Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria.
Atherosclerosis. 2013 Aug;229(2):469-74. doi: 10.1016/j.atherosclerosis.2013.05.027. Epub 2013 Jun 10.
Short telomere length has been described to be associated with biological aging including atherosclerosis phenotypes. However, information in patients with symptomatic peripheral arterial disease (PAD) is sparse. We therefore aimed to investigate whether inter-individual differences in relative telomere length (RTL) are associated with symptomatic PAD.
We measured RTL by a quantitative PCR method in the CAVASIC Study, a cohort of 241 male Caucasian patients diagnosed with intermittent claudication and 249 age- and diabetes-matched controls.
We observed significantly shorter mean RTL in patients than in controls (1.24 ± 0.19 vs. 1.32 ± 0.23, p < 0.001). Each shortening of RTL by one standard deviation significantly increased the odds for PAD by 44%: age-adjusted OR = 1.44 (95%CI 1.19-1.75, p < 0.001). This association remained significant after additional adjustment for log-C-reactive protein, glomerular filtration rate, HDL cholesterol, current smoking and log N-terminal pro-B-type natriuretic peptide (NT-proBNP). Excluding patients with prevalent cardiovascular disease revealed very similar results. When we compared the model fit of the various adjustment models including cardiac risk factors and/or NT-proBNP the addition of RTL significantly improved discrimination between patients and controls.
This study in a male cohort of patients with intermittent claudication and age- and diabetes-matched controls indicates a significant association of shorter relative telomere length with PAD. Our results reinforce RTL as a marker for PAD that reflects the influence of genetic and environmental risk factors. Moreover, the association remains significant after excluding patients and controls free from prevalent cardiovascular disease.
端粒长度较短与生物学衰老有关，包括动脉粥样硬化表型。然而，在有症状的外周动脉疾病（PAD）患者中，相关信息较为匮乏。因此，我们旨在研究个体间相对端粒长度（RTL）的差异是否与有症状的 PAD 相关。
我们在 CAVASIC 研究中通过定量 PCR 方法测量 RTL，该研究纳入了 241 名被诊断为间歇性跛行的男性白种人患者和 249 名年龄和糖尿病相匹配的对照者。
我们发现患者的平均 RTL 明显短于对照组（1.24 ± 0.19 对 1.32 ± 0.23，p < 0.001）。每缩短一个 RTL 的标准差，PAD 的可能性就会增加 44%：校正年龄后的 OR = 1.44（95%CI 1.19-1.75，p < 0.001）。这种关联在进一步调整 C 反应蛋白、肾小球滤过率、HDL 胆固醇、当前吸烟和 N 端脑钠肽前体（NT-proBNP）后仍然显著。排除有心血管疾病的患者后，结果也非常相似。当我们比较包括心脏危险因素和/或 NT-proBNP 的各种调整模型的模型拟合度时，加入 RTL 显著改善了患者与对照组之间的区分度。
这项研究纳入了间歇性跛行的男性患者和年龄及糖尿病相匹配的对照者，表明较短的相对端粒长度与 PAD 显著相关。我们的结果强化了 RTL 作为 PAD 标志物的作用，反映了遗传和环境危险因素的影响。此外，在排除无心血管疾病的患者和对照者后，这种关联仍然显著。
