您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2023, Vol. 61 ›› Issue (8): 79-85.doi: 10.6040/j.issn.1671-7554.0.2023.0224

• 公共卫生与管理学 • 上一篇    

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

于晴晴1,常开锋2,李吉庆1,张凯1,付苹1,刘晓雯1,赵英淇1,薛付忠1   

  1. 1.山东大学公共卫生学院生物统计学系, 山东 济南 250012;2.山东省平邑县疾病预防控制中心办公室, 山东 平邑 273300
  • 发布日期:2023-08-30
  • 通讯作者: 薛付忠. E-mail:xuefzh@sdu.edu.cn
  • 基金资助:
    国家重点研发计划(2020YFC2003500)

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

YU Qingqing1, CHANG Kaifeng2, LI Jiqing1, ZHANG Kai1, FU Ping1,LIU Xiaowen1, ZHAO Yingqi1, XUE Fuzhong1   

  1. 1. Department of Biostatistics, School of Public Health, Shandong University, Jinan 250012, Shandong, China;
    2. Pingyi Center for Disease Control and Prevention, Pingyi 273300, Shandong, China
  • Published:2023-08-30

摘要: 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81 791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26 514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。

关键词: 非甾体抗炎药, 高血压, 心脑血管疾病, 队列研究, 中介效应

Abstract: 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.

Key words: Non-steroidal anti-inflammatory drugs, Hypertension, Cardio-cerebrovascular diseases, Cohort study, Mediating effects

中图分类号: 

  • R54
[1] 蔡青青, 沈赟, 戴佩芳, 等. 非甾体类抗炎药物与高血压风险的研究进展[J]. 中国临床药学杂志, 2016, 25(5): 329-332. CAI Qingqing, SHEN Yun, DAI Peifang, et al. Research progress of nonsteroidal anti-inflammatory drugs and hypertension risk[J]. Chinese Journal of Clinical Pharmacy, 2016, 25(5): 329-332.
[2] El-Yazbi AF, Eid AH, El-Mas MM. Cardiovascular and renal interactions between cyclosporine and NSAIDs: underlying mechanisms and clinical relevance [J]. Pharmacol Res, 2018, 129: 251-261. doi: 10.1016/j.phrs.2017.11.029.
[3] 罗桢敏, 杨科朋, 陈劲柏, 等. 从NSAIDs心血管不良反应机制探讨老年人用药管理[J]. 中国药物滥用防治杂志, 2021, 27(5): 707-710. LUO Zhenmin, YANG Kepeng, CHEN Jinbai, et al. Discussion on medication management in the elderly from the mechanism of cardiovascular adverse reactions of NSAIDs [J]. Chinese Journal of Drug Abuse Prevention and Treatment, 2021, 27(5): 707-710.
[4] Liew JW, Ward MM, Reveille JD, et al. Nonsteroidal antiinflammatory drug use and association with incident hypertension in ankylosing spondylitis [J]. Arthritis Care Res(Hoboken), 2020, 72(11): 1645-1652.
[5] Ricciotti E, Castro C, Tang SY, et al. Cyclooxygenase-2, Asymmetric Dimethylarginine, and the Cardiovascular Hazard from Nonsteroidal Anti-Inflammatory Drugs [J]. Circulation, 2018, 138(21): 2367-2378.
[6] Ruschitzka F, Borer JS, Krum H, et al. Differential blood pressure effects of ibuprofen, naproxen, and celecoxib in patients with arthritis: the PRECISION-ABPM(prospective randomized evaluation of celecoxib integrated safety versus ibuprofen or naproxen ambulatory blood pressure measurement)trial [J]. Eur Heart J, 2017, 38(44): 3282-3292.
[7] Schjerning AM, McGettigan P, Gislason G. Cardiovascular effects and safety of(non-aspirin)NSAIDs [J]. Nat Rev Cardiol, 2020, 17(9): 574-584.
[8] García-Poza P, de Abajo FJ, Gil MJ, et al. Risk of ischemic stroke associated with non-steroidal anti-inflammatory drugs and paracetamol: a population-based case-control study [J]. J Thromb Haemost, 2015, 13(5): 708-718.
[9] Chen AI, Lee YH, Perng WT, et al. Celecoxib and Etoricoxib may reduce risk of ischemic stroke in patients with rheumatoid arthritis: a nationwide retrospective cohort study [J]. Front Neurol, 2022, 13: 1018521. doi: 10.3389/fneur.2022.1018521.
[10] Barthélémy O, Limbourg T, Collet JP, et al. Impact of non-steroidal anti-inflammatory drugs(NSAIDs)on cardiovascular outcomes in patients with stable atherothrombosis or multiple risk factors [J]. Int J Cardiol, 2013, 163(3): 266-271.
[11] 施倩雯, 魏永越, 李清雅, 等. 疾病预后研究的中介分析方法评价[J]. 中国卫生统计, 2017, 34(3): 390-396. SHI Qianwen, WEI Yongyue, LI Qingya, et al. Evaluation of mediation analysis methods in survival data [J]. Chinese Journal of Health Statistics, 2017, 34(3): 390-396.
[12] 施倩雯. 生存资料的中介分析方法评价[D]. 南京: 南京医科大学, 2017.
[13] Morrison A, Ramey DR, van Adelsberg J, et al. Systematic review of trials of the effect of continued use of oral non-selective NSAIDs on blood pressure and hypertension [J]. Curr Med Res Opin, 2007, 23(10): 2395-2404.
[14] Spence JD, Grosser T, FitzGerald GA. Acetaminophen, nonsteroidal anti-inflammatory drugs, and hypertension [J]. Hypertension, 2022, 79(9): 1922-1926.
[15] Tso J, Hollowed C, Liu C, et al. Nonsteroidal anti-inflammatory drugs and cardiovascular risk in American football [J]. Med Sci Sports Exerc, 2020, 52(12): 2522-2528.
[16] Zhu L, Xu C, Huo X, et al. The cyclooxygenase-1/mPGES-1/endothelial prostaglandin EP4 receptor pathway constrains myocardial ischemia-reperfusion injury [J]. Nat Commun, 2019, 10(1): 1888. doi: 10.1038/s41467-019-09492-4.
[17] Foy MC, Vaishnav J, Sperati CJ. Drug-induced hypertension [J]. Endocrinol Metab Clin North Am, 2019, 48(4): 859-873.
[18] Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs(NSAIDs)and organ damage: a current perspective [J]. Biochem Pharmacol,2020, 180: 114147. doi: 10.1016/j.bcp.2020.114147.
[19] Jo HA, Kim DK, Park S, et al. Cardiovascular risk of nonsteroidal anti-inflammatory drugs in dialysis patients: a nationwide population-based study [J]. Nephrol Dial Transplant, 2021, 36(5): 909-917.
[20] Schjerning Olsen AM, Gislason GH, McGettigan P, et al. Association of NSAID use with risk of bleeding and cardiovascular events in patients receiving antithrombotic therapy after myocardial infarction [J]. JAMA, 2015, 313(8): 805-814.
[21] Masclee GMC, Straatman H, Arfè A, et al. Risk of acute myocardial infarction during use of individual NSAIDs: a nested case-control study from the SOS project [J]. PLoS One, 2018, 13(11): e0204746. doi: 10.1371/journal.pone.0204746.
[22] Bally M, Dendukuri N, Rich B, et al. Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of individual patient data [J]. BMJ, 2017, 357: j1909. doi: 10.1136/bmj.j1909.
[23] Mayor S. NSAIDs double risk of bleeding in patients taking antithrombotics after myocardial infarction, study finds [J]. BMJ, 2015, 350: h1043. doi: 10.1136/bmj.h1043.
[24] Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis [J]. BMJ, 2011, 342: c7086. doi: 10.1136/bmj.c7086.
[25] Khan S, Andrews KL, Chin-Dusting JPF. Cyclo-Oxygenase(COX)inhibitors and cardiovascular risk: are non-steroidal anti-inflammatory drugs really anti-inflammatory? [J]. Int J Mol Sci, 2019, 20(17): 4262.
[26] 李志万, 石炜. 非甾体抗炎药物和抗血压药物联用对血压的影响[J]. 海峡药学, 2016, 28(6): 125-127. LI Zhiwan, SHI Wei. Effect of non-steroidal anti-inflammatory drugs combined with antihypertensive drugs on blood pressure [J]. Strait Pharmaceutical Journal, 2016, 28(6): 125-127.
[27] Ingrasciotta Y, Sultana J, Giorgianni F, et al. Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study [J]. PLoS One, 2015, 10(4): e0122899. doi: 10.1371/journal.pone.0122899.
[28] Floor-Schreudering A, De Smet PA, Buurma H, et al. NSAID-antihypertensive drug interactions: which outpatients are at risk for a rise in systolic blood pressure? [J]. Eur J Prev Cardiol, 2015, 22(1): 91-99.
[1] 吴逸南 葛志明 李方 贺红 姜虹 张运. 自发性高血压大鼠肾脏血管紧张素转换酶2的表达[J]. 山东大学学报(医学版), 2209, 47(6): 5-.
[2] 邬雨洁,张明泉,纪永利,赵璐,王越,陈沙沙. 寒痉汤及其拆方对寒凝证高血压大鼠血清炎症因子、血管内皮功能及纤维化的影响[J]. 山东大学学报 (医学版), 2022, 60(6): 10-18.
[3] 宋钰峰,宁豪,姚志刚,吴海虎,刘非凡,吕家驹. 肾上腺海绵状血管瘤临床及影像特征[J]. 山东大学学报 (医学版), 2022, 60(2): 37-42.
[4] 吕岩红,张志勉. 2 809名体检人群中高血压与幽门螺杆菌感染的关联性[J]. 山东大学学报 (医学版), 2022, 60(2): 43-47.
[5] 曹义海. 血管生成在疾病治疗中的应用与展望[J]. 山东大学学报 (医学版), 2021, 59(9): 9-14.
[6] 刘新雨,王权,琚号杰,孙晓杰. 认知功能在老年人社会资本与身体功能健康间的中介作用[J]. 山东大学学报 (医学版), 2021, 59(11): 100-107.
[7] 贾明旺,廖广园,熊明媚,徐文婷,王银玲,王懿春. 84例妊娠合并肺高血压患者预后的临床分析[J]. 山东大学学报 (医学版), 2021, 59(1): 34-39.
[8] 许琴,高梅,王海民,曹凌瑕,孙成林. 常染色体显性多囊肾病伴原发性醛固酮增多症1例[J]. 山东大学学报 (医学版), 2020, 58(4): 118-120.
[9] 安嬿,王律,陈参参,范秀珍. 206名护理硕士生心理资本与科研动机的调查分析[J]. 山东大学学报 (医学版), 2020, 58(12): 102-108.
[10] 王雪纯,董利,曹衍雯,董凯歌,王艺霖,袁莹,李士保,贾存显. 共情在大学生手机依赖倾向与人际交往困扰间的中介作用[J]. 山东大学学报 (医学版), 2019, 57(9): 119-124.
[11] 国雪杰,杨孝荣,桑少伟,刘兵艳,吕明. 济南市平阴县农村成年居民高血压知晓现状及影响因素[J]. 山东大学学报 (医学版), 2019, 57(12): 103-109.
[12] 王倩,徐凌忠,朱静,张娇,谢苏,于子航. 山东省农村老年高血压患者心理健康状况及其影响因素[J]. 山东大学学报 (医学版), 2019, 57(1): 92-100.
[13] 薛莉,胡文琦,魏然,张安然,林君芬,马伟. 2011~2013年高温热浪对苍南县高血压门诊就诊量的影响[J]. 山东大学学报 (医学版), 2018, 56(8): 63-69.
[14] 曹瑾,季晓康,孙秀彬,蒋正,薛付忠. γ-谷氨酰转肽酶与高尿酸血症关系的队列分析[J]. 山东大学学报(医学版), 2017, 55(6): 124-128.
[15] 于涛,刘焕乐,冯新,徐付印,陈亚飞,薛付忠,张成琪. 基于健康管理队列的高血压风险预测模型[J]. 山东大学学报(医学版), 2017, 55(6): 61-65.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!