4.6 Article

Telomere Length and Vascular Phenotypes in a Population-Based Cohort of Children and Midlife Adults

Journal

Publisher

WILEY
DOI: 10.1161/JAHA.119.012707

Keywords

aging; arterial stiffness; atherosclerosis; carotid intima-media thickness; CheckPoint (Child Health Check Point) study; LSAC (Longitudinal Study of Australian Children); pulse-wave velocity

Funding

  1. National Health and Medical Research Council (NHMRC) of Australia [1041352, 1109355]
  2. Royal Children's Hospital Foundation [2014-241]
  3. Murdoch Children's Research Institute (MCRI)
  4. University of Melbourne
  5. National Heart Foundation of Australia [100660]
  6. Financial Markets Foundation for Children [2014-055, 2016-310]
  7. Victorian Government's Operational Infrastructure Support Program
  8. NHMRC Postgraduate Scholarship [1115167]
  9. NHMRC Senior Research Fellowship [1045161, 1046518]
  10. MCRI Clinician Scientist Award
  11. NHMRC Early Career Fellowship [1091124]
  12. National Heart Foundation Postdoctoral Fellowship [101239]
  13. Federal Research Grant of Finland
  14. Juho Vainio Foundation
  15. NHMRC Fellowship [1064629]
  16. Honorary Future Leader Fellowship of the National Heart Foundation of Australia [100369]
  17. Cure Kids New Zealand
  18. National Health and Medical Research Council of Australia [1115167] Funding Source: NHMRC

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Background-Telomere length has been inversely associated with cardiovascular disease in adulthood, but its relationship to preclinical cardiovascular phenotypes across the life course remains unclear. We investigated associations of telomere length with vascular structure and function in children and midlife adults. Methods and Results-Population-based cross-sectional Check Point (Child Health CheckPoint) study of 11- to 12-year-old children and their parents, nested within the LSAC (Longitudinal Study of Australian Children). Telomere length (telomeric genomic DNA [T]/beta-globin single-copy gene [S] [T/S ratio]) was measured by quantitative polymerase chain reaction from blood-derived genomic DNA. Vascular structure was assessed by carotid intima-media thickness, and vascular function was assessed by carotid-femoral pulse-wave velocity and carotid elasticity. Mean (SD) T/S ratio was 1.09 (0.55) in children (n=1206; 51% girls) and 0.81 (0.38) in adults (n 1343; 87% women). Linear regression models, adjusted for potential confounders, revealed no evidence of an association between T/S ratio and carotid intima-media thickness, carotid-femoral pulse-wave velocity, or carotid elasticity in children. In adults, longer telomeres were associated with greater carotid elasticity (0.14% per 10-mm Hg higher per unit of T/S ratio; 95% CI, 0.04%-0.2%; P=0.007), but not carotid intima-media thickness (-0.9 mu m; 95% CI, -14 to 13 mu m; P=0.9) or carotid-femoral pulse-wave velocity (-0.10 m/s; 95% CI, -0.3 to 0.07 m/s; P=0.2). In logistic regression analysis, telomere length did not predict poorer vascular measures at either age. Conclusions-In midlife adults, but not children, there was some evidence that telomere length was associated with vascular elasticity but not thickness. Associations between telomere length and cardiovascular phenotypes may become more evident in later life, with advancing pathological changes.

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