Telomere length trajectory and its determinants in persons with coronary artery disease: longitudinal findings from the heart and soul study.
Telomere length trajectory and its determinants in persons with coronary artery disease: longitudinal findings from the heart and soul study.
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DOI：
10.1371/journal.pone.0008612
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发表时间：
2010-01-08
期刊：
影响因子：
3.7
通讯作者：
Whooley MA
中科院分区：
文献类型：
--
作者：
Farzaneh-Far R;Lin J;Epel E;Lapham K;Blackburn E;Whooley MA
白细胞端粒长度是一种新兴的生物学年龄标志物，已被证明可预测心血管疾病的发病率和死亡率。然而，冠状动脉疾病患者端粒长度的自然史尚未研究。我们试图研究冠状动脉疾病患者端粒长度的纵向轨迹，并确定端粒缩短的独立预测因子。在一项对608名稳定性冠状动脉疾病患者的前瞻性队列研究中，我们测量了基线时的白细胞端粒长度，并在5年随访后再次测量。我们使用多变量线性和逻辑回归模型来确定白细胞端粒轨迹的独立预测因子。基线和随访时端粒长度呈正态分布。平均端粒长度每年减少42个碱基对（p<0.001）。观察到三种不同的端粒轨迹：45%的参与者缩短，32%的参与者维持，23%的参与者延长。端粒缩短的最有力预测因子是基线端粒长度（每SD增加的OR = 7.6; 95%CI 5.5，10.6）。 端粒缩短的其他独立预测因素为年龄（OR每10年= 1.6; 95%CI 1.3，2.1）、男性（OR = 2.4; 95%CI 1.3，4.7）和腰臀比（OR每增加0.1 = 1.4; 95%CI 1.0，2.0）。 冠心病患者白细胞端粒长度可增加也可减少。端粒长度轨迹受基线端粒长度的影响很大，可能是负反馈调节。年龄、男性和腹部肥胖独立预测端粒缩短。心血管疾病中端粒衰老的机制及其可逆性值得进一步研究。
Leukocyte telomere length, an emerging marker of biological age, has been shown to predict cardiovascular morbidity and mortality. However, the natural history of telomere length in patients with coronary artery disease has not been studied. We sought to investigate the longitudinal trajectory of telomere length, and to identify the independent predictors of telomere shortening, in persons with coronary artery disease. In a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline, and again after five years of follow-up. We used multivariable linear and logistic regression models to identify the independent predictors of leukocyte telomere trajectory. Baseline and follow-up telomere lengths were normally distributed. Mean telomere length decreased by 42 base pairs per year (p<0.001). Three distinct telomere trajectories were observed: shortening in 45%, maintenance in 32%, and lengthening in 23% of participants. The most powerful predictor of telomere shortening was baseline telomere length (OR per SD increase = 7.6; 95% CI 5.5, 10.6). Other independent predictors of telomere shortening were age (OR per 10 years = 1.6; 95% CI 1.3, 2.1), male sex (OR = 2.4; 95% CI 1.3, 4.7), and waist-to-hip ratio (OR per 0.1 increase = 1.4; 95% CI 1.0, 2.0). Leukocyte telomere length may increase as well as decrease in persons with coronary artery disease. Telomere length trajectory is powerfully influenced by baseline telomere length, possibly suggesting negative feedback regulation. Age, male sex, and abdominal obesity independently predict telomere shortening. The mechanisms and reversibility of telomeric aging in cardiovascular disease deserve further study.