title: Leukocyte telomere length and hemostatic factors in a South African cohort: the SABPA Study.
abstract: BACKGROUND
  Incident atherothrombotic disease is predicted by leukocyte telomere length, a marker of biological age, and hemostatic factor levels, indicating a hypercoagulable state. We hypothesized that shorter telomeres are associated with elevated circulating levels of hemostatic factors.
  
  
  METHODS
  We examined 171 South African (black) and 182 Caucasian (white) schoolteachers (mean age ± standard deviation, 48.5 ± 9.0 years; 50.4% women). Levels of fibrinogen, von Willebrand factor antigen (VWF:Ag), D-dimer and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) were measured in plasma, and values were log-transformed before analysis. Relative average telomere length (content of telomere PCR product/content of human β-globin PCR product ratio, i.e. telomere/single-copy gene ratio) was assessed with multiplex quantitative real-time PCRs. Multivariate analyses included demographics, metabolic factors, health behavior, and medication.
  
  
  RESULTS
  Africans had shorter mean telomere length (0.82, 95% confidence interval [CI] 0.79-0.86 vs. 1.07, 95% CI 1.04-1.10) and higher fibrinogen (B = 0.085, 95% CI 0.061-0.109) and PAI-1:Ag (B = 0.255, 95% CI 0.206-0.303) levels, but lower VWF:Ag levels (B = - 0.059, 95% CI - 0.089 to - 0.028), than Caucasians. Shorter telomeres were associated with higher fibrinogen (B = - 0.045, 95% CI - 0.088 to - 0.001), VWF:Ag (B = - 0.137, 95% CI - 0.193 to - 0.081) and D-dimer (B = - 0.201, 95% CI - 0.377 to - 0.025) levels, conditional on ethnicity. An interaction emerged between ethnicity and telomere length for VWF:Ag level; that is, shorter telomeres were associated with higher VWF:Ag levels in Caucasians (B = - 0.170, 95% CI - 0.232 to - 0.108) but not in Africans.
  
  
  CONCLUSIONS
  Shorter telomeres were associated with increased levels of several hemostatic factors after adjustment for confounding variables, whereby ethnicity partially moderated this effect. A relationship between accelerated biological aging and hypercoagulability might contribute to the risk of premature atherothrombotic events.
authors.affiliation: Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland; Department of Psychosomatic Medicine, Clinic Barmelweid, Barmelweid, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: von Känel
authors.forename: N T
authors.initials: NT
authors.lastname: Malan
authors.forename: M
authors.initials: M
authors.lastname: Hamer
authors.forename: F H
authors.initials: FH
authors.lastname: van der Westhuizen
authors.forename: L
authors.initials: L
authors.lastname: Malan
mesh_terms: D000328:Adult; D000465:Algorithms; D044383:Black People; D002318:Cardiovascular Diseases / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D015994:Incidence; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry; D012984:Software; D013019:South Africa; D016615:Telomere / Q000648:ultrastructure*; D014841:von Willebrand Factor / Q000737:chemistry
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C036309:fibrin fragment D; D014841:von Willebrand Factor; D005340:Fibrinogen
keywords: blood coagulation; cardiovascular disease; ethnicity; fibrinolysis; genetics