Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study
Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study
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DOI：
10.1016/s0140-6736(07)60071-3
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发表时间：
2007-01-13
期刊：
影响因子：
168.9
通讯作者：
Samani, Nilesh J.
中科院分区：
文献类型：
--
作者：
Brouilette, Scott W.;Moore, Jasbir S.;Samani, Nilesh J.
生物老化的个体间差异可能影响冠心病的易感性。我们的目的是确定是否平均白细胞端粒长度是一个预测的发展coronaryheartdisease.Methods我们比较了端粒长度在招募484个人在苏格兰西部的一级预防研究（WOSCOPS）谁继续发展冠心病事件与那些从1058匹配的对照组谁保持免费的事件。我们还调查了端粒长度和观察到的他汀类药物治疗的临床获益之间是否存在任何关联。结果：在对照组中，平均端粒长度随年龄的增长每十年下降9%（95%CI 3.6-14.1; p=0.001）;在病例中观察到了几乎相同的趋势（每十年-5.9%，-3.1至14.1; p=0.1902）。端粒长度处于中间和最低三分位数的个体比处于最高三分位数的个体更容易发生冠心病事件（冠心病的比值比[OR]：1.51，95%CI 1.15-1.98;中间三分位数p=0.0029;最低三分位数1.44，1.10-1.90，p=0.0090）。在安慰剂治疗的患者中，与端粒长度最高的三分位数相比，端粒长度较低的两个三分位数的患者患冠心病的风险几乎是最高三分位数的两倍（中间三分位数为1.93，1.33-2.80，p=0.0005;最低三分位数为1.94，1.33-2.84，p=0.0006）。相比之下，在接受普伐他汀治疗的患者中，端粒较短导致的风险增加大大减弱（1.12，0.75-1.69，p=0.5755）; 1.02，0.68-1.52，p=0.9380（最低）。解释平均白细胞端粒长度是中年人未来冠心病事件的预测因子，高风险的男性，并可以确定谁将受益于他汀类药物治疗的个人。我们的研究结果支持了这样一个假设，即生物老化的差异可能会导致冠心病发病年龄的风险和变异性。
Background Inter-individual differences in biological ageing could affect susceptibility to coronary heart disease. Our aim was to determine whether mean leucocyte telomere length is a predictor of the development of coronary heart disease.Methods We compared telomere lengths at recruitment in 484 individuals in the West of Scotland Primary Prevention Study (WOSCOPS) who went on to develop coronary heart disease events with those from 1058 matched controls who remained event free. We also investigated whether there was any association between telomere length and observed clinical benefit of statin treatment in WOSCOPS.Findings Mean telomere length decreased with age by 9% per decade (95% CI 3.6-14.1; p=0.001) in controls; much the same trend was seen in cases (-5.9% per decade, -3.1 to 14.1; p=0.1902). Individuals in the middle and the lowest tertiles of telomere length were more at risk of developing a coronary heart disease event than were individuals in the highest tertile (odds ratio [OR] for coronary heart disease: 1.51, 95% CI 1.15-1.98; p=0.0029 in the middle tertile; 1.44, 1.10-1.90, p=0.0090 in the lowest). In placebo-treated patients, the risk of coronary heart disease was almost double in those in the lower two tertiles of telomere length compared with those in the highest tertile (1.93, 1.33-2.80, p=0.0005 in the middle tertile; 1.94, 1.33-2.84, p=0.0006 in the lowest). By contrast, in patients treated with pravastatin, the increased risk with shorter telomeres was substantially attenuated (1.12, 0.75-1.69, p=0.5755 in the middle tertile; 1.02, 0.68-1.52, p=0.9380 in the lowest).Interpretation Mean leucocyte telomere length is a predictor of future coronary heart disease events in middle-aged, high-risk men and could identify individuals who would benefit most from statin treatment. Our findings lend support to the hypothesis that differences in biological ageing might contribute to the risk-and variability in age of onset-of coronary heart disease.