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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 the effect of shortening telomere length of peripheral white blood cells on the risk of cardiovascular and cerebrovascular death in first stroke patients. Methods This prospective follow-up study included 1662 first-episode strokes within 3 weeks of onset of acute onset in seven clinical centers in China from December 2000 to December 2001. According to the International Classification of Diseases, 9th Edition Peripheral venous blood was extracted from patients with atherosclerotic cerebral infarction (725 cases), lacunar infarction (481 cases) and intracerebral hemorrhage (456 cases). The patients were followed up by real-time fluorescence quantitative polymerase chain reaction Methods Polymerase chain reaction (PCR) was used to detect telomere length of peripheral white blood cells. The relationship between telomere length and the risk of all-cause death and cardiovascular death after stroke was analyzed by Cox survival regression model. Results All subjects were followed up (median follow-up, 4.5 years), and 312 died, of whom 181 died of cardiovascular and cerebrovascular diseases. After adjusting for age, sex, body mass index, smoking, alcohol consumption, lipids, blood glucose, diabetes mellitus, hypertension, and family history of stroke, we found an increased risk of all-cause mortality in patients with atherosclerotic cerebral infarction 69% [adjusted relative risk (adj.RR) 1.69, 95% confidence interval (CI) 1.07-2.67; P = 0.02] and increased risk of cardiovascular and cerebrovascular death 2.57 times longer than long telomere (adj.RR 2.57, 95% CI 1.24-5.31; P = 0.01). Telomere shortening and all-cause mortality were not found in patients with lacunar infarction and intracerebral hemorrhage (adj.RR1.14, 95% CI 0.59-2.18, P = 0.35; adj.RR 0.92, 95% CI 0.57 ~ 1.50, P = 0.59), risk of cardiovascular and cerebrovascular death (adj.RR1.95,95% CI0.76 ~ 4.97, P = 0.24; adj.RR1.06,95% CI0.59 ~ 1.89, P = 0.56) Relationship. Conclusions The telomere shortening of peripheral white blood cells may be an important factor to evaluate the risk of all-cause and cardiovascular death in patients with atherosclerotic cerebral infarction.