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Article(id=1324077847886824034, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324077716676424398, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202510151, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1760284800000, receivedDateStr=2025-10-13, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793614359113, onlineDateStr=2026-11-02, pubDate=1773072000000, pubDateStr=2026-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793614359113, onlineIssueDateStr=2026-11-02, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793614359113, creator=13701087609, updateTime=1793614359113, updator=13701087609, issue=Issue{id=1324077716676424398, tenantId=1146029695717560320, journalId=1227665162245664772, year='2026', volume='53', issue='5', pageStart='769', pageEnd='960', issueExtLink='null', onlineDate='null', pubDate='1773072000000', pubDateStr='2026-03-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793614327830, creator='13701087609', updateTime=1793614418028, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1324078095132655884, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324077716676424398, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1324078095132655885, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324077716676424398, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=803, endPage=808, ext={EN=ArticleExt(id=1324077848121705059, articleId=1324077847886824034, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Association of serum uric acid with all-cause and cause-specific mortality among hypertensive adults using diuretics, columnId=1240413921954295836, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods, runingTitle=null, highlight=null, articleAbstract=
Objective

To examine the associations between serum uric acid and all-cause, cardiovascular, and cancer mortality among hypertensive adults using diuretics.

Methods

We included hypertensive adults who reported diuretic use across 10 cycles (1999—2018) of the National Health and Nutrition Examination Survey (NHANES). Weighted Kaplan-Meier curves,Cox proportional hazards regression models, and restricted cubic splines were applied to examine the associations between serum uric acid levels and all-cause, cardiovascular, and cancer mortality. Subgroup analyses were conducted.

Results

Among 3 744 hypertensive adults treated with diuretics, we prospectively observed a mean follow up of 7.9 years and recorded 1 428 deaths from all causes, including 563 cardiovascular deaths and 248 cancer deaths. Weighted Kaplan-Meier analyses indicated a significantly higher cumulative incidence of all cause, cardiovascular, and cancer mortality in the hyperuricemia group versus the non-hyperuricemia group (P<0.05). After adjustment for covariates, elevated serum uric acid levels were associated with increased risks of all-cause and cardiovascular mortality, with hazard ratios (HRs) of 1.05 (95% CI: 1.01-1.09) and 1.10 (95% CI: 1.02-1.18), respectively. Weighted restricted cubic splines revealed linear dose-response relationships between serum uric acid levels and both all-cause and cardiovascular mortality (P for nonlinear >0.05). Subgroup analyses were consistent and showed no interactions (P>0.05). Uric acid levels were not significantly associated with cancer mortality.

Conclusion

Among hypertensive diuretic users, serum uric acid is linearly and positively associated with risks of all-cause and cardiovascular mortality.

, authors=Chao WU, Yan-hong LU, Jing-jing MA, authorsList=Chao WU, Yan-hong LU, Jing-jing MA, authorCompany=null, correspAuthors=Jing-jing MA, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1324077849237389932, articleId=1324077847886824034, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=使用利尿剂的高血压患者血清尿酸水平与全因死亡以及特定疾病死亡的关联, columnId=1228016567632462653, journalTitle=现代预防医学, columnName=流行病与统计方法, runingTitle=null, highlight=null, articleAbstract=
目的

探讨使用利尿剂的高血压人群血清尿酸水平与全因死亡、心血管疾病死亡以及肿瘤死亡之间的关联。

方法

纳入美国国家健康与营养调查(National Health and Nutrition Examination Survey, NHANES) 1999—2018年10个周期中使用利尿剂的高血压成年患者。采用加权Kaplan-Meier生存分析、Cox比例风险回归模型以及限制性立方样条曲线分析血清尿酸水平与全因死亡、心血管疾病死亡以及肿瘤死亡之间关联，并进行亚组分析。

结果

共纳入3 744名使用利尿剂的高血压成年患者，对其进行平均7.9年的随访，其中全因死亡1 428人，心血管相关死亡563人，肿瘤相关死亡248人。加权Kaplan-Meier生存曲线显示高尿酸组相比非高尿酸组，全因死亡风险、心血管疾病死亡、肿瘤疾病相关死亡风险增加（P<0.05）。调整协变量后，血清尿酸水平与全因死亡和心血管死亡风险增加，风险比分别为1.05（95% CI：1.01～1.09）和1.10（95% CI：1.02～1.18）。加权限制性立方样条曲线分析发现血清尿酸水平与全因死亡风险以及心血管死亡风险成线性相关(P for nonlinear>0.05)，亚组分析结果一致且未发现交互作用(P>0.05)。尿酸水平与肿瘤死亡风险关联性无统计学差异。

结论

在使用利尿剂的高血压人群中，血清尿酸水平与全因死亡和心血管疾病相关死亡风险呈现线性正相关。

, authors=武超, 陆妍宏, 马晶晶, authorsList=武超, 陆妍宏, 马晶晶, authorCompany=null, correspAuthors=马晶晶, authorNote=

武超（1989—），男，硕士，主管药师，研究方向：临床药学

, correspAuthorsNote=
马晶晶，E -mail:
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武超（1989—），男，硕士，主管药师，研究方向：临床药学

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武超（1989—），男，硕士，主管药师，研究方向：临床药学

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Prevalence and predictors of cirrhosis and portal hypertension in the United States[J].Hepatology, 2025, 82(5): 1229-1240., articleTitle=Prevalence and predictors of cirrhosis and portal hypertension in the United States, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1324077851233878637, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, xref=null, ext=[AuthorCompanyExt(id=1324077851246461550, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, companyId=1324077851233878637, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Pharmacy, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China), AuthorCompanyExt(id=1324077851254850159, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, companyId=1324077851233878637, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=苏州大学附属第四医院药学部，江苏 苏州 215000)])], figs=[ArticleFig(id=1324077855876973195, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=EN, label=Figure 1, caption=Flowchart of study-population screening and selection, figureFileSmall=wMOBBXlDeuxn9IEM8AZz3A==, figureFileBig=9XhAK1H9qVUbDvz5ivy6iQ==, tableContent=null), ArticleFig(id=1324077855973442188, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=CN, label=图1, caption=纳入研究人群筛选流程图, figureFileSmall=wMOBBXlDeuxn9IEM8AZz3A==, figureFileBig=9XhAK1H9qVUbDvz5ivy6iQ==, tableContent=null), ArticleFig(id=1324077856246071949, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=EN, label=Figure 2, caption=Weighted Kaplan-Meier survival analysis of serum uric acid levels and mortality in hypertensive adults using diuretics, figureFileSmall=6jchmjdRmkDs78nI6HQaWw==, figureFileBig=XgcQn0vo3EJ2dkoIuMs8nw==, tableContent=null), ArticleFig(id=1324077856338346638, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=CN, label=图2, caption=使用利尿剂的高血压患者血清尿酸水平与死亡的加权Kaplan-Meier生存分析

注：图A为全因死亡率；图B为心血管疾病相关死亡率；图C为肿瘤相关死亡率。

, figureFileSmall=6jchmjdRmkDs78nI6HQaWw==, figureFileBig=XgcQn0vo3EJ2dkoIuMs8nw==, tableContent=null), ArticleFig(id=1324077856426427023, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=EN, label=Figure 3, caption=Weighted restricted cubic spline plots of serum uric acid levels and mortality in hypertensive adults using diuretics, figureFileSmall=pjsqJuNAKJNuv5q+1EDuhw==, figureFileBig=4hwwO0aXVxUz3qglxdMhZg==, tableContent=null), ArticleFig(id=1324077856518701712, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=CN, label=图3, caption=使用利尿剂的高血压患者血清尿酸水平与死亡之间的加权限制性立方样条曲线

注：图A为全因死亡率；图B为心血管疾病相关死亡率；图C为肿瘤相关死亡率。

, figureFileSmall=pjsqJuNAKJNuv5q+1EDuhw==, figureFileBig=4hwwO0aXVxUz3qglxdMhZg==, tableContent=null), ArticleFig(id=1324077856602587793, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=EN, label=Figure 4, caption=Forest plots of subgroup analyses for serum uric acid levels and mortality in hypertensive adults using diuretics, figureFileSmall=yRMZDYFIlBoTBgkKimZwag==, figureFileBig=p5MAsmu1iR5oER6kC7IWcw==, tableContent=null), ArticleFig(id=1324077856686473874, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=CN, label=图4, caption=使用利尿剂的高血压患者血清尿酸水平与死亡之间的亚组分析森林图

注：图A为全因死亡率；图B为心血管疾病相关死亡率。

, figureFileSmall=yRMZDYFIlBoTBgkKimZwag==, figureFileBig=p5MAsmu1iR5oER6kC7IWcw==, tableContent=null), ArticleFig(id=1324077856774554259, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=EN, label=Table 1, caption=

Baseline characteristics of the study population

, figureFileSmall=null, figureFileBig=null, tableContent=
项目总人数(n=3 744)非高尿酸血症(n=1 943)高尿酸血症(n=1 801)t/Z/χ2值P值
年龄（岁）64.29±0.3163.60±0.4165.06±0.3814.7910.003
性别1.4370.360
男1 626 (40.19)862 (41.05)764 (39.24)
女2 118 (59.81)1 081 (58.95)1 037 (60.76)
种族10.0970.057
非西班牙裔白人1 872 (73.02)957 (72.44)915 (73.66)
非西班牙裔黑人1 111 (16.13)553 (15.50)558 (16.83)
墨西哥裔美国人353 (3.19)200 (3.59)153 (2.76)
其它408 (7.65)233 (8.47)175 (6.75)
婚姻状况1.5970.840
已婚或同居2 044 (60.13)1 080 (60.35)964 (59.88)
独居1 700 (39.87)863 (39.65)837 (40.12)
家庭收入与贫困水平比4.4780.190
<1.31 237 (24.94)645 (25.07)592 (24.80)
1.3-3.51 575 (40.94)790 (39.14)785 (42.93)
>3.5932 (34.12)508 (35.79)424 (32.27)
教育水平0.1230.940
高中以下575 (8.97)302 (9.09)273 (8.84)
高中或同等学力1 553 (39.50)806 (39.59)747 (39.40)
高中以上1 616 (51.53)835 (51.32)781 (51.76)
BMI/(kg/m2)32.81±0.1831.77±0.2033.97±0.2761.445<0.001
吸烟状态5.4420.084
从不吸烟2 065 (55.86)1 102 (57.88)963 (53.62)
曾经吸烟1 594 (42.13)793 (39.92)801 (44.57)
当前吸烟85 (2.02)48 (2.20)37 (1.81)
运动情况13.2680.420
轻度运动2 421 (60.37)1 206 (58.95)1 215 (61.94)
适度运动885 (26.20)483 (27.13)402 (25.17)
强烈运动438 (13.43)254 (13.92)184 (12.89)
糖尿病4.9170.005
是1 190 (26.81)586 (23.98)604 (29.94)
否2 554 (73.19)1 357 (76.02)1 197 (70.06)
心力衰竭83.665<0.001
是682 (15.98)246 (10.57)436 (21.96)
否3 062 (84.02)1 697 (89.43)1 365 (78.04)
冠心病3.5660.034
是552 (13.52)266 (12.00)286 (15.21)
否3 192 (86.48)1 677 (88.00)1 515 (84.79)
卒中3.4960.007
是484 (10.99)232 (9.57)252 (12.57)
否3 260 (89.01)1 711 (90.43)1 549 (87.43)
总胆固醇(mg/L)1 910.14±10.571 913.28±13.391 906.67±15.650.422<0.001
高密度脂蛋白(mg/L)520.74±3.74539.04±6.42500.49±5.5157.626<0.001
甘油三酯(mg/L)1 707.44±32.561 623.24±50.021 800.53±37.4351.394<0.001
肌酐(μmol/L)92.49±0.8684.22±0.98101.63±1.2198.778<0.001
利尿剂使用时间（d）2 329.57±60.942 257.61±75.562 409.13±95.840.0610.370
2种以上利尿剂联用242 (5.82)71 (3.33)171 (8.57)52.736<0.001
全因死亡1 428 (32.52)650 (27.71)778 (37.83)37.619<0.001
心血管疾病相关死亡563 (12.64)242 (10.16)321 (15.40)21.084<0.001
肿瘤相关死亡248 (5.44)117 (4.60)131 (6.36)2.3690.031
), ArticleFig(id=1324077856871023252, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=CN, label=表1, caption=

参与者的基线特征

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项目总人数(n=3 744)非高尿酸血症(n=1 943)高尿酸血症(n=1 801)t/Z/χ2值P值
年龄（岁）64.29±0.3163.60±0.4165.06±0.3814.7910.003
性别1.4370.360
男1 626 (40.19)862 (41.05)764 (39.24)
女2 118 (59.81)1 081 (58.95)1 037 (60.76)
种族10.0970.057
非西班牙裔白人1 872 (73.02)957 (72.44)915 (73.66)
非西班牙裔黑人1 111 (16.13)553 (15.50)558 (16.83)
墨西哥裔美国人353 (3.19)200 (3.59)153 (2.76)
其它408 (7.65)233 (8.47)175 (6.75)
婚姻状况1.5970.840
已婚或同居2 044 (60.13)1 080 (60.35)964 (59.88)
独居1 700 (39.87)863 (39.65)837 (40.12)
家庭收入与贫困水平比4.4780.190
<1.31 237 (24.94)645 (25.07)592 (24.80)
1.3-3.51 575 (40.94)790 (39.14)785 (42.93)
>3.5932 (34.12)508 (35.79)424 (32.27)
教育水平0.1230.940
高中以下575 (8.97)302 (9.09)273 (8.84)
高中或同等学力1 553 (39.50)806 (39.59)747 (39.40)
高中以上1 616 (51.53)835 (51.32)781 (51.76)
BMI/(kg/m2)32.81±0.1831.77±0.2033.97±0.2761.445<0.001
吸烟状态5.4420.084
从不吸烟2 065 (55.86)1 102 (57.88)963 (53.62)
曾经吸烟1 594 (42.13)793 (39.92)801 (44.57)
当前吸烟85 (2.02)48 (2.20)37 (1.81)
运动情况13.2680.420
轻度运动2 421 (60.37)1 206 (58.95)1 215 (61.94)
适度运动885 (26.20)483 (27.13)402 (25.17)
强烈运动438 (13.43)254 (13.92)184 (12.89)
糖尿病4.9170.005
是1 190 (26.81)586 (23.98)604 (29.94)
否2 554 (73.19)1 357 (76.02)1 197 (70.06)
心力衰竭83.665<0.001
是682 (15.98)246 (10.57)436 (21.96)
否3 062 (84.02)1 697 (89.43)1 365 (78.04)
冠心病3.5660.034
是552 (13.52)266 (12.00)286 (15.21)
否3 192 (86.48)1 677 (88.00)1 515 (84.79)
卒中3.4960.007
是484 (10.99)232 (9.57)252 (12.57)
否3 260 (89.01)1 711 (90.43)1 549 (87.43)
总胆固醇(mg/L)1 910.14±10.571 913.28±13.391 906.67±15.650.422<0.001
高密度脂蛋白(mg/L)520.74±3.74539.04±6.42500.49±5.5157.626<0.001
甘油三酯(mg/L)1 707.44±32.561 623.24±50.021 800.53±37.4351.394<0.001
肌酐(μmol/L)92.49±0.8684.22±0.98101.63±1.2198.778<0.001
利尿剂使用时间（d）2 329.57±60.942 257.61±75.562 409.13±95.840.0610.370
2种以上利尿剂联用242 (5.82)71 (3.33)171 (8.57)52.736<0.001
全因死亡1 428 (32.52)650 (27.71)778 (37.83)37.619<0.001
心血管疾病相关死亡563 (12.64)242 (10.16)321 (15.40)21.084<0.001
肿瘤相关死亡248 (5.44)117 (4.60)131 (6.36)2.3690.031
), ArticleFig(id=1324077856967492245, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=EN, label=Table 2, caption=

Weighted Cox regression results for the associations between serum uric acid and mortality among hypertensive adults using diuretics

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变量(参考组)模型1模型2模型3模型4
HR (95%CI)P值HR (95%CI)P值HR (95%CI)P值HR (95%CI)P值
全因死亡
血清尿酸1.17 (1.13～1.21)<0.0011.14 (1.09～1.18)<0.0011.08 (1.04～1.13)<0.0011.05 (1.01～1.09)0.021
高尿酸血症(否)
是1.48 (1.31～1.67)<0.0011.38 (1.21～1.56)<0.0011.24 (1.08～1.42)0.0021.16 (1.02～1.33)0.028
心血管疾病相关死亡
血清尿酸1.24 (1.17～1.31)<0.0011.20 (1.12～1.29)<0.0011.14 (1.06～1.23)<0.0011.10 (1.02～1.18)0.011
高尿酸血症(否)
是1.64 (1.31～2.06)<0.0011.51 (1.21～1.88)<0.0011.35 (1.07～1.71)0.0121.27 (1.01～1.60)0.045
肿瘤疾病相关死亡
血清尿酸1.15 (1.05～1.25)0.0031.08 (0.98～1.19)0.1251.06 (0.96～1.17)0.2711.04 (0.94～1.15)0.435
高尿酸血症(否)
是1.49 (1.01～2.02)0.0091.43 (1.05～1.95)0.0221.36 (0.98～1.89)0.0671.32 (0.95～1.84)0.100
), ArticleFig(id=1324077857038795414, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324077847886824034, language=CN, label=表2, caption=

使用利尿剂的高血压患者血清尿酸与死亡的加权Cox回归结果

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变量(参考组)模型1模型2模型3模型4
HR (95%CI)P值HR (95%CI)P值HR (95%CI)P值HR (95%CI)P值
全因死亡
血清尿酸1.17 (1.13～1.21)<0.0011.14 (1.09～1.18)<0.0011.08 (1.04～1.13)<0.0011.05 (1.01～1.09)0.021
高尿酸血症(否)
是1.48 (1.31～1.67)<0.0011.38 (1.21～1.56)<0.0011.24 (1.08～1.42)0.0021.16 (1.02～1.33)0.028
心血管疾病相关死亡
血清尿酸1.24 (1.17～1.31)<0.0011.20 (1.12～1.29)<0.0011.14 (1.06～1.23)<0.0011.10 (1.02～1.18)0.011
高尿酸血症(否)
是1.64 (1.31～2.06)<0.0011.51 (1.21～1.88)<0.0011.35 (1.07～1.71)0.0121.27 (1.01～1.60)0.045
肿瘤疾病相关死亡
血清尿酸1.15 (1.05～1.25)0.0031.08 (0.98～1.19)0.1251.06 (0.96～1.17)0.2711.04 (0.94～1.15)0.435
高尿酸血症(否)
是1.49 (1.01～2.02)0.0091.43 (1.05～1.95)0.0221.36 (0.98～1.89)0.0671.32 (0.95～1.84)0.100
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使用利尿剂的高血压患者血清尿酸水平与全因死亡以及特定疾病死亡的关联
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武超 , 陆妍宏 , 马晶晶
现代预防医学 | 流行病与统计方法 2026,53(5): 803-808
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现代预防医学 |流行病与统计方法 2026 , 53 (5) : 803 -808
使用利尿剂的高血压患者血清尿酸水平与全因死亡以及特定疾病死亡的关联
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武超（1989—），男，硕士，主管药师，研究方向：临床药学

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武超, 陆妍宏, 马晶晶
作者信息
  • 苏州大学附属第四医院药学部，江苏 苏州 215000
通讯作者:
马晶晶，E -mail:
作者简介:

武超（1989—），男，硕士，主管药师，研究方向：临床药学

Association of serum uric acid with all-cause and cause-specific mortality among hypertensive adults using diuretics
Chao WU, Yan-hong LU, Jing-jing MA
Affiliations
  • Department of Pharmacy, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China
出版时间: 2026-03-10 doi: 10.20043/j.cnki.MPM.202510151
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摘要
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目的

探讨使用利尿剂的高血压人群血清尿酸水平与全因死亡、心血管疾病死亡以及肿瘤死亡之间的关联。

方法

纳入美国国家健康与营养调查(National Health and Nutrition Examination Survey, NHANES) 1999—2018年10个周期中使用利尿剂的高血压成年患者。采用加权Kaplan-Meier生存分析、Cox比例风险回归模型以及限制性立方样条曲线分析血清尿酸水平与全因死亡、心血管疾病死亡以及肿瘤死亡之间关联，并进行亚组分析。

结果

共纳入3 744名使用利尿剂的高血压成年患者，对其进行平均7.9年的随访，其中全因死亡1 428人，心血管相关死亡563人，肿瘤相关死亡248人。加权Kaplan-Meier生存曲线显示高尿酸组相比非高尿酸组，全因死亡风险、心血管疾病死亡、肿瘤疾病相关死亡风险增加（P<0.05）。调整协变量后，血清尿酸水平与全因死亡和心血管死亡风险增加，风险比分别为1.05（95% CI：1.01～1.09）和1.10（95% CI：1.02～1.18）。加权限制性立方样条曲线分析发现血清尿酸水平与全因死亡风险以及心血管死亡风险成线性相关(P for nonlinear>0.05)，亚组分析结果一致且未发现交互作用(P>0.05)。尿酸水平与肿瘤死亡风险关联性无统计学差异。

结论

在使用利尿剂的高血压人群中，血清尿酸水平与全因死亡和心血管疾病相关死亡风险呈现线性正相关。

高血压  /  利尿剂  /  尿酸  /  全因死亡  /  心血管死亡
Objective

To examine the associations between serum uric acid and all-cause, cardiovascular, and cancer mortality among hypertensive adults using diuretics.

Methods

We included hypertensive adults who reported diuretic use across 10 cycles (1999—2018) of the National Health and Nutrition Examination Survey (NHANES). Weighted Kaplan-Meier curves,Cox proportional hazards regression models, and restricted cubic splines were applied to examine the associations between serum uric acid levels and all-cause, cardiovascular, and cancer mortality. Subgroup analyses were conducted.

Results

Among 3 744 hypertensive adults treated with diuretics, we prospectively observed a mean follow up of 7.9 years and recorded 1 428 deaths from all causes, including 563 cardiovascular deaths and 248 cancer deaths. Weighted Kaplan-Meier analyses indicated a significantly higher cumulative incidence of all cause, cardiovascular, and cancer mortality in the hyperuricemia group versus the non-hyperuricemia group (P<0.05). After adjustment for covariates, elevated serum uric acid levels were associated with increased risks of all-cause and cardiovascular mortality, with hazard ratios (HRs) of 1.05 (95% CI: 1.01-1.09) and 1.10 (95% CI: 1.02-1.18), respectively. Weighted restricted cubic splines revealed linear dose-response relationships between serum uric acid levels and both all-cause and cardiovascular mortality (P for nonlinear >0.05). Subgroup analyses were consistent and showed no interactions (P>0.05). Uric acid levels were not significantly associated with cancer mortality.

Conclusion

Among hypertensive diuretic users, serum uric acid is linearly and positively associated with risks of all-cause and cardiovascular mortality.

Hypertension  /  Diuretics  /  Uric acid  /  All-cause mortality  /  Cardiovascular mortality
武超, 陆妍宏, 马晶晶. 使用利尿剂的高血压患者血清尿酸水平与全因死亡以及特定疾病死亡的关联. 现代预防医学, 2026 , 53 (5) : 803 -808 . DOI: 10.20043/j.cnki.MPM.202510151
Chao WU, Yan-hong LU, Jing-jing MA. Association of serum uric acid with all-cause and cause-specific mortality among hypertensive adults using diuretics[J]. Modern Preventive Medicine, 2026 , 53 (5) : 803 -808 . DOI: 10.20043/j.cnki.MPM.202510151
正文
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据世界卫生组织《全球高血压报告》，全球高血压患者已达13亿，其所致死亡超过任何其他行为、代谢或环境因素[1-2]。利尿剂作为高血压治疗的重要药物被广泛应用，但长期使用往往会造成患者尿酸增高等不良反应的发生[3]。既往的研究表明，尿酸不仅可以引起痛风，还和多种不良健康结局密切相关，如血脂异常、糖尿病、慢性肾病、脑血管疾病等。目前的研究对于尿酸与死亡的相关性结论并不相同且存在矛盾。基于此，本研究通过使用美国国家健康和营养调查(National Health and Nutrition Examination Survey, NHANES)数据对使用利尿剂高血压患者的血清尿酸水平与全因死亡、心血管疾病相关死亡以及肿瘤相关死亡进行探讨。
1　资料与方法
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1.1　研究对象
通过提取1999—2018年NHANES数据库10个周期受访者的数据进行研究。纳入标准：高血压受访者；使用利尿剂；年龄≥18岁。排除标准：死亡数据缺失受访者；血清尿酸数据缺失者。最终确定3 744例受访者纳入研究进行分析。见图1。
1.2　高尿酸、高血压病史的界定标准以及死亡数据
高尿酸血症定义为男性血清尿酸盐水平>70 mg/L和女性血清尿酸盐水平 >60 mg/L[4]。高血压受访者界定标准由三个方面完成，满足其中一个界定为高血压患者[5-6]：（1）自我报告高血压病史；（2）使用抗高血压药物；（3）体格检查时发现平均收缩压≥140 mm Hg或舒张压≥90 mm Hg。为了确定随访期间的死亡率状况，我们利用了NHANES公共使用关联死亡率文件[7]。依据国际疾病分类第十次修订版确定的全因死亡率、心血管疾病相关死亡率和肿瘤相关死亡率。肿瘤相关死亡定义为C00～C97，心血管病死亡定义为ICD-10编码中I00～I09、I11、I13或I20～I51。
1.3　协变量的确定
本研究选择的协变量主要参考既往文献纳入[8-9]，包括人口学信息，如年龄、性别、种族、婚姻状况、家庭收入与贫困水平比、教育程度，以及生活方式如吸烟、运动等。此外，本研究还纳入患者的糖尿病、心衰、冠心病、卒中等疾病史和血清生化指标（如血清胆固醇、高密度脂蛋白、甘油三酯、肌酐水平）。
1.4　统计学处理
采用多重填补方法对缺失小于20%的数据进行填补[10]，考虑了复杂的抽样设计和按照NHANES分析准则的抽样权重[11]。权重的设计计算原则为：代表性调查样本×权重=总人口数量。基线特征描述中连续变量使用均值和标准误，分类变量的权重百分比（%）表示。使用加权Kaplan-Meier生存曲线分别绘制全因死亡、心血管相关死亡以及肿瘤相关死亡的生存曲线，并通过log-rank 检验评估不同组的生存概率差异。加权多变量Cox比例风险回归分析，以评估风险比(hazard ratio, HR)和95%置信区间(confidence interal, CI)。根据临床意义以及既往文献[8-9]，构建四个调整模型，模型1未调整协变量；模型2调整年龄、性别和婚姻状况；模型3在模型2基础上增加身体质量指数（body mass index，BMI）、运动状况、家庭收入与贫困水平比、吸烟状态、糖尿病、心衰、冠心病以及中风病史；模型4在模型3基础上增加肌酐水平以及2种以上利尿剂联用。此外，通过加权限制性立方样条回归分析血清尿酸水平与死亡的非线性关系，并使用亚组分析评估在不同人群中的一致性和交互作用。数据分析使用R语言软件（4.2.2版）以及风锐统计软件（2.3.1版）进行，检验水准α=0.05。
2　结果
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2.1　参与者的基线特征
3 744名参与者分为高尿酸组1 801人和非高尿酸组1 943人，其中全因死亡1 428人，心血管相关死亡563人，肿瘤相关死亡248人。高尿酸组人群具有更高的年龄、BMI、血清胆固醇、高密度脂蛋白、甘油三酯以及肌酐水平，糖尿病、心衰、冠心病以及卒中的患病率也更高。见表1。
2.2　使用利尿剂的高血压患者尿酸水平与死亡率的相关性
对参与者进行平均7.9年的随访，加权Kaplan-Meier生存分析表明，高尿酸组比较非高尿酸组患者全因死亡率、心血管相关疾病死亡率以及肿瘤相关死亡率显著增加（P<0.05）。见图2。将血清尿酸作为连续变量进行加权Cox回归分析。调整年龄、性别、婚姻状态、BMI、运动情况、收入水平、吸烟状态、疾病史（糖尿病、心衰、冠心病、卒中）、血清肌酐以及2种以上利尿剂联用潜在混杂因素后，血尿酸水平每增加一个单位，患者全因死亡风险增加5%（HR= 1.05，95% CI：1.01～1.09，P=0.021），患者心血管疾病相关死亡风险增加10%（HR=1.10，95% CI：1.02～1.18，P=0.011）。血清尿酸作为分类变量时，高尿酸组比较非高尿酸组患者全因死亡率和心血管疾病相关死亡率与连续变量结果一致。但对于肿瘤相关死亡率，加权Cox分析，调整潜在混杂因素后，未发现统计学差异（P>0.05）。见表2。
2.3　剂量反应关系
按照模型4调整协变量后，加权限制性立方样条曲线分别对使用利尿剂的高血压患者血清尿酸水平与全因死亡、心血管疾病相关死亡以及肿瘤相关死亡进行剂量相关性分析，血清尿酸水平与全因死亡、心血管疾病相关死亡以及肿瘤相关死亡呈现线性相关（P for nonlinear>0.05），但与全因死亡率、心血管疾病相关死亡呈现显著相关（P for overall <0.05），与肿瘤相关死亡统计学差异不显著（P for overall >0.05）。见图3。
2.4　亚组分析
在年龄、性别、BMI、糖尿病、心衰的亚组中，使用利尿剂的高血压患者血清尿酸水平与全因死亡、心血管疾病呈现正相关关系，且各组未检测到交互作用（P>0.05）。见图4。
3　讨论
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本研究的结果显示，使用利尿剂的高血压人群血清尿酸的升高与全因死亡、心血管疾病相关死亡风险显著增加有关，而血清尿酸水平与肿瘤相关死亡风险未发现统计学差异。
血清尿酸水平与全因死亡率以及心血管死亡率的关系一直存在争议。一项韩国的队列研究证实在调查的健康参与者中血清尿酸水平与全因死亡和心血管死亡之间并无关联[12]。此外，对于上海的社区队列研究发现男性和女性的尿酸水平与全因死亡以及男性中尿酸水平与心血管疾病相关死亡无显著相关性，而女性中尿酸水平与心血管疾病相关死亡显著相关[13]。上述两项研究对象均为健康人群，我们在美国使用利尿剂的人群中发现，经过调整混杂因素后，尿酸水平每增加10 mg/L，患者全因死亡风险增加5%，心血管疾病死亡风险增加10%，这一关联结果在性别等亚组中稳定存在。日本人群和意大利人群的研究中显示尿酸水平与全因死亡率显著增加有关，这些与我们的研究结果相似[14-15]。
本研究发现使用利尿剂的高血压患者中，尿酸水平与全因死亡、心血管疾病死亡风险呈现线性相关，经过模型4协变量调整后高尿酸血症的患者全因死亡风险与心血管疾病死亡风险分别是非高尿酸血症患者的1.16倍和1.27倍。先前的研究发现慢性肾衰[16]人群、脂肪性肝病人群[17]以及使用降尿酸药物人群[14]中呈现J型或者U型非线性相关，提示在不同人群中，尿酸对死亡的影响并不相同。值得注意的是，在使用利尿剂人群中关于尿酸与全因死亡关系的研究并不充分，一项关于1971—1992年美国人群的研究提出在使用利尿剂的男性人群中，血清尿酸水平与心血管死亡率之间没有关联[18]，这与我们的结果并不相同。然而，我们注意到该研究的男性样本量仅为79人且仅纳入年龄、种族、BMI、吸烟状况以及饮酒作为混杂因素进行分析，而我们的研究一共纳入10个周期的美国NHANES数据并进行了加权分析，这可能是造成结果差异的一个因素。
血清尿酸水平与肿瘤相关性死亡最早的权威证据来自瑞典马尔默地区队列研究[19]，该研究报道高尿酸血症与肿瘤相关性死亡之间存在显著的正相关，但该关联仅限于前2.5年内发生的死亡事件。随后针对老年人群的研究[20]在3年随访期内未发现高尿酸血症与肿瘤相关死亡之间的显著关联。这些报道提示血清尿酸对肿瘤相关死亡的影响可能集中于早期死亡，对晚期死亡的影响较为有限。本研究包含NHANES数据库1999—2018年10个周期内使用利尿剂的高血压患者，未观察到尿酸水平与肿瘤疾病相关死亡存在关联。
关于利尿剂、尿酸与死亡的关联机制，可能是利尿剂通过竞争性抑制基底侧OAT1/3、顶侧NPT4及MRP4等多条肾尿酸转运通路，阻断尿酸分泌并促进其重吸收[21]；同时诱发容量收缩，进一步刺激尿酸重吸收，从而升高血清尿酸。持续升高的尿酸激活NLRP3炎症小体释放IL-1β，经氧化应激与肾素-血管紧张素途径损伤内皮、减少NO生成，加速动脉粥样硬化和心肌损伤，从而增加心脑血管事件及代谢病风险，最终升高全因死亡风险[9,22]。此外，在一项对果蝇肿瘤生存的研究中表明[23]，肿瘤通过抑制肠道抗菌肽导致菌群失调并释放肽聚糖，激活肾脏NF-κB信号，诱导尿酸代谢相关基因失衡，造成血清及肾脏尿酸沉积；累积的尿酸通过抑制线粒体复合物III、增加活性氧并激活NLRP3炎症小体与IL-1β介导的炎症反应，最终促进宿主死亡。
本研究高血压患者定义通过问卷调查、体格检查以及高血压药物使用情况三个部分共同组成[24]，相对于以往文献单独使用问卷具有更加准确的人群确定，减少了人群的自我报告的偏移。使用多重插补以“插补-分析-合并”策略替代整例删除，在保全样本量的同时准确量化缺失不确定性，提升估计精度与统计效能。此外，加权样本的使用增强了我们的研究结果对更广泛的美国成年人群体的适用性。本研究存在一定的局限性。首先，关联性分析无法得出因果关系。其次，由于NHANES数据库缺少利尿剂使用起始时间以及剂量等相关数据，可能对结果造成一定的影响。最后，本研究人群全部来自美国NHANES数据，对结论的外推需谨慎。
在使用利尿剂的高血压人群中，血清尿酸水平与全因死亡和心血管疾病相关死亡风险呈现线性正相关。因此，对于该类患者应重点关注血清尿酸的变化，并针对性地开展不良生活方式以及健康教育的临床干预。

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2026年第53卷第5期
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doi: 10.20043/j.cnki.MPM.202510151
  • 接收时间：2025-10-13
  • 首发时间：2026-11-02
  • 出版时间：2026-03-10
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    苏州大学附属第四医院药学部，江苏 苏州 215000

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
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