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Article(id=1322954325001122784, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1322954253676979072, articleNumber=null, orderNo=null, doi=10.16016/j.2097-0927.202508075, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1755964800000, receivedDateStr=2025-08-24, revisedDate=1762704000000, revisedDateStr=2025-11-10, acceptedDate=null, acceptedDateStr=null, onlineDate=1793346490382, onlineDateStr=2026-10-30, pubDate=1764432000000, pubDateStr=2025-11-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793346490382, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793346490382, creator=13701087609, updateTime=1793346490382, updator=13701087609, issue=Issue{id=1322954253676979072, tenantId=1146029695717560320, journalId=1319373162502258839, year='2025', volume='47', issue='22', pageStart='2725', pageEnd='2880', issueExtLink='null', onlineDate='null', pubDate='1764432000000', pubDateStr='2025-11-30', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793346473378, creator='13701087609', updateTime=1793346473378, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=2805, endPage=2813, ext={EN=ArticleExt(id=1322954325441524705, articleId=1322954325001122784, tenantId=1146029695717560320, journalId=1319373162502258839, language=EN, title=Elevated risk of recurrent stroke in females after patent foramen ovale closure for cryptogenic stroke:A 4-year retrospective cohort study, columnId=1320435174995772212, journalTitle=Journal of Army Medical University, columnName=Clinical Medicine, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the effect of gender on prognosis after transcatheter patent foramen ovale (PFO) closure in patients with cerebral infarction or transient ischemic attack.

Methods

A retrospective cohort study was conducted involving patients with cerebral infarction or transient ischemic attack (TIA) who underwent PFO closure at our hospital between January 2013 and December 2023. The patients were grouped by gender, and related data were collected, including age, comorbidities, Risk of Paradoxical Embolism (RoPE) score, laboratory results, findings of transthoracic/transesophageal echocardiography (TTE/TEE), and post-procedural complications, such as device-related thrombosis (DRT), recurrent stroke, bleeding, and atrial fibrillation (AF).

Results

A total of 112 patients were enrolled, including 59 males and 53 females, at a mean age of 42.47±12.35 years. The females had significantly higher preoperative RoPE score than the males (6.6±1.4 vs 6.0±1.5, P=0.046), and a statistical difference was observed in the distribution of infarction sites between them (Chi-square=10.25, P=0.006), indicating that the males were prone to posterior circulation infarction. Intraoperative transthoracic echocardiography revealed a greater distance from the PFO to the aortic root in the females (9.3±2.4 mm vs 7.6±2.0 mm, P<0.001). During a median follow-up of 4 years, the male group had 1 case of myocardial infarction, 1 cerebral hemorrhage, 1 paroxysmal AF, 2 gingival bleeding episodes, and 1 skin ecchymosis. In the female group, 1 case experienced pulmonary embolism, 1 paroxysmal atrial fibrillation, 3 gingival bleeding episodes, 2 skin ecchymoses, 2 recurrent cerebral infarctions, and 2 recurrent TIAs. There was no statistical difference in overall adverse events between gender (P=0.291). Although the females had higher rates of recurrent cerebral infarction and TIA, this difference lacked statistical significance (P=0.222). Multivariate Cox regression analysis indicated that after adjusting for various potential confounding factors, such as RoPE score, age, hypertension, coronary heart disease, and other factors, gender was not an independent predictor of composite endpoint events after surgery.

Conclusion

Gender does not significantly affect overall prognosis after PFO closure in patients with cerebral infarction or TIA. However, females showed a trend toward higher rates of recurrent cerebral infarction and TIA.

, authors=Weiwei XIAO1, 2, Feng LIU1, 2, Chen WAN1, 2, Xiang XU1, 2, Hao GAO1, 2, Xiaolong LI1, 2, Xin WEI1, 2, Zhiyuan SONG1, 2, Huakang LI1, 2, authorsList=Weiwei XIAO, Feng LIU, Chen WAN, Xiang XU, Hao GAO, Xiaolong LI, Xin WEI, Zhiyuan SONG, Huakang LI, authorCompany=null, correspAuthors=Huakang LI, authorNote=null, correspAuthorsNote=null, copyrightStatement=© 2025 Journal of Army Medical University, copyrightOwner=Editorial Office of Journal of Army Medical University, 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=1322954327467373541, articleId=1322954325001122784, tenantId=1146029695717560320, journalId=1319373162502258839, language=CN, title=女性隐源性卒中患者卵圆孔未闭封堵术后卒中复发风险存在升高趋势：一项随访4年的回顾性队列研究, columnId=1320435175822050102, journalTitle=陆军军医大学学报, columnName=论著·临床医学, runingTitle=null, highlight=null, articleAbstract=
目的

探讨性别对卵圆孔未闭（patent foramen ovale，PFO）合并脑梗死/短暂性脑缺血发作（transient ischemic attack，TIA）患者卵圆孔未闭封堵术预后的影响。

方法

采用回顾性队列研究，纳入2013年1月至2023年12月于陆军军医大学第一附属医院住院并行卵圆孔未闭封堵术的脑梗死或 TIA患者为研究对象。按性别进行分组，收集患者的资料，包括年龄、合并的基础疾病、反常栓塞风险评分（the Risk of Paradoxical Embolism Score，RoPE）评分、检验资料、经胸和经食道超声心动图结果等；术后随访中记录了器械相关血栓（device-related thrombosis，DRT）、卒中、出血和心房颤动等并发症。

结果

一共112例患者选入本研究，其中男性59例，女性53例，平均年龄42.47±12.35岁。女性术前RoPE评分显著高于男性（6.6±1.4 vs 6.0±1.5，P=0.046），二者在梗死部位分布存在性别差异趋势（χ²=10.25，P=0.006），男性更易发生后循环梗死。术中经胸超声测量显示，女性卵圆孔距主动脉根部距离显著大于男性（9.3±2.4 vs 7.6±2.0，P<0.001）。术后中位随访期4年，男性组发生心肌梗死1例、脑出血1例、阵发性心房颤动1例、牙龈出血2例、皮肤淤青1例；女性组发生肺栓塞1例、阵发性心房颤动1例、牙龈出血3例、皮肤淤青2例、脑梗死复发2例、TIA复发2例。总体不良事件发生率方面二者无统计学差异（P=0.291），女性组在脑梗死和TIA复发率方面高于男性，但二者相比无统计学差异（P=0.222）。通过多因素Cox回归分析，并在校正了包括RoPE评分、年龄、高血压、冠心病等多种潜在混杂因素后，本研究结果表明，性别并非患者术后复合终末事件的独立预测因素。

结论

PFO合并脑梗死/TIA患者行卵圆孔未闭封堵术对预后的影响无性别差异，但是女性在脑梗死及TIA复发方面较男性有增加趋势。

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李华康，E-mail：
LIHuakang，E-mail：
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Clin Focus，2023，38（6）：500-503., articleTitle=Analysis of demographic，clinical and imaging in patients with acute cerebral infarction caused by patent foramen ovale, refAbstract=null), Reference(id=1322954343057600587, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, doi=10.1161/JAHA.123.030359, pmid=null, pmcid=null, year=2023, volume=12, issue=19, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=22, rfOrder=18, authorNames=FARJAT-PASOS J I, GUEDENEY P, HOUDE C, journalName=J Am Heart Assoc, refType=null, unstructuredReference=FARJAT-PASOS J I，GUEDENEY P，HOUDE C，et al. Sex differences in patients with cryptogenic cerebrovascular events undergoing transcatheter closure of patent foramen ovale［J］. J Am Heart Assoc，2023，12（19）：e030359., articleTitle=Sex differences in patients with cryptogenic cerebrovascular events undergoing transcatheter closure of patent foramen ovale, refAbstract=null), Reference(id=1322954343128903756, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, doi=10.1016/j.ahjo.2022.100199, pmid=null, pmcid=null, year=2022, volume=21, issue=null, pageStart=100199, pageEnd=null, url=null, language=null, rfNumber=23, rfOrder=19, authorNames=ASGHAR A, STEFANESCU SCHMIDT A C, SAHAKYAN Y, journalName=Am Heart J Plus, refType=null, unstructuredReference=ASGHAR A，STEFANESCU SCHMIDT A C，SAHAKYAN Y，et al. Sex differences in baseline profiles and short-term outcomes in patients undergoing closure of patent foramen ovale［J］. Am Heart J Plus，2022，21：100199., articleTitle=Sex differences in baseline profiles and short-term outcomes in patients undergoing closure of patent foramen ovale, refAbstract=null), Reference(id=1322954343367979085, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, doi=null, pmid=null, pmcid=null, year=2022, volume=49, issue=3, pageStart=376, pageEnd=383, url=null, language=null, rfNumber=24, rfOrder=20, authorNames=张蕾, 张晓春, 张源, journalName=复旦学报（医学版）, refType=null, unstructuredReference=张蕾，张晓春，张源，等. 老年卵圆孔未闭患者经导管封堵效果的单中心分析［J］. 复旦学报（医学版），2022，49（3）：376-383., articleTitle=老年卵圆孔未闭患者经导管封堵效果的单中心分析, refAbstract=null), Reference(id=1322954343439282254, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, doi=null, pmid=null, pmcid=null, year=2022, volume=49, issue=3, pageStart=376, pageEnd=383, url=null, language=null, rfNumber=24, rfOrder=21, authorNames=ZHANG L, ZHANG X C, ZHANG Y, journalName=Fudan Univ J Med Sci, refType=null, unstructuredReference=ZHANG L，ZHANG X C，ZHANG Y，et al. Single-center efficacy analysis of transcatheter closure for elderly patients with patent foramen ovale［J］. Fudan Univ J Med Sci，2022，49（3）：376-383., articleTitle=Single-center efficacy analysis of transcatheter closure for elderly patients with patent foramen ovale, refAbstract=null), Reference(id=1322954343502196815, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, doi=10.1007/s00392-023-02263-8, pmid=null, pmcid=null, year=2023, volume=112, issue=12, pageStart=1824, pageEnd=1834, url=null, language=null, rfNumber=25, rfOrder=22, authorNames=JURCZYK D, MACHEREY-MEYER S, RAWISH E, journalName=Clin Res Cardiol, refType=null, unstructuredReference=JURCZYK D，MACHEREY-MEYER S，RAWISH E，et al. New-onset atrial fibrillation after percutaneous patent foramen ovale closure：a meta-analysis［J］. Clin Res Cardiol，2023，112（12）：1824-1834., articleTitle=New-onset atrial fibrillation after percutaneous patent foramen ovale closure：a meta-analysis, refAbstract=null), Reference(id=1322954343728689232, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, doi=10.1093/eurheartj/ehad305, pmid=null, pmcid=null, year=2023, volume=44, issue=36, pageStart=3469, pageEnd=3477, url=null, language=null, rfNumber=26, rfOrder=23, authorNames=SKIBSTED C V, KORSHOLM K, PEDERSEN L, journalName=Eur Heart J, refType=null, unstructuredReference=SKIBSTED C V，KORSHOLM K，PEDERSEN L，et al. Long-term risk of atrial fibrillation or flutter after transcatheter patent foramen ovale closure：a nationwide Danish study［J］. Eur Heart J，2023，44（36）：3469-3477., articleTitle=Long-term risk of atrial fibrillation or flutter after transcatheter patent foramen ovale closure：a nationwide Danish study, refAbstract=null), Reference(id=1322954343804186706, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, doi=10.1001/jamaneurol.2020.2619, pmid=null, pmcid=null, year=2020, volume=77, issue=12, pageStart=1479, pageEnd=1480, url=null, language=null, rfNumber=27, rfOrder=24, authorNames=ROHATGI N, SMILOWITZ N R, LANSBERG M G, journalName=JAMA Neurol, refType=null, unstructuredReference=ROHATGI N，SMILOWITZ N R，LANSBERG M G. Perioperative stroke risk reduction in patients with patent foramen ovale［J］. JAMA Neurol，2020，77（12）：1479-1480., articleTitle=Perioperative stroke risk reduction in patients with patent foramen ovale, refAbstract=null), Reference(id=1322954343879684179, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, doi=10.1002/ccd.30019, pmid=null, pmcid=null, year=2022, volume=99, issue=5, pageStart=1551, pageEnd=1557, url=null, language=null, rfNumber=28, rfOrder=25, authorNames=ANDERSEN A, MATZEN K L, ANDERSEN G, journalName=Catheter Cardiovasc Interv, refType=null, unstructuredReference=ANDERSEN A，MATZEN K L，ANDERSEN G，et al. Atrial fibrillation after closure of patent foramen ovale in the REDUCE clinical study［J］. Catheter Cardiovasc Interv，2022，99（5）：1551-1557., articleTitle=Atrial fibrillation after closure of patent foramen ovale in the REDUCE clinical study, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1322954328717276134, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, xref=1, ext=[AuthorCompanyExt(id=1322954328725664743, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, companyId=1322954328717276134, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Cardiovascular Medicine，Laboratory of Chronobiology and Cardiometabolic Disease), AuthorCompanyExt(id=1322954328734053352, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, companyId=1322954328717276134, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院心血管内科，代谢生物钟与心血管疾病中心)]), AuthorCompany(id=1322954329107346409, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, xref=2, ext=[AuthorCompanyExt(id=1322954329124123626, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, companyId=1322954329107346409, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease，Ministry of Education，First Affiliated Hospital，Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954329136706539, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, companyId=1322954329107346409, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2老年心脑血管病教育部重点实验室，重庆)])], figs=[ArticleFig(id=1322954337697280044, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=EN, label=Figure 1, caption=Kaplan-Meier survival curves for composite endpoint events after PFO closure，stratified by gender, figureFileSmall=y1TDk5NcEZ3llFnP+z2Bnw==, figureFileBig=ePy02A5fcIf+Ksh3gMtlAw==, tableContent=null), ArticleFig(id=1322954337772777517, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=CN, label=图1, caption=不同性别PFO封堵术后患者复合终末事件的生存曲线

Composite endpoint events include pulmonary embolism，myocardial infarction，cerebral hemorrhage，paroxysmal atrial fibrillation，recurrent cerebral infarction/transient ischemic attack （TIA），gingival bleeding，and ecchymosis. PFO：Patent foramen ovale

, figureFileSmall=y1TDk5NcEZ3llFnP+z2Bnw==, figureFileBig=ePy02A5fcIf+Ksh3gMtlAw==, tableContent=null), ArticleFig(id=1322954337944743982, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=EN, label=Table 1, caption=

Baseline characteristics of 112 patients with PFO and cerebral infarction/TIA ［x¯±s，n （%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Baseline characteristicsMale（n=59）Female（n=53）t/χ²Pvalue
Age / years44±13.240.8±11.21.3860.169
BMI / （kg/m²）23.6±3.623.0±3.5-0.6050.546
RoPE score6.0±1.56.6±1.4-2.0160.046
Smoking history32 （54.2）1 （1.9）36.817<0.001
TIA7 （11.9）10 （18.9）1.0640.302
Cerebral infarction52 （88.1）43 （81.1）1.0000.317
Hypertension8 （13.5）14 （26.5）2.9230.087
Coronary heart disease5 （8.5）4 （7.5）01.000
Hyperlipidemia8 （13.5）4 （7.5）1.0550.304
Cerebral infarction site10.2500.006
Anterior circulation29（55.8）37（86.0）
Posterior circulation12（23.1）3（7.0）
Anterior and posterior circulation11（21.1）3（7.0）
), ArticleFig(id=1322954338020241455, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=CN, label=表1, caption=

112例PFO合并脑梗死/TIA患者的基线特征 ［x¯±s，例（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Baseline characteristicsMale（n=59）Female（n=53）t/χ²Pvalue
Age / years44±13.240.8±11.21.3860.169
BMI / （kg/m²）23.6±3.623.0±3.5-0.6050.546
RoPE score6.0±1.56.6±1.4-2.0160.046
Smoking history32 （54.2）1 （1.9）36.817<0.001
TIA7 （11.9）10 （18.9）1.0640.302
Cerebral infarction52 （88.1）43 （81.1）1.0000.317
Hypertension8 （13.5）14 （26.5）2.9230.087
Coronary heart disease5 （8.5）4 （7.5）01.000
Hyperlipidemia8 （13.5）4 （7.5）1.0550.304
Cerebral infarction site10.2500.006
Anterior circulation29（55.8）37（86.0）
Posterior circulation12（23.1）3（7.0）
Anterior and posterior circulation11（21.1）3（7.0）
), ArticleFig(id=1322954338091544624, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=EN, label=Table 2, caption=

Preoperative echocardiographic features of the participants ［x¯±s，n （%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Baseline characteristicsMale（n=59）Female（n=53）t/χ²Pvalue
Transesophageal echocardiography
No shunt7（11.9）3（5.7）0.6690.413
Patent foramen ovale width /mm1.90±0.801.81±0.500.4620.462
Atrial septal aneurysm01（1.9）0.2940.473
Long tunnel type3（5.1）01.1620.281
Right-to-left shunt at rest7.7400.052
Grade 010（17.0）11（20.8）
Grade I23（39.0）26（49.1）
Grade II18（30.5）5（9.4）
Grade Ⅲ8（13.6）11（20.8）
Right-to-left shunt under valsalva maneuver0.527
Grade 03（5.1）1（1.9）
Grade I5（8.5）9（17.0）
Grade II18（30.5）15（28.3）
Grade Ⅲ33（55.9）28（52.8）
Stroke volume /mL68.3±9.762.0±11.93.0560.003
Left ventricular end-diastolic volume /mL106.1±12.496.6±17.33.3020.001
Left ventricular ejection fraction /%64.3±4.564.0±5.50.3140.754
Right atrial diameter /mm19.3±1.418.9±1.21.4420.152
Right atrial transverse diameter /mm33.9±3.332.6±5.41.5180.132
Left atrial anteroposterior diameter/ mm33.6±3.432.7±4.31.3290.186
Left ventricular internal dimension /mm47.1±2.744.9±2.94.169<0.001
Pulmonary artery diameter /mm20.2±1.119.7±1.42.4020.018
Ascending aorta diameter /mm30.7±3.229.6±2.92.0180.046
Interventricular septum thickness /mm10.1±1.59.3±1.72.4700.015
Left ventricular posterior wall thickness /mm9.4±1.88.7±1.02.2750.025
), ArticleFig(id=1322954338192207921, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=CN, label=表2, caption=

患者术前超声特征 ［x¯±s，例（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Baseline characteristicsMale（n=59）Female（n=53）t/χ²Pvalue
Transesophageal echocardiography
No shunt7（11.9）3（5.7）0.6690.413
Patent foramen ovale width /mm1.90±0.801.81±0.500.4620.462
Atrial septal aneurysm01（1.9）0.2940.473
Long tunnel type3（5.1）01.1620.281
Right-to-left shunt at rest7.7400.052
Grade 010（17.0）11（20.8）
Grade I23（39.0）26（49.1）
Grade II18（30.5）5（9.4）
Grade Ⅲ8（13.6）11（20.8）
Right-to-left shunt under valsalva maneuver0.527
Grade 03（5.1）1（1.9）
Grade I5（8.5）9（17.0）
Grade II18（30.5）15（28.3）
Grade Ⅲ33（55.9）28（52.8）
Stroke volume /mL68.3±9.762.0±11.93.0560.003
Left ventricular end-diastolic volume /mL106.1±12.496.6±17.33.3020.001
Left ventricular ejection fraction /%64.3±4.564.0±5.50.3140.754
Right atrial diameter /mm19.3±1.418.9±1.21.4420.152
Right atrial transverse diameter /mm33.9±3.332.6±5.41.5180.132
Left atrial anteroposterior diameter/ mm33.6±3.432.7±4.31.3290.186
Left ventricular internal dimension /mm47.1±2.744.9±2.94.169<0.001
Pulmonary artery diameter /mm20.2±1.119.7±1.42.4020.018
Ascending aorta diameter /mm30.7±3.229.6±2.92.0180.046
Interventricular septum thickness /mm10.1±1.59.3±1.72.4700.015
Left ventricular posterior wall thickness /mm9.4±1.88.7±1.02.2750.025
), ArticleFig(id=1322954338292871218, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=EN, label=Table 3, caption=

Intraoperative outcomes of the patients after intervention therapy ［x¯±s，n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Intraoperative parametersMale（n=59）Female（n=53）tPvalue
Right atrial systolic pressure /mmHg11.5±3.111.8±4.2-0.4660.642
Right atrial diastolic pressure /mmHg3.6±2.73.7±3.1-0.2110.825
Right atrial mean pressure /mmHg6.6±2.87.1±3.4-0.7290.468
Right ventricular systolic pressure /mmHg32.8±6.431.8±6.80.7910.431
Right ventricular diastolic pressure /mmHg4.0±3.63.4±3.90.7720.381
Right ventricular mean pressure /mmHg14.1±3.614.0±4.00.1690.866
Pulmonary artery systolic pressure /mmHg29.6±5.828.3±6.21.1400.257
Pulmonary artery diastolic pressure /mmHg11.3±5.210.7±3.90.7170.475
Pulmonary artery mean pressure /mmHg17.9±4.617.1±4.30.8660.388
Distance from foramen ovale to aortic root /mm7.6±2.09.3±2.4-4.040<0.001
Occluder size0.392
18/1802（3.8）
25/2554（91.5）49（92.5）
30/304（6.8）2（3.8）
Atrial septal defect occluder （24 mm）1（1.7）0
), ArticleFig(id=1322954338389340211, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=CN, label=表3, caption=

患者介入术中结果 ［x¯±s，例（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Intraoperative parametersMale（n=59）Female（n=53）tPvalue
Right atrial systolic pressure /mmHg11.5±3.111.8±4.2-0.4660.642
Right atrial diastolic pressure /mmHg3.6±2.73.7±3.1-0.2110.825
Right atrial mean pressure /mmHg6.6±2.87.1±3.4-0.7290.468
Right ventricular systolic pressure /mmHg32.8±6.431.8±6.80.7910.431
Right ventricular diastolic pressure /mmHg4.0±3.63.4±3.90.7720.381
Right ventricular mean pressure /mmHg14.1±3.614.0±4.00.1690.866
Pulmonary artery systolic pressure /mmHg29.6±5.828.3±6.21.1400.257
Pulmonary artery diastolic pressure /mmHg11.3±5.210.7±3.90.7170.475
Pulmonary artery mean pressure /mmHg17.9±4.617.1±4.30.8660.388
Distance from foramen ovale to aortic root /mm7.6±2.09.3±2.4-4.040<0.001
Occluder size0.392
18/1802（3.8）
25/2554（91.5）49（92.5）
30/304（6.8）2（3.8）
Atrial septal defect occluder （24 mm）1（1.7）0
), ArticleFig(id=1322954338506780724, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=EN, label=Table 4, caption=

Outcomes of endpoint events in the patients after surgery ［x¯±s，n （%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Endpoint eventsMale
（n=59）		Female
（n=53）		χ²Pvalue
Pulmonary embolism01（1.9）0.473
Myocardial infarction1（1.7）01.000
Cerebral hemorrhage1（1.7）01.000
Atrial fibrillation1（1.7）1（1.9）1.000
Recurrent cerebral infarction02（3.8）0.222
Recurrent TIA02（3.8）0.478
Gingival bleeding2（3.4）3（5.7）0.907
Skin bruising1（1.7）2（3.8）0.616
Total terminal events6（10.1）9（17.0）1.120.291
Post-cerebral infarction symptoms9（17.3）2（4.7）2.550.110
), ArticleFig(id=1322954338703913013, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=CN, label=表4, caption=

患者终末事件结果 ［x¯±s，例（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Endpoint eventsMale
（n=59）		Female
（n=53）		χ²Pvalue
Pulmonary embolism01（1.9）0.473
Myocardial infarction1（1.7）01.000
Cerebral hemorrhage1（1.7）01.000
Atrial fibrillation1（1.7）1（1.9）1.000
Recurrent cerebral infarction02（3.8）0.222
Recurrent TIA02（3.8）0.478
Gingival bleeding2（3.4）3（5.7）0.907
Skin bruising1（1.7）2（3.8）0.616
Total terminal events6（10.1）9（17.0）1.120.291
Post-cerebral infarction symptoms9（17.3）2（4.7）2.550.110
), ArticleFig(id=1322954338787799094, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=EN, label=Table 5, caption=

Multivariate cox regression analysis of gender impact on composite endpoint

, figureFileSmall=null, figureFileBig=null, tableContent=
VariableβSEWaldPvalueHazard Ratio95% CI
Adjusted for RoPE score
Gender （male vs female）0.6600.5351.5210.2171.940.68~5.53
RoPE score-0.2940.1752.8190.0930.750.53~1.05
Adjusted for hypertension
Gender （male vs female）0.4670.5390.7520.3861.600.56~4.59
Hypertension （yes vs no）-0.2950.5960.2440.6210.750.23~2.40
Adjusted for age
Gender （male vs female）0.5700.5331.1460.2841.770.62~5.02
Age0.0200.0220.8570.3541.020.98~1.07
Adjusted for smoking
Gender （male vs female）0.7750.7271.1350.2872.170.52~9.02
Smoking （yes vs no）-0.4530.8050.3160.5740.640.13~3.08
Adjusted for coronary heart disease
Gender （male vs female）0.5230.5290.9790.3231.690.60~4.75
Coronary heart disease （yes vs no）-1.3050.6524.0070.0450.270.08~0.97
Adjusted for left ventricular posterior wall thickness
Gender （male vs female）0.8760.5762.3140.1282.400.78~7.43
Left ventricular posterior wall thickness0.3110.09311.0300.0011.371.14~1.64
Adjusted for left ventricular wall and coronary heart disease
Gender （male vs female）0.7720.5661.8620.1722.170.71~6.56
Coronary heart disease-0.8980.6771.7600.1850.410.19~0.91
Left ventricular posterior wall thickness0.2880.1018.1980.0041.331.10~1.62
), ArticleFig(id=1322954338859102263, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954325001122784, language=CN, label=表5, caption=

性别对复合终末影响的多因素Cox回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
VariableβSEWaldPvalueHazard Ratio95% CI
Adjusted for RoPE score
Gender （male vs female）0.6600.5351.5210.2171.940.68~5.53
RoPE score-0.2940.1752.8190.0930.750.53~1.05
Adjusted for hypertension
Gender （male vs female）0.4670.5390.7520.3861.600.56~4.59
Hypertension （yes vs no）-0.2950.5960.2440.6210.750.23~2.40
Adjusted for age
Gender （male vs female）0.5700.5331.1460.2841.770.62~5.02
Age0.0200.0220.8570.3541.020.98~1.07
Adjusted for smoking
Gender （male vs female）0.7750.7271.1350.2872.170.52~9.02
Smoking （yes vs no）-0.4530.8050.3160.5740.640.13~3.08
Adjusted for coronary heart disease
Gender （male vs female）0.5230.5290.9790.3231.690.60~4.75
Coronary heart disease （yes vs no）-1.3050.6524.0070.0450.270.08~0.97
Adjusted for left ventricular posterior wall thickness
Gender （male vs female）0.8760.5762.3140.1282.400.78~7.43
Left ventricular posterior wall thickness0.3110.09311.0300.0011.371.14~1.64
Adjusted for left ventricular wall and coronary heart disease
Gender （male vs female）0.7720.5661.8620.1722.170.71~6.56
Coronary heart disease-0.8980.6771.7600.1850.410.19~0.91
Left ventricular posterior wall thickness0.2880.1018.1980.0041.331.10~1.62
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肖巍巍 1, 2 , 刘锋 1, 2 , 万陈 1, 2 , 许祥 1, 2 , 高昊 1, 2 , 李小龙 1, 2 , 魏欣 1, 2 , 宋治远 1, 2 , 李华康 1, 2
陆军军医大学学报 | 论著·临床医学 2025,47(22): 2805-2813
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陆军军医大学学报 |论著·临床医学 2025 , 47 (22) : 2805 -2813
女性隐源性卒中患者卵圆孔未闭封堵术后卒中复发风险存在升高趋势：一项随访4年的回顾性队列研究
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肖巍巍1, 2, 刘锋1, 2, 万陈1, 2, 许祥1, 2, 高昊1, 2, 李小龙1, 2, 魏欣1, 2, 宋治远1, 2, 李华康1, 2
作者信息
  • 1陆军军医大学（第三军医大学）第一附属医院心血管内科，代谢生物钟与心血管疾病中心
  • 2老年心脑血管病教育部重点实验室，重庆
通讯作者:
李华康，E-mail：
LIHuakang，E-mail：
Elevated risk of recurrent stroke in females after patent foramen ovale closure for cryptogenic stroke:A 4-year retrospective cohort study
Weiwei XIAO1, 2, Feng LIU1, 2, Chen WAN1, 2, Xiang XU1, 2, Hao GAO1, 2, Xiaolong LI1, 2, Xin WEI1, 2, Zhiyuan SONG1, 2, Huakang LI1, 2
Affiliations
  • 1Department of Cardiovascular Medicine，Laboratory of Chronobiology and Cardiometabolic Disease
  • 2Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease，Ministry of Education，First Affiliated Hospital，Army Medical University （Third Military Medical University），Chongqing，China
出版时间: 2025-11-30 doi: 10.16016/j.2097-0927.202508075
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摘要
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目的

探讨性别对卵圆孔未闭（patent foramen ovale，PFO）合并脑梗死/短暂性脑缺血发作（transient ischemic attack，TIA）患者卵圆孔未闭封堵术预后的影响。

方法

采用回顾性队列研究，纳入2013年1月至2023年12月于陆军军医大学第一附属医院住院并行卵圆孔未闭封堵术的脑梗死或 TIA患者为研究对象。按性别进行分组，收集患者的资料，包括年龄、合并的基础疾病、反常栓塞风险评分（the Risk of Paradoxical Embolism Score，RoPE）评分、检验资料、经胸和经食道超声心动图结果等；术后随访中记录了器械相关血栓（device-related thrombosis，DRT）、卒中、出血和心房颤动等并发症。

结果

一共112例患者选入本研究，其中男性59例，女性53例，平均年龄42.47±12.35岁。女性术前RoPE评分显著高于男性（6.6±1.4 vs 6.0±1.5，P=0.046），二者在梗死部位分布存在性别差异趋势（χ²=10.25，P=0.006），男性更易发生后循环梗死。术中经胸超声测量显示，女性卵圆孔距主动脉根部距离显著大于男性（9.3±2.4 vs 7.6±2.0，P<0.001）。术后中位随访期4年，男性组发生心肌梗死1例、脑出血1例、阵发性心房颤动1例、牙龈出血2例、皮肤淤青1例；女性组发生肺栓塞1例、阵发性心房颤动1例、牙龈出血3例、皮肤淤青2例、脑梗死复发2例、TIA复发2例。总体不良事件发生率方面二者无统计学差异（P=0.291），女性组在脑梗死和TIA复发率方面高于男性，但二者相比无统计学差异（P=0.222）。通过多因素Cox回归分析，并在校正了包括RoPE评分、年龄、高血压、冠心病等多种潜在混杂因素后，本研究结果表明，性别并非患者术后复合终末事件的独立预测因素。

结论

PFO合并脑梗死/TIA患者行卵圆孔未闭封堵术对预后的影响无性别差异，但是女性在脑梗死及TIA复发方面较男性有增加趋势。

卵圆孔未闭  /  脑梗死  /  短暂性脑缺血发作  /  性别
Objective

To investigate the effect of gender on prognosis after transcatheter patent foramen ovale (PFO) closure in patients with cerebral infarction or transient ischemic attack.

Methods

A retrospective cohort study was conducted involving patients with cerebral infarction or transient ischemic attack (TIA) who underwent PFO closure at our hospital between January 2013 and December 2023. The patients were grouped by gender, and related data were collected, including age, comorbidities, Risk of Paradoxical Embolism (RoPE) score, laboratory results, findings of transthoracic/transesophageal echocardiography (TTE/TEE), and post-procedural complications, such as device-related thrombosis (DRT), recurrent stroke, bleeding, and atrial fibrillation (AF).

Results

A total of 112 patients were enrolled, including 59 males and 53 females, at a mean age of 42.47±12.35 years. The females had significantly higher preoperative RoPE score than the males (6.6±1.4 vs 6.0±1.5, P=0.046), and a statistical difference was observed in the distribution of infarction sites between them (Chi-square=10.25, P=0.006), indicating that the males were prone to posterior circulation infarction. Intraoperative transthoracic echocardiography revealed a greater distance from the PFO to the aortic root in the females (9.3±2.4 mm vs 7.6±2.0 mm, P<0.001). During a median follow-up of 4 years, the male group had 1 case of myocardial infarction, 1 cerebral hemorrhage, 1 paroxysmal AF, 2 gingival bleeding episodes, and 1 skin ecchymosis. In the female group, 1 case experienced pulmonary embolism, 1 paroxysmal atrial fibrillation, 3 gingival bleeding episodes, 2 skin ecchymoses, 2 recurrent cerebral infarctions, and 2 recurrent TIAs. There was no statistical difference in overall adverse events between gender (P=0.291). Although the females had higher rates of recurrent cerebral infarction and TIA, this difference lacked statistical significance (P=0.222). Multivariate Cox regression analysis indicated that after adjusting for various potential confounding factors, such as RoPE score, age, hypertension, coronary heart disease, and other factors, gender was not an independent predictor of composite endpoint events after surgery.

Conclusion

Gender does not significantly affect overall prognosis after PFO closure in patients with cerebral infarction or TIA. However, females showed a trend toward higher rates of recurrent cerebral infarction and TIA.

patent foramen ovale  /  cerebral infarction  /  transient ischemic attack  /  gender differences
肖巍巍, 刘锋, 万陈, 许祥, 高昊, 李小龙, 魏欣, 宋治远, 李华康. 女性隐源性卒中患者卵圆孔未闭封堵术后卒中复发风险存在升高趋势：一项随访4年的回顾性队列研究. 陆军军医大学学报, 2025 , 47 (22) : 2805 -2813 . DOI: 10.16016/j.2097-0927.202508075
Weiwei XIAO, Feng LIU, Chen WAN, Xiang XU, Hao GAO, Xiaolong LI, Xin WEI, Zhiyuan SONG, Huakang LI. Elevated risk of recurrent stroke in females after patent foramen ovale closure for cryptogenic stroke:A 4-year retrospective cohort study[J]. Journal of Army Medical University, 2025 , 47 (22) : 2805 -2813 . DOI: 10.16016/j.2097-0927.202508075
正文
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卵圆孔未闭（patent foramen ovale，PFO）是一种普遍存在的心脏结构性病变，在人群中的发病率约25%。当静脉系统血栓经PFO进入动脉系统并栓塞至脑血管（或更罕见的累及冠状动脉、内脏及外周动脉）时，可引发临床症状［1］，如缺血性卒中、偏头痛等。自1877年COHNHEIM首次报道PFO与年轻女性致死性卒中的关联以来，PFO逐渐被确认为全身性血栓事件的潜在媒介［2］。多项研究证实，PFO与心源性卒中密切相关，尤其常见于缺乏其他血管危险因素的年轻患者［1，3］。PFO相关性卒中定义为：存在PFO但无其他明确病因，且伴有皮质大片白质或视网膜梗死的缺血性卒中。其病理机制可能与反常栓塞［4-5］以及心房性心脏病协同致病机制相关［6］，而反常栓塞风险评分（RoPE评分）可用于量化PFO相关卒中的因果概率［7-8］。大量临床研究证据共同确立了PFO封堵术在二级预防中的地位。多项研究（包括关键的荟萃分析及RCT研究）一致表明，与单纯药物治疗（包括抗血小板治疗）相比，PFO封堵术能显著降低缺血性卒中的复发风险，其效果至少不劣于甚至优于药物［5，9-13］。因此，该术式已被国内外指南及中国专家共识推荐为预防隐源性卒中复发的有效策略［14］。随着PFO封堵术的广泛应用，术后预后的影响因素日益受到关注。其中，性别差异在卵圆孔未闭相关脑梗死的流行病学特征、发病机制及治疗转归等方面仍存争议。既往研究提示，在危险因素层面，女性患者更多受到非传统因素的影响［15］，例如先兆偏头痛与妊娠期并发症；相反，男性患者则主要关联于传统血管危险因素，诸如高血压与吸烟史。此外，男性卒中风险表现出对解剖学因素的更强依赖性，例如较高的右向左分流程度或合并房间隔瘤［15-16］。在治疗反应上，性别差异同样显现［17］：PFO封堵术后，男性患者具有更高的急性肾损伤发生风险；而女性患者则在出血并发症及复合终点事件（包括缺血性卒中与短暂性脑缺血发作）方面表现出显著更高的发生率。总体而言，性别作为影响PFO合并脑梗死患者预后的重要因素，其具体作用尚未完全明确，争议依然存在。为明确性别对术后结局的具体作用，本研究通过回顾性分析本中心接受PFO封堵术的脑梗死/短暂性脑缺血发作（transient ischemic attack，TIA）患者队列，旨在探讨性别因素对预后的独立影响。
1　资料与方法
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1.1　研究对象
选择2013年1月至2023年12月在陆军军医大学第一附属医院住院并行PFO封堵术的脑梗死/TIA患者为研究对象。按性别分为男性组和女性组。纳入标准：①年龄16~60岁；②既往明确诊断脑梗死/短暂性脑缺血发作合并卵圆孔未闭患者；③成功行经导管卵圆孔未闭封堵术，排除标准：①术前合并房颤；②临床资料不完整。所有患者签署手术知情同意书，该研究经陆军军医大学第一附属医院伦理委员会批准［（B）KY2024055］。
卵圆孔未闭相关脑梗死诊断标准［14］：①经头颅CT和（或）MRI检测单一皮质梗死或多发小的散在病变；②经头颅CT和（或）MRI检测排除腔隙性缺血性卒中；③经MRA和（或）CTA排除供应缺血脑组织的动脉存在≥50%管腔狭窄程度的颅内外动脉粥样硬化；④无心源性栓塞的高危风险；⑤对18~45岁青年卒中患者及伴其他系统特征的卒中患者需排除其他少见病因，如血管炎、动脉夹层、偏头痛或血管痉挛、药物滥用等。TIA定义为局灶性神经功能缺损症状持续时间<24 h，且影像学检查未发现急性梗死病灶。
1.2　仪器器材
本研究所用PFO封堵装置为北京华医圣杰有限公司生产，其中1例因卵圆孔过大使用了房缺封堵器（上海形状记忆合金）。
1.3　资料收集
从医院心血管病专病库、病历系统收集患者一般信息及相关检查资料，包括年龄、性别、BMI、合并疾病（高血压、冠心病、糖尿病等）、反常栓塞风险评分（the risk of paracloxical embolism score，RoPE）评分、常规化验检查（血常规、血脂、血糖、肾功能等）、经胸超声心动图检查、经食道超声心动图检查、手术术中相关资料、出院时抗栓方案等资料。
1.4　手术过程
所有患者在陆军军医大学第一附属医院心血管内科导管室完成介入手术，主刀手术者均为具有5年以上结构性心脏病介入经验的副主任医师。手术过程：患者取仰卧位，常规消毒铺单，局麻下行右股静脉穿刺，成功后留置静脉鞘，静注肝素。导丝引导下送入右心导管测定肺动脉、右心室和右心房压力。经右心导管将导丝经卵圆孔送至左房，将导管送入左上肺静脉，造影显示肺静脉情况后，将加硬导丝沿右心导管送入左上肺静脉，超声证实卵圆孔未闭，退出右心导管，在导丝引导下将卵圆孔未闭封堵器引导鞘管放至左房，拔出导丝与鞘心，将卵圆孔未闭封堵器装到传送导丝顶端后经引导鞘管送至左房，逐渐释放封堵器嵌顿于房间隔卵圆窝处超声显示封堵良好，观察数分钟，超声下反复推送传送导丝见封堵装置固定良好，遂完全释放卵圆孔未闭封堵器，堵塞卵圆孔未闭成功。撤出导管，无菌敷料加压包扎。
1.5　术后抗栓方案
所有患者术后给予阿司匹林（100 mg/d） + 氯吡格雷（75 mg/d） 双联抗血小板治疗6个月后，改为单药维持1年（阿司匹林100 mg/d或氯吡格雷75 mg/d）。1例患者因术前发现左心房血栓，改用利伐沙班（20 mg/d）抗凝治疗。
1.6　随访方案
患者术后通过门诊、电话和住院进行随访，术后1月、3月、6月及1年各随访1次，以后年度随访。随访内容包括有无出血、栓塞等并发症；检查方面复查心电图、经胸心脏超声，观察有无心律失常、封堵器位置有无移位，有无残余分流及器械相关血栓形成。
预后结局主要包括：脑梗死/TIA的复发、术后出血事件、肺栓塞、心肌梗死及心律失常等复合终末事件。
本研究的主要结局指标为复合终末事件，其定义为术后随访期间发生的任何以下事件：①脑梗死或TIA复发，脑梗死定义为新出现的局灶性神经功能缺损症状或体征，并经头颅CT或MRI证实存在责任梗死灶符合PFO-AS诊断标准；TIA定义为局灶性神经功能缺损症状持续时间<24 h，且影像学检查未发现急性梗死责任病灶。②术后出血事件，定义为需要临床干预或导致血红蛋白显著下降的自发性出血，包括但不限于消化道出血、颅内出血、皮肤黏膜严重出血等。③肺栓塞，经CT肺动脉造影或核素肺通气/灌注扫描确诊的症状性肺栓塞。④心律失常，主要指术后新发的、有临床意义的房颤或房扑，并经心电图或24 h动态心电图记录证实。⑤心肌梗死，a.存在急性心肌损伤的生化证据，定义为血清心脏肌钙蛋白水平至少一次高于正常参考值上限的第99百分位数，并呈现典型的升高和/或回落动态变化；b.同时至少具备一项急性心肌缺血的临床证据，包括但不限于：典型的缺血性胸痛症状、新发生的缺血性心电图改变（如ST-T变化或新出现病理性Q波）、影像学检查提示新的存活心肌丢失或室壁运动异常，或经冠状动脉造影证实存在冠状动脉血栓。
1.7　统计分析
使用SPSS 27和 R 4.4.2软件对收集数据进行统计处理。计量资料进行正态性检验，符合正态分布者以x¯±s表示，两组间比较采用独立样本t检验或单因素方差分析；不符合正态分布者以M（P25，P75）表示，两组间比较采用Mann-Whitney U检验。计数资料以例数（%）表示，组间比较采用χ2检验（或Fisher精确检验）；按分组绘制Kaplan-Meier生存曲线。分析影响预后因素采用多因素Cox回归分析，解决小样本偏倚问题采用Firth回归分析。P<0.05认为差异具有统计学意义。
2　结果
收起
2.1　患者的基线特征
一共112例患者入选本研究，其中男性59例，女性53例，二者相比，女性的RoPE评分更高（P=0.046），二者在脑梗死部位的分布存在差异（P=0.006），男性更易发生后循环梗死，女性更易发生前循环梗死，见表1。
2.2　患者的超声基线特征
基线超声特征比较：男性患者左心室大小、左心室每搏输出量、左心室舒张末期容积、肺动脉内径、升主动脉内径高于女性（P<0.05），见表 2。
2.3　介入术中相关结果
女性患者卵圆孔距主动脉根部距离显著长于男性（P<0.001），而右心房、右心室、左心室各腔室压力大小无统计学差异，见表3。
2.4　术后随访
术后随访中位数4年，最长12年，最短1年，术后共112例患者完成随访。术中心脏超声即时评估及术后住院期间复查经胸超声均未见房间隔水平残余分流。随访期间记录主要不良事件：1例女性发生器械相关血栓（device-related thrombosis，DRT）合并肺栓塞，1例男性发生活动性颅内出血（脑出血），1例男性术后新发心肌梗死。新发阵发性心房颤动共2例（男性1例，女性1例），轻微出血事件中，牙龈出血5例（男性2例，女性3例），皮肤淤青3例（男性1例，女性2例）。在复合终末事件中，男性组与女性组分别记录6例和9例事件，组间比较发生率无明显统计学差异（P=0.291）。由于复合终末总事件数较少（n=15），为避免小样本偏倚，采用Firth回归进行敏感性分析，结果与主分析一致（OR=1.65，95%CI：0.52~5.27，P=0.397），进一步证实性别非终末事件的显著影响因素。术后随访期间，脑梗死复发2例（P=0.222）及TIA复发2例（P=0.478）均发生于女性患者，但两者相比较无统计学差异。对脑梗死后遗症（偏瘫、失语等）的分析显示，11例患者存在后遗症，其中男性占9例，女性占2例，性别差异无统计学意义，（P=0.11），具体见表4。以患者总的终末事件对2组患者做生存分析，两组间未见统计学差异（P=0.319），但女性终末事件较男性有增加的趋势，具体见图1。为评估性别对复合终末事件的独立影响，我们构建了多因素Cox比例风险回归模型，分别校正不同的潜在混杂因素，包括年龄、吸烟、并发症（高血压、冠心病）、RoPE评分、左室后壁厚度等，在所有校正模型中，性别均未显示出与复合终末事件的独立统计学关联，见表5。
3　讨论
收起
近年来，随着心血管疾病介入治疗的广泛应用，性别是否为影响患者预后的独立因素已成为临床研究的重要方向［18］。随着对PFO相关性脑梗死研究的深入，有越来越多的研究关注性别差异对其临床表现和预后的影响。本研究的多因素Cox回归分析揭示，在校正了RoPE评分、年龄、高血压、吸烟史等多种潜在混杂因素后，性别并非复合终末事件的独立预测因素。尽管本研究未发现性别是PFO封堵术后预后的独立预测因素，但这一结论在当前存在争议的研究背景下具有重要价值，提示PFO相关卒中的性别差异问题可能比既往认知更为复杂。
3.1　临床表现差异的探讨
本研究观察到男性后循环梗死比例更高、神经功能缺损症状有更严重的趋势，这与BADEA等［16］认为男性可能是独立危险因素的观点部分吻合。然而，在多因素分析中，性别的影响未达显著性，提示临床症状的严重性可能与性别相关的其他混杂因素有关。例如，男性可能拥有更高的血栓负荷或更活跃的PFO通道［19］，此外男性在体力劳动和Valsalva动作相关活动中的参与度更高，可能更容易引发短暂右向左分流，增加栓塞风险［20］。既往的荟萃研究提示女性患者虽常表现为症状较轻的多发小梗死灶［21］，且RoPE评分通常更高［22］，但本研究中RoPE评分在多因素模型中亦未显示出显著的独立预后价值，这与FARJAT-PASOS等［22］的发现不尽相同，可能与研究人群的异质性有关。此外本研究随访到1位后循环梗死的患者，术后出现了脑积水，这可能与脑干梗死影响脑脊液循环有关，提示对于脑干梗死的患者需要更加警惕脑积水的问题。
3.2　封堵术后预后的性别差异
本研究未发现性别对复合终末事件的独立影响，这与ASGHAR等［23］关于短期预后（包括卒中复发、短暂性脑缺血发作和并发症）无性别差异的结论一致。然而，这与FARJAT-PASOS［22］和张蕾等［24］报告的女性（尤其是老年女性）预后更差的研究存在分歧。这种不一致的可能与其常合并高血压、房颤等基础疾病有关，提示PFO相关栓塞可能并非其主要病因。本研究的分析显示，当校正年龄、高血压等因素后，性别的效应被大大削弱。近期研究进一步指出，女性PFO患者中，自身免疫性疾病［14］、先兆偏头痛［15］等非传统危险因素的高发生率，可能是导致其术后综合预后不良（如卒中复发或出血事件）的关键机制，而这些因素在既往研究中未被充分评估和校正。
3.3　封堵术后房颤发生的性别差异
PFO 封堵术总并发症发生率为1%~3%［19］，其中术后新发房颤是近年来关注焦点。一项荟萃分析［25］指出PFO封堵术后房颤总体发生率为5.1%，显著高于非手术组（1.6%），且不同的封堵器房颤发生率存在差异，如 CardioSEAL 和 Starflex术后房颤发生率可能更高。丹麦国家注册研究［26］提示PFO封堵术本身并未增加长期房颤发生风险，但术后3个月内房颤风险显著增加，因此该时间段内应加强房颤筛查并及时调整抗栓策略。ROHATGI等［27］发现大多数术后房颤发生在封堵术后前45 d，且多为阵发性（良性），仅3.8% 进展为永久性房颤。关于房颤的性别差异，MAS 等［9］发现女性术后房颤发生率高于男性，其机制可能与封堵器相关炎症反应有关。与之相反的是REDUCE 研究［28］证实男性性别是术后房颤的唯一独立预测因子，提示男性患者需尤其警惕术后房颤风险。本研究也证明PFO封堵术后短期房颤发生率为1.8%，均为1月内发生，未发现性别差异。
3.4　本研究局限性
本研究是一项回顾性队列研究，样本量有限，未来需开展多中心、前瞻性研究来进一步验证性别差异是否对于卵圆孔未闭封堵术预后产生影响。
综上所述，本研究表明，在PFO相关脑梗死/TIA患者中，性别并非PFO封堵术后复合终末事件的独立预测因素。尽管观察到临床表现存在某些性别差异，但这些差异可能更多地与年龄、合并症及非传统危险因素等相关联，而非性别本身。未来需要更大规模的前瞻性研究，并在分析中纳入更全面的混杂因素，以进一步探究性别在PFO封堵术后预后中的确切作用。

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2025年第47卷第22期
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doi: 10.16016/j.2097-0927.202508075
  • 接收时间：2025-08-24
  • 首发时间：2026-10-30
  • 出版时间：2025-11-30
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  • 收稿日期：2025-08-24
  • 修回日期：2025-11-10
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    1陆军军医大学（第三军医大学）第一附属医院心血管内科，代谢生物钟与心血管疾病中心
    2老年心脑血管病教育部重点实验室，重庆

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Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
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
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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