缺血性卒中后感染介导了低密度脂蛋白胆固醇与全因死亡风险之间的U形曲线关系  

U-shaped association between low-density lipoprotein cholesterol levels and risk of all-cause mortality mediated by post-stroke infection in acute ischemic stroke

作　　者：陈子墨 谷鸿秋 莫荆麟 杨凯璇 姜英玉 杨昕 王春娟 许杰 孟霞 姜勇 李昊 刘丽萍 王伊龙 赵性泉 李子孝 王拥军 Zi-Mo Chen;Hong-Qiu Gu;Jing-Lin Mo;Kai-Xuan Yang;Ying-Yu Jiang;Xin Yang;Chun-Juan Wang;Jie Xu;Xia Meng;Yong Jiang;Hao Li;Li-Ping Liu;Yi-Long Wang;Xing-Quan Zhao;Zi-Xiao Li;Yong-Jun Wang(Beijing Tiantan Hospital,Capital Medical University,Beijing 100071,China;China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing 100071,China;National Center for Healthcare Quality Management in Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing 100071,China;Advanced Innovation Center for Human Brain Protection,Capital Medical University,Beijing 100071,China;Research Unit of Artificial Intelligence in Cerebrovascular Disease,Chinese Academy of Medical Sciences,Beijing 100071,China;Center for Excellence in Brain Science and Intelligence Technology,Chinese Academy of Sciences,Shanghai 200031,China)

机构地区：[1]Beijing Tiantan Hospital,Capital Medical University,Beijing 100071,China [2]China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing 100071,China [3]National Center for Healthcare Quality Management in Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing 100071,China [4]Advanced Innovation Center for Human Brain Protection,Capital Medical University,Beijing 100071,China [5]Research Unit of Artificial Intelligence in Cerebrovascular Disease,Chinese Academy of Medical Sciences,Beijing 100071,China [6]Center for Excellence in Brain Science and Intelligence Technology,Chinese Academy of Sciences,Shanghai 200031,China

出　　处：《Science Bulletin》2023年第12期1327-1335,M0004,共10页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(81870905 and U20A20358);the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5-029);the Capital's Funds for Health Improvement and Research(2020-1-2041).

摘　　要：在缺血性卒中急性期,尚不清楚低水平的低密度脂蛋白胆固醇(LDL-C)的病理生理意义,本研究旨在评估LDL-C水平、卒中后感染和全因死亡间的关系.研究共纳入804,855名缺血性卒中患者.通过多元logistic回归模型分析LDL-C水平、感染和死亡之间的关系,采用基于反事实框架的中介分析,以阐明卒中后感染的中介效应,研究发现LDL-C与死亡风险之间呈U形曲线关系,死亡风险最低的LDL-C水平为2.67mmol/L.经多因素校正后,与LDL-C=2.50~2.99mmol/L相比,LDL-C<1.0mmol/L患者的死亡风险比值比(OR)为2.22(95%置信区间(CI):1.77~2.79),LDL-C5.0mmol/L患者的OR为1.22(95%CI:0.98~1.50).LDL-C与死亡之间关联的38.20%(95%CI:5.96~70.45,P=0.020)由感染介导:在逐步剔除存在心血管危险因素的患者后,LDL-C与全因死亡间的U形曲线关系及感染的中介效应与主要分析一致,而死亡风险最低时的LDL-C水平逐渐升高.在缺血性卒中急性期,LDL-C水平与全因死亡之间存在U形曲线关系,其被卒中后感染介导。During the acute stage of ischemic stroke,it remains unclear how to interpret the low low-density lipoprotein cholesterol(LDL-C)level.We aimed to evaluate the association between LDL-C levels,poststroke infection,and all-cause mortality.804,855 ischemic stroke patients were included.Associations between LDL-C levels,infection,and mortality risk were estimated by multivariate logistic regression models and displayed by restricted cubic spline curves.Mediation analysis was performed under counterfactual framework to elucidate the mediation effect of post-stroke infection.The association between LDL-C and mortality risk was U-shaped.The nadir in LDL-C level with the lowest mortality risk was 2.67 mmol/L.Compared with the group with LDL-C=2.50–2.99 mmol/L,the multivariable-adjusted odds ratio for mortality was 2.22(95%confidence intervals(CI):1.77–2.79)for LDL-C<1.0 mmol/L and 1.22(95%CI:0.98–1.50)for LDL-C≥5.0 mmol/L.The association between LDL-C and all-cause mortality was 38.20%(95%CI:5.96–70.45,P=0.020)mediated by infection.After stepwise excluding patients with increasing numbers of cardiovascular risk factors,the U-shaped association between LDL-C and all-cause mortality and the mediation effects of infection remained consistent with the primary analysis,but the LDL-C interval with the lowest mortality risk increased progressively.The mediation effects of infection were largely consistent with the primary analysis in subgroups of age≥65 years,female,body mass index<25 kg/m^(2),and National Institutes of Health Stroke Scale≥16.During the acute stage of ischemic stroke,there is a U-shaped association between LDL-C level and all-cause mortality,where post-stroke infection is an important mediating mechanism.

关 键 词：全因死亡 死亡风险 卒中后感染 病理生理意义 心血管危险因素 多元LOGISTIC回归 缺血性卒中 低密度脂蛋白胆固醇 

分 类 号：R743.3[医药卫生—神经病学与精神病学]