Division of Cardiology, San Francisco General Hospital, San Francisco, California, USA.
PLoS One. 2010 Jan 8;5(1):e8612. doi: 10.1371/journal.pone.0008612.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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).
CONCLUSIONS/SIGNIFICANCE: 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.
白细胞端粒长度作为生物学年龄的新兴标志物，已被证明可预测心血管发病率和死亡率。然而，冠状动脉疾病患者端粒长度的自然史尚未得到研究。我们试图研究患有冠状动脉疾病的人群中端粒长度的纵向轨迹，并确定端粒缩短的独立预测因素。
方法/主要发现：在一项 608 名稳定型冠状动脉疾病患者的前瞻性队列研究中，我们在基线时和随访 5 年后测量了白细胞端粒长度。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素。基线和随访端粒长度呈正态分布。平均端粒长度每年缩短 42 个碱基对（p<0.001）。观察到三种不同的端粒轨迹：45%的参与者端粒缩短，32%的参与者端粒维持不变，23%的参与者端粒延长。端粒缩短的最强预测因素是基线端粒长度（每增加一个标准差的比值比为 7.6；95%置信区间为 5.5，10.6）。端粒缩短的其他独立预测因素包括年龄（每增加 10 岁的比值比为 1.6；95%置信区间为 1.3，2.1）、男性（比值比为 2.4；95%置信区间为 1.3，4.7）和腰围-臀围比（每增加 0.1 的比值比为 1.4；95%置信区间为 1.0，2.0）。
结论/意义：冠状动脉疾病患者的白细胞端粒长度可能会增加，也可能会减少。端粒长度轨迹受基线端粒长度的强烈影响，可能提示负反馈调节。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和可逆性值得进一步研究。
