外周血白细胞端粒长度与初发卒中患者心脑血管死亡风险的关系

Short Telomere Length in Blood Leukocytes Might Contribute to the Risk of Cardio-cerebrovascular Mortality in a Large Prospective Stroke Population

目的 探讨外周血白细胞端粒长度缩短对初发卒中患者心脑血管死亡风险的影响。方法 本研究为前瞻性随访研究,纳入2000年12月至2001年12月全国7家临床中心的急性起病的发病3周内的1662例初发卒中患者,根据国际疾病分类第9版标准分为动脉粥样硬化性脑梗死(725例)、腔隙性脑梗死(481例)和脑出血(456例),患者发病后4～5周抽取外周静脉血,通过实时荧光定量聚合酶链反应法(polymerase chain reaction,PCR)检测外周白细胞端粒长度。通过Cox生存回归模型分析端粒长度与卒中后全因死亡和心脑血管死亡风险的关系。结果 所有研究对象随访中[随访时间4.5年(中位数)],312例死亡,其中181例死于心脑血管疾病。校正年龄、性别、体重指数、吸烟、饮酒、血脂、血糖、糖尿病、高血压、卒中家族史后,发现在动脉粥样硬化性脑梗死患者中,端粒较短时发生全因死亡的风险增加69%[校正相对风险(adjusted relative risk,adj.RR)1.69,95%可信区间(confidenceinterval,CI)1.07～2.67;P=0.02],心脑血管死亡风险增加是长端粒组的2.57倍(adj.RR2.57,95%CI1.24～5.31;P=0.01)。腔隙性脑梗死和脑出血患者中,未发现端粒缩短与全因死亡(adj.RR1.14,95%CI0.59～2.18,P=0.35;adj.RR0.92,95%CI0.57～1.50,P=0.59)、心脑血管死亡风险(adj.RR1.95,95%CI0.76～4.97,P=0.24;adj.RR1.06,95%CI0.59～1.89,P=0.56)的关系。结论 外周血白细胞端粒缩短有可能作为评估动脉粥样硬化性脑梗死患者发生全因死亡和心脑血管死亡风险的重要因素。

Objective To investigate whether telomere length shortening in blood leukocytes contributes to the risk of post-stroke prognosis in a large prospective cohort of patients with first onset stroke in Chinese population. Methods Patients with first onset stroke within 21 days of an acute event were recruited from December 2000 to December 2001 from seven clinical centers. Peripheral venous blood sample was collected at recruitment. The present study included 1662 stroke patients（725 cerebral atherothrombosis, 481 lacunar infarction, and 456 intracerebral hemorrhage）. Relative telomere length in blood leukocytes was measured by a quantitative real-time polymerase chain reaction（PCR）-based technique. Cox proportional hazards models were used to examine the association between telomere length and post-stroke all-cause death or eardio-eerebrovascular death. Results Stroke patients were prospectively followed up for median 4.5 years, and 312 deaths（of which 181 deaths caused by fatal stroke or coronary heart disease） were documented. After adjustment for age, gender, body mass index, smoking, alcohol intake, dyslipidemia, tasting glucose, diabetes, family history of stroke, and hypertension, results showed that atherothrombotic stroke patients with shorter telomeres had 69% increased risk（adjusted relative risk[adj.RR]l.69, 95% confidence interval[CI] 1.07-2.67; P=0.02） for post-stroke all-cause death, and 2.57-fold risk for cardio-cerebrovascular death（adj.RR 2.57, 95%C1 1.24-5.31; P=0.01） in comparison of the lowest to highest tertile. In the follow-up patients with lacunar infarction or hemorrhagic stroke, shorter telomere length was not related to the risk of all-cause death（adj. RR 1.14, 95%C1 0.59~2.18, P=0.35; adj.RR 0.92, 95%CI 0.57-1.50, P=0.59, respectively）, and cardio-cerebrovascular death（adj.RR 1.95, 95%C1 0.76-4.97, P=0.24; adj.RR 1.06, 95%CI 0.59-1.89, P=0.56, respectively）. Conclusion Shorter telomere length in blood leukocytes may serve as a potential marker for the risk of cardio-cerebrovascular death for patients with first onset cerebral atherothrombotic stroke.