Brouilette Scott W, Moore Jasbir S, McMahon Alex D, Thompson John R, Ford Ian, Shepherd James, Packard Chris J, Samani Nilesh J
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Lancet. 2007 Jan 13;369(9556):107-14. doi: 10.1016/S0140-6736(07)60071-3.
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.
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.
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).
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.
生物衰老的个体差异可能影响冠心病易感性。我们的目的是确定平均白细胞端粒长度是否为冠心病发生的预测指标。
我们比较了苏格兰西部初级预防研究（WOSCOPS）中484名发生冠心病事件个体在招募时的端粒长度与1058名匹配的无事件发生对照者的端粒长度。我们还研究了WOSCOPS中端粒长度与观察到的他汀类药物治疗临床获益之间是否存在关联。
对照组中平均端粒长度随年龄每十年下降9%（95%CI 3.6 - 14.1；p = 0.001）；病例组也有类似趋势（每十年下降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发生冠心病事件的风险更高（冠心病的优势比[OR]：中间三分位数为1.51，95%CI 1.15 - 1.98；p = 0.0029；最低三分位数为1.44，1.10 - 1.90，p = 0.0090）。在接受安慰剂治疗的患者中，端粒长度处于较低两个三分位数的个体患冠心病的风险几乎是处于最高三分位数个体的两倍（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显著减弱（中间三分位数为1.12，0.75 - 1.69，p = 0.5755；最低三分位数为1.02，0.68 - 1.52，p = 0.9380）。
平均白细胞端粒长度是中年高危男性未来冠心病事件的预测指标，并且可以识别出能从他汀类药物治疗中获益最大的个体。我们的研究结果支持如下假说：生物衰老的差异可能导致冠心病的风险及发病年龄的变异性。
