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Article(id=1241036329186816330, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241036327177744706, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202505163, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1746979200000, receivedDateStr=2025-05-12, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773815718218, onlineDateStr=2026-03-18, pubDate=1757433600000, pubDateStr=2025-09-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773815718218, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773815718218, creator=13701087609, updateTime=1773815718218, updator=13701087609, issue=Issue{id=1241036327177744706, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='17', pageStart='3073', pageEnd='3264', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773815717738, creator=13701087609, updateTime=1773840080282, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241138511152206262, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241036327177744706, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241138511152206263, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241036327177744706, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=3080, endPage=3085, ext={EN=ArticleExt(id=1241036330940035414, articleId=1241036329186816330, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Association between circadian syndrome and frailty in middle-aged and older Chinese adults, columnId=1240413921954295836, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the relationship between circadian syndrome (CircS), changes in CircS and the progression of frailty, providing a theoretical basis for the early prevention of frailty and the development of interventions.

Methods

Based on data from the 2011—2018 China Health and Retirement Longitudinal Study (CHARLS), the frailty index (FI) was constructed using 39 health deficits to examine frailty, and CircS was diagnosed by metabolic syndrome (MetS) components, sleep and depression. Changes in CircS were obtained by comparing the status of CircS in 2011 and 2015. The relationships between CircS, changes in CircS, and the risk of frailty, as well as FI trajectories, were analyzed by Cox proportional hazards regression and linear mixed-effects models.

Results

In the fully adjusted Cox regression model, CircS was significantly associated with the risk of frailty (HR=1.604, P<0.001). Individuals with abnormal component scores of 6 (HR=2.110, P<0.001) or 7 (HR=3.136, P<0.001) showed a substantial increase in the risk of frailty compared with no CircS. Compared with persistent CircS-free individuals, those newly developing CircS (HR=2.534, P<0.001), and those with persistent CircS (HR=3.681, P<0.001) were at higher risk of frailty. In fully adjusted linear mixed-effects models, FI increased significantly faster in participants with CircS compared with individuals without CircS (β=3.932, P<0.001) and tended to increase significantly as the number of abnormal components increased (Ptrend<0.001). Participants with CircS had the greatest increase in FI compared with individuals who were persistently CircS-free (β=5.588, P<0.001). Age (P=0.013) and alcohol consumption (P=0.023) interacted with CircS, but the direction of the effect of CircS on frailty remained consistent across subgroups.

Conclusion

CircS and its changes were positively associated with the progression of frailty among Chinese middle-aged and older adults, underscoring the importance of early identification of CircS and monitoring the changes in CircS to reduce the risk of frailty and mitigate the progression of frailty.

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目的

分析昼夜节律综合征（circadian syndrome, CircS）及其变化与衰弱进展之间的关系，为衰弱早期预防及干预措施制定提供理论依据。

方法

基于中国健康与养老追踪调查（China Health and Retirement Longitudinal Study,CHARLS）2011—2018年数据，使用39个健康缺陷指标构建衰弱指数判断衰弱，CircS通过代谢综合征（metabolic syndrome, MetS）指标、睡眠和抑郁来诊断，比较2011和2015年CircS患病状况判断其变化，使用Cox回归和线性混合效应模型分析CircS及变化与衰弱发生风险、衰弱指数轨迹之间的关系。

结果

在完全校正的Cox回归模型中，CircS与衰弱发生风险的增加显著相关（HR=1.604，P<0.001）。与无CircS相比，CircS异常成分数为6（HR=2.110，P<0.001）或7（HR=3.136，P<0.001）时，衰弱风险大幅增加。与持续无CircS相比，新发CircS（HR=2.534，P<0.001）和持续患有CircS（HR=3.681，P<0.001）群体发生衰弱的风险更大。在完全校正的线性混合效应模型中，与未患CircS相比，患CircS参与者的FI增长显著加快（β=3.932，P<0.001），随着CircS异常成分数的增加，衰弱指数呈显著增长趋势（P趋势<0.001）。与持续无CircS相比，一直患CircS的参与者衰弱指数增长幅度最大（β=5.588，P<0.001）。年龄（P=0.013）和饮酒（P=0.023）与CircS具有交互作用，但在不同亚组中，CircS对衰弱影响方向保持一致。

结论

中国中老年人CircS患病及变化与衰弱存在正相关关系，强调早期识别CircS及监测CircS患病情况变化对降低衰弱发生风险及延缓衰弱进程的重要性。

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周立业，E-mail:
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点，除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=ls7NEMfJPZjLB5SaiSjCPA==, magXml=BGxqahaMKxX1Mkn7HFIFlw==, pdfUrl=null, pdf=kA/q8Ghkg5qcXVD/DDKSXA==, pdfFileSize=993112, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=op4VWwMrtNg7JHCteYixXw==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=3YVmKwO8CKr371X6hAZqwQ==, mapNumber=null, authorCompany=null, fund=null, authors=

荆晓欢（2000—），女，硕士在读，研究方向：社会医学与卫生事业管理

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荆晓欢（2000—），女，硕士在读，研究方向：社会医学与卫生事业管理

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荆晓欢（2000—），女，硕士在读，研究方向：社会医学与卫生事业管理

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JAMA Netw Open, 2022, 5(3): e223849., articleTitle=Association of habitual alcohol intake with risk of cardiovascular disease, refAbstract=null)], funds=[Fund(id=1241139378697859407, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, awardId=32301421, language=CN, fundingSource=国家自然科学基金项目(32301421), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241139371085198265, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, xref=1., ext=[AuthorCompanyExt(id=1241139371093586873, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, companyId=1241139371085198265, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Management, Shanxi Medical University, Taiyuan, Shanxi 030001, China), AuthorCompanyExt(id=1241139371101975482, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, companyId=1241139371085198265, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山西医科大学管理学院，山西 太原 030001)]), AuthorCompany(id=1241139372595147713, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, xref=2., ext=[AuthorCompanyExt(id=1241139372607730625, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, companyId=1241139372595147713, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.山西医科大学公共卫生学院卫生检验与检疫教研室)])], figs=[ArticleFig(id=1241139377473122541, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=EN, label=Figure 1, caption=Flowchart for screening the population with CircS and frailty among middle-aged and older people in China, figureFileSmall=kRmeYTFxiKEyRzJ1fOefrg==, figureFileBig=c2x0cmqLGd37XypM0gOyKg==, tableContent=null), ArticleFig(id=1241139377573785844, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=CN, label=图1, caption=中国中老年人CircS与衰弱人群筛选流程图, figureFileSmall=kRmeYTFxiKEyRzJ1fOefrg==, figureFileBig=c2x0cmqLGd37XypM0gOyKg==, tableContent=null), ArticleFig(id=1241139377716392196, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=EN, label=Figure 2, caption=Subgroup analysis and interaction of CircS with frailty and the trajectories of the FI, figureFileSmall=DA9lrPBjBfe0B0X0o4fcEA==, figureFileBig=KwYKdrTawDBZ84UCQjlwjw==, tableContent=null), ArticleFig(id=1241139377829638413, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=CN, label=图2, caption=CircS与衰弱及衰弱指数轨迹的亚组分析和交互作用

注：图A为Cox回归模型显示的亚组分析和交互作用结果；图B为线性混合效应模型显示的亚组分析和交互作用结果；图A、B调整的协变量包括年龄、性别、教育、婚姻、吸烟、饮酒、居住地、BMI。

, figureFileSmall=DA9lrPBjBfe0B0X0o4fcEA==, figureFileBig=KwYKdrTawDBZ84UCQjlwjw==, tableContent=null), ArticleFig(id=1241139377959661849, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=EN, label=Table 1, caption=

Baseline characteristics of the study population ［M（P25，P75）, n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总体非CircSCircSZ/χ2值P值
总人数5 8563 5492 307
年龄(岁)58.00(52.00～64.00)58.00(51.00～64.00)59.00(53.00～65.00)-145.159<0.001
年龄组(岁)13.172<0.001
<603 283(56.06)2 057(57.96)1 226(53.14)
≥602 573(43.94)1 492(42.04)1 081(46.86)
性别297.847<0.001
男2 661(45.44)1 934(54.49)727(31.51)
女3 195(54.56)1 615(45.51)1 580(68.49)
教育15.141<0.001
高中以下5 265(89.91)3 147(88.67)2 118(91.81)
高中及以上591(10.09)402(11.33)189(8.19)
婚姻7.3350.007
已婚或有配偶5 261(89.84)3 219(90.70)2 042(88.51)
其他595(10.16)330(9.30)265(11.49)
吸烟155.982<0.001
否3 620(61.82)1 967(55.42)1 653(71.65)
是2 236(38.18)1 582(44.58)654(28.35)
饮酒103.244<0.001
否3 928(67.08)2 202(62.05)1 726(74.82)
是1 928(32.92)1 347(37.95)581(25.18)
居住地47.014<0.001
农村3 889(66.41)2 478(69.82)1 411(61.16)
城市1 967(33.59)1 071(30.18)896(38.84)
BMI(kg/m2)23.28(21.01～25.97)22.18(20.25～24.41)25.28(22.90～27.57)-138.968<0.001
BMI分组(kg/m2)645.273<0.001
<253 930(67.11)2 828(79.68)1 102(47.77)
≥251 926(32.89)721(20.32)1 205(52.23)
FI13.24(8.60～19.20)11.65(7.84～16.69)16.22(11.04～22.64)-164.41<0.001
衰弱193.461<0.001
否5 185(88.54)3 308(93.21)1 877(81.36)
是671(11.46)241(6.79)430(18.64)
), ArticleFig(id=1241139378068713758, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=CN, label=表1, caption=

研究人群基线特征［M（P25，P75）, n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总体非CircSCircSZ/χ2值P值
总人数5 8563 5492 307
年龄(岁)58.00(52.00～64.00)58.00(51.00～64.00)59.00(53.00～65.00)-145.159<0.001
年龄组(岁)13.172<0.001
<603 283(56.06)2 057(57.96)1 226(53.14)
≥602 573(43.94)1 492(42.04)1 081(46.86)
性别297.847<0.001
男2 661(45.44)1 934(54.49)727(31.51)
女3 195(54.56)1 615(45.51)1 580(68.49)
教育15.141<0.001
高中以下5 265(89.91)3 147(88.67)2 118(91.81)
高中及以上591(10.09)402(11.33)189(8.19)
婚姻7.3350.007
已婚或有配偶5 261(89.84)3 219(90.70)2 042(88.51)
其他595(10.16)330(9.30)265(11.49)
吸烟155.982<0.001
否3 620(61.82)1 967(55.42)1 653(71.65)
是2 236(38.18)1 582(44.58)654(28.35)
饮酒103.244<0.001
否3 928(67.08)2 202(62.05)1 726(74.82)
是1 928(32.92)1 347(37.95)581(25.18)
居住地47.014<0.001
农村3 889(66.41)2 478(69.82)1 411(61.16)
城市1 967(33.59)1 071(30.18)896(38.84)
BMI(kg/m2)23.28(21.01～25.97)22.18(20.25～24.41)25.28(22.90～27.57)-138.968<0.001
BMI分组(kg/m2)645.273<0.001
<253 930(67.11)2 828(79.68)1 102(47.77)
≥251 926(32.89)721(20.32)1 205(52.23)
FI13.24(8.60～19.20)11.65(7.84～16.69)16.22(11.04～22.64)-164.41<0.001
衰弱193.461<0.001
否5 185(88.54)3 308(93.21)1 877(81.36)
是671(11.46)241(6.79)430(18.64)
), ArticleFig(id=1241139378165182757, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=EN, label=Table 2, caption=

Relationship between CircS, changes in CircS and frailty

, figureFileSmall=null, figureFileBig=null, tableContent=
变量模型1模型2模型3
HR(95%CI)P值HR(95%CI)P值HR(95%CI)P值
CircS二分类
否ref.ref.ref.
是1.871(1.680～2.083)<0.0011.654(1.481～1.847)<0.0011.604(1.426～1.803)<0.001
CircS异常成分数
<4ref.ref.ref.
41.673(1.461～1.916)<0.0011.528(1.333～1.753)<0.0011.510(1.312～1.737)<0.001
51.732(1.477～2.031)<0.0011.493(1.269～1.756)<0.0011.434(1.209～1.699)<0.001
62.571(2.116～3.124)<0.0012.200(1.807～2.680)<0.0012.110(1.721～2.586)<0.001
73.988(2.852～5.578)<0.0013.351(2.390～4.700)<0.0013.136(2.228～4.4138)<0.001
CircS变化
持续无CircSref.ref.ref.
新发CircS2.636(1.957～3.551)<0.0012.569(1.903～3.468)<0.0012.534(1.874～3.426)<0.001
CircS康复1.756(1.099～2.808)0.0191.689(1.056～2.701)0.0291.684(1.051～2.698)0.030
持续CircS4.136(2.224～7.691)<0.0013.684(1.976～6.867)<0.0013.681(1.968～6.886)<0.001
), ArticleFig(id=1241139378265846065, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=CN, label=表2, caption=

CircS及变化与衰弱的关系

, figureFileSmall=null, figureFileBig=null, tableContent=
变量模型1模型2模型3
HR(95%CI)P值HR(95%CI)P值HR(95%CI)P值
CircS二分类
否ref.ref.ref.
是1.871(1.680～2.083)<0.0011.654(1.481～1.847)<0.0011.604(1.426～1.803)<0.001
CircS异常成分数
<4ref.ref.ref.
41.673(1.461～1.916)<0.0011.528(1.333～1.753)<0.0011.510(1.312～1.737)<0.001
51.732(1.477～2.031)<0.0011.493(1.269～1.756)<0.0011.434(1.209～1.699)<0.001
62.571(2.116～3.124)<0.0012.200(1.807～2.680)<0.0012.110(1.721～2.586)<0.001
73.988(2.852～5.578)<0.0013.351(2.390～4.700)<0.0013.136(2.228～4.4138)<0.001
CircS变化
持续无CircSref.ref.ref.
新发CircS2.636(1.957～3.551)<0.0012.569(1.903～3.468)<0.0012.534(1.874～3.426)<0.001
CircS康复1.756(1.099～2.808)0.0191.689(1.056～2.701)0.0291.684(1.051～2.698)0.030
持续CircS4.136(2.224～7.691)<0.0013.684(1.976～6.867)<0.0013.681(1.968～6.886)<0.001
), ArticleFig(id=1241139378374897976, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=EN, label=Table 3, caption=

Longitudinal associations between CircS, changes in CircS and the FI

, figureFileSmall=null, figureFileBig=null, tableContent=
变量模型1模型2模型3
β(95%CI)P值β(95%CI)P值β(95%CI)P值
CircS二分类
否ref.ref.ref.
是4.569(4.161～4,977)<0.0013.925(3.520～4.330)<0.0013.932(3.508～4.355)<0.001
CircS异常成分数
<4ref.ref.ref.
54.220(3.606～4.835)<0.0013.466(2.862～4.069)<0.0013.583(2.962～4.204)<0.001
67.006(6.172～7.841)<0.0016.265(5.452～7.079)<0.0016.351(5.524～7.178)<0.001
711.727(10.263～13.191)<0.00110.833(9.410～12.255)<0.00110.867(9.446～12.288)<0.001
趋势检验<0.001<0.001<0.001
CircS变化
持续无CircSref.ref.ref.
新发CircS2.438(1.637～3.240)<0.0012.252(1.462～3.042)<0.0012.267(1.479～3.054)<0.001
CircS康复3.179(2.466～3.892)<0.0012.961(2.262～3.661)<0.0013.079(2.376～3.782)<0.001
持续CircS6.105(5.509～6.702)<0.0015.490(4.884～6.095)<0.0015.588(4.948～6.228)<0.001
), ArticleFig(id=1241139378475561281, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241036329186816330, language=CN, label=表3, caption=

CircS及CircS变化与衰弱指数之间的纵向关联

, figureFileSmall=null, figureFileBig=null, tableContent=
变量模型1模型2模型3
β(95%CI)P值β(95%CI)P值β(95%CI)P值
CircS二分类
否ref.ref.ref.
是4.569(4.161～4,977)<0.0013.925(3.520～4.330)<0.0013.932(3.508～4.355)<0.001
CircS异常成分数
<4ref.ref.ref.
54.220(3.606～4.835)<0.0013.466(2.862～4.069)<0.0013.583(2.962～4.204)<0.001
67.006(6.172～7.841)<0.0016.265(5.452～7.079)<0.0016.351(5.524～7.178)<0.001
711.727(10.263～13.191)<0.00110.833(9.410～12.255)<0.00110.867(9.446～12.288)<0.001
趋势检验<0.001<0.001<0.001
CircS变化
持续无CircSref.ref.ref.
新发CircS2.438(1.637～3.240)<0.0012.252(1.462～3.042)<0.0012.267(1.479～3.054)<0.001
CircS康复3.179(2.466～3.892)<0.0012.961(2.262～3.661)<0.0013.079(2.376～3.782)<0.001
持续CircS6.105(5.509～6.702)<0.0015.490(4.884～6.095)<0.0015.588(4.948～6.228)<0.001
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中国中老年人昼夜节律综合征与衰弱的关联性研究
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荆晓欢 1 , 付梓煊 1 , 徐晓芳 1 , 杨秀娟 2 , 周立业 1
现代预防医学 | 流行病与统计方法 2025,52(17): 3080-3085
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现代预防医学 | 流行病与统计方法 2025, 52(17): 3080-3085
中国中老年人昼夜节律综合征与衰弱的关联性研究
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荆晓欢1, 付梓煊1, 徐晓芳1, 杨秀娟2, 周立业1
作者信息
  • 1.山西医科大学管理学院，山西 太原 030001
  • 2.山西医科大学公共卫生学院卫生检验与检疫教研室

    • 荆晓欢（2000—），女，硕士在读，研究方向：社会医学与卫生事业管理

通讯作者:

周立业，E-mail:
Association between circadian syndrome and frailty in middle-aged and older Chinese adults
Xiao-huan JING1, Zi-xuan FU1, Xiao-fang XU1, Xiu-juan YANG2, Li-ye ZHOU1
Affiliations
  • School of Management, Shanxi Medical University, Taiyuan, Shanxi 030001, China
出版时间: 2025-09-10 doi: 10.20043/j.cnki.MPM.202505163
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摘要
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目的

分析昼夜节律综合征（circadian syndrome, CircS）及其变化与衰弱进展之间的关系，为衰弱早期预防及干预措施制定提供理论依据。

方法

基于中国健康与养老追踪调查（China Health and Retirement Longitudinal Study,CHARLS）2011—2018年数据，使用39个健康缺陷指标构建衰弱指数判断衰弱，CircS通过代谢综合征（metabolic syndrome, MetS）指标、睡眠和抑郁来诊断，比较2011和2015年CircS患病状况判断其变化，使用Cox回归和线性混合效应模型分析CircS及变化与衰弱发生风险、衰弱指数轨迹之间的关系。

结果

在完全校正的Cox回归模型中，CircS与衰弱发生风险的增加显著相关（HR=1.604，P<0.001）。与无CircS相比，CircS异常成分数为6（HR=2.110，P<0.001）或7（HR=3.136，P<0.001）时，衰弱风险大幅增加。与持续无CircS相比，新发CircS（HR=2.534，P<0.001）和持续患有CircS（HR=3.681，P<0.001）群体发生衰弱的风险更大。在完全校正的线性混合效应模型中，与未患CircS相比，患CircS参与者的FI增长显著加快（β=3.932，P<0.001），随着CircS异常成分数的增加，衰弱指数呈显著增长趋势（P趋势<0.001）。与持续无CircS相比，一直患CircS的参与者衰弱指数增长幅度最大（β=5.588，P<0.001）。年龄（P=0.013）和饮酒（P=0.023）与CircS具有交互作用，但在不同亚组中，CircS对衰弱影响方向保持一致。

结论

中国中老年人CircS患病及变化与衰弱存在正相关关系，强调早期识别CircS及监测CircS患病情况变化对降低衰弱发生风险及延缓衰弱进程的重要性。

昼夜节律综合征  /  衰弱  /  纵向研究  /  中老年人
Objective

To analyze the relationship between circadian syndrome (CircS), changes in CircS and the progression of frailty, providing a theoretical basis for the early prevention of frailty and the development of interventions.

Methods

Based on data from the 2011—2018 China Health and Retirement Longitudinal Study (CHARLS), the frailty index (FI) was constructed using 39 health deficits to examine frailty, and CircS was diagnosed by metabolic syndrome (MetS) components, sleep and depression. Changes in CircS were obtained by comparing the status of CircS in 2011 and 2015. The relationships between CircS, changes in CircS, and the risk of frailty, as well as FI trajectories, were analyzed by Cox proportional hazards regression and linear mixed-effects models.

Results

In the fully adjusted Cox regression model, CircS was significantly associated with the risk of frailty (HR=1.604, P<0.001). Individuals with abnormal component scores of 6 (HR=2.110, P<0.001) or 7 (HR=3.136, P<0.001) showed a substantial increase in the risk of frailty compared with no CircS. Compared with persistent CircS-free individuals, those newly developing CircS (HR=2.534, P<0.001), and those with persistent CircS (HR=3.681, P<0.001) were at higher risk of frailty. In fully adjusted linear mixed-effects models, FI increased significantly faster in participants with CircS compared with individuals without CircS (β=3.932, P<0.001) and tended to increase significantly as the number of abnormal components increased (Ptrend<0.001). Participants with CircS had the greatest increase in FI compared with individuals who were persistently CircS-free (β=5.588, P<0.001). Age (P=0.013) and alcohol consumption (P=0.023) interacted with CircS, but the direction of the effect of CircS on frailty remained consistent across subgroups.

Conclusion

CircS and its changes were positively associated with the progression of frailty among Chinese middle-aged and older adults, underscoring the importance of early identification of CircS and monitoring the changes in CircS to reduce the risk of frailty and mitigate the progression of frailty.

Circadian syndrome  /  Frailty  /  Longitudinal study  /  Middle-aged and older adults
荆晓欢, 付梓煊, 徐晓芳, 杨秀娟, 周立业. 中国中老年人昼夜节律综合征与衰弱的关联性研究. 现代预防医学, 2025 , 52 (17) : 3080 -3085 . DOI: 10.20043/j.cnki.MPM.202505163
Xiao-huan JING, Zi-xuan FU, Xiao-fang XU, Xiu-juan YANG, Li-ye ZHOU. Association between circadian syndrome and frailty in middle-aged and older Chinese adults[J]. Modern Preventive Medicine, 2025 , 52 (17) : 3080 -3085 . DOI: 10.20043/j.cnki.MPM.202505163
正文
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衰弱作为一种常见的老年综合征，表现为生理储备减少，对压力源抵抗力降低，是机体多系统累积衰退的结果[1]，增加了跌倒、疼痛、过早死亡[2-4]等不良健康结局的发生风险。随着全球人口老龄化加剧，衰弱已成为新兴健康负担。在中国大于50岁人群中衰弱患病率为13.1%[5]，并呈现随着年龄增长而增加的趋势[6]。值得注意的是，衰弱是一个动态可逆过程，识别衰弱相关危险因素并采取干预措施有利于改善衰弱状态[7]。昼夜节律综合征(circadian syndrome, CircS)由Zimmet等提出并概念化，考虑代谢疾病与昼夜节律的共同作用，将代谢综合征（metabolic syndrome, Mets）与抑郁、睡眠不足结合，加深了对多种非传染性疾病的病因学理解[8]。目前，MetS对衰弱的影响已在多项研究中证明[9-10]。而CircS与衰弱的关系，仅一项针对美国的研究显示，CircS会增加衰弱风险[11]。目前尚缺乏CircS对衰弱长期发展影响的纵向研究和中国证据，同时CircS状态变化如何影响衰弱也尚未阐明。基于此，本研究利用中国健康与养老追踪调查数据(China Health and Retirement Longitudinal Study, CHARLS)，探究中国中老年人群中，CircS及其病程转变对衰弱发生和发展趋势的影响，为早期识别衰弱风险因素和制定有效的预防策略提供科学依据。
1　对象与方法
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1.1　研究对象
本研究利用CHARLS前四期（2011、2013、2015和2018年）数据，2011年数据为基线。排除标准：（1）年龄小于45岁；（2）协变量缺失或异常；（3）血检未空腹；（4）2011和2015年CircS数据缺失；（5）2011—2018年衰弱诊断指标应答小于20%。具体流程见图1。最终，共5 856人纳入研究。符合基线标准的参与者中，5 185人仅有基线CircS数据且基线无衰弱，3 557人基线和随访数据完整，3 187人基线和随访数据完整且基线无衰弱，以上参与者进一步纳入研究。将排除缺失值后的样本与原始样本进行差异性比较，发现两样本在关键变量上不存在显著差异（P>0.05）。
1.2　衰弱指数计算及衰弱诊断
本研究使用衰弱指数评估衰弱情况[12-13]，选择39个项目计算衰弱指数，包括6项日常生活能力（如穿衣）、5项工具性生活能力（如做家务）、9项身体功能障碍（如跑1公里）、视力障碍、听力障碍、自评健康状况、自我报告的14种慢性病（如高血压）、认知功能、抑郁症状。其中日常生活能力，工具性生活能力和身体功能障碍依据完成困难程度依次赋分0、0.33、0.67、1。其中0代表没有困难，1代表无法完成。视力障碍、听力障碍、抑郁症状及慢性病中不存在健康缺陷赋分0，存在健康缺陷赋分1。自评健康状况根据严重情况赋分0、0.25、0.5、0.75和1，其中0代表很好，1代表很不好。认知功能为连续变量，取值0～1。为使样本量最大化，保留39个项目中缺失<20%的个体，同时在分子和分母中删除缺失项目[14]。将有完整数据的项目得分相加，除以项目数并乘以100，得到取值为0～100的衰弱指数，衰弱指数≥25为存在衰弱，得分越高表示衰弱越严重[15]。
1.3　CircS诊断及CircS变化
CircS由7个项目定义，包括腹式肥胖（男性腰围≥90 cm，女性腰围≥80 cm）、高空腹甘油三酯（≥1 500 mg/L或接受高甘油三酯药物治疗）、低高密度脂蛋白胆固醇（男性<400 mg/L，女性<500 mg/L或接受低高密度脂蛋白胆固醇药物治疗）、高血压（收缩压≥130 mm Hg和/或舒张压≥85 mm Hg或接受高血压药物治疗）、高血糖（空腹血糖≥1 000 mg/L或接受高血糖药物治疗）、睡眠不足（睡眠时间≤6 h）、抑郁症状（CES-D-10得分≥10），满足其中任意4项及以上可判断患有CircS[8]。CircS严重程度以异常成分数（<4、4、5、6、7）表示。CircS变化分4种，2011和2015年均未患CircS为持续无CircS人群，2011年未患CircS但2015年患有CircS为新发CircS人群，2011年患有CircS但2015年未患CircS为CircS康复人群，2011和2015年均患有CircS为持续患有CircS人群。
1.4　协变量
本研究协变量包括年龄、年龄分组（<60岁、≥60岁）、性别（男、女）、教育（高中以下、高中及以上）、婚姻（已婚或有配偶、其他）、吸烟（是、否）、饮酒（是、否）、居住地（城市、农村）、BMI、BMI分组（<25 kg/m2、≥25 kg/m2）。
1.5　统计分析
使用R 4.4.1软件进行统计分析。符合正态分布的连续变量用（）表示，不符合正态分布的连续变量用［M（P25，P75）］表示，分类变量用频数和百分比表示。使用Mann-Whitney U检验比较连续变量差异，χ2检验比较分类变量差异。使用Cox回归分析CircS与衰弱风险的关系，模型中纳入时间与暴露变量交互项，检验是否违反了比例风险假设。结果显示，交互项在统计学上不显著（P>0.05），未违反比例风险假设。使用线性混合效应模型分析CircS与衰弱指数轨迹的关系，个体差异为随机效应，随访时间和CircS为固定效应。此外，以CircS异常成分数和变化分别作为自变量重复以上分析。亚组分析中，所有协变量作为分层因素，构建Cox回归和线性混合效应模型，评估CircS在不同亚组中对衰弱及衰弱指数的效应是否存在差异。将原始数据多重插补，利用Cox回归和线性混合效应模型进行敏感性分析。检验水准α=0.05。
2　结果
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2.1　基线特征
共纳入研究5 856人，年龄中位数58岁，女性3 195(54.56%)人，衰弱者671(11.46%)人。与未患CircS相比，患有CircS人群中位年龄更大，BMI和衰弱指数得分更高，女性、高中以下学历、其他婚姻状况、不吸烟、不饮酒、城市居民组内所占比例更高。两组人群在年龄、性别、教育、婚姻、吸烟、饮酒、居住地、BMI、衰弱指数、衰弱状况上的差异均具有统计学意义（P<0.05）。见表1。
2.2　CircS及CircS变化与衰弱发生风险之间的关联
Cox回归结果显示，所有模型中CircS与衰弱均呈正相关关系，调整所有协变量后，与无CircS相比，患有CircS使衰弱风险增加60.4%（HR=1.604，P<0.001）。同时，与CircS异常成分数<4（无CircS）相比，随着CircS异常成分数为4、5、6、7时，衰弱风险依次增加51.0%（HR=1.510，P<0.001）、43.4%（HR= 1.434，P<0.001）、111.0%（HR=2.110，P<0.001）、213.6%（HR=3.136，P<0.001）。异常成分数为6和7时，衰弱发生风险大幅增加。与持续无CircS相比，持续患CircS人群中衰弱发生风险增加最多（HR= 3.681，P<0.001），其次为新发CircS（HR=2.534，P<0.001），而CircS康复人群中衰弱发生风险增加最少（HR=1.684，P=0.030）。见表2。
2.3　CircS及CircS变化与衰弱指数轨迹之间的关联
线性混合效应模型结果显示，调整所有协变量后，与无CircS相比，患有CircS的参与者衰弱指数每年增加3.932（P<0.001），随着CircS异常成分数增加，衰弱指数升高速度逐渐增快，趋势性检验显著（P<0.001），当异常成分数为7时，衰弱指数每年增长10.867（P<0.001）。与持续无CircS人群相比，新发CircS人群衰弱指数每年增加2.267（P<0.001），CircS康复人群衰弱指数每年增加3.079（P<0.001），持续患有CircS人群衰弱指数增加最多，平均每年增加5.588（P<0.001）。见表3。
2.4　亚组分析
亚组分析结果显示，不同分组中，CircS对衰弱发生风险及FI发展的影响大致一致。在Cox回归模型中，年龄因素可改变CircS对衰弱发生的影响（P=0.013）。在线性混合效应模型中，观察到饮酒与CircS具有交互作用（P=0.023）。见图2。
2.5　敏感性分析
多重插补后的样本与排除缺失值后的样本进行差异性对比，结果显示二者之间不存在显著差异（P>0.05）。敏感性分析证实了研究结果的稳健性。Cox回归中，CircS与衰弱风险呈正相关关系（P<0.001）,随着CircS异常成分数的增加，衰弱风险呈增长趋势（P<0.001）,与排除缺失值后的分析结果一致。线性混合效应模型中，与无CircS相比，CircS导致衰弱指数每年增加4.472（P<0.001）,随着CircS异常成分数的增加，衰弱指数升高速度逐渐增快（P<0.001），与排除缺失值后的分析结果相比上升幅度更大，但二者主要结果保持一致。
3　讨论
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本研究是以CHARLS 2011年数据为基线，2013、2015和2018年数据为随访进行的一项纵向研究。既往研究中，已证明高血压、糖尿病、睡眠障碍和抑郁等CircS组成成分与衰弱的关系[16-19]，而直接验证CircS与衰弱关系的研究较少。本研究强调了中国中老年人群中CircS及变化与衰弱长期发生发展的正相关关系，与Sun等[11]对美国人群研究结果一致。研究发现，CircS会增加衰弱风险，加快衰弱指数进展。CircS异常成分数与衰弱风险及衰弱指数呈正相关关系，且呈现异常成分数越多，衰弱指数增加越快的趋势。与一直未患CircS人群相比，其他三种变化显著影响衰弱发生和衰弱指数趋势，其中新发与持续患有CircS能够大幅增加衰弱风险。亚组分析中，尽管年龄和饮酒对CircS影响衰弱进展具有交互作用，但CircS对衰弱及衰弱指数的影响在不同人群中仍基本保持一致。提示可将CircS及其变化作为衰弱风险和衰弱指数进展的独立预测因子。
CircS可能通过昼夜节律紊乱和代谢相关疾病的作用对衰弱产生影响。视交叉上核(SCN)可在时钟基因作用下调节睡眠—觉醒周期，能量代谢等环节，同时影响多种组织及内分泌系统[20]。现代社会环境和生活方式可能会造成SCN功能异常，扰乱内源性昼夜节律[11,20]，导致一系列生理和心理障碍。同时，研究表明衰老与昼夜节律紊乱有内在联系，昼夜节律破坏会放大衰老危害[21-22]。而衰弱作为衰老过程中一个中间状态[23]，可能易受到昼夜节律的影响。研究发现昼夜节律紊乱可能会导致更高的衰弱风险[21]。目前昼夜节律紊乱影响衰弱的具体作用机制尚不明确，但可能与线粒体调节、氧化应激、炎症反应、胰岛素抵抗、端粒长度变化等因素有关。线粒体调节可控制氧化磷酸化，昼夜节律基因改变会影响线粒体正常调节功能，导致细胞氧化损伤，进而影响衰弱进程[24-26]。此外，随着年龄增长，线粒体发生改变，导致老年人对胰岛素抵抗增强，影响脂肪和肌肉组织功能，造成机体衰弱[27]。Chung等人[28]认为免疫系统失调和衰老过程中氧化还原状态改变会增加全身炎症状况，导致多种老年综合征发生。同时，昼夜节律紊乱会影响SIRT1（一种去乙酰化酶）表达、端粒长度及端粒酶活性，而SIRT1也会影响端粒和生物钟导致衰老和年龄相关疾病[29]。MetS作为代表多种代谢异常的临床综合征，与衰弱发生发展的关系已经明确[10,30]。值得注意的是，氧化应激、炎症反应、胰岛素抵抗等也被视为MetS与衰弱之间的潜在病理机制[31-32]。因此，昼夜节律紊乱和代谢疾病可能通过相似的机制对衰弱产生影响。了解CircS影响衰弱的生理病理机制有助于寻找预防和改善衰弱的时间窗，利用衰弱可逆的特性，在有效时间内改善衰弱状况。
本研究结果表明，与CircS二分类结果相比，以CircS异常成分数预测衰弱风险及衰弱指数轨迹能更精确地识别高风险人群。异常成分数为6或7的CircS群体衰弱风险更高，衰弱恶化速度更快。此外，新发展为CircS和持续患CircS大大增加了衰弱风险。提示应将CircS异常成分数为6或7，新发CircS和持续患CircS患者作为预防衰弱的重点人群。此外，亚组分析显示，基线无衰弱症状的个体中，年龄较小的群体更易发生衰弱，这可能是由于年轻群体代谢更加活跃，更容易受到机体功能紊乱的影响，从而导致衰弱风险增加[10]。与不饮酒群体相比，饮酒人群衰弱进展较慢。研究发现，轻中度饮酒人群心血管患病风险更低，而良好的生活习惯，社会经济条件等往往与适度饮酒相关[33]。因此，饮酒人群衰弱指数增加较慢可能与适度饮酒人群本身良好生活习惯有关。
本研究使用全国调查的CHARLS数据进行研究，样本量相对较大，研究结果具有较好的代表性。但本研究仍存在以下缺陷，首先，睡眠及衰弱诊断数据均通过自我报告的问卷获得，可能存在回忆偏差。其次，衰弱以衰弱指数进行评估，认为所有健康缺陷权重一致，忽略了不同健康问题对个体健康状况影响的差异。第三，本研究样本均来自中国，研究结果无法拓展到其他国家。最后，由于数据限制，只获得两年CircS数据，且随访时间较短，可能无法全面捕捉CircS变化对衰弱的长期影响。同时CHARLS数据中未包含膳食、营养等衰弱影响因素，未将其列入协变量进行调整。未来的研究中，应尝试进行更长时间的随访，使用更具有代表性的衰弱诊断方法，探究CircS长期变化对衰弱的影响。
综上所述，本研究发现，中国中老年群体中CircS及其变化与衰弱进展具有相关关系。强调了早期识别CircS及监测CircS变化对于制定科学管理措施来识别高危人群、预防衰弱并减缓衰弱进程的重要性。CircS有望成为中国中老年群体中预测衰弱风险及发展轨迹的有效指标。
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  • 国家自然科学基金项目(32301421)
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2025年第52卷第17期
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doi: 10.20043/j.cnki.MPM.202505163
  • 接收时间：2025-05-12
  • 首发时间：2026-03-18
  • 出版时间：2025-09-10
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  • 收稿日期：2025-05-12
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    1.山西医科大学管理学院，山西 太原 030001
    2.山西医科大学公共卫生学院卫生检验与检疫教研室

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