Leukocyte telomere length and hemostatic factors in a South African cohort: The SABPA Study

Abstract

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.