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Article(id=1228016572208448486, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1228016566646801206, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202503008, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1740758400000, receivedDateStr=2025-03-01, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1770711566259, onlineDateStr=2026-02-10, pubDate=1758729600000, pubDateStr=2025-09-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1770711566259, onlineIssueDateStr=2026-02-10, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1770711566259, creator=13701087609, updateTime=1770711566259, updator=13701087609, issue=Issue{id=1228016566646801206, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='18', pageStart='3265', pageEnd='3456', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1770711564932, creator=13701087609, updateTime=1770711815039, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1228017615784833769, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1228016566646801206, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1228017615784833770, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1228016566646801206, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=3450, endPage=3456, ext={EN=ArticleExt(id=1228016573349298228, articleId=1228016572208448486, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Relationship between the ratio of non-high-density lipoprotein sterols to high-density lipoprotein cholesterol and new-onset stroke in different glucose metabolic states, columnId=1228016569138213037, journalTitle=Modern Preventive Medicine, columnName=Clinical Medicine and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) and new-onset stroke in different glucose metabolism states, and to provide new perspectives on stroke prevention and treatment.

Methods

Based on data from the China Health and Retirement Longitudinal Study (CHARLS), a total of 8 567 participants were selected to participate in five surveys in 2011, 2013, 2015, 2018, and 2020. First, the cumulative risk of stroke onset was estimated using the Kaplan-Meier method based on NHHR quartile groupings, and the Log-rank test was used to compare differences between groups. Second, the association between NHHR and new-onset stroke in the total population and in individuals with different glucose metabolic status was analyzed using Cox proportional risk regression models, and interaction analyses were performed.

Results

A total of 745 (8.4%) participants had a new stroke during the 9-year follow-up period. The incidence of stroke in the NHHR quartiles from Q1 to Q4 groups was 6.1%, 8.2%, 9.4%, and 11.1%, respectively. Kaplan-Meier analysis showed a significant difference in cumulative incidence risk of stroke among the different NHHR groups (P<0.05). Cox regression modeling showed that the risk of stroke was increased by 34%, 56%, and 75% in Q2, Q3, and Q4 groups, respectively, compared with Q1 group, with HR and 95% CI of 1.34 (1.07-1.68), 1.56 (1.25-1.95), and 1.75 (1.41-2.18). In prediabetic and diabetic patients, elevated NHHR increased the risk of stroke onset, whereas the association was not observed in the normoglycemic group, and there was a significant interaction between NHHR and glucose metabolic status (P=0.020).

Conclusion

NHHR is positively associated with the risk of new stroke and shows different characteristics in different glycaemic states.

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目的

探讨不同糖代谢状态下非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值（NHHR）与新发脑卒中的关系，为脑卒中防治提供新视角。

方法

基于中国健康与养老追踪调查（CHARLS）数据，选择参加2011年、2013年、2015年、2018年和2020年五次调查数据，共计纳入8 567名参与者。首先根据NHHR四分位数分组，采用Kaplan-Meier法估算脑卒中的累积发病风险，并使用Log-rank检验比较组间差异。其次，使用Cox比例风险回归模型分析总人群及不同糖代谢状态个体NHHR与新发脑卒中的关系，并进行交互作用分析。

结果

9年随访期间，共有745（8.4%）名参与者新发脑卒中。NHHR四分位数从Q1到Q4组脑卒中发病率分别为6.1%、8.2%、9.4%和11.1%。Kaplan-Meier分析显示，不同NHHR组脑卒中的累积发病风险存在明显差异(P<0.05)。Cox回归模型显示：与Q1组相比，Q2、Q3和Q4组脑卒中风险分别增加34%、56%和75%，其HR及95% CI分别为1.34（1.07~1.68）、1.56（1.25~1.95）和1.75（1.41~2.18）。在糖尿病前期和糖尿病患者中，NHHR升高会增加脑卒中发病风险，而血糖正常组未观察到该关联，且NHHR与葡萄糖代谢状态存在交互作用（P=0.020）。

结论

NHHR与新发脑卒中风险呈正相关，且在不同糖代谢状态下表现出不同的特征。

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谭志生，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=XGarotrQSWZ/18fNVcn//w==, magXml=PAmfGt7IdvuieAVXM/eyDA==, pdfUrl=null, pdf=mbBT0LWdwP9H88YH3JkAOw==, pdfFileSize=941860, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=PvW7g/a2Oclzv6IzZY2KKw==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=AAYmrIagFK1QBJOuMFGWpA==, mapNumber=null, authorCompany=null, fund=null, authors=

翟燕珍(1979—)，女，本科，副主任护师，研究方向：疾病与健康管理

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Journal of Cardiovascular Translational Research, 2024, 17(1): 133-152., articleTitle=Diabetes mellitus to accelerated atherosclerosis: shared cellular and molecular mechanisms in glucose and lipid metabolism, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1228016576100761867, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, xref=null, ext=[AuthorCompanyExt(id=1228016576134316303, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, companyId=1228016576100761867, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510900, China), AuthorCompanyExt(id=1228016576155287826, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, companyId=1228016576100761867, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=南方医科大学第五附属医院，广东　广州　510900)])], figs=[ArticleFig(id=1228016577992393143, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, language=EN, label=Fig.1, caption=Cumulative risk of stroke in different populations, figureFileSmall=FavJzprgiYvdURON2T6v5A==, figureFileBig=PvW7g/a2Oclzv6IzZY2KKw==, tableContent=null), ArticleFig(id=1228016578084667838, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, language=CN, label=图1, caption=不同人群发生脑卒中的累积风险

注：A:总人群；B：血糖正常人群；C：糖尿病前期人群；D糖尿病人群。

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Basic characteristics of the study population［() or n(%)］

, figureFileSmall=null, figureFileBig=null, tableContent=
基线特征研究对象NHHRF/χ2值P值
Q1Q2Q3Q4
年龄(岁)58.0±8.658.2±9.058.0±8.857.8±8.358.0±8.40.9920.396
性别20.057<0.001
男3 856(45.0)1 041(48.6)900(42.0)941(44.0)974(45.5)
女4 711(55.0)1 101(51.4)1 242(58.0)1 200(56.0)1 168(54.5)
户口类型68.444<0.001
农业7 177(83.8)1 881(87.9)1 833(85.6)1 770(82.7)1 693(79.0)
非农业1 387(16.2)260(12.1)309(14.4)369(17.3)449(21.0)
学历29.874<0.001
文盲3 950(46.1)1 046(48.9)1 003(46.9)976(45.6)925(43.2)
小学1 876(21.9)465(21.7)481(22.5)464(21.7)466(21.8)
初中1 806(21.1)428(20.0)424(19.8)485(22.7)469(21.9)
≥高中929(10.9)202(9.4)232(10.8)214(10.0)281(13.1)
婚姻状况14.0190.003
已婚同居7 267(84.8)1 784(83.3)1 791(83.6)1 832(85.6)1 860(86.8)
其他1 300(15.2)358(16.7)351(16.4)309(14.4)282(13.2)
吸烟8.8840.031
是3 195(37.3)853(39.8)772(36.0)771(36.0)799(37.3)
否5 371(62.7)1 288(60.2)1 370(64.0)1 370(64.0)1 343(62.7)
饮酒(次/月)75.547<0.001
≥12 149(25.1)677(31.6)525(24.5)482(22.5)465(21.7)
<1698(8.2)181(8.5)180(8.4)161(7.5)176(8.2)
不喝酒5 717(66.8)1 282(59.9)1 437(67.1)1 498(70.0)1 500(70.1)
心脏病23.724<0.001
是928(10.9)198(9.3)220(10.3)219(10.3)291(13.6)
否7 606(89.1)1 931(90.7)1 916(89.7)1 915(89.7)1 844(86.4)
高血压137.096<0.001
是3 099(36.2)607(28.4)704(32.9)839(39.2)949(44.3)
否5 464(63.8)1 534(71.6)1 438(67.1)1 300(60.8)1 192(55.7)
血糖状况439.437<0.001
正常3 419(39.9)1 062(49.6)971(45.3)841(39.3)545(25.4)
糖尿病前期3 788(44.2)879(41.0)902(42.1)992(46.3)1 015(47.4)
糖尿病1 360(15.9)201(9.4)269(12.6)308(14.4)582(27.2)
), ArticleFig(id=1228016578936111598, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, language=CN, label=表1, caption=

研究对象的基本特征［()或n(%)］

, figureFileSmall=null, figureFileBig=null, tableContent=
基线特征研究对象NHHRF/χ2值P值
Q1Q2Q3Q4
年龄(岁)58.0±8.658.2±9.058.0±8.857.8±8.358.0±8.40.9920.396
性别20.057<0.001
男3 856(45.0)1 041(48.6)900(42.0)941(44.0)974(45.5)
女4 711(55.0)1 101(51.4)1 242(58.0)1 200(56.0)1 168(54.5)
户口类型68.444<0.001
农业7 177(83.8)1 881(87.9)1 833(85.6)1 770(82.7)1 693(79.0)
非农业1 387(16.2)260(12.1)309(14.4)369(17.3)449(21.0)
学历29.874<0.001
文盲3 950(46.1)1 046(48.9)1 003(46.9)976(45.6)925(43.2)
小学1 876(21.9)465(21.7)481(22.5)464(21.7)466(21.8)
初中1 806(21.1)428(20.0)424(19.8)485(22.7)469(21.9)
≥高中929(10.9)202(9.4)232(10.8)214(10.0)281(13.1)
婚姻状况14.0190.003
已婚同居7 267(84.8)1 784(83.3)1 791(83.6)1 832(85.6)1 860(86.8)
其他1 300(15.2)358(16.7)351(16.4)309(14.4)282(13.2)
吸烟8.8840.031
是3 195(37.3)853(39.8)772(36.0)771(36.0)799(37.3)
否5 371(62.7)1 288(60.2)1 370(64.0)1 370(64.0)1 343(62.7)
饮酒(次/月)75.547<0.001
≥12 149(25.1)677(31.6)525(24.5)482(22.5)465(21.7)
<1698(8.2)181(8.5)180(8.4)161(7.5)176(8.2)
不喝酒5 717(66.8)1 282(59.9)1 437(67.1)1 498(70.0)1 500(70.1)
心脏病23.724<0.001
是928(10.9)198(9.3)220(10.3)219(10.3)291(13.6)
否7 606(89.1)1 931(90.7)1 916(89.7)1 915(89.7)1 844(86.4)
高血压137.096<0.001
是3 099(36.2)607(28.4)704(32.9)839(39.2)949(44.3)
否5 464(63.8)1 534(71.6)1 438(67.1)1 300(60.8)1 192(55.7)
血糖状况439.437<0.001
正常3 419(39.9)1 062(49.6)971(45.3)841(39.3)545(25.4)
糖尿病前期3 788(44.2)879(41.0)902(42.1)992(46.3)1 015(47.4)
糖尿病1 360(15.9)201(9.4)269(12.6)308(14.4)582(27.2)
), ArticleFig(id=1228016579049357813, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, language=EN, label=Table 2, caption=

Relationship between NHHR quartiles and new strokes

, figureFileSmall=null, figureFileBig=null, tableContent=
NHHR脑卒中人数/总人数模型1模型2
HR(95% CI)P值HR (95% CI)P值
Q1131/2 1421.00(ref)1.00(ref)
Q2175/2 1421.38(1.10~1.73)0.0061.34(1.07~1.68)0.012
Q3202/2 1411.63(1.31~2.04)<0.0011.56(1.25~1.95)<0.001
Q4237/2 1421.92(1.55~2.37)<0.0011.75(1.41~2.18)<0.001
趋势性检验<0.001<0.001
), ArticleFig(id=1228016579162604029, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, language=CN, label=表2, caption=

NHHR四分位数与新发脑卒中的关系

, figureFileSmall=null, figureFileBig=null, tableContent=
NHHR脑卒中人数/总人数模型1模型2
HR(95% CI)P值HR (95% CI)P值
Q1131/2 1421.00(ref)1.00(ref)
Q2175/2 1421.38(1.10~1.73)0.0061.34(1.07~1.68)0.012
Q3202/2 1411.63(1.31~2.04)<0.0011.56(1.25~1.95)<0.001
Q4237/2 1421.92(1.55~2.37)<0.0011.75(1.41~2.18)<0.001
趋势性检验<0.001<0.001
), ArticleFig(id=1228016579288433160, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, language=EN, label=Table 3, caption=

Relationship between NHHR quartiles of new strokes in different glucose metabolic states

, figureFileSmall=null, figureFileBig=null, tableContent=
NHHR脑卒中人数/总人数模型1模型2
HR(95% CI)P值HR (95% CI)P值
正常人群
Q163/1 0621.00(ref)1.00(ref)
Q269/9711.21(0.86~1.70)0.2841.19(0.84~1.67)0.333
Q365/8411.36(0.96~1.92)0.0831.32(0.93~1.88)0.122
Q446/5451.44(0.99~2.11)0.0591.38(0.94~2.03)0.101
趋势性检验0.2090.325
糖尿病前期
Q156/8791.00(ref)1.00(ref)
Q273/9021.34(0.95~1.90)0.0991.30(0.91~1.84)0.146
Q3105/9921.80(1.30~2.49)<0.0011.74(1.25~2.42)0.001
Q4110/1 0151.87(1.36~2.59)<0.0011.77(1.28~2.46)0.001
趋势性检验<0.0010.001
糖尿病
Q112/2011.00(ref)1.00(ref)
Q233/2692.22(1.15~4.31)0.0182.17(1.11~4.22)0.023
Q332/3081.91(0.98~3.72)0.0581.77(0.91~3.47)0.095
Q481/5822.63(1.43~4.84)0.0022.28(1.23~4.22)0.009
趋势性检验0.0140.057
), ArticleFig(id=1228016579389096468, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1228016572208448486, language=CN, label=表3, caption=

不同糖代谢状态下NHHR四分位数新发脑卒中的关系

, figureFileSmall=null, figureFileBig=null, tableContent=
NHHR脑卒中人数/总人数模型1模型2
HR(95% CI)P值HR (95% CI)P值
正常人群
Q163/1 0621.00(ref)1.00(ref)
Q269/9711.21(0.86~1.70)0.2841.19(0.84~1.67)0.333
Q365/8411.36(0.96~1.92)0.0831.32(0.93~1.88)0.122
Q446/5451.44(0.99~2.11)0.0591.38(0.94~2.03)0.101
趋势性检验0.2090.325
糖尿病前期
Q156/8791.00(ref)1.00(ref)
Q273/9021.34(0.95~1.90)0.0991.30(0.91~1.84)0.146
Q3105/9921.80(1.30~2.49)<0.0011.74(1.25~2.42)0.001
Q4110/1 0151.87(1.36~2.59)<0.0011.77(1.28~2.46)0.001
趋势性检验<0.0010.001
糖尿病
Q112/2011.00(ref)1.00(ref)
Q233/2692.22(1.15~4.31)0.0182.17(1.11~4.22)0.023
Q332/3081.91(0.98~3.72)0.0581.77(0.91~3.47)0.095
Q481/5822.63(1.43~4.84)0.0022.28(1.23~4.22)0.009
趋势性检验0.0140.057
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不同糖代谢状态下非高密度脂蛋白胆固醇和高密度脂蛋白胆固醇的比值与新发脑卒中的关系
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翟燕珍 , 谭志生
现代预防医学 | 临床与预防 2025,52(18): 3450-3456
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现代预防医学 | 临床与预防 2025, 52(18): 3450-3456
不同糖代谢状态下非高密度脂蛋白胆固醇和高密度脂蛋白胆固醇的比值与新发脑卒中的关系
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翟燕珍, 谭志生
作者信息
  • 南方医科大学第五附属医院，广东　广州　510900

    • 翟燕珍(1979—)，女，本科，副主任护师，研究方向：疾病与健康管理

通讯作者:

谭志生，E-mail:
Relationship between the ratio of non-high-density lipoprotein sterols to high-density lipoprotein cholesterol and new-onset stroke in different glucose metabolic states
Yan-zhen ZHAI, Zhi-sheng TAN
Affiliations
  • The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510900, China
出版时间: 2025-09-25 doi: 10.20043/j.cnki.MPM.202503008
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摘要
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目的

探讨不同糖代谢状态下非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值（NHHR）与新发脑卒中的关系，为脑卒中防治提供新视角。

方法

基于中国健康与养老追踪调查（CHARLS）数据，选择参加2011年、2013年、2015年、2018年和2020年五次调查数据，共计纳入8 567名参与者。首先根据NHHR四分位数分组，采用Kaplan-Meier法估算脑卒中的累积发病风险，并使用Log-rank检验比较组间差异。其次，使用Cox比例风险回归模型分析总人群及不同糖代谢状态个体NHHR与新发脑卒中的关系，并进行交互作用分析。

结果

9年随访期间，共有745（8.4%）名参与者新发脑卒中。NHHR四分位数从Q1到Q4组脑卒中发病率分别为6.1%、8.2%、9.4%和11.1%。Kaplan-Meier分析显示，不同NHHR组脑卒中的累积发病风险存在明显差异(P<0.05)。Cox回归模型显示：与Q1组相比，Q2、Q3和Q4组脑卒中风险分别增加34%、56%和75%，其HR及95% CI分别为1.34（1.07~1.68）、1.56（1.25~1.95）和1.75（1.41~2.18）。在糖尿病前期和糖尿病患者中，NHHR升高会增加脑卒中发病风险，而血糖正常组未观察到该关联，且NHHR与葡萄糖代谢状态存在交互作用（P=0.020）。

结论

NHHR与新发脑卒中风险呈正相关，且在不同糖代谢状态下表现出不同的特征。

非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇  /  脑卒中  /  糖代谢状态  /  队列研究
Objective

To investigate the relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) and new-onset stroke in different glucose metabolism states, and to provide new perspectives on stroke prevention and treatment.

Methods

Based on data from the China Health and Retirement Longitudinal Study (CHARLS), a total of 8 567 participants were selected to participate in five surveys in 2011, 2013, 2015, 2018, and 2020. First, the cumulative risk of stroke onset was estimated using the Kaplan-Meier method based on NHHR quartile groupings, and the Log-rank test was used to compare differences between groups. Second, the association between NHHR and new-onset stroke in the total population and in individuals with different glucose metabolic status was analyzed using Cox proportional risk regression models, and interaction analyses were performed.

Results

A total of 745 (8.4%) participants had a new stroke during the 9-year follow-up period. The incidence of stroke in the NHHR quartiles from Q1 to Q4 groups was 6.1%, 8.2%, 9.4%, and 11.1%, respectively. Kaplan-Meier analysis showed a significant difference in cumulative incidence risk of stroke among the different NHHR groups (P<0.05). Cox regression modeling showed that the risk of stroke was increased by 34%, 56%, and 75% in Q2, Q3, and Q4 groups, respectively, compared with Q1 group, with HR and 95% CI of 1.34 (1.07-1.68), 1.56 (1.25-1.95), and 1.75 (1.41-2.18). In prediabetic and diabetic patients, elevated NHHR increased the risk of stroke onset, whereas the association was not observed in the normoglycemic group, and there was a significant interaction between NHHR and glucose metabolic status (P=0.020).

Conclusion

NHHR is positively associated with the risk of new stroke and shows different characteristics in different glycaemic states.

NHHR  /  Stroke  /  Glucose metabolic status  /  Cohort study
翟燕珍, 谭志生. 不同糖代谢状态下非高密度脂蛋白胆固醇和高密度脂蛋白胆固醇的比值与新发脑卒中的关系. 现代预防医学, 2025 , 52 (18) : 3450 -3456 . DOI: 10.20043/j.cnki.MPM.202503008
Yan-zhen ZHAI, Zhi-sheng TAN. Relationship between the ratio of non-high-density lipoprotein sterols to high-density lipoprotein cholesterol and new-onset stroke in different glucose metabolic states[J]. Modern Preventive Medicine, 2025 , 52 (18) : 3450 -3456 . DOI: 10.20043/j.cnki.MPM.202503008
正文
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脑卒中因其高发病率、高致残率和高致死率的“三高”特点，成为全球范围内导致成年人致残和死亡的主要原因之一[1]。近年来，随着人口老龄化趋势的加剧和生活方式的改变，脑卒中的发病率呈上升趋势。尤其在我国，脑卒中的发生例数已从1990年的170万增至2019年的390万，增长幅度高达124%，且呈现出年轻化趋势[2]。因此，识别脑卒中的危险因素，对于预防和减少脑卒中的发生发展具有重要意义。
血脂异常和血糖代谢异常是脑卒中的重要危险因素[3-4]。血脂异常主要表现为总胆固醇（Total cholesterol，TC）、甘油三酯（triglycerides，TG）和低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）水平升高，以及高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）水平降低，这些均可促进动脉粥样硬化的形成，增加脑卒中的发病风险[5]。此外，糖代谢异常，包括糖尿病前期和糖尿病，可通过引发氧化应激、慢性炎症和内皮功能障碍等机制，进一步损害血管的重塑和生长，导致脑血管疾病的发生[6]。
近年来，非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值(non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio，NHHR)作为一种新兴的血脂评估指标，逐渐受到学术界关注。NHHR不仅能有效反映血脂异常情况，还与心血管疾病的发生风险密切相关[7-8]。然而，关于NHHR与脑卒中风险之间的关系，尤其是在不同糖代谢状态下，目前的研究仍相对缺乏。鉴于此，本研究基于中国健康与养老追踪调查的数据，深入分析了不同糖代谢状态下NHHR与新发脑卒中之间的关系，旨在为脑卒中的预防和干预提供新的视角和科学依据。
1　对象和方法
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1.1　研究对象
本研究数据来源于中国健康与养老追踪调查（the China Health and Retirement Longitudinal Study ,CHARLS）。CHARLS是一项针对中国45岁及以上人群及其配偶的全国代表性纵向调查，旨在收集能够反映中国45岁以上家庭与个人情况的高质量微观数据，以分析中国人口老龄化现状，推动老龄化的跨学科研究[9]。该调查项目已获得北京大学生物医学伦理委员会批准，所有参与者均已签署知情同意书。
本研究选取了CHARLS在2011年、2013年、2015年、2018年和2020年开展的五次调查数据。其中，2011年调查的样本量为17 707人。基于以下原因对样本进行了筛选，最终共排除了9 140名个体：（1）年龄<45岁；（2）基线时(2011年)已患有脑卒中；（3）缺乏TC和HDL-C信息；（4）缺失血糖信息；（5）在后续随访过程中发生失访。经过细致筛选，本研究最终共纳入8 567名研究对象。
在本研究中，共有2 429（22.1%）名研究对象发生失访。失访者的平均年龄为64.2±10.9岁，其中男性1 320（54.3%）人，女性1 109（45.7%）人。为了评估是否有选择偏倚，对失访者与未失访者的人口学特征（包括年龄、性别、学历、婚姻状况等）以及健康相关因素（如吸烟、饮酒、高血压、心脏病等）进行了详细比较。统计学检验结果显示，失访者与未失访者在上述各项特征及健康因素上均未发现显著差异（P>0.05）。
1.2　资料收集
1.2.1　NHHR
在采集血液样本前，受试者需禁食一晚。主要采集研究对象的静脉血，样本采集由当地疾控中心的专业人员负责。采集后的静脉血经过初步分离处理，并在低温条件下运输至中国疾控中心的实验室进行后续分析。其中，TC、HDL-C和空腹血糖的测定采用酶比色法；糖化血红蛋白的测定采用高效液相色谱法。NHHR的计算公式为：NHHR=(TC - HDL-C) / HDL-C，即通过总胆固醇减去高密度脂蛋白胆固醇后的差值，再除以高密度脂蛋白胆固醇得出。
1.2.2　血糖状况
本研究中，糖尿病的诊断标准为：空腹血糖（FPG）≥126 mg/dL或糖化血红蛋（HbA1c）≥6.5%，或受试者自我报告曾被医生诊断为糖尿病，或正在服用降糖药物。糖尿病前期的判定标准为空腹血糖（FPG）为100~125 mg/dL或糖化血红蛋白（HbA1c）为5.7%~6.4%[10]。既不符合糖尿病诊断标准，也不符合糖尿病前期标准的受试者被归类为正常人群。
1.2.3　脑卒中、高血压和心脏病
脑卒中的诊断基于研究对象是否曾被医生确诊患有脑卒中。
高血压的诊断标准为：研究对象自我报告曾被医生诊断为高血压，或正在使用抗高血压药物，或其平均收缩压/舒张压（SBP/DBP）≥140/90 mmHg[11]。
心脏病的诊断则基于研究对象是否曾被医生确诊患有心脏病。
1.3　协变量
所有协变量均由经过专业培训的访谈者在基线调查时通过标准化问卷获得。问卷内容涵盖人口学特征和健康相关因素。人口学特征包括年龄、性别、户口类型、婚姻状况和学历，其中婚姻状况分为“已婚同居”和其他类型，学历分为文盲、小学、中学、高中及以上。健康相关因素则包括自我报告的吸烟和饮酒情况，以及医生诊断的疾病（如高血压、糖尿病、心脏病、中风）。
1.4　统计学方法
使用SPSS 26.0和R软件(4.2.2版)进行统计分析。连续变量用均数±标准差进行描述，而分类变量则以计数（百分比）呈现。基线特征的比较中，连续变量采用单因素方差分析，分类变量则采用卡方检验。
本研究首先根据NHHR的四分位数将研究对象分为四组：Q1（NHHR≤2.094）、Q2（2.094<NHHR≤2.835）、Q3（2.835<NHHR≤3.786）和Q4（NHHR>3.786）。随后，采用Kaplan-Meier法估算各组新发脑卒中的累积发病风险，并通过Log-rank检验比较组间差异。其次，运用Cox比例风险回归模型分析NHHR与新发脑卒中风险之间的关系。此外，为探究不同糖代谢状态下NHHR与新发脑卒中的关系，分别对正常人群、糖尿病前期人群和糖尿病人群进行了分层分析，并分析其潜在的交互作用。本研究采用双侧检验，检验水准为α=0.05。
2　结果
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2.1　研究对象基本特征
本研究共纳入8 567名参与者，其平均年龄为58.0±8.6岁，其中男性3 856人（45.0%），女性4 711人（55.0%）。在糖代谢状况方面，3 419名研究对象（39.9%）血糖正常，3 788人（44.2%）被诊断为糖尿病前期，1 360人（15.9%）患有糖尿病。此外，10.9%的研究对象报告患有心脏病，36.2%的研究对象患有高血压。
在NHHR四分位数分布上，与最低四分位数的参与者相比，NHHR四分位数较高的参与者往往更年轻，且更倾向于为女性、非农业户口、已婚同居，并具有更高的教育程度。进一步比较不同NHHR四分位数参与者的基线特征发现，四个亚组在性别、户口类型、学历、婚姻状况、吸烟和饮酒习惯、高血压、心脏病以及血糖状况等方面均存在显著差异（P<0.05），具体结果见表1。
2.2　NHHR四分位数与新发脑卒中风险
在长达9年的随访期间，共有745（8.4%）名参与者新发脑卒中。按NHHR四分位数分组，从Q1到Q4，脑卒中的发病率分别为6.1%、8.2%、9.4%和11.1%。Kaplan-Meier生存分析曲线（图1A）显示，不同NHHR四分位数组的脑卒中累积发病率存在显著差异（P<0.001）。在调整性别、年龄、学历、婚姻状况等潜在混杂因素后（模型2），与NHHR最低的Q1组相比，Q2、Q3和Q4组的脑卒中风险分别增加34%、56%和75%，其HR及95% CI分别为1.34（1.07~1.68）、1.56（1.25~1.95）和1.75（1.41~2.18）。
2.3　不同糖代谢状态下NHHR四分位数与新发脑卒中风险
在9年随访期间，血糖正常的参与者中有243人（7.1%）新发脑卒中；糖尿病前期的参与者中有344人（9.1%）新发脑卒中，糖尿病患者中有158人（11.6%）新发脑卒中。Kaplan-Meier曲线（图1B~D）显示，不同NHHR四分位数组中，糖尿病前期和糖尿病患者的脑卒中累积发病风险存在显著差异（P<0.05），而血糖正常组的NHHR四分位数组间无显著差异（P=0.231）。
表3结果显示，在调整潜在混杂因素后（模型2），对于糖尿病前期患者，与Q1组相比，Q3组的HR为1.74（95% CI： 1.25~2.42），Q4组的HR为1.77（95% CI：1.28~2.46）。对于糖尿病患者，Q2组的HR为2.17（95% CI ：1.11~4.22），Q4组的HR为2.28（95% CI ：1.23~4.22）。然而，在血糖正常组中，NHHR四分位数组之间未观察到显著差异（所有P值>0.05）。
2.4　交互作用分析
本研究进一步探究了NHHR四分位数与血糖状态对脑卒中风险的交互作用。结果显示，NHHR与血糖状态之间存在显著的交互作用（P=0.020）。具体而言，NHHR对脑卒中风险的影响在不同血糖状态下有所不同。在正常血糖状态下，NHHR的增加并不会增加脑卒中的发病风险；而在糖尿病前期和糖尿病状态下，NHHR的增加会导致脑卒中风险的增加。
3　讨论
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本研究基于中国健康与养老追踪调查（CHARLS）的数据，探讨了不同糖代谢状态下NHHR与新发脑卒中之间的关系。研究结果表明，NHHR与新发脑卒中风险呈正相关，且在不同糖代谢状态下表现出不同的特征。具体而言，在糖尿病前期和糖尿病患者中，NHHR升高会增加脑卒中发病风险，而在血糖正常人群中未观察到这种关联。
近年来，NHHR作为一种新兴的血脂评估指标，逐渐受到广泛关注。NHHR综合了总胆固醇和高密度脂蛋白胆固醇信息，能够更全面地反映个体的血脂代谢状态[12]。与传统血脂指标相比，NHHR不仅涵盖了动脉粥样硬化的主要危险因素（如LDL-C和TC），还纳入了具有抗动脉粥样硬化作用的HDL-C，因此被认为是一种更具综合性的血脂风险评估指标[7]。本研究发现，NHHR的四分位数越高，新发脑卒中的风险也越高，这一结果与既往研究一致。例如，Ma等人在一项包含29 928名成年人的横断面研究中发现，NHHR与脑卒中患病率呈正相关[13]；同样，Liu等人在一项包含9 259名参与者的前瞻性队列研究中也发现，NHHR的升高是中国中老年人脑卒中和心脏病的重要危险因素[14]。高水平的NHHR导致脑卒中风险增加的潜在机制可能与其所反映的血脂异常对血管内皮功能的损害密切相关。高NHHR值通常提示个体存在较高的LDL-C水平和较低的HDL-C水平，这种血脂谱可能促进动脉粥样硬化的发展，进而增加脑卒中的发生风险[15-16]。
本研究的另一个重要发现是，NHHR与新发脑卒中的关系在不同糖代谢状态下表现出显著差异。具体而言：在糖尿病前期和糖尿病患者中，NHHR升高与脑卒中风险增加呈正相关，而在血糖正常人群中未观察到这种关联。这一结果提示，糖代谢异常可能加剧了NHHR对脑卒中风险的影响。糖尿病前期和糖尿病患者常伴有胰岛素抵抗、慢性炎症和氧化应激等病理生理改变，这些因素可能导致血管内皮功能障碍和动脉粥样硬化的加速发展[17-18]，从而在糖代谢异常的背景下，NHHR的升高可能进一步推动动脉粥样硬化进程，增加脑卒中的风险[8]。此外，本研究还发现NHHR与糖代谢状态之间存在显著交互作用（P=0.020），这进一步证实了糖代谢状态在NHHR与脑卒中风险关系中的调节作用，提示我们在临床实践中，对于糖代谢异常的个体，应更加重视NHHR的监测和管理，以更精准地评估脑卒中风险。
本研究结果为脑卒中的预防和干预提供了新的视角。一方面，NHHR作为一种简单且易于计算的血脂评估指标，有望成为脑卒中风险评估的重要工具，尤其在糖代谢异常的高危人群中更具应用价值。另一方面，本研究凸显了糖代谢状态在脑卒中发病机制中的重要作用，提示在未来的脑卒中预防策略中，应将血脂管理和血糖代谢调控相结合，以实现更精准的风险评估和更有效的干预措施。
尽管本研究采用了前瞻性队列研究设计，但仍存在一些局限性。首先，脑卒中相关信息是通过问卷调查收集的，这可能会导致回忆偏倚。其次，本研究不能对脑卒中类型（如缺血性脑卒中和出血性脑卒中）进行区分，而这两类脑卒中的发病机制和危险因素可能存在差异。未来的研究应进一步探讨NHHR与不同类型脑卒中之间的关系，并在更多人群中验证本研究的发现。最后，尽管本研究调整了多个混杂因素，但仍可能存在一些潜在的混杂因素，如饮食习惯、体力活动水平等，这些因素也可能会影响脑卒中发生风险。
综上所述，本研究揭示了NHHR与新发脑卒中风险之间的正相关性，并强调了糖代谢状态在其中的关键作用。这些发现为脑卒中的预防和干预提供了新的科学依据，提示在未来的临床实践中，应更加重视糖代谢异常人群的血脂管理，以有效降低脑卒中的发生风险。
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doi: 10.20043/j.cnki.MPM.202503008
  • 接收时间：2025-03-01
  • 首发时间：2026-02-10
  • 出版时间：2025-09-25
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    南方医科大学第五附属医院，广东　广州　510900

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谭志生，E-mail:
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