端粒长度与心房颤动风险：对生物学衰老与实际年龄衰老作用的见解
Telomere length and the risk of atrial fibrillation: insights into the role of biological versus chronological aging.
作者信息
Roberts Jason D, Dewland Thomas A, Longoria James, Fitzpatrick Annette L, Ziv Elad, Hu Donglei, Lin Jue, Glidden David V, Psaty Bruce M, Burchard Esteban G, Blackburn Elizabeth H, Olgin Jeffrey E, Heckbert Susan R, Marcus Gregory M
机构信息
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
出版信息
Circ Arrhythm Electrophysiol. 2014 Dec;7(6):1026-32. doi: 10.1161/CIRCEP.114.001781. Epub 2014 Nov 8.
BACKGROUND
Advanced age is the most important risk factor for atrial fibrillation (AF); however, the mechanism remains unknown. Telomeres, regions of DNA that shorten with cell division, are considered reliable markers of biological aging. We sought to examine the association between leukocyte telomere length (LTL) and incident AF in a large population-based cohort using direct LTL measurements and genetic data. To further explore our findings, we compared atrial cell telomere length and LTL in cardiac surgery patients.
METHODS AND RESULTS
Mean LTL and the TERT rs2736100 single nucleotide polymorphism were assessed as predictors of incident AF in the Cardiovascular Health Study (CHS). Among the surgical patients, within subject comparison of atrial cell telomere length versus LTL was assessed. Among 1639 CHS participants, we observed no relationship between mean LTL and incident AF before and after adjustment for potential confounders (adjusted hazard ratio, 1.09; 95% confidence interval: 0.92-1.29; P=0.299); chronologic age remained strongly associated with AF in the same model. No association was observed between the TERT rs2736100 single nucleotide polymorphism and incident AF (adjusted hazard ratio: 0.95; 95% confidence interval: 0.88-1.04; P=0.265). In 35 cardiac surgery patients (26 with AF), atrial cell telomere length was longer than LTL (1.19 ± 0.20 versus 1.02 ± 0.25 [T/S ratio], P<0.001), a finding that remained consistent within the AF subgroup.
CONCLUSIONS
Our study revealed no evidence of an association between LTL and incident AF and no evidence of relative atrial cell telomere shortening in AF. Chronological aging independent of biological markers of aging is the primary risk factor for AF.
背景
高龄是心房颤动（AF）最重要的危险因素；然而，其机制尚不清楚。端粒是随着细胞分裂而缩短的DNA区域，被认为是生物衰老的可靠标志物。我们试图在一个大型的基于人群的队列中，使用直接的端粒长度测量和基因数据，研究白细胞端粒长度（LTL）与新发AF之间的关联。为了进一步探究我们的发现，我们比较了心脏手术患者的心房细胞端粒长度和LTL。
方法与结果
在心血管健康研究（CHS）中，评估平均LTL和TERT rs2736100单核苷酸多态性作为新发AF的预测指标。在手术患者中，评估心房细胞端粒长度与LTL的受试者内比较。在1639名CHS参与者中，我们观察到在调整潜在混杂因素之前和之后，平均LTL与新发AF之间均无关联（调整后的风险比为1.09；95%置信区间：0.92 - 1.29；P = 0.299）；在同一模型中，实际年龄与AF仍密切相关。未观察到TERT rs2736100单核苷酸多态性与新发AF之间存在关联（调整后的风险比：0.95；95%置信区间：0.88 - 1.04；P = 0.265）。在35名心脏手术患者（26名患有AF）中，心房细胞端粒长度长于LTL（1.19±0.20对1.02±0.25 [T/S比值]，P<0.001），这一发现在AF亚组中保持一致。
结论
我们的研究未发现LTL与新发AF之间存在关联的证据，也未发现AF中心房细胞端粒相对缩短的证据。独立于衰老生物标志物的实际衰老，是AF的主要危险因素。
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