Telomere Attrition and Cardiovascular Disease

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Telomeres, specialized structures at chromosomal ends, are involved in replicative senescence of cultured somatic cells. Telomere length has been implicated as a possible biomarker of biological aging and is associated with age-related diseases, including essential hypertension, diabetes and atherosclerosis. These disorders may reflect heightened states of oxidative stress and inflammation, which are factors expected to increase telomere erosion in white blood cells (WBCs). Preliminary data have demonstrated measures of vascular disease to be associated with shortened telomeres in older adults. Data from the Cardiovascular Health Study (CHS), a longitudinal cohort of adults over age 65 initially recruited in 1989/90 and followed for up to ten annual clinic exams, will be evaluated for (1) associations between WBC telomere length and incidence of cardiovascular disease (CVD) including myocardial infarction, stroke and peripheral vascular disease; (2) risk of total and cause-specific mortality associated with shortened telomeres; and (3) rates of telomere attrition over time in relation to vascular disease status. A total of 1500 CHS participants will be randomly selected for these analyses with DMA availability as the only exclusion criterion. Using the Southern method for determination of telomere restriction fragments (TRFs), baseline WBC TRF length will be measured from blood samples collected in 1992/93. Rate of telomere attrition will be estimated using TRF determination of 1200 follow-up samples collected five or more years later in participants surviving this long. Survival analyses will be done to investigate associations between telomere dynamics (i.e. telomere length and attrition rate) and incident vascular disease, subclinical measures of CVD, mortality, and cause of death. Linear mixed models will evaluate telomere erosion over time by disease status. Results of this study will enhance the understanding of the relationships between telomere dynamics and cardiovascular morbidity and mortality providing new insights into the biology of human aging.