Telomere Attrition and Cardiovascular Disease

端粒是位于染色体末端的特殊结构，与培养的体细胞的复制衰老有关。端粒长度被认为是生物衰老的一个可能的生物标志物，并与年龄相关的疾病有关，包括高血压、糖尿病和动脉粥样硬化。这些疾病可能反映了氧化应激和炎症状态的加剧，这些因素预计会增加白细胞(WBC)的端粒侵蚀。初步数据表明，血管疾病的衡量标准与老年人端粒缩短有关。心血管健康研究(CHS)的数据来自心血管健康研究(CHS)，该研究最初从/90招募了65岁以上的成年人，并跟踪进行了长达10年的临床检查，将评估以下因素：(1)白细胞端粒长度与包括心肌梗死、中风和外周血管疾病在内的心血管疾病(CVD)的发病率之间的关系；(2)与端粒缩短相关的总死亡率和原因特异性死亡率的风险；(3)随着时间的推移，端粒磨损率与血管疾病状况有关的风险。总共1500名社区卫生服务参与者将被随机挑选用于这些分析，DMA可获得性是唯一排除标准。使用Southern方法测定端粒限制性片段(TRF)，将从1992/93年采集的血液样本中测量基线WBC TRF长度。存活5年或更长时间的参与者的端粒损失率将通过对5年后或更长时间后收集的1200个随访样本的TRF测定来估计。将进行生存分析，以调查端粒动力学(即端粒长度和磨损率)与发生的血管疾病、心血管疾病的亚临床指标、死亡率和死亡原因之间的关系。线性混合模型将根据疾病状态评估端粒随时间的侵蚀。这项研究的结果将加强对端粒动力学与心血管发病率和死亡率之间关系的理解，为人类衰老的生物学提供新的见解。

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.