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Article(id=1241022944445518183, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241022939957621542, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202410137, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1728662400000, receivedDateStr=2024-10-12, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773812527047, onlineDateStr=2026-03-18, pubDate=1742832000000, pubDateStr=2025-03-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773812527047, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773812527047, creator=13701087609, updateTime=1773812527047, updator=13701087609, issue=Issue{id=1241022939957621542, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='6', pageStart='961', pageEnd='1152', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773812525976, creator=13701087609, updateTime=1773815469296, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241035285174219432, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241022939957621542, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241035285174219433, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241022939957621542, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=983, endPage=988, ext={EN=ArticleExt(id=1241022944734925166, articleId=1241022944445518183, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=A cohort study of changes in frailty status and risk of developing atrial fibrillation, columnId=1228016567443718970, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods Advances, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the association between changes in frailty status and new-onset atrial fibrillation (AF).

Methods

Based on questionnaire data and anthropometric data collected from the baseline and second repeat surveys of the UK Biobank (UKB), frailty status was assessed by the Fried frailty phenotype, categorized as non-frailty, pre-frailty or frailty, and changes in frailty status were assessed by combining frailty status at baseline and at the second repeat survey. The association between change in frailty status and new-onset AF was assessed using a Cox proportional risk model, and subgroup analyses were performed according to frailty status at the time of the second repeat survey by sex, age, overweight, hypertension, dyslipidemia and diabetes.

Results

A total of 56 394 study participants were included. In the non-frailty group, the risk of AF in those who progressed from non-frailty to pre-frailty or frailty was 1.23 times higher than in those who did not change (HR=1.23, 95% CI: 1.05-1.44, P=0.010). In the pre-frailty group, those who recovered to non-frailty and those who developed frailty had 0.74 (HR=0.74, 95% CI: 0.60-0.93, P=0.009) and 1.71 (HR=1.71, 95% CI: 1.16-2.54, P=0.007) times the risk of developing AF compared with the unchanged population, respectively. In the frailty group, the risk of AF was 0.38 times higher in those who returned to pre-frailty or non-frailty than in those who remained unchanged (HR=0.38, 95% CI: 0.16-0.87, P=0.022).

Conclusion

Worsening of frailty status increases the risk of AF occurrence, whereas recovery from frailty status decreases the risk of AF occurrence.

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目的

探究虚弱状态的变化与新发房颤的关联。

方法

基于英国生物银行（UK Biobank, UKB）基线调查和第二次重复调查收集的问卷数据和人体测量数据，通过Fried虚弱表型进行虚弱状态评估，分为非虚弱、虚弱前期或虚弱， 联合基线和第二次重复调查时的虚弱状态评估虚弱状态的变化。使用Cox比例风险模型评估虚弱状态变化与新发房颤的关联，并根据第二次重复调查时的虚弱状态按性别、年龄、是否超重、是否患高血压、是否血脂异常和是否患糖尿病进行亚组分析。

结果

共纳入56 394名研究对象。在非虚弱组中，由非虚弱发展为虚弱前期或虚弱的人群发生房颤的风险是未变化人群的1.23倍（HR=1.23，95% CI：1.05~1.44，P=0.010）。在虚弱前期组中，恢复为非虚弱的人群和发展为虚弱的人群发生房颤的风险分别是未变化人群的0.74倍（HR=0.74，95% CI：0.60~0.93，P=0.009）和 1.71倍（HR=1.71, 95% CI：1.16~2.54，P=0.007）。在虚弱组中，恢复为虚弱前期或非虚弱的人群发生房颤的风险是未变化人群的0.38倍（HR=0.38，95% CI：0.16~0.87，P=0.022）。

结论

虚弱状态的恶化会增加房颤发生的风险，而虚弱状态的恢复会降低房颤发生的风险。

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许欢，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=hPXjuytvAGg9KGxIU3u5fQ==, magXml=f72HK+LFK0/aL3srXqKr+Q==, pdfUrl=null, pdf=MlCtW2r1uy+lfqAWzOZCCA==, pdfFileSize=726998, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=sswZzRw7l+UNdbCcDwZohQ==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=OYKwkjg6yltCgD5rERH+kQ==, mapNumber=null, authorCompany=null, fund=null, authors=

程盼（1994—），女，硕士在读，研究方向：流行病与卫生统计学

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程盼（1994—），女，硕士在读，研究方向：流行病与卫生统计学

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程盼（1994—），女，硕士在读，研究方向：流行病与卫生统计学

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Open Heart, 2021, 8(2): e001624., articleTitle=Age-specific atrial fibrillation incidence, attributable risk factors and risk of stroke and mortality:results from the MORGAM Consortium, refAbstract=null), Reference(id=1241022958387384411, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, doi=null, pmid=null, pmcid=null, year=2023, volume=10, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=Wu G, Wu J, Lu Q, journalName=Frontiers in Cardiovascular Medicine, refType=null, unstructuredReference=Wu G, Wu J, Lu Q, et al. Association between cardiovascular risk factors and atrial fibrillation [J]. Frontiers in Cardiovascular Medicine, 2023, 10: 1110424., articleTitle=Association between cardiovascular risk factors and atrial fibrillation, refAbstract=null), Reference(id=1241022958479659107, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, doi=null, pmid=null, pmcid=null, year=2022, volume=12, issue=3, pageStart=3575, pageEnd=3620, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=Perazza LR, Brown-Borg HM, Thompson LV, journalName=Comprehensive Physiology, refType=null, unstructuredReference=Perazza LR, Brown-Borg HM, Thompson LV. Physiological systems in promoting frailty[J]. Comprehensive Physiology, 2022, 12(3): 3575-3620., articleTitle=Physiological systems in promoting frailty, refAbstract=null), Reference(id=1241022958567739499, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, doi=null, pmid=null, pmcid=null, year=2024, volume=38, issue=1, pageStart=14, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=Han P, Zhao XX, Li XX, journalName=Human Cell, refType=null, unstructuredReference=Han P, Zhao XX, Li XX, et al. Pathophysiology, molecular mechanisms, and genetics of atrial fibrillation[J]. Human Cell, 2024, 38(1): 14., articleTitle=Pathophysiology, molecular mechanisms, and genetics of atrial fibrillation, refAbstract=null), Reference(id=1241022958685180020, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, doi=null, pmid=null, pmcid=null, year=2022, volume=23, issue=3, pageStart=1416, pageEnd=null, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=Andelova K, Bacova BS, Sykora M, journalName=International Journal of Molecular Sciences, refType=null, unstructuredReference=Andelova K, Bacova BS, Sykora M, et al. Mechanisms underlying antiarrhythmic properties of cardioprotective agents impacting inflammation and oxidative stress[J]. International Journal of Molecular Sciences, 2022, 23(3): 1416., articleTitle=Mechanisms underlying antiarrhythmic properties of cardioprotective agents impacting inflammation and oxidative stress, refAbstract=null), Reference(id=1241022960190935164, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, doi=null, pmid=null, pmcid=null, year=2023, volume=12, issue=5, pageStart=679, pageEnd=null, url=null, language=null, rfNumber=[22], rfOrder=21, authorNames=Deng JL, Jiang YQ, Chen ZB, journalName=Cells (Basel, Switzerland), refType=null, unstructuredReference=Deng JL, Jiang YQ, Chen ZB, et al. Mitochondrial dysfunction in cardiac arrhythmias[J]. Cells (Basel, Switzerland), 2023, 12(5): 679., articleTitle=Mitochondrial dysfunction in cardiac arrhythmias, refAbstract=null), Reference(id=1241022960350318729, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, doi=null, pmid=null, pmcid=null, year=2015, volume=44, issue=3, pageStart=471, pageEnd=477, url=null, language=null, rfNumber=[23], rfOrder=22, authorNames=Theou O, O’connell M, King-Kallimanis BL, journalName=Age and Ageing, refType=null, unstructuredReference=Theou O, O’connell M, King-Kallimanis BL, et al. Measuring frailty using self-report and test-based health measures[J]. Age and Ageing, 2015, 44(3): 471-477., articleTitle=Measuring frailty using self-report and test-based health measures, refAbstract=null)], funds=[Fund(id=1241022956176987030, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, awardId=81973151; 82103943; 82073667, language=CN, fundingSource=国家自然科学基金(81973151; 82103943; 82073667), fundOrder=null, country=null), Fund(id=1241022956244095901, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, awardId=2023NSFSC0038, language=CN, fundingSource=四川省自然科学基金项目(2023NSFSC0038), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241022947331199382, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, xref=1．, ext=[AuthorCompanyExt(id=1241022947339587991, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, companyId=1241022947331199382, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Epidemiology and Health Statistics, West China School of Public Health/West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China), AuthorCompanyExt(id=1241022947347976600, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, companyId=1241022947331199382, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1．四川大学华西公共卫生学院/华西第四医院流行病与卫生统计学系，四川　成都　610041)]), AuthorCompany(id=1241022947486388640, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, xref=2．, ext=[AuthorCompanyExt(id=1241022947503165858, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, companyId=1241022947486388640, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2．四川省人民医院（电子科技大学附属医院）超声心脏电生理学与生物力学四川省重点实验室)])], figs=[ArticleFig(id=1241022953433912088, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=EN, label=Fig.1, caption=Schematic representation of frailty status transition groups, figureFileSmall=+XUIN3DFQbLWoYFWM3xbpg==, figureFileBig=sswZzRw7l+UNdbCcDwZohQ==, tableContent=null), ArticleFig(id=1241022953513603874, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=CN, label=图1, caption=虚弱状态转变分组示意图, figureFileSmall=+XUIN3DFQbLWoYFWM3xbpg==, figureFileBig=sswZzRw7l+UNdbCcDwZohQ==, tableContent=null), ArticleFig(id=1241022953706541879, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=EN, label=Fig.2, caption=Subgroup analysis of the association between frailty and incident atrial fibrillation, figureFileSmall=1Rh2ULfhiQLKdvVJTnGMOA==, figureFileBig=APAJhM3JJhKOMADh/S2ctg==, tableContent=null), ArticleFig(id=1241022953798816576, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=CN, label=图2, caption=虚弱与新发房颤关联的亚组分析, figureFileSmall=1Rh2ULfhiQLKdvVJTnGMOA==, figureFileBig=APAJhM3JJhKOMADh/S2ctg==, tableContent=null), ArticleFig(id=1241022953895285578, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=EN, label=Table 1, caption=

Basic characteristics of the participants*

, figureFileSmall=null, figureFileBig=null, tableContent=
特征变量参与者(n=56 394)房颤发病P值
否 (n=55 327)是 (n=1 067)
性别(%)<0.001
女29 509(52.3)29 148(52.7)361(33.8)
男26 885(47.7)26 179(47.3)706(66.2)
年龄(岁， %)<0.001
<6015 758(27.9)15 657(28.3)101(9.5)
≥6040 636(72.1)39 670(71.7)966(90.5)
教育程度(%)<0.001
高中及以上45 167(80.1)44 366(80.2)801(75.1)
高中以下11 024(19.5)10 760(19.4)264(24.7)
吸烟状态(%)<0.001
现在1 911(3.4)1 872(3.4)39(3.7)
从不35 176(62.4)34 605(62.5)571(53.5)
以前19 113(33.9)18 663(33.7)450(42.2)
饮酒频率(%)0.013
从不3 817(6.8)3 747(6.8)70(6.6)
偶尔5 893(10.4)5 793(10.5)100(9.4)
一个月1~3次6 484(11.5)6 369(11.5)115(10.8)
一周1~2次14 888(26.4)14 636(26.5)252(23.6)
一周3~4次15 673(27.8)15 363(27.8)310(29.1)
每天/几乎每天9 628(17.1)9 409(17.0)219(20.5)
高血压(%)<0.001
否21 725(38.5)21 468(38.8)257(24.1)
是34 669(61.5)33 859(61.2)810(75.9)
糖尿病(%)<0.001
否48 502(86.0)47 652(86.1)850(79.7)
是7 892(14.0)7 675(13.9)217(20.3)
血脂异常(%)
否24 057(42.7)23 725(42.9)332(31.1)
是32 337(57.3)31 602(57.1)735(68.9)
超重(%)<0.001
否22 555(40.0)22 208(40.1)347(32.5)
是33 839(60.0)33 119(59.9)720(67.5)
睡眠呼吸暂停综合症(%)0.15
否55 645(98.7)54 598(98.7)1 047(98.1)
是749(1.3)729(1.3)20(1.9)
心血管疾病(%)<0.001
否52 967(93.9)52 069(94.1)898(84.2)
是3 427(6.1)3 258(5.9)169(15.8)
癌症史(%)<0.001
否46 480(82.4)45 665(82.5)815(76.4)
是9 914(17.6)9 662(17.5)252(23.6)
虚弱状态(%)<0.001
非虚弱31 070(55.1)30 558(55.2)512(48.0)
虚弱前期23 967(42.5)23 466(42.4)501(47.0)
虚弱1 357(2.4)1 303(2.4)54(5.1)
), ArticleFig(id=1241022954063057749, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=CN, label=表1, caption=

参与者的基本特征描述*

, figureFileSmall=null, figureFileBig=null, tableContent=
特征变量参与者(n=56 394)房颤发病P值
否 (n=55 327)是 (n=1 067)
性别(%)<0.001
女29 509(52.3)29 148(52.7)361(33.8)
男26 885(47.7)26 179(47.3)706(66.2)
年龄(岁， %)<0.001
<6015 758(27.9)15 657(28.3)101(9.5)
≥6040 636(72.1)39 670(71.7)966(90.5)
教育程度(%)<0.001
高中及以上45 167(80.1)44 366(80.2)801(75.1)
高中以下11 024(19.5)10 760(19.4)264(24.7)
吸烟状态(%)<0.001
现在1 911(3.4)1 872(3.4)39(3.7)
从不35 176(62.4)34 605(62.5)571(53.5)
以前19 113(33.9)18 663(33.7)450(42.2)
饮酒频率(%)0.013
从不3 817(6.8)3 747(6.8)70(6.6)
偶尔5 893(10.4)5 793(10.5)100(9.4)
一个月1~3次6 484(11.5)6 369(11.5)115(10.8)
一周1~2次14 888(26.4)14 636(26.5)252(23.6)
一周3~4次15 673(27.8)15 363(27.8)310(29.1)
每天/几乎每天9 628(17.1)9 409(17.0)219(20.5)
高血压(%)<0.001
否21 725(38.5)21 468(38.8)257(24.1)
是34 669(61.5)33 859(61.2)810(75.9)
糖尿病(%)<0.001
否48 502(86.0)47 652(86.1)850(79.7)
是7 892(14.0)7 675(13.9)217(20.3)
血脂异常(%)
否24 057(42.7)23 725(42.9)332(31.1)
是32 337(57.3)31 602(57.1)735(68.9)
超重(%)<0.001
否22 555(40.0)22 208(40.1)347(32.5)
是33 839(60.0)33 119(59.9)720(67.5)
睡眠呼吸暂停综合症(%)0.15
否55 645(98.7)54 598(98.7)1 047(98.1)
是749(1.3)729(1.3)20(1.9)
心血管疾病(%)<0.001
否52 967(93.9)52 069(94.1)898(84.2)
是3 427(6.1)3 258(5.9)169(15.8)
癌症史(%)<0.001
否46 480(82.4)45 665(82.5)815(76.4)
是9 914(17.6)9 662(17.5)252(23.6)
虚弱状态(%)<0.001
非虚弱31 070(55.1)30 558(55.2)512(48.0)
虚弱前期23 967(42.5)23 466(42.4)501(47.0)
虚弱1 357(2.4)1 303(2.4)54(5.1)
), ArticleFig(id=1241022954180498270, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=EN, label=Table 2, caption=

The number and percentage change in frailty status among participants

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基线调查 (n)第二次重复调查n (%)
非虚弱(36 635)↗非虚弱23 278(63.5)
→虚弱前期13 070(35.7)
↘虚弱287(0.8)
虚弱前期(19 031)↗非虚弱7 723(40.6)
→虚弱前期10 475(55.0)
↘虚弱833(4.4)
虚弱(728)↗非虚弱69(9.5)
→虚弱前期422(58.0)
↘虚弱237(32.5)
), ArticleFig(id=1241022955715613548, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=CN, label=表2, caption=

参与者虚弱状态变化的数量和百分比

, figureFileSmall=null, figureFileBig=null, tableContent=
基线调查 (n)第二次重复调查n (%)
非虚弱(36 635)↗非虚弱23 278(63.5)
→虚弱前期13 070(35.7)
↘虚弱287(0.8)
虚弱前期(19 031)↗非虚弱7 723(40.6)
→虚弱前期10 475(55.0)
↘虚弱833(4.4)
虚弱(728)↗非虚弱69(9.5)
→虚弱前期422(58.0)
↘虚弱237(32.5)
), ArticleFig(id=1241022955854025586, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=EN, label=Table 3, caption=

Association of changes in frailty status with new-onset atrial fibrillation

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HR值（95% CI）P*
模型1a模型2b
维持非虚弱1.00[参照组]1.00[参照组]
非虚弱发展为虚弱前期/虚弱1.32(1.13~1.54)1.23(1.05~1.44)0.010
维持虚弱前期1.00[参照组]1.00[参照组]
虚弱前期恢复为非虚弱0.72(0.57~0.89)0.74(0.60~0.93)0.009
虚弱前期发展为虚弱1.92(1.31~2.84)1.71(1.16~2.54)0.007
维持虚弱1.00[参照组]1.00[参照组]
虚弱恢复为虚弱前期/非虚弱0.34(0.15~0.75)0.38(0.16~0.87)0.022
), ArticleFig(id=1241022956009214850, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241022944445518183, language=CN, label=表3, caption=

虚弱状态变化与新发房颤的关联

, figureFileSmall=null, figureFileBig=null, tableContent=
HR值（95% CI）P*
模型1a模型2b
维持非虚弱1.00[参照组]1.00[参照组]
非虚弱发展为虚弱前期/虚弱1.32(1.13~1.54)1.23(1.05~1.44)0.010
维持虚弱前期1.00[参照组]1.00[参照组]
虚弱前期恢复为非虚弱0.72(0.57~0.89)0.74(0.60~0.93)0.009
虚弱前期发展为虚弱1.92(1.31~2.84)1.71(1.16~2.54)0.007
维持虚弱1.00[参照组]1.00[参照组]
虚弱恢复为虚弱前期/非虚弱0.34(0.15~0.75)0.38(0.16~0.87)0.022
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虚弱状态变化与心房颤动发生风险的队列研究
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程盼 1 , 唐钰铃 1 , 左传隆 1 , 张婷 1 , 刘元元 1 , 郭冰 1 , 张菊英 1 , 邓燕 2 , 许欢 1 , 赵星 1
现代预防医学 | 流行病与统计方法 2025,52(6): 983-988
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现代预防医学 | 流行病与统计方法 2025, 52(6): 983-988
虚弱状态变化与心房颤动发生风险的队列研究
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程盼1, 唐钰铃1, 左传隆1, 张婷1, 刘元元1, 郭冰1, 张菊英1, 邓燕2, 许欢1 , 赵星1
作者信息
  • 1．四川大学华西公共卫生学院/华西第四医院流行病与卫生统计学系，四川　成都　610041
  • 2．四川省人民医院（电子科技大学附属医院）超声心脏电生理学与生物力学四川省重点实验室

    • 程盼（1994—），女，硕士在读，研究方向：流行病与卫生统计学

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许欢，E-mail:
A cohort study of changes in frailty status and risk of developing atrial fibrillation
Pan CHENG1, Yu-ling TANG1, Chuan-long ZUO1, Ting ZHANG1, Yuan-yuan LIU1, Bing GUO1, Ju-ying ZHANG1, Yan DENG2, Huan XU1 , Xing ZHAO1
Affiliations
  • Department of Epidemiology and Health Statistics, West China School of Public Health/West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China
出版时间: 2025-03-25 doi: 10.20043/j.cnki.MPM.202410137
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摘要
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目的

探究虚弱状态的变化与新发房颤的关联。

方法

基于英国生物银行（UK Biobank, UKB）基线调查和第二次重复调查收集的问卷数据和人体测量数据，通过Fried虚弱表型进行虚弱状态评估，分为非虚弱、虚弱前期或虚弱， 联合基线和第二次重复调查时的虚弱状态评估虚弱状态的变化。使用Cox比例风险模型评估虚弱状态变化与新发房颤的关联，并根据第二次重复调查时的虚弱状态按性别、年龄、是否超重、是否患高血压、是否血脂异常和是否患糖尿病进行亚组分析。

结果

共纳入56 394名研究对象。在非虚弱组中，由非虚弱发展为虚弱前期或虚弱的人群发生房颤的风险是未变化人群的1.23倍（HR=1.23，95% CI：1.05~1.44，P=0.010）。在虚弱前期组中，恢复为非虚弱的人群和发展为虚弱的人群发生房颤的风险分别是未变化人群的0.74倍（HR=0.74，95% CI：0.60~0.93，P=0.009）和 1.71倍（HR=1.71, 95% CI：1.16~2.54，P=0.007）。在虚弱组中，恢复为虚弱前期或非虚弱的人群发生房颤的风险是未变化人群的0.38倍（HR=0.38，95% CI：0.16~0.87，P=0.022）。

结论

虚弱状态的恶化会增加房颤发生的风险，而虚弱状态的恢复会降低房颤发生的风险。

虚弱变化  /  心房颤动  /  前瞻性研究
Objective

To investigate the association between changes in frailty status and new-onset atrial fibrillation (AF).

Methods

Based on questionnaire data and anthropometric data collected from the baseline and second repeat surveys of the UK Biobank (UKB), frailty status was assessed by the Fried frailty phenotype, categorized as non-frailty, pre-frailty or frailty, and changes in frailty status were assessed by combining frailty status at baseline and at the second repeat survey. The association between change in frailty status and new-onset AF was assessed using a Cox proportional risk model, and subgroup analyses were performed according to frailty status at the time of the second repeat survey by sex, age, overweight, hypertension, dyslipidemia and diabetes.

Results

A total of 56 394 study participants were included. In the non-frailty group, the risk of AF in those who progressed from non-frailty to pre-frailty or frailty was 1.23 times higher than in those who did not change (HR=1.23, 95% CI: 1.05-1.44, P=0.010). In the pre-frailty group, those who recovered to non-frailty and those who developed frailty had 0.74 (HR=0.74, 95% CI: 0.60-0.93, P=0.009) and 1.71 (HR=1.71, 95% CI: 1.16-2.54, P=0.007) times the risk of developing AF compared with the unchanged population, respectively. In the frailty group, the risk of AF was 0.38 times higher in those who returned to pre-frailty or non-frailty than in those who remained unchanged (HR=0.38, 95% CI: 0.16-0.87, P=0.022).

Conclusion

Worsening of frailty status increases the risk of AF occurrence, whereas recovery from frailty status decreases the risk of AF occurrence.

Changes in frailty  /  Atrial fibrillation  /  Prospective study
程盼, 唐钰铃, 左传隆, 张婷, 刘元元, 郭冰, 张菊英, 邓燕, 许欢, 赵星. 虚弱状态变化与心房颤动发生风险的队列研究. 现代预防医学, 2025 , 52 (6) : 983 -988 . DOI: 10.20043/j.cnki.MPM.202410137
Pan CHENG, Yu-ling TANG, Chuan-long ZUO, Ting ZHANG, Yuan-yuan LIU, Bing GUO, Ju-ying ZHANG, Yan DENG, Huan XU, Xing ZHAO. A cohort study of changes in frailty status and risk of developing atrial fibrillation[J]. Modern Preventive Medicine, 2025 , 52 (6) : 983 -988 . DOI: 10.20043/j.cnki.MPM.202410137
正文
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心房颤动是临床上最常见的持续性心率失常。随着全球人口老龄化和慢性病生存率的增加，房颤的发病率和患病率均在上升。2010年至2019年，全球房颤患病人数从3 350万人显著上升至5 900万，并预计将持续上升[1]。房颤与中风、心力衰竭和死亡有关，其流行趋势的加剧将造成巨大的经济和临床负担[2]。因此，早期识别并深入理解房颤的危险因素是必要的。
虚弱是一种由于多种生理系统储备减少而更易受健康压力源影响的状态[3]。越来越多的证据表明虚弱会增加不良健康后果的风险，是多种老年相关疾病（如跌倒、残疾和全因死亡率）的预测因素[4]。随着虚弱逐渐成为一种新兴的健康负担，已经引起了心脏病学界的广泛关注[5-6]。
既往研究表明，虚弱和虚弱前期可以增加房颤发生的风险[7-8]，但这些研究都只关注基线评估的虚弱状态，未考虑虚弱状态的动态变化对房颤发生风险的影响。与单一的基线虚弱状态评估相比，研究虚弱状态的变化可以更全面地反映生物学关联。更重要的是，越来越多的证据表明，经过适当的干预，虚弱状态是可以逆转的[9-10]。评估从虚弱状态中恢复的人群发生房颤的风险，对于在房颤的临床管理和治疗策略中实施针对性的虚弱干预措施至关重要。因此，迫切需要深入研究虚弱状态的动态变化与房颤发病风险之间的潜在联系。
本研究利用英国生物银行（UK Biobank, UKB）的数据研究虚弱状态的变化与房颤发病风险的关系，旨在为预防和管理老龄人口的房颤提供新的证据。
1　材料与方法
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1.1　数据来源
UKB是一项规模庞大且详尽的前瞻性研究，于2006—2010年期间招募了超过50万名年龄在40~69岁之间的参与者。该研究收集并持续获取有关参与者表型和基因型细节的数据，包括问卷调查、物理测量、样本分析、加速度计测量、多模态成像数据、全基因组基因分型信息以及长期跟踪随访的信息[11]。有关该研究收集的详细信息可通过英国生物银行官方网站查询(https://www.ukbiobank.ac.uk/)。该研究遵循赫尔辛基宣言的规定，并获得了西北多中心研究伦理委员会的批准（REC reference: 11/NW/03 820），所有参与者均签署了知情同意书。本研究利用UKB数据的申请号为117 185。
1.2　研究对象
本研究利用基线调查（2006—2010）和第二次重复调查（2014+）的数据进行分析。第二次重复调查的总人数为65 654，首先排除第二次重复调查时患有房颤的患者（n=5 569）；其次排除两次调查中任意一期暴露变量或协变量缺失的参与者（n=3 674）；再次排除无法识别患病日期的参与者（n=17）；最终，共纳入56 394名参与者。
1.3　虚弱状态变化评估
本研究采用Fried虚弱表型来评估参与者的身体虚弱状况，该指标不仅具备可修改和易测量的特性，还能够识别出如年轻人等隐藏着生理储备减少状况的个体[12]。Fried虚弱表型由 5 项标准组成，包括体重减轻、自觉疲惫、体力活动下降、步速减慢和握力下降，Fried等人在心血管健康研究中首次描述了这一表型[3]。如果个体满足上述5项中的3项或以上，则可诊断为虚弱（Frailty）；如果满足1~2项，则为虚弱前期（Pre-frailty）；如果0项则为非虚弱（Non-frailty）。为了适应UKB的数据，我们根据以往的研究对几项标准进行了调整，具体的标准可参考已出版的文章[13]。
虚弱状态的变化是联合基线和第二次重复调查时的虚弱状态来评估的，示意图如下（图1）:
1.4　协变量
参考既往文献[14]，本研究选取年龄（<60岁或≥60岁）、性别（男性或女性）、教育程度（高中及以上或高中以下）、吸烟状况（从不、现在或以前）、饮酒频率（从不、偶尔、1~3次/月、1~2次/周、3~4次/周或每天/几乎每天）、高血压（是或否）、糖尿病（是或否）、血脂异常（是或否）、超重（是或否，以BMI=25 kg/m2为界）、睡眠呼吸暂停综合症（是或否）、心血管疾病（是或否）和癌症病史（是/否）作为协变量进行后续分析。
1.5　结局定义
本研究的结局是新发房颤，根据国际疾病分类第十版修订（International Classification of Diseases 10th Revision, ICD-10）中的编码（I48）以及手术操作分类第4版（Office of Population Censuses and Surveys Classification of Interventions and Procedures version 4, OPCS-4）中的编码（K57.1, K62.1, K62.2, K62.3, K62.4, X50.1, X50.2）所定义，并从初级保健记录、住院电子健康记录以及死亡登记记录中获取。从第2次重复调查开始随访，终点为首次发生房颤事件、死亡、失访或删失（2022年12月19日），以先发生者为准。
1.6　统计分析
描述性分析中，连续变量用均数和标准差（正态分布）或中位数和四分位数间距（非正态分布）描述，而分类变量则用频数和百分比描述。
为了评估虚弱状态变化与新发房颤的关联，以各状态中维持不变者作为参照组，采用Cox比例风险模型计算各组风险比（Hazard Ratio, HR）及其95%置信区间（Confidence Interval, CI）。共拟合两个模型：模型1调整性别和年龄，模型2进一步对上述所有协变量进行调整。为了识别出更易受虚弱影响的亚人群，以第二次重复调查时参与者的虚弱状态，以非虚弱组作为参照组，根据性别、年龄、心脏代谢危险因素（高血压、糖尿病、血脂异常、超重）进行亚组分析。
上述所有模型的比例风险假设采用 Schoenfeld 残差法检验，未发现有明显违规。本研究使用R软件4.3.1版本进行数据分析及绘图。检验水准α=0.05（双侧）。
2　结果
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2.1　研究对象基本特征
表1总结了本研究参与者第二次重复调查时的基本特征。在56 394名参与者中，超过一半的研究对象为女性（29 509人，52.3%）、大于等于60岁（40 636人， 72.1%）、高中及以上学历（45 167人，80.1%）、从不吸烟（35 176人，62.4%）、患有高血压（34 669人，61.5%）、血脂异常（32 337人，57.3%）和超重（33 839人，60.0%）。在中位随访时间4.1年的期间中，共有1 067人（1.90%）发生房颤。房颤发病与未发病人群相比，男性居多、年龄较大、受教育程度更低，从不吸烟者更少，患高血压、糖尿病、血脂异常、超重，睡眠呼吸暂停综合征、心血管疾病和癌症慢性病者更多，虚弱前期和虚弱者也更多。
2.2　虚弱状态变化与新发房颤的关联
表2显示了从基线到第二次重复调查时虚弱状态发生变化的人数和百分比。在基线36 635名非虚弱的参与者中，有13 357（36.5%）人发展为虚弱前期或虚弱状态。在基线728名虚弱的参与者中，有 491（67.5%）人恢复到虚弱前期或非虚弱状态。
表3展示了虚弱状态变化与新发房颤关联的Cox比例风险模型结果。在全调整的模型2中，非虚弱组中，由非虚弱发展为虚弱前期或虚弱的人群发生房颤的风险是一直维持非虚弱人群的1.23倍（HR=1.23，95% CI：1.05~1.44，P=0.010）。在虚弱前期组中，恢复为非虚弱的人群发生房颤的风险是一直维持虚弱前期人群的0.74倍（HR=0.74，95% CI：0.60~0.93，P=0.009）；发展为虚弱的人群发生房颤的风险是一直维持虚弱前期人群的1.71倍（HR=1.71, 95% CI：1.16~2.54，P=0.007）。在虚弱组中，恢复为虚弱前期或非虚弱的人群发生房颤的风险是一直维持虚弱人群的0.38倍（HR=0.38，95% CI：0.16~0.87，P=0.022）。
2.3　亚组分析
图2展示了根据性别，年龄，是否超重，是否患高血压，是否患糖尿病、是否血脂异常进行亚组分析的结果。性别亚组中，女性和男性人群中虚弱者发生房颤的风险分别是非虚弱者的2.64倍（HR=2.64， 95% CI：1.70~4.10）和2.28倍（HR=2.28，95% CI：1.54~3.36）。年龄亚组中，小于60岁的人群中各虚弱状态发生房颤的风险没有显著差异，在大于等于60岁的人群中，虚弱者发生房颤的风险是非虚弱者的2.58倍（HR=2.58, 95% CI：1.91~3.47）。超重和未超重人群中，虚弱者发生房颤的风险分别是非虚弱者的2.33倍（HR=2.33，95% CI：1.67~3.23）和3.06倍（HR=3.06, 95% CI：1.65~5.67）。患高血压人群中，虚弱者发生房颤的风险是非虚弱者的2.46倍（HR=2.46, 95% CI：1.80~3.35），未患高血压人群中，虚弱前期者发生房颤的风险是非虚弱者的1.36倍（HR=1.36, 95% CI：1.06~1.75）。患糖尿病和未患糖尿病人群中，虚弱者发生房颤的风险分别是非虚弱者的2.83倍（HR=2.83, 95% CI：1.76~4.53）和2.13倍（HR=2.13， 95% CI：1.45~3.12）。血脂异常的人群中，虚弱者发生房颤的风险是非虚弱者的2.55倍（HR=2.55, 95% CI：1.84~3.52），血脂未发生异常的人群中，各虚弱状态发生房颤的风险没有显著差异。各分层因素与虚弱状态之间没有观察到显著的交互作用。
3　讨论
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在这项前瞻性的队列研究中，我们探讨了虚弱状态的变化与新发房颤的关联。与维持非虚弱状态的参与者相比，由非虚弱状态进展到虚弱前期/虚弱状态的参与者发生房颤的风险升高。然而，由虚弱前期恢复到非虚弱状态的参与者和由虚弱恢复到虚弱前期/非虚弱状态的参与者与其相对应状态维持不变的参与者相比，发生房颤的风险有所降低。
随着全球人口老龄化进程的加快，虚弱和房颤已日益成为重要的公共卫生问题。先前的研究表明，虚弱与房颤之间存在着密切的联系。一方面，虚弱影响房颤患者的治疗和预后[15]；另一方面，房颤会加速虚弱状态的恶化[16]。最近一项利用UKB数据的前瞻性研究进一步表明虚弱和虚弱前期会增加房颤发生的风险，相应的HR（95% CI）分别是1.47 (1.41~1.53)和1.18 (1.15~1.22)[7]；另一项关于虚弱与包括房颤在内的心率失常的研究也得出相似的结果[8]。但这些研究都只关注基线虚弱状态，未考虑虚弱状态动态变化对房颤的影响。研究虚弱的动态变化可以为房颤的预防和治疗提供了一个全面的视角。通过观察虚弱状态的变化趋势，可以预测个体未来的房颤风险，为早期干预提供依据。另外，不同的个体在虚弱状态的演变上可能存在差异，动态研究可以揭示这些差异，有助于个性化治疗。
虽然亚组分析结果显示各亚组因素与虚弱状态独立影响房颤的发生，但是在各亚组中，除了年龄小于60岁和未发生血脂异常的人群中，虚弱前期/虚弱者发生房颤的风险都显著高于非虚弱者。既往研究表明房颤发病率随年龄增长而增加，即使在调整已知风险因素的差异后，房颤的发病率也会随着年龄的增长呈指数级增加[17]。而虚弱也最常见于老年人中，因此要着重关注60岁以上人群中的虚弱管理对于房颤的影响。既往关于血脂异常与房颤的研究数据有限，并且结论不一。一些观察性研究发现了“胆固醇悖论”， 即胆固醇水平与房颤之间存在反向关系，而另一些则显示出不显著的关联[18]。未来的研究需采取更加科学严谨的方法深入探究血脂异常与房颤的关联。尽管如此，我们的研究提示在血脂异常的人群中管理虚弱也可能降低房颤发生的风险。
目前，虚弱和房颤之间的生物学机制尚不明确。但基础研究结果表明，虚弱和房颤之间有着共同的病理生理机制，如炎症、线粒体功能障碍和氧化应激等[19-20]。炎症反应涉及多种细胞因子通过不同的分子机制发挥作用，与包括心律失常在内的各种心血管病理生理状况有关[21]。此外，心肌细胞中由线粒体产生的过量活性氧能够干扰细胞的能量代谢、氧化还原状态和电生理功能，从而诱发心率失常的发生[22]。线粒体功能障碍是通过多种机制导致虚弱的主要因素，线粒体功能障碍导致的氧化应激损害各种生理过程并触发与虚弱直接相关的炎症介质的释放[19]。因此，在未来的研究中，评估炎症、线粒体功能障碍和氧化应激水平对于揭示虚弱与房颤之间的潜在机制将具有重要价值。
本研究具有重要的临床和公共卫生意义。首先，有必要将虚弱评估纳入房颤的常规管理和治疗中，特别是在老年人群中。虚弱或虚弱前期的个体应被视为预防房颤的主要目标。其次，由于虚弱状态是动态变化的，恢复到非虚弱的个体发生房颤的风险降低，因此，需要采取有效的干预措施来扭转虚弱状态。非虚弱个体也需要评估其患上虚弱的风险因素，以便及早发现高危个体，并采取相应预防措施，延缓虚弱的进展。
此外，本研究也具有一定的局限性。首先，由于房颤可能在没有明显症状的情况下发生，因此可能存在一些未被诊断的房颤事件，低估了房颤的实际发病率，从而影响虚弱对房颤风险的评估。其次，除握力外，虚弱组分和某些协变量都是自我报告的，可能会带来报告偏差。然而，一项关于虚弱评估方法的研究表明，无论虚弱是自我报告还是通过测试评估，其特征在很大程度上都是一致的[23]。再次，尽管本研究考虑了已知的混杂因素，但仍不能完全排除残余混杂因素的可能性。最后，由于本研究是观察性的，因此无法确定观察到的关联是否代表因果关系。
综上所述，虚弱状态的恶化会增加房颤发生的风险，而虚弱状态的恢复可以降低房颤发生的风险。因此，采取积极的虚弱管理措施，尤其在老年人群中，可能会有效减轻房颤所带来的疾病负担。
基金
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  • 国家自然科学基金(81973151; 82103943; 82073667)
  • 四川省自然科学基金项目(2023NSFSC0038)
文献
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2025年第52卷第6期
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doi: 10.20043/j.cnki.MPM.202410137
  • 接收时间：2024-10-12
  • 首发时间：2026-03-18
  • 出版时间：2025-03-25
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  • 收稿日期：2024-10-12
基金
国家自然科学基金(81973151; 82103943; 82073667)
四川省自然科学基金项目(2023NSFSC0038)
作者信息
    1．四川大学华西公共卫生学院/华西第四医院流行病与卫生统计学系，四川　成都　610041
    2．四川省人民医院（电子科技大学附属医院）超声心脏电生理学与生物力学四川省重点实验室

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