Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria,
Center for Biomedical Research, Medical University of Vienna, Vienna, Austria.
Cardiorenal Med. 2024;14(1):524-532. doi: 10.1159/000541112. Epub 2024 Sep 9.
Patients with chronic kidney disease, especially those with end-stage kidney disease (ESKD) on hemodialysis (HD), are at increased risk for cardiovascular disease (CVD), including myocardial infarction and ischemic stroke. A shortening in telomere length, as a parameter for accelerated vascular aging, is an established biomarker for CVD in the general population. We aimed to elucidate the role of telomere length in ESKD patient on HD and its association with cardiovascular outcomes.
Telomere length was measured in a prospective population-based cohort study of prevalent HD patients. DNA was isolated from whole blood, sampled at baseline, and analyzed for telomere length via a qPCR-based approach. The risk for the occurrence of the independently adjudicated three-point major adverse cardiovascular event outcome (myocardial infarction, ischemic stroke, and cardiovascular death) was statistically analyzed considering the competing risk of non-cardiovascular death.
In the cohort of 308 patients with ESKD (115 [37.3%] women, median [25th-75th percentile] age: 67.0 [56.8-76.0]), the median telomere length was 1.51 kb (25th-75th percentile 0.6-3.2 kb). The 3P-MACE outcome occurred with an incidence rate of 9.4 per 100 patient-years. Patients with longer telomere length more frequently had vascular nephropathy compared to patients with shorter telomere length. Interestingly, patients in the highest quartile of telomere length had a 1.8-fold increased risk for 3P-MACE (95% CI: 1.051-3.201, p = 0.033), after multivariable adjustment for age, history of stroke, myocardial infarction, venous thromboembolism, presence of heart valve replacement, atrial fibrillation, smoking, anticoagulation, or immunosuppressive use.
Surprisingly, in this high-risk cohort of patients with ESKD on HD, longer telomere lengths were associated with increased risk of cardiovascular events.
患有慢性肾脏病（CKD）的患者，尤其是接受血液透析（HD）治疗的终末期肾脏病（ESKD）患者，心血管疾病（CVD）的风险增加，包括心肌梗死和缺血性中风。端粒长度缩短作为血管老化加速的参数，是一般人群 CVD 的既定生物标志物。我们旨在阐明端粒长度在 ESKD 患者 HD 中的作用及其与心血管结局的关系。
在一项前瞻性基于人群的 ESKD 患者队列研究中测量了端粒长度。在基线时从全血中分离出 DNA，并通过基于 qPCR 的方法分析端粒长度。考虑到非心血管死亡的竞争风险，使用统计学方法分析了独立裁定的三点主要不良心血管事件结局（心肌梗死、缺血性中风和心血管死亡）发生的风险。
在 308 例 ESKD 患者（115 [37.3%] 名女性，中位数[25 百分位数-75 百分位数]年龄：67.0 [56.8-76.0]）的队列中，端粒长度中位数为 1.51 kb（25 百分位数-75 百分位数 0.6-3.2 kb）。3P-MACE 结局的发生率为每 100 患者年 9.4 例。与端粒长度较短的患者相比，端粒长度较长的患者更频繁地患有血管性肾病。有趣的是，端粒长度最高四分位患者发生 3P-MACE 的风险增加了 1.8 倍（95%CI：1.051-3.201，p = 0.033），调整年龄、中风史、心肌梗死、静脉血栓栓塞、心脏瓣膜置换、心房颤动、吸烟、抗凝或免疫抑制治疗后。
令人惊讶的是，在这个接受 HD 治疗的 ESKD 高危患者队列中，较长的端粒长度与心血管事件风险增加相关。
