高尿酸血症与脑卒中发病风险及高血压的中介效应研究

目的 研究高尿酸血症与脑卒中发病风险间的关联以及高血压的中介效应。方法 本研究以2015年中国成人慢性病与营养监测为基线数据，脑卒中发病数据来源于2013-2020年住院病案首页数据库，死亡数据来源于2015-2020年全国死因监测系统，将数据库进行匹配链接后建立回顾性队列。采用Cox比例风险回归模型分析高尿酸血症与脑卒中及其亚型发病风险间的关联强度，采用限制性立方样条分析血尿酸水平与脑卒中发病风险间的剂量-反应关系，采用因果中介效应模型分析高血压在高尿酸血症与脑卒中及其亚型发病风险间的中介效应，并按照性别和年龄组进行亚组分析。结果 共纳入研究对象124 352人，累计随访612 911.36人年，随访期间共4 638人发生脑卒中，其中缺血性脑卒中3 919人，出血性脑卒中689人，总人群脑卒中、缺血性脑卒中和出血性脑卒中发病密度分别为756.72/10万人年、641.37/10万人年和114.60/10万人年。Cox比例风险回归模型分析结果显示，调整混杂因素后，与非高尿酸血症患者相比，高尿酸血症患者的脑卒中发病风险升高16%［风险比（HR）=1.16，95%CI：1.06~1.27］、缺血性脑卒中发病风险升高12%（HR=1.12，95%CI：1.01~1.24）、出血性脑卒中发病风险升高39%（HR=1.39，95%CI：1.11~1.75）。因果中介效应分析结果显示，调整协变量后，高血压在高尿酸血症与脑卒中、缺血性脑卒中、出血性脑卒中发病风险间存在中介效应，中介效应百分比分别为36.07%、39.98%、25.34%，在男性和<65岁人群内的中介效应百分比更高。结论 高尿酸血症是脑卒中的发病危险因素，高血压在高尿酸血症与脑卒中发病风险关联中存在中介效应。

Mediating effect of hypertension on risk of stroke associated with hyperuricemia

Objective To investigate the association between hyperuricemia and the risk for stroke occurrence, as well as the mediating effect of hypertension on this association. Methods In this study, the China Chronic Diseases and Nutrition Surveillance system in 2015 was used as baseline data. We identified hospital admissions for stroke using the electronic homepage of inpatient medical records from 2013-2020, and death data were obtained from the 2015-2020 National Mortality Surveillance System. A retrospective cohort was established after matching and linking the database. The Cox proportional hazard regression model was used to analyze the relationship between hyperuricemia and the risk of stroke and its subtypes. Restricted cubic spline analysis was conducted to examine the dose-response relationship between serum uric acid levels and the risk for stroke. Mediation analysis was performed to investigate the mediating effect of hypertension on the association between hyperuricemia and the risk for stroke and its subtypes. Subgroup analyses were conducted based on gender and age groups. Results A total of 124 352 study subjects were included, with an accumulative follow-up time of 612 911.36 person-years. During the follow-up period, 4 638 cases of stroke were found, including 3 919 cases of ischemic stroke and 689 cases of hemorrhagic stroke. The incidence density of stroke was 756.72 per 100 000 person-years, 641.37 per 100 000 person-years for ischemic stroke, and 114.60 per 100 000 person-years for hemorrhagic stroke. Multivariable Cox proportional hazards regression models showed that after adjusting for covariates, compared to those without hyperuricemia, individuals with hyperuricemia had a 16% higher risk for stroke [hazard ratio (HR)=1.16, 95%CI: 1.06-1.27], a 12% higher risk of ischemic stroke (HR=1.12, 95%CI: 1.01-1.24), and a 39% higher risk of hemorrhagic stroke (HR=1.39, 95%CI: 1.11-1.75). Mediation analysis showed that hypertension partially mediated the associations between hyperuricemia and the risk for stroke, ischemic stroke, and hemorrhagic stroke, with mediation proportions of 36.07%, 39.98%, and 25.34%, respectively. The mediating effect is pronounced in the male population and individuals below 65. Conclusion Hyperuricemia is a risk factor for stroke, and hypertension partially mediates the effect of hyperuricemia on stroke.