Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
Arterioscler Thromb Vasc Biol. 2010 Aug;30(8):1649-56. doi: 10.1161/ATVBAHA.110.205492. Epub 2010 May 27.
To determine the association between leukocyte telomere length (TL) and atherosclerosis and its clinical sequelae stroke and myocardial infarction.
Within the scope of the prospective population-based Bruneck Study, leukocyte TL was measured by quantitative polymerase chain reaction in 800 women and men aged 45 to 84 years (in 1995). The manifestation of cardiovascular disease (CVD) (1995-2005) and the progression of atherosclerosis (1995-2000) were carefully assessed. The TL was shorter in men than in women (age-adjusted mean [95% CI], 1.41 [1.33 to 1.49] versus 1.55 [1.47 to 1.62]; P=0.02) and inversely correlated to age (r=-0.22, P<0.001) and family history of CVD (P=0.03). Participants with CVD events during follow-up (n=88) had significantly shorter telomeres (age- and sex-adjusted mean [95% CI], 1.25 [1.08 to 1.42] versus 1.51 [1.45 to 1.57]; P<0.001). In multivariable Cox models, baseline TL emerged as a significant and independent risk predictor for the composite CVD end point and its individual components (myocardial infarction and stroke); however, this was not the case for de novo stable angina and intermittent claudication. Subjects in the top and bottom TL tertile group differed in their CVD risk by a factor of 2.72 (95% CI, 1.41 to 5.28), which is the risk ratio attributable to a 13.9-year difference in chronological age. Remarkably, in our atherosclerosis progression model, TL was strongly associated with advanced, but not early, atherogenesis. All findings were consistent in women and men.
Our findings indicate a differential role of telomere shortening in the various stages of atherosclerosis, with preferential involvement in advanced vessel pathology and acute vascular syndromes.
确定白细胞端粒长度（TL）与动脉粥样硬化及其临床后果中风和心肌梗死之间的关联。
在前瞻性人群为基础的布伦克研究范围内，对 800 名年龄在 45 至 84 岁的男女（1995 年）进行了定量聚合酶链反应测量白细胞 TL。仔细评估了心血管疾病（CVD）的表现（1995-2005 年）和动脉粥样硬化的进展（1995-2000 年）。男性的 TL 比女性短（年龄调整均值[95%置信区间]，1.41[1.33 至 1.49]比 1.55[1.47 至 1.62]；P=0.02），与年龄呈负相关（r=-0.22，P<0.001）和 CVD 家族史（P=0.03）。在随访期间发生 CVD 事件的参与者（n=88）的端粒明显较短（年龄和性别调整均值[95%置信区间]，1.25[1.08 至 1.42]比 1.51[1.45 至 1.57]；P<0.001）。在多变量 Cox 模型中，基线 TL 是复合 CVD 终点及其各个成分（心肌梗死和中风）的显著且独立的风险预测因子；然而，对于新发稳定型心绞痛和间歇性跛行则并非如此。TL 处于顶端和底部 tertile 组的受试者的 CVD 风险相差 2.72 倍（95%置信区间，1.41 至 5.28），这是与实际年龄相差 13.9 岁的风险比。值得注意的是，在我们的动脉粥样硬化进展模型中，TL 与晚期但不是早期的动脉粥样发生强烈相关。所有发现均在女性和男性中一致。
我们的研究结果表明，端粒缩短在动脉粥样硬化的各个阶段中发挥着不同的作用，与晚期血管病变和急性血管综合征的关系更为密切。
