Background:
Telomeres are nucleotide repeat regions at the ends of chromosomes that maintain chromosomal structural integrity and genomic stability. Telomeres from circulating leukocytes can be readily measured; mean leukocyte telomere length (LTL) tends to decrease with age, vary by race/ ethnicity and is a putative marker of cellular aging. In studies of mainly white populations, shorter LTL has been associated with cardio-metabolic risk factors and increased risks of mortality and coronary heart disease (CHD), yet it is not clear whether these findings extend to other race/ethnicity groups. We sought to assess the relationship of LTL with risks of incident CHD and total mortality in a racially diverse population of post-menopausal women.
Methods:
Using a nested case-cohort design, African American (AA) and white women with incident CHD or mortality during a maximal follow-up of 19.4 years were randomly selected from the Women’s Health Initiative. LTL from baseline blood samples was assayed by Southern blotting. Race-stratified and risk factor-adjusted Cox proportional hazards models, weighted to account for the sampling scheme, were used to estimate the hazard of CHD or mortality.
Results:
A total of 1,525 women (858 whites and 667 AA) were included in the analyses. In whites, there were 367 incident CHD (292 mortality) events, while AA experienced 269 incident CHD (265 mortality) events. Cross-sectional LTL associations (p<0.05) with age, current smoking, and US recruitment region were observed in AA, whereas in whites, LTL was associated with age, current smoking and HDL cholesterol. Whites with longer LTL at baseline were less likely to have incident CHD, HR=0.58 (95%CI: 0.40-0.84), p=0.004, yet no significant association was observed in AA, HR=1.07 (95%CI: 0.71-1.61), p=0.74. This LTL-CHD association varied significantly by race/ethnicity, p=0.028. Similar trends were observed for total mortality, with longer LTL associated with reduced hazard in whites, HR=0.70 (95%CI: 0.46-1.06), but a slightly increased hazard in AA, HR=1.10 (95%CI: 0.80-1.53), though neither association was significant. In exploratory analyses of cause-specific mortality, increased LTL was associated with an increased, but non-significant hazard of cancer mortality in both AA and whites, p=0.17 and 0.28 respectively.
Conclusion:
We describe LTL associations with incident mortality, CHD and cardiovascular risk factors in post-menopausal women; these findings appear to vary by race/ethnicity. As a marker of chronic inflammation and cellular stress, LTL is robustly associated with CHD in whites, even after adjustment for cardio-metabolic risk factors including C-reactive protein, yet it does not appear to be associated with CHD in AA. Future studies exploring these race-specific differences may be warranted.
A cohurt study on association and inflammatiory markers of cardio metabolic risk factors in pre and post menopausal women
