosclerosis. Longitudinal follow-up of PESA participants will assess long-term associations between telomere length and progression of subclinical atherosclerosis.
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Fernández-Alvira
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Mount Sinai School of Medicine, New York, New York. Electronic address: valentin.fuster@mssm.edu.
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Dorado
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Nora
authors.initials: N
authors.lastname: Soberón
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Flores
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Gallardo
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Pocock
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Blasco
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. Electronic address: vandres@cnic.es.
authors.forename: Vicente
authors.initials: V
authors.lastname: Andrés
mesh_terms: D000328:Adult; D000367:Age Factors; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000235:genetics*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007962:Leukocytes / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000235:genetics; D016615:Telomere; D059506:Telomere Shortening; D014463:Ultrasonography
chemical_list: D008077:Lipoproteins, LDL
keywords: cardiovascular disease; leukocyte telomere length; short telomeres