脑血管病急性期血尿酸/血肌酐比值与脑血管事件复发及死亡的关系:一项前瞻性队列研究

Correlation of Serum Uric Acid to Serum Creatinine Ratio with the Recurrence of Cerebrovascular Events and Mortality in Patients with Acute Cerebrovascular Disease:a Prospective Cohort Study

背景脑卒中在世界各地有较高的死亡率和复发率。血尿酸(SUA)是嘌呤代谢的产物,已被认为是心脑血管病的危险因素。血尿酸/血肌酐比值(SUA/Scr)是代表肾功能标准化的SUA,目前有关SUA/Scr在急性脑血管病中的作用仍有争议。目的探讨脑血管病急性期SUA/Scr与脑血管事件复发和死亡的关系。方法本研究为前瞻性队列研究,选取2006年9月—2019年9月天津市环湖医院连续收治的首次发生脑血管事件的13313例患者为研究队列,并对患者进行随访,随访截至2020年9月。随访方式为门诊及电话相结合。随访主要终点事件为全因死亡,次要终点事件为脑血管事件复发、心血管事件复发、其他血管事件发生(如下肢动静脉栓塞)。采用Cox比例风险回归模型探究SUA/Scr与脑血管事件复发与死亡的关系。结果根据脑血管病急性期SUA/Scr四分位数,将患者分为Q1组(SUA/Scr≤3.16,n=3520)、Q2组(3.16<SUA/Scr≤3.94,n=3280)、Q3组(3.94<SUA/Scr≤4.92,n=3270)、Q4组(SUA/Scr>4.92,n=3243)。截至随访结束,774例(5.8%)患者死亡,2064例(15.5%)患者复发脑血管事件。脑血管病急性期SUA/Scr位于Q1~Q4的患者中,男性复发脑血管病的例数依次为302、375、408、337例,女性依次为99、125、169、249例;男性复发脑梗死的例数依次为261、314、345、283例,女性依次为90、101、142、205例;男性复发大动脉粥样硬化型脑梗死的例数依次为154、191、214、183例,女性依次为58、52、45、31例;男性全因死亡的例数依次为165、128、131、88例,女性依次为57、63、62、80例;男性因脑梗死死亡的例数依次为93、72、70、46例,女性依次为31、33、36、44例;男性因大动脉粥样硬化型脑梗死死亡的例数依次为58、52、45、31例,女性依次为17、18、27、24例。调整多项混杂因素后,SUA/Scr位于Q4相较于Q1是男性急性脑梗死复发的影响因素(HR=0.690,95%CI=0.500~0.953,P=0.026);SUA/Scr位于Q4相较于Q1是男性脑梗死亚组患者大动脉粥样硬化型脑梗死复发的影响因素(HR=0.740,95%CI=0.578~0.947,P=0.017)。SUA/Scr位于Q4相较于Q1是男性全因死亡、因脑梗死死亡的影响因素(HR=0.575,95%CI=0.368~0.901,P=0.003;HR=0.610,95%CI=0.353~0.814,P=0.011)。SUA/Scr位于Q3、Q4相较于Q1是男性出院后死亡的影响因素(HR=0.656,95%CI=0.476~0.904,P=0.010;HR=0.582,95%CI=0.409~0.829,P=0.001)。SUA/Scr位于Q4相较于Q1是男性脑梗死亚组患者因大动脉粥样硬化型脑梗死死亡的影响因素(HR=0.580,95%CI=0.386~0.873,P=0.007)。结论一定范围内,脑血管病急性期SUA/Scr升高对男性患者脑血管事件复发及死亡有一定的保护作用,低SUA/Scr与男性大动脉粥样硬化型脑梗死的死亡和复发风险升高有关,但与小动脉闭塞型脑梗死和心源性卒中复发和死亡无关。在女性患者中没有观察到SUA/Scr与脑血管事件复发及死亡的关系。

Background Stroke is featured by high mortality and recurrent rate worldwide.Serum uric acid(SUA)is the product of purine metabolism that has been identified as a risk factor for cardiovascular disease.The serum uric acid/serum creatinine ratio(SUA/Scr)is a renal function-normalized SUA.The role of SUA/Scr in acute cerebrovascular disease remains controversial.Objective To identify the correlation of SUA/Scr with the recurrence and mortality of cerebrovascular events in patients with acute cerebrovascular disease.Methods This was a prospective cohort study involving patients with the initial cerebrovascular event consecutively admitted in Tianjin Huanhu Hospital from September 2006 to September 2019.All patients were followed up in the outpatient clinic combined with telephone contact until September 2020.The primary outcome was all-cause mortality.The secondary outcomes were recurrent cerebrovascular events,recurrent cardiovascular events and other vascular events(e.g.,arteriovenous thrombosis of lower extremities).Cox proportional hazard models were used to explore the correlation of SUA/Scr with the recurrence and mortality of cerebrovascular events in patients with acute cerebrovascular disease.Results According to the quartiles of SUA/Scr levels,patients with acute cerebrovascular disease were divided into Q1 group(SUA/Scr≤3.16,n=3520),Q2 group(3.16<SUA/Scr≤3.94,n=3280),Q3 group(3.94<SUA/Scr≤4.92,n=3270)and Q4 group(SUA/Scr>4.92,n=3243).At the end of the follow-up,774(5.8%)patients died,while 2064(15.5%)reported recurrences of cerebrovascular events.In Q1-Q4 groups,there were 302,375,408 and 337 male cases of recurrences of cerebrovascular events,and 99,125,169 and 249 female cases of recurrences of cerebrovascular events,respectively.There were 261,314,345 and 283 male cases of recurrences of cerebral infarction,and 90,101,142 and 205 female cases of recurrences of cerebral infarction in Q1-Q4 groups,respectively.There were 154,191,214 and 183 male cases of recurrences of large atherosclerotic cerebral infarction,and 58,52,45 and 31 female cases of recurrences of large atherosclerotic cerebral infarction in Q1-Q4 groups,respectively.All-cause mortality in men was 165,128,131 and 88 cases in Q1-Q4 groups,respectively,and 57,63,62 and 80 cases in women.The mortality of men due to cerebral infarction was 93,72,70,and 46 cases in Q1-Q4 groups,respectively,and 31,33,36,and 44 cases in women.The mortality of men due to large artery atherosclerotic cerebral infarction was 58,52,45,and 31 cases in Q1-Q4 groups,respectively,and 17,18,27 and 24 cases in women.After adjusting for multiple confounding factors,SUA/Scr in Q4 compared with Q1 was an influencing factor for the recurrence of acute cerebral infarction in men(HR=0.690,95%CI=0.500-0.953,P=0.026).SUA/Scr in Q4 compared with Q1 was an influencing factor for the recurrence of large artery atherosclerotic cerebral infarction in the male cerebral infarction subgroup(HR=0.740,95%CI=0.578-0.947,P=0.017).SUA/Scr in Q4 compared with Q1 was an influencing factor for all-cause mortality(HR=0.575,95%CI=0.368-0.901,P=0.003)and death from cerebral infarction in men(HR=0.610,95%CI=0.353-0.814,P=0.011).SUA/Scr in Q3(HR=0.656,95%CI=0.476-0.904,P=0.010)and Q4(HR=0.582,95%CI=0.409-0.829,P=0.001)compared with Q1 was an influencing factor for male death after discharge.SUA/Scr in Q4 compared with Q1 was an influencing factor for death due to large artery atherosclerotic cerebral infarction in the male cerebral infarction subgroup(HR=0.580,95%CI=0.386-0.873,P=0.007).Conclusion Within a certain range,the increased SUA/Scr ratio in the acute stage of cerebrovascular disease has a certain protective effect on the recurrence and death of cerebrovascular events in male patients.Low SUA/Scr ratio is associated with the increased risk of death and recurrence of male patients with large artery atherosclerotic cerebral infarction,but not correlated with small artery occlusion cerebral infarction and cardiogenic stroke.SUA/Scr is not correlated with cerebrovascular event recurrence or death in female patients.