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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (5): 1047-1055. doi: 10.19723/j.issn.1671-167X.2022.05.035

• 论著 • 上一篇    下一篇

抗高血压药物对二氧化氮长期暴露与慢性肾脏病关联的修饰效应

马麟1,吴静依2,李双成3,李鹏飞2,4,*(),张路霞2,4,5,*()   

  1. 1. 北京大学医学部学科建设办公室, 北京 100191
    2. 浙江省北大信息技术高等研究院, 杭州 311215
    3. 北京大学地表过程分析与模拟教育部重点实验室, 北京大学城市与环境学院, 北京 100871
    4. 北京大学健康医疗大数据国家研究院, 北京 100191
    5. 北京大学第一医院肾内科, 北京大学肾脏病研究所, 北京 100034
  • 收稿日期:2022-05-09 出版日期:2022-10-18 发布日期:2022-10-14
  • 通讯作者: 李鹏飞,张路霞 E-mail:pfli@aiit.org.cn;zhanglx@bjmu.edu.cn
  • 作者简介:李鹏飞，信息技术高级工程师，北京大学信息技术高等研究院(浙江)智慧医疗研究中心副主任、高级研究员，北京大学健康医疗大数据国家研究院大数据平台技术负责人。担任中国医院协会健康医疗大数据应用管理专业委员会委员、中华预防医学会肾脏病预防与控制专业委员会委员等学术职务。
    主要研究方向为健康医疗大数据智能治理、分析与应用，特别是在大数据驱动的重大疾病智能管理体系和基于精准医疗理念的肿瘤智能防治技术领域开展了系统性的研究工作。近5年，主持研发了“未数”健康医疗大数据智能分析平台、北京大学人民医院肺癌大数据平台、武汉市COVID-19医疗救治监测可视化平台等项目，获评浙江省数字经济“五新”优秀案例、浙江省软件产业高质量发展重点项目、浙江省人工智能优秀解决方案等。累计发表SCI收录及中文核心期刊论文20余篇，申请发明专利21项(授权8项)、软件著作权13项|张路霞，教授，主任医师，博士生导师；现任北京大学健康医疗大数据国家研究院副院长；获得国家杰出青年科学基金、教育部新世纪优秀人才支持计划等基金支持；担任中国医院协会健康医疗大数据应用管理专业委员会首届副主任委员兼秘书长、中华预防医学会肾脏病预防与控制专业委员会副主任委员兼秘书长、Science合作期刊Health Data Science创刊副主编等学术职务。
    长期致力于健康医疗大数据的治理与应用研究以及慢性肾脏病的疾病负担与管理模式研究，迄今在New England Journal of Medicine、Lancet和British Medical Journal等期刊发表研究论文103篇，累计他引2 958次，出版中文专著4部。2020年和2021年连续入选爱思唯尔“中国高被引学者”榜单，获2021年中国女医师协会五洲女子科技奖
  • 基金资助:
    国家自然科学基金(72125009);北大百度基金(2020BD004);北大百度基金(2020BD005)

Effect of modification of antihypertensive medications on the association of nitrogen dioxide long-term exposure and chronic kidney disease

Lin MA1,Jing-yi WU2,Shuang-cheng LI3,Peng-fei LI2,4,*(),Lu-xia ZHANG2,4,5,*()   

  1. 1. Office of Development Planning and Academic Development, Peking University, Beijing 100191, China
    2. Advanced Institute of Information Technology, Peking University, Hangzhou 311215, China
    3. Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China
    4. National Institute of Health Data Science, Peking University, Beijing 100191, China
    5. Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing 100034, China
  • Received:2022-05-09 Online:2022-10-18 Published:2022-10-14
  • Contact: Peng-fei LI,Lu-xia ZHANG E-mail:pfli@aiit.org.cn;zhanglx@bjmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(72125009);the PKU-Baidu Fund(2020BD004);the PKU-Baidu Fund(2020BD005)

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摘要：

目的: 探讨抗高血压药物对二氧化氮(nitrogen dioxide，NO2)和慢性肾脏病(chronic kidney disease，CKD)关联的修饰效应。方法: 基于中国CKD流行病学调查研究的2007—2010年全国成年人代表性横断面数据进行NO2暴露数据的收集与匹配，按照是否合并高血压和使用抗高血压药物进行分层，采用广义相加混合效应模型研究不同人群NO2长期暴露与CKD的关联效应及差异，分别利用自然样条平滑函数拟合NO2和CKD的暴露反应关系，分析抗高血压药物对NO2-CKD关联及暴露反应曲线的修饰效应。结果: 共纳入45 136例研究对象，平均年龄为(49.5±15.3)岁，NO2年平均暴露浓度为(7.2±6.4) μg/m3，使用抗高血压药物者共6 517人(14.4%)，CKD患者为4 833人(10.7%)。调整混杂因素后，合并高血压、未使用抗高血压药物的人群中，NO2长期暴露能导致CKD风险显著增加(OR：1.38，95%CI：1.24~1.54，P < 0.001)；使用抗高血压药物的人群中，NO2长期暴露与CKD风险无显著关联(OR：0.96，95%CI：0.86~1.07，P=0.431)。NO2-CKD的暴露反应曲线显示，NO2暴露与CKD的关联存在一定的非线性趋势。抗高血压药物对NO2-CKD关联和暴露反应曲线均具有显著的效应修饰作用(交互项P值< 0.001)。结论: NO2的长期暴露与CKD风险的关联受到抗高血压药物的修饰作用，使用抗高血压药物可有效降低NO2的长期暴露对CKD的影响。

关键词: 抗高血压药, 二氧化氮, 慢性肾脏病, 修饰效应

Abstract:

Objective: To investigate the potential effect of modification of antihypertensive medications on the association of nitrogen dioxide (NO2) long-term exposure and chronic kidney disease (CKD). Methods: Data of the national representative sample of adult population from the China National Survey of Chronic Kidney Disease (2007-2010) were included in the analyses, and exposure data of NO2 were collected and matched. Generalized mixed-effects models were used to analyze the associations between NO2 and CKD, stratified by the presence of hypertension and taking antihypertensive medications. The stratified exposure-response curves of NO2 and CKD were fitted using the natural spine smoothing function. The modifying effects of antihypertensive medications on the association and the exposure-response curve of NO2 and CKD were analyzed. Results: Data of 45 136 participants were included, with an average age of (49.5±15.3) years. The annual average exposure concentration of NO2 was (7.2±6.4) μg/m3. Altogether 6 517 (14.4%) participants were taking antihypertensive medications, and 4 833 (10.7%) participants were identified as having CKD. After adjustment for potential confounders, in the hypertension population not using antihypertensive medications, long-term exposure to NO2 was associated with a significant increase risk of CKD (OR: 1.38, 95%CI: 1.24-1.54, P < 0.001); while in the hypertension population using antihypertensive medications, no significant association between long-term exposure to NO2 and CKD (OR: 0.96, 95%CI: 0.86-1.07, P=0.431) was observed. The exposure-response curve of NO2 and CKD suggested that there was a non-linear trend in the association between NO2 and CKD. The antihypertension medications showed significant modifying effects both on the association and the exposure-response curve of NO2 and CKD (interaction P < 0.001). Conclusion: The association between long-term exposure to NO2 and CKD was modified by antihypertensive medications. Taking antihypertensive medications may mitigate the effect of long-term exposure to NO2 on CKD.

Key words: Antihypertensive agents, Nitrogen dioxide, Chronic kidney disease, Effect modification

中图分类号: 

  • R692

表1

研究人群的基本特征"

Items All
(n=45 136)		 Without HBP
(n=29 725)		 HBP+without anti-HBP
(n=8 894)		 HBP+anti-HBP
(n=6 517)		 Missing P
CKD 4 833(10.7) 2 056(6.9) 1 377(15.5) 1 400(21.5) 0 < 0.001
NO2/(μg/m3) 7.2±6.4 6.7±6.2 7.5±6.4 8.9±7.0 0 < 0.001
Age 49.5±15.3 45.5±14.3 54.4±14.5 61.4±11.7 0 < 0.001
Female 25 706(57.0) 17 488(58.8) 4 354(49.0) 3 864(59.3) 0 < 0.001
Rural 21 748(48.2) 14 539(48.9) 4 600(51.7) 2 609(40.0) 0 < 0.001
Region 0 < 0.001
  South 10 241(22.7) 7 596(25.6) 1 573(17.7) 1 072(16.4)
  North 15 124(33.5) 9 504(32.0) 3 141(35.3) 2 479(38.0)
  East 10 089(22.4) 5 522(18.6) 2 567(28.9) 2 000(30.7)
  Middle 2 661(5.9) 2 011(6.8) 386(4.3) 264(4.1)
  Northwest 4 026(8.9) 2 676(9.0) 819(9.2) 531(8.1)
  Southwest 2 995(6.6) 2 416(8.1) 408(4.6) 171(2.6)
Education 119 < 0.001
  None 4 630(10.3) 2 217(7.5) 1 321(14.9) 1 092(16.8)
  Primary school 8 395(18.6) 4 826(16.2) 2 071(23.3) 1 498(23.0)
  Middle school 12 517(27.7) 8 362(28.1) 2 486(28.0) 1 669(25.6)
  High school 11 332(25.1) 7 916(26.6) 1 977(22.2) 1 439(22.1)
  College and above 8 143(18.0) 6 325(21.3) 1 016(11.4) 802(12.3)
Smoking 39 < 0.001
  Never 34 452(76.3) 22 876(77.0) 6 356(71.5) 5 220(80.1)
  Sometimes 1 071(2.4) 702(2.4) 236(2.7) 133(2.0)
  Almost once a day 9 574(21.2) 6 119(20.6) 2 294(25.8) 1 161(17.8)
Alcohol consumption 96 < 0.001
  < 1 time/week 38 031(84.3) 25 430(85.6) 6 999(78.7) 5 602(86.0)
  1-2 times/week 2 485(5.5) 1 656(5.6) 532(6.0) 297(4.6)
  >3 times/week 4 524(10.0) 2 569(8.6) 1 350(15.2) 605(9.3)
Exercise 9 277 < 0.001
  Never 21 413(47.4) 14 146(47.6) 4 634(52.1) 2 633(40.4)
  0-3 h/week 4 807(10.7) 3 227(10.9) 840(9.4) 740(11.4)
  >3 h/week 9 639(21.4) 5 803(19.5) 1 831(20.6) 2 005(30.8)
BMI/(kg/m2) 23.9±3.7 23.0±3.4 25.2±3.7 25.7±3.8 332 < 0.001
Total cholesterol 4.9±1.3 4.7±1.3 5.0±1.3 5.2±1.6 17 < 0.001
Diabetes 10 568(23.4) 5 090(17.1) 2 841(31.9) 2 637(40.5) 43 < 0.001
CVD 1 152(2.6) 294(1.0) 201(2.3) 657(10.1) 0 < 0.001
Nephrotoxic medications used 1 468(3.3) 808(2.7) 314(3.5) 346(5.3) 0 < 0.001
eGFR/(mL/min·1.73 m2) 101.1±27.6 103.6±27.6 99.6±27.3 92.1±25.6 0 < 0.001
uACR/(mg/g) 6.7(3.0, 14.4) 6.0(2.8, 11.9) 8.1(3.4, 18.3) 10.1(4.3, 24.2) 0 < 0.001
Albuminuria 6 030(13.4) 3 162(10.6) 1 488(16.7) 1 380(21.2) 0 < 0.001

表2

抗高血压药物对NO2与CKD关联的修饰效应"

Per 10 μg/m3
increase of NO2		 Univariate analysis Model 1 Model 2 Model 3
OR P Pinteraction OR P Pinteraction OR P Pinteraction OR P Pinteraction
All 1.36
(1.30, 1.41)		 < 0.001 < 0.001 1.40
(1.33, 1.46)		 < 0.001 < 0.001 1.45
(1.39, 1.52)		 < 0.001 < 0.001 1.45
(1.37, 1.52)		 < 0.001 < 0.001
Without HBP 1.57
(1.48, 1.67)		 < 0.001 1.70
(1.60, 1.82)		 < 0.001 1.74
(1.62, 1.86)		 < 0.001 1.70
(1.59, 1.83)		 < 0.001
HBP+without anti-HBP 1.12
(1.02, 1.22)		 0.013 1.25
(1.14, 1.38)		 < 0.001 1.41
(1.27, 1.55)		 < 0.001 1.38
(1.24, 1.54)		 < 0.001
HBP+anti-HBP 0.92
(0.85, 1.00)		 0.065 0.91
(0.83, 1.00)		 0.048 0.91
(0.83, 1.01)		 0.064 0.96
(0.86, 1.07)		 0.431

表3

抗高血压药物对NO2与eGFR关联的修饰效应"

Per 10 μg/m3
increase of NO2		 Univariate analysis Model 1 Model 2 Model 3
RR P Pinteraction RR P Pinteraction RR P Pinteraction RR P Pinteraction
All 1.03
(1.03, 1.03)		 < 0.001 < 0.001 1.06
(1.06, 1.06)		 < 0.001 < 0.001 1.06
(1.06, 1.07)		 < 0.001 < 0.001 1.06
(1.06, 1.07)		 < 0.001 0.002
Without HBP 1.04
(1.03, 1.04)		 < 0.001 1.06
(1.06, 1.07)		 < 0.001 1.06
(1.06, 1.07)		 < 0.001 1.06
(1.06, 1.07)		 < 0.001
HBP+without anti-HBP 1.07
(1.07, 1.07)		 < 0.001 1.06
(1.06, 1.07)		 < 0.001 1.07
(1.07, 1.08)		 < 0.001 1.07
(1.07, 1.08)		 < 0.001
HBP+anti-HBP 1.02
(1.02, 1.03)		 < 0.001 1.04
(1.04, 1.05)		 < 0.001 1.06
(1.05, 1.06)		 < 0.001 1.06
(1.05, 1.06)		 < 0.001

表4

调整不同环境协变量后抗高血压药物对NO2与CKD关联的修饰效应"

Per 10 μg/m3 increase of NO2 Adjusted for PM2.5 Adjusted for temperature Adjusted for relative humidity
OR P Pinteraction OR P Pinteraction OR P Pinteraction
All 1.80
(1.70, 1.90)		 < 0.001 < 0.001 1.55
(1.46, 1.64)		 < 0.001 < 0.001 1.45
(1.37, 1.53)		 < 0.001 < 0.001
Without HBP 2.12
(1.96, 2.28)		 < 0.001 1.90
(1.75, 2.06)		 < 0.001 1.77
(1.64, 1.92)		 < 0.001
HBP+without anti-HBP 1.65
(1.46, 1.86)		 < 0.001 1.38
(1.22, 1.56)		 < 0.001 1.28
(1.14, 1.44)		 < 0.001
HBP+anti-HBP 1.19
(1.06, 1.34)		 0.004 0.94
(0.83, 1.07)		 0.343 0.89
(0.79, 1.00)		 0.052

图1

抗高血压药物对NO2-CKD暴露反应曲线的修饰效应"

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