中老年人群高血压在非甾体抗炎药暴露与心脑血管疾病风险关联中的中介分析

Mediation effects of hypertension on the association between exposure to non-steroidal anti-inflammatory drugs and risk of cardio-cerebrovascular diseases in middle-aged and elderly people

目的探讨高血压在非甾体抗炎药(NSAIDs)暴露与心脑血管疾病风险关联中的中介效应。方法基于国家健康医疗大数据研究院平邑协作中心平台构建随访队列,NSAIDs暴露定义为每年累积剂量(cDDDs)≥30,分别采用广义估计方程模型(GEE)和Cox比例风险回归模型估计NSAIDs与血压及心脑血管疾病之间的关联。采用Baron-Kenny法探究高血压在NSAIDs与心脑血管疾病关联中的中介效应。结果随访队列共纳入81791例研究对象,中位随访时间4.25(IQR:3.22~4.46)年,心脑血管疾病发生结局26514例。多因素GEE结果显示,NSAIDs暴露与收缩压升高(β=0.98,95%CI:0.67~1.29)、舒张压降低(β=-0.19,95%CI:-0.37~-0.01)及高血压风险增加(OR=1.13,95%CI:1.08~1.18)均呈显著相关;多因素Cox模型显示,NSAIDs与心脑血管疾病、脑血管疾病及心血管疾病关联的HR分别为1.13(95%CI:1.10~1.16)、1.13(95%CI:1.09~1.17)和1.17(95%CI:1.13~1.21)。中介分析发现,高血压在NSAIDs暴露与心脑血管疾病关系中起到部分中介作用,中介比例为9.27%。结论NSAIDs有升高收缩压、降低舒张压的作用,是心脑血管疾病发病的危险因素。高血压是NSAIDs和心脑血管疾病之间的中介因素。

Objective To explore the mediation effects of hypertension on the association between exposure to non-steroidal anti-inflammatory drugs(NSAIDs)and the risk of cardio-cerebrovascular diseases.Methods A follow-up cohort was constructed based on Pingyi Collaboration Center of National Institute of Health and Medical Big Data.NSAIDs exposure was defined as annual cumulative dose≥30 cDDDs.The association between NSAIDs and blood pressure and cardio-cerebrovascular diseases were assessed with generalized estimation equation model(GEE)and Cox proportional risk regression model.The mediating effects of hypertension were evaluated with Baron-Kenny method.Results A total of 81,791 subjects were involved.The median follow-up time was 4.25(IQR:3.22-4.46)years,with 26,514 cardio-cerebrovascular disease outcomes.Multivariate GEE results showed that NSAIDs exposure was significantly associated with increased systolic blood pressure(β=0.98,95%CI:0.67-1.29),decreased diastolic blood pressure(β=-0.19,95%CI:-0.37-0.01),and increased risk of hypertension(OR=1.13,95%CI:1.08-1.18).Multivariate Cox model showed that the HR of NSAIDs associated with cardio-cerebrovascular diseases,cerebrovascular diseases and cardiovascular diseases were 1.13(95%CI:1.10-1.16),1.13(95%CI:1.09-1.17)and 1.17(95%CI:1.13-1.21),respectively.Mediation analysis showed that hypertension played a partial mediating role in the relationship between NSAIDs exposure and cardio-cerebrovascular diseases,with a mediating proportion of 9.27%.Conclusion NSAIDs,which can increase systolic blood pressure and decrease diastolic blood pressure,is a risk factor for cardio-cerebrovascular diseases.Hypertension is a mediating factor between NSAIDs and cardio-cerebrovascular diseases.